Aggregation-induced emission photosensitizer/bacteria biohybrids enhance Cerenkov radiation-induced photodynamic therapy by activating anti-tumor immunity for synergistic tumor treatment.
Cerenkov radiation-induced photodynamic therapy (CR-PDT) gets rid of the limited tissue penetration depth of the external light source and provides a feasible scheme for the PDT excited by the internal light. However, due to the low luminescence intensity of Cerenkov radiation, CR-PDT alone cannot effectively inhibit tumor growth, curbing the potential clinical translation of CR-PDT. Herein, we reported an AIE-PS/bacteria biohybrid (EcN@TTVP) composed of Escherichia coli Nissle 1917 (EcN) loaded with aggregation-induced emission photosensitizer (AIE-PS) termed TTVP, which enhanced CR-PDT by activating anti-tumor immunity for synergistic tumor treatment. The preferential tumor-colonized EcN@TTVP and radiopharmaceutical 18F-fluorodeoxyglucose (18F-FDG) were administered sequentially to enable them to co-enrich in the tumor site, thereby triggering CR-PDT and promoting immunogenic tumor cell death. Most importantly, EcN acting as immunoadjuvants enhanced the maturation of dendritic cells (DCs) and priming of cytotoxic T cells (CTLs). Therefore, under the synergistic treatment of CR-PDT and immunotherapy, AIE-PS/bacteria biohybrids resulted in either efficient tumor remission or a survival prolongation in tumor-bearing mice, which presented significant advantages over single CR-PDT. Remarkably, no obvious toxic effects were observed during the treatment. In this study, we proposed a synergistic therapeutic strategy based on EcN@TTVP for combined CR-PDT and immunotherapy against tumors. Moreover, this strategy may have great potential in clinical translation and provide references for deep-seated tumor treatment. STATEMENT OF SIGNIFICANCE: PDT is restricted due to the shallow penetration depth of light into tumor tissues. Using CR as the excitation light source for PDT can overcome the aforementioned issue and greatly expand the application of PDT. However, the low efficacy of single CR-PDT limits further its applications. Therefore, the design and development of feasible strategies to improve the efficacy of CR-PDT are of immediate importance. Introducing probiotics to our study can be used not only as tumor-targeting carriers of photosensitizers but also as immunoadjuvants. Under co-stimulation by immunogenic tumor cell death triggered by CR-PDT and probiotics acting as immunoadjuvants, anti-tumor immune responses were effectively activated, thus remarkably enhancing the efficacy of CR-PDT.


Chronic Kidney Disease Alters Vitamin A Homeostasis via Effects on Hepatic RBP4 Protein Expression and Metabolic Enzymes.
Vitamin A, via retinoic acid (RA), is a critical micronutrient. Normally, plasma concentrations are tightly regulated. Concentrations of vitamin A metabolites (13cis-RA, atRA) and relationships between RBP4 and retinoids have never been fully evaluated in adult patients with CKD. We measured retinoid and RBP4 concentrations in plasma and urine from 55 adult patients with CKD and 21 matched healthy subjects. RBP4 and retinol levels were increased approximately twofold in patients with CKD, with a negative correlation between plasma retinol and eGFR (p = 0.006) and plasma RBP4 and eGFR (p = 0.0007). RBP4 renal clearance was higher in patients with CKD than healthy subjects but not associated with eGFR. Circulating concentrations of atRA increased and concentrations of 13cis-RA decreased in subjects with CKD with no change in RA-to-retinol ratio. Increases in circulating retinol, RBP4, and atRA may be due to increased hepatic RBP4 synthesis, retinyl ester hydrolysis, and/or hepatic secretion of RBP4-retinol.


Avoidant coping style and post-traumatic stress following motor vehicle accidents.
Predictors of post-traumatic intrusive symptomatology were studied in 56 motor vehicle accident (MVA) survivors 12 months after their MVA. Measures were obtained on Ss' subjective response to the trauma, objective indices of injury severity, coping response (Coping Style Questionnaire), and post-traumatic stress (Impact of Event Scale; IES). Significant levels of intrusive and avoidance symptomatology were reported by 20% of MVA survivors. An avoidant coping style and compensation accounted for 41% of variance of IES-Intrusion scores. Findings are discussed in terms of the role of avoidance behaviour in post-traumatic adjustment.


Pure Laparoscopic Donor Right Hepatectomy for Rare Non-Bifurcation Portal Vein Variation Donor and Reconstruction Technique.
Pure laparoscopic donor right hepatectomy (PLDRH) is a technical demanding procedure, and many centers have strict selection criteria especially an anatomical variation. Portal vein variation is considered as a contra-indication for this procedure in most centers. We presented a case of PLDRH in donor who had rare non-bifurcation portal vain variation. The donor was 45-year-old female. Pre-operative imaging showed a rare non-bifurcation portal vain variation. The procedure was following the routine step of laparoscopic donor right hepatectomy except the hilar dissection phase. All portal branches should not be dissected before division of bile duct to prevent vascular injury. Regarding bench surgery, all portal branches were reconstructed together. Finally, the explanted portal vein bifurcation was used to reconstruct all portal vein branches as a single orifice. The liver graft was successfully transplanted. The graft was well functioned, and all portal branches were patented. This technique facilitated identification and safely divided all portal branches. PLDRH in donor with this rare portal vein variation can be performed safely by a highly experienced team and good reconstruction technique. Pure laparoscopic donor right hepatectomy (PLDRH) is a technical demanding procedure, and many centers have strict selection criteria especially an anatomical variation. Portal vein variation is considered as a contra-indication for this procedure in most centers. Lapisatepun and colleagues report PLDRH in rare non-bifurcation portal vein variation, and reconstruction technique was scanty reported.


Neuroanatomical localization of substance p: implications for central cardiovascular control.
The presence of substance P (SP) neurons in pathways known to be involved in the central control of the cardiovascular system has been studied with neuroanatomical and neurochemical techniques. SP-immunoreactive (SP-I) neurons are found in afferent baro- and chemoreceptor pathways which transmit information from peripheral receptors to the nucleus tractus solitarius. In addition, SP-I neurons located in the nucleus interfascicularis hypoglossi of the ventral medulla innervate the intermediolateral cell column, the site of origin of preganglionic sympthetic nerves. The role of these SP-I neurons in cardiovascular control remains to be determined.


Performance measurement for green supplier selection based on data envelopment analysis.
With increasing global awareness of sustainable development and environmental protection, the importance of green supplier selection has become widely recognized. Recently, more and more literature focus on the green supplier selection issue and measurement of supplier performance; the measurement indicators mainly defined two sets of criteria, including management criteria and green criteria. A novel methodology based on data envelopment analysis (DEA) has been developed, which is effective for solving multi-criteria decision problems in supplier selection and evaluating the performance of a set of homogeneous decision-making units (DMUs). To solve the green supplier selection problem, previous studies apply the DEA method by dividing management criteria as inputs and green criteria as outputs. This paper aims to propose a DEA-type green supplier selection methodology by considering the management criteria and green criteria. Unlike the previous method, we define a reasonable and effective division of measurement indicators, where management criteria consist of input variables, desirable and undesirable output variables, while green criteria consist of desirable and undesirable output variables. We also provide an improved model with multi-criteria and multi-objective programming by considering DEA efficiency decomposition, which evaluates management, green, and overall efficiency of candidate suppliers simultaneously. The multi-criteria decision model will help companies to select the best green supplier. To demonstrate the applicability and effectiveness of our proposed model, we present a numerical example at last.


Epidemiological and clinical characteristics of patients with human monkeypox infection in Mexico: a nationwide observational study.
Human monkeypox, a zoonosis historically endemic to West and South Africa, has led to a worldwide outbreak driven by human-to-human transmission resulting in an international public health emergency. Endemic and outbreak monkeypox cases may differ in their affected populations, clinical features, and outcomes. Thus, profiling cases of the current monkeypox outbreak worldwide is crucial. We performed a nationwide observational surveillance-based study from May 24 to September 5, 2022. Patients that met the operational clinical definition of monkeypox or symptomatic close contacts of confirmed cases were tested by real-time polymerase chain reaction. Clinical data were collected with a standardized case-report form. We report epidemiologic, sociodemographic, and clinical characteristics of confirmed cases. Five-hundred and sixty-five human monkeypox confirmed cases were analysed; 97.2% were men, of whom 59.5% identified as men who have sex with men, and 54.5% had human immunodeficiency virus infection. The median age was 34 years. All patients but one had rash (99.8%), 78.9% had fever, and 47.8% reported myalgia. The anogenital area was the most commonly affected one by rash (49.6%), and proctitis occurred in 6.2% of patients. Six patients required hospitalization, of which one died due to causes unrelated to monkeypox. The 2022 monkeypox outbreak in Mexico is mainly driven by middle-aged men who have sex with men, of which a large proportion are persons who live with human immunodeficiency virus infection. Clinical features such as the high proportion of anogenital lesions suggest sexual contact is a pivotal transmission mechanism in this outbreak. This research was supported by grant A1-S-18342 from Consejo Nacional de Ciencia y Tecnología (CONACyT), Mexico (to S.I.V.-F.).


A multimedia perioperative record keeper for clinical research.
To develop a multimedia perioperative recordkeeper that provides: 1. synchronous, real-time acquisition of multimedia data, 2. on-line access to the patient's chart data, and 3. advanced data analysis capabilities through integrated, multimedia database and analysis applications. To minimize cost and development time, the system design utilized industry standard hardware components and graphical. software development tools. The system was configured to use a Pentium PC complemented with a variety of hardware interfaces to external data sources. These sources included physiologic monitors with data in digital, analog, video, and audio as well as paper-based formats. The development process was guided by trials in over 80 clinical cases and by the critiques from numerous users. As a result of this process, a suite of custom software applications were created to meet the design goals. The Perioperative Data Acquisition application manages data collection from a variety of physiological monitors. The Charter application provides for rapid creation of an electronic medical record from the patient's paper-based chart and investigator's notes. The Multimedia Medical Database application provides a relational database for the organization and management of multimedia data. The Triscreen application provides an integrated data analysis environment with simultaneous, full-motion data display. With recent technological advances in PC power, data acquisition hardware, and software development tools, the clinical researcher now has the ability to collect and examine a more complete perioperative record. It is hoped that the description of the MPR and its development process will assist and encourage others to advance these tools for perioperative research.


Efficacy of skin barrier creams (I). The repetitive irritation test (RIT) in the guinea pig.
An animal model for the evaluation of skin protective creams against chemical irritants is described. The irritants were applied daily for 2 weeks to shaved back skin of young guinea pigs: sodium lauryl sulphate (5% aq.; 30 min), sodium hydroxide (0.5% aq.; 2 min), and toluene (20% eth.; 2 min). The barrier cream was applied 2 h prior to and immediately after exposure to the irritant. Control animals were treated with the irritant only. The irritant reaction was scored on a 4-point scale for erythema and quantified with regard to transepidermal water loss (TEWL) by evaporimetry and skin blood flow volume (BFV) by laser Doppler velocimetry. A total of 90 guinea pigs, consisting of individual panels of 5 to 10 animals, was tested. While one barrier cream (Stokoderm) significantly suppressed the irritation due to sodium lauryl sulphate and toluene, the other (Contra-Alkali) failed to do so and even aggravated the response, which was particularly evident with sodium hydroxide. This model may be useful in developing more effective barrier creams.


Improvement of Sexually Transmitted Disease Screening Among HIV-Infected Men Who Have Sex With Men Through Implementation of a Standardized Sexual Risk Assessment Tool.
Screening for gonorrhea (GC) and chlamydia (CT) and syphilis among HIV-positive (HIV+) men who have sex with men (MSM) is recommended at least annually. However, significant gaps in screening coverage exist. We conducted a quality improvement intervention to determine whether informing providers of preintervention screening rates and routinizing sexual risk assessment would improve sexually transmitted disease (STD) screening in a large HIV care clinic. In partnership with Kaiser Permanente Northern California, we developed and implemented a 10-item assessment addressing sexual and other behavioral risk factors among HIV+ MSM. We analyzed the proportion of patients screened for GC/CT and syphilis in a preintervention period (June 25-September 26, 2012) and during the intervention period (June 25-September 26, 2013). Of 364 HIV+ MSM seen for care during the intervention period, 47.3% completed the sexual risk assessment. Improvements in GC/CT screening and syphilis screening were observed; when comparing the preintervention period with the intervention period, the proportion of HIV+ MSM receiving GC/CT screening increased by 26.8% (31.6%-40.1%, P = 0.01) at any anatomical site and by 45% (19.5%-28.3%, P = 0.003) at the pharyngeal site. Syphilis screening significantly increased by 18.8% (48.7%-58.0%, P = 0.009). Overall STD screening increases were observed after this intervention that included didactic training on the urgency of STD screening needs for HIV+ MSM, a presentation of preintervention clinic STD screening data, and the implementation of self-reported sexual risk assessment. Additional efforts are needed to determine feasible ways to accurately assess the appropriateness of STD screening and success of interventions to improve STD screening.


Correlation between regional enterocolitis and cutaneous polyarteritis nodosa. Two case reports and review of the literature.
Dermatological manifestations of chronic infammatory bowel disease are numerous. We report herein 2 cases that demonstrated the uncommon association of cutaneous polyarteritis nodosa with regional enterocolitis. The clinical and histopathological features of this skin disease are important. Particular emphasis is placed on its relative benignity, in contrast to the serious prognosis associated with systemic polyarteritis nodosa.


Molecular targets in lymphomas.
A large proportion of patients with lymphomas are curable with standard chemotherapy. There is a plateau, however, in cure rate with chemotherapy alone. Advances in molecular biology have led to a better understanding of the pathogenesis of lymphomas. This article provides examples of how molecular therapy is going to change the treatment of lymphomas.


Equilibrium and kinetic studies on biosorption of 2,4,6-trichlorophenol from aqueous solutions by Acacia leucocephala bark.
Biosorption of 2,4,6-trichlorophenol (2,4,6-TCP) from aqueous solution by biomass prepared from Acacia leucocephala bark, an agricultural solid waste has been investigated in the present study. All the experiments are carried out by batch mode technique. The resulting biosorbent was characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) techniques. The effect of experimental parameters such as contact time, effect of pH (2-10), initial concentration of adsorbate (50-200 mg L(-1)) and amount of biosorbent dosage was evaluated. The removal was found to be pH dependent, and maximum removal was found to be at pH 5.0. The equilibrium time was found to be 3h. The biosorbent dose was increased, and the percentage removal of 2,4,6-TCP was increased, while the adsorption capacity at equilibrium q(e) (mg g(-1)) (amount of 2,4,6-TCP loaded per unit weight of adsorbent) decreased. Biosorption kinetic and isotherm studies showed the pseudo-second-order kinetics with a good correlation coefficient (R(2)=0.999), and both Langmuir and Freundlich isotherms were the best choices to describe the adsorption behaviors. The maximum monolayer biosorption capacity of A. leucocephala bark for 2,4,6-TCP was found to be 256.4 mg g(-1), at 30±1°C according to Langmuir model. This study demonstrated for the first time that the A. leucocephala bark could be an alternative for more costly adsorbents used for removal of 2,4,6-TCP from aqueous media.


Omics-based analysis of honey bee (Apis mellifera) response to Varroa sp. parasitisation and associated factors reveals changes impairing winter bee generation.
The extensive annual loss of honey bees (Apis mellifera L.) represents a global problem affecting agriculture and biodiversity. The parasitic mite Varroa destructor, associated with viral co-infections, plays a key role in this loss. Despite years of intensive research, the complex mechanisms of Varroa - honey bee interaction are still not fully defined. Therefore, this study employed a unique combination of transcriptomic, proteomic, metabolomic, and functional analyses to reveal new details about the effect of Varroa mites and naturally associated factors, including viruses, on honey bees. We focused on the differences between Varroa parasitised and unparasitised ten-day-old worker bees collected before overwintering from the same set of colonies reared without anti-mite treatment. Supplementary comparison to honey bees collected from colonies with standard anti-Varroa treatment can provide further insights into the effect of a pyrethroid flumethrin. Analysis of the honey bees exposed to mite parasitisation revealed alterations in the transcriptome and proteome related to immunity, oxidative stress, olfactory recognition, metabolism of sphingolipids, and RNA regulatory mechanisms. The immune response and sphingolipid metabolism were strongly activated, whereas olfactory recognition and oxidative stress pathways were inhibited in Varroa parasitised honey bees compared to unparasitised ones. Moreover, metabolomic analysis confirmed the depletion of nutrients and energy stores, resulting in a generally disrupted metabolism in the parasitised workers. The combined omics-based analysis conducted on strictly parasitised bees revealed the key molecular components and mechanisms underlying the detrimental effects of Varroa sp. and its associated pathogens. This study provides the theoretical basis and interlinked datasets for further research on honey bee response to biological threats and the development of efficient control strategies against Varroa mites.


Microbial production of the plant-derived fungicide physcion.
Physcion is a characteristic component of the traditional herb rhubarb with diverse pharmacological activities that has been commercially approved as an herbal fungicide. Nevertheless, its extremely low contents, costly purification procedure and geographically restricted planting severely hinder its application. Here, a cell factory was constructed in the filamentous fungus Aspergillus terreus for physcion production via microbial fermentation by integrating a pathway-modified emodin accumulation module and a position-selective emodin methylation module. Specifically, 1.71 g/L emodin accumulated when the transcriptional activator GedR and the emodin-1-OH-O-methyltransferase GedA in the geodin biosynthetic pathway were overexpressed and knocked out, respectively. Subsequently, potential emodin-3-OH-O-methyltransferase candidates were enzymatically screened in vitro and introduced into the emodin-accumulating mutant in vivo to generate a physcion-producing strain showing the highest titre of 6.3 g/L in fed-batch fermentation. Thus, our study provides an alternative strategy for the highly efficient, economical production of physcion and a representative example for microbial synthetic biology.


[Characteristics of the action of tetrapeptidamide on the body in short- and long-term administration].
It has been elucidated that the structures of the motor system of the rabbit and rat brain undergo significant alterations in monoamine metabolism 30 min after the administration of the synthetic enkephalin analogue Tyr-D-Ala-Gly-Phe-NH2 and in acetylcholinesterase activity and protein metabolism on the 3rd-6th day. It i suggested that a prolonged tetrapeptidamine-induced change in the motor functions may be due to a specific response on the part of the corticosubcortical structures of the motor systems.


Light microscopic methods to visualize mitochondria on tissue sections.
Mitochondria are cytoplasmic, double-membrane organelles, a main role of which is to synthesize ATP, the universal energy 'supply' of cells. In the last three decades, molecular genetic, biochemical, immunological and cell biological techniques have been applied in a coordinated fashion to unveil the pathogenesis of known mitochondrial disorders, as well as to explore the role of mitochondria in aging and neurodegenerative diseases. Once to be thought to be rare, it is now clear that mitochondrial dysfunction is an important cause of neurological and cardiac diseases, and age-related disorders such as cancer. Here, we review, illustrate, and provide updated protocols of two histochemical, and three immunohistochemical methods that in our opinion are the most reliable tools to visualize mitochondria on tissue sections from normal and disease specimens.


Pharyngeal wall and soft palate motion after two common speech surgeries.
To assess how pharyngeal wall and soft palate motion are affected after two common interventions for velopharyngeal insufficiency. A retrospective observational study was performed. A database of patients who had undergone Furlow palatoplasty or pharyngeal flap surgery between 2011 and 2019 and had video-archived preoperative and postoperative nasopharyngoscopy recordings was created. Recordings were deidentified and randomized, with 5 randomly-selected videos duplicated to determine intra-rater reliability. The videos were scored by 3 experienced raters using a modified Golding-Kushner scale. Pre- and postoperative scores were compared using paired t-test. Inter- and intra-rater reliability were estimated using intra-class correlation (ICC). There were 17 patients who met inclusion criteria. The mean age was 6.9 years (range 3-22 years, 59% male). In the Furlow palatoplasty group (n = 9), an increase in left soft palate motion was noted postoperatively (t(8) = 2.71, p = 0.02). In the pharyngeal flap group (n = 8), increases in lateral pharyngeal wall motion (left: t(7) = 3.58, p = 0.008, right: t(7) = 3.84, p = 0.006) and right soft palate motion (t(6) = 2.49, p = 0.04) were identified. Intra-rater reliability and inter-rater agreement were lower than prior studies utilizing the Golding Kushner scale. Our results provide objective evidence that Furlow palatoplasty and pharyngeal flap surgeries achieve velopharyngeal closure by increasing movement at different anatomical sites. Palatal and pharyngeal wall motion observed during preoperative nasopharyngoscopy may influence a surgeon's choice of intervention.


Study on the soluble and insoluble fume and hexavalent chromium emitted from a new covered electrode with micro and nano sized-sodium and potassium titanate-based flux.
The present study discusses the effect of the addition of nano-sized arc stabilizing materials on fume emissions and its solubility characteristics. Micro and nano-sized sodium/potassium titanates were added to the SMAW electrode flux as a substitute for the conventional sodium and potassium silicate compounds. The total and soluble metal concentration of fumes from the newly developed electrodes were estimated and compared with that of commercially available electrodes. The estimation of fume formation rate and breathing zone concentration of fumes followed the ISO 15011-1 and ISO 10882-1 standard. An average 50% reduction in the soluble fraction of fumes was observed from the electrodes containing micro-sized potassium-titanate compounds, and the reduction was further improved by 60% when nano-sodium titanate was added to the flux. Whereas, the reduction in soluble metal concentration for potassium titanate coated electrodes were 45% and 55%, in that order, for their micro and nano-structured forms. The soluble fraction of hexavalent chromium from the electrodes containing 100% nano sodium/potassium titanates was reduced up to 50% in each impactor stage. The inclusion of nano-sized sodium titanate in the flux resulted in a reduction in fume formation rate up to 55% and breathing zone concentration of fumes by 58% compared to the conventional sodium silicate coated electrodes. The electrode assaying 100% nano-potassium titanate showed a reduction of 59% in fume formation rate and 61% in breathing zone concentration compared to that of conventional potassium silicate-coated electrodes.


Treatment of osteoarthritis in the hand and wrist. Nonoperative treatment.
Osteoarthritis should initially be treated conservatively with the use of oral medication, intra-articular steroid injections, hand therapy, and splinting. The reduction of pain and the resultant increase in function to the patient are the ultimate goals of this treatment.


An automated method for the simultaneous determination of pravastatin, 3-hydroxy isomeric metabolite, pravalactone and fenofibric acid in human plasma by sensitive liquid chromatography combined with diode array and tandem mass spectrometry detection.
In this study, a sensitive and selective method based on liquid chromatography combined with diode array and tandem mass spectrometry detection (LC-DAD-MS/MS) was developed for the simultaneous quantitative determination of fenofibric acid, pravastatin and its main metabolites in human plasma. In this method, an automated solid-phase extraction (SPE) on disposable extraction cartridges (DECs) is used to isolate the compounds from the biological matrix and to prepare a cleaner sample before injection and analysis in the LC-DAD-MS/MS system. On-line LC-DAD-MS/MS system using an atmospheric pressure ionization (TurboIonSpray) was then developed for the simultaneous determination of pravastatin, 3-hydroxy isomeric metabolite (3-OH metab), pravalactone and fenofibric acid. The separation is obtained on an endcapped dodecyl silica based stationary phase using a mobile phase consisting of a mixture of acetonitrile, methanol and 5mM ammonium acetate solution (30:30:40, v/v/v). Sulindac and triamcinolone were used as internal standards (ISs). The detection of the fenofibric acid and sulindac was achieved by means of a DAD system. The MS/MS ion transitions monitored were m/z 442.2-->269.1, 442.2-->269.1, 424.3-->183.0 and 435.2-->397.2 for pravastatin, 3-OH metab, pravalactone and triamcinolone, respectively. The method was validated regarding stability, selectivity, extraction efficiency, response function, trueness, precision lower limit of quantitation and matrix effect. The limits of quantitation (LOQs) were around 0.50 ng/ml for pravastatin, 0.25 ng/ml for 3-OH metab, 0.05 ng/ml for pravalactone and 0.25 microg/ml for fenofibric acid.


Decoding the view expectation during learned maze navigation from human fronto-parietal network.
Humans use external cues and prior knowledge about the environment to monitor their positions during spatial navigation. View expectation is essential for correlating scene views with a cognitive map. To determine how the brain performs view expectation during spatial navigation, we applied a multiple parallel decoding technique to functional magnetic resonance imaging (fMRI) when human participants performed scene choice tasks in learned maze navigation environments. We decoded participants' view expectation from fMRI signals in parietal and medial prefrontal cortices, whereas activity patterns in occipital cortex represented various types of external cues. The decoder's output reflected participants' expectations even when they were wrong, corresponding to subjective beliefs opposed to objective reality. Thus, view expectation is subjectively represented in human brain, and the fronto-parietal network is involved in integrating external cues and prior knowledge during spatial navigation.


Preferences for multigene panel testing for hereditary breast cancer risk among ethnically diverse BRCA-uninformative families.
Until recently, genetic testing for hereditary breast cancer has primarily focused on pathogenic variants in the BRCA1 and BRCA2 (BRCA) genes. However, advances in DNA sequencing technologies have made simultaneous testing for multiple genes possible. We examined correlates of interest in multigene panel testing and risk communication preferences in an ethnically diverse sample of women who tested negative for BRCA mutations previously but remain at high risk based on their family history (referred to as "BRCA-uninformative") and their at-risk female family members. Two-hundred and thirteen women with a previous breast cancer diagnosis and a BRCA-uninformative test result and their first-degree relatives completed a survey on interest in multigene panel testing, communication preferences, and sociodemographic, psychological, and clinical factors. Stepwise logistic regression was used to identify factors associated with testing interest. Chi-square analyses were used to test differences in risk communication preferences. Interest in multigene panel testing was high (84%) and did not considerably differ by cancer status or ethnicity. In multivariable analysis, factors significantly associated with interest in genetic testing were having had a mammogram in the past 2 years (odds ratio (OR) = 4.04, 95% confidence interval (CI) 1.80-9.02) and high cancer worry (OR = 3.77, 95% CI 1.34-10.60). Overall, the most commonly preferred genetic communication modes were genetic counselors, oncologists, and print materials. However, non-Hispanic women were more likely than Hispanic women to prefer web-based risk communication (p < 0.001). Hispanic and non-Hispanic women from BRCA-uninformative families have a high level of interest in gene panel testing. Cancer-related emotions and communication preferences should be considered in developing targeted genetic risk communication strategies.


Six-month outcomes after individualized nutritional support during the hospital stay in medical patients at nutritional risk: Secondary analysis of a prospective randomized trial.
Among medical inpatients at risk of malnutrition, the use of individualized nutritional support during the hospital stay was found to reduce complications and improve mortality at short-term. We evaluated clinical outcomes at 6-months follow-up. We randomly assigned 2028 patients to receive protocol-guided individualized nutritional support to reach protein and energy goals (intervention group) or hospital food as usual (control group) during the hospital stay. The intervention was discontinued at hospital discharge and further nutritional support was based on the discretion of the treating team. We had complete follow-up information of 1995 patients (98%), which were included in the final analysis. The primary endpoint was all-cause mortality at 6-months. Prespecified secondary end points included non-elective hospital readmissions, functional outcome and quality of life. At 6-month, 231 of 994 (23.2%) intervention group patients had died compared to 246 of 999 (24.6%) control group patients, resulting in a hazard ratio for death of 0.90 (95%CI 0.76 to 1.08, p = 0.277). Compared to control patients, intervention group patients had similar rates of hospital readmission (27.3% vs. 27.6%, HR 1.00 (95%CI 0.84 to 1.18), p = 0.974), falls (11.2% vs. 10.9%, HR 0.96 (95%CI 0.72 to 1.27), p = 0.773) and similar quality of life and activities of daily living scores. While individualized nutritional support during the hospital stay significantly reduced short-term mortality, there was no legacy effect on longer term outcomes. Future trials should investigate whether continuation of nutritional support after hospital discharge reduces the high malnutrition-associated mortality rates in this vulnerable patient population. ClinicalTrials.gov number, NCT02517476.


Parent report of children's sleep disordered breathing symptoms and limited academic progress in reading, writing, and math.
To estimate via questionnaire within a population sample of New Zealand (NZ) children aged 6-to-10 years, the prevalence of sleep disordered breathing (SDB) and those struggling academically, and to identify individual and shared risk factors (health and demographic) for parent-reported SDB symptoms and academic difficulties. In this cross-sectional study, parents/caregivers of children were recruited through schools and social media to complete an online questionnaire covering health and demographic factors, their children's SDB symptoms (Pediatric Sleep Questionnaire; PSQ) and parental ratings of academic performance based on teacher feedback relative to expected progress in the national curriculum (well below/below/at/above) in reading, writing, and math. A total of 1205 children (53% male) aged (mean) eight years two months were included, comprising 79.4% NZ European/other and 15.0% Māori. The survey-weighted prevalence of SDB (based on the PSQ) was 17.5%. This was higher amongst those with academic difficulties rated 'below/well below' expected progress for reading, writing and math (estimated at 24.0%, 31.0% and 27.5% respectively), with increased odds (adjusted odds ratios) for poor progress of 1.9 (95% CI: 1.2, 3.0), 1.8 (95% CI: 1.2, 2.7) and 2.4 (95% CI: 1.6, 3.7) respectively. There were no shared risk factors common to both SDB and academic difficulties identified from multivariate analyses. The findings suggest that children with parent-reported SDB symptoms may be at high risk for poor progress in reading, writing, and math. Future research could examine whether treatment of SDB reduces barriers to learning and offsets educational risk.


Nitrate runoff loss and source apportionment in a typical subtropical agricultural watershed.
Nitrate (NO3-) loss and enrichment in water bodies caused by fertilization are a major environmental problem in agricultural areas. However, the quantitative contribution of different NO3- sources, especially chemical fertilizers (CF) and soil organic nitrogen (SON), to NO3- runoff loss remains unclear. In this study, a systematic investigation of NO3- runoff and its sources was conducted in a subtropical agricultural watershed located in Yujiang County, Jiangxi Province, China. A semi-monthly sampling was performed at the inlet and outlet from March 2018 to February 2019. Hydrochemical and dual NO3- isotope (15 N and 18O) approaches were combined to estimate the NO3- runoff loss and quantify the contribution of different sources with a Bayesian isotope mixing model. Source apportionment by Stable Isotope Analysis in R (SIAR) suggested that NO3- in runoff was mainly derived from nitrification of ammonium (NH4+) mineralized from SON (37-52%) and manure/sewage (M&S) (25-47%), while the contribution of CF was relatively small (14-25%). The contribution of various sources showed seasonal variations, with a greater contribution of CF in the wet growing season (March to August). Compared with the inlet which contributed 37-40% to runoff NO3-, SON contributed more at the outlet (49-52%). Denitrification in the runoff was small and appeared to be confined to the dry season (September to February), with an estimated NO3- loss of 2.73 kg N ha-1. The net NO3- runoff loss of the watershed was 34.5 kg N ha-1 yr-1, accounting for 15% of the annual fertilization rate (229 kg N ha-1 yr-1). Besides M&S (22%), fertilization and remineralization of SON (CF + SON) were the main sources for the NO3- runoff loss (78%), suggesting accelerated nitrification of NH4+ from CF (24%) and SON mineralization (54%). Our study indicates that NO3- runoff loss in subtropical agricultural watersheds is dominated by nonpoint source pollution from fertilization. SON played a more important role than CF. Besides, the contribution of sewage should not be neglected. Our data suggest that a combination of more rational fertilizer N application (CF), better management of SON, and better treatment of domestic sewage could alleviate NO3- pollution in subtropical China.


Canine awake head-out plethysmography (HOP): characterization of external resistive loading and spontaneous laryngeal paralysis.
We applied a novel head-out plethysmographic (HOP) method to study awake canine responses to external resistive loading and natural laryngeal paralysis. Measurements of inspiratory and expiratory specific airway resistance (sRaw(insp), sRaw(exp)) were obtained before and after uni- and bidirectional loading (R(add) = 5 cmH(2)O/L/s) in large-breed dogs (n = 9). Mean sRaw(insp) after inspiratory, and sRaw(exp) after expiratory loading were 31.4 and 33.3 cmH(2)Os, respectively. Bidirectional loads induced a significantly greater rise in both sRaw(insp) and sRaw(exp) (55.1 and 61.3 cmH(2)Os) compared to unidirectional loading (P < 0.001). Yet, type of loading did not affect flow-volume indices. The mean R(aw) of dogs was 4.81 cmH(2)O/L/s. Expiratory loading resulted in a significant 8.8% increase in functional-residual-capacity (FRC), compared to FRC(baseline) (76.7 ml/kg). Dogs (n = 5) with laryngeal paralysis demonstrated a significant increase in sR(aw) and R(aw) compared to controls without changes in FRC. In conclusion, HOP precisely characterized sR(aw) in response to external resistive loading. Hence, we could accurately quantify airway obstruction in awake dogs with laryngeal paralysis.


Response of rat testis to localized induced hyperthermia.
A method is presented in which the rat testis is extensively mobilized through a low abdominal incision, but in which its blood supply is carefully preserved. Localized hyperthermia is induced in this mobilized testis by water bath immersion. The tissue temperature is measured during and after immersion by means of a thermocouple inserted into the tissue. The relative sensitivity of spermatogenic tissue to increased temperature is confirmed and the relative resistance of Sertoli and Leydig cells is noted. Minimal or absent inflammatory reaction to thermal destruction of testicular cells is found as long as the tubule is intact. A marked peritesticular inflammatory response is noted when the total testicular tissue is destroyed at the highest temperature tested.


Long-term developmental, behavioral, and attachment outcomes after international adoption.
Children adopted internationally and their families are a heterogeneous group. Internationally-adopted children have been reported to have a range of developmental and behavioral difficulties. The authors describe the current evidence documenting developmental outcomes for children and common behavioral and mental health concerns including attachment difficulties that may impact children and their families after international adoption. Pediatricians must be thoughtful to individualize the care of adoptive children and not make assumptions shortly after adoption. It is critical to avoid using "standard" parenting advice that may not apply to children who have experienced loss, deprivation, separation, and instability in their early lives. By listening to families, carefully evaluating children, and monitoring progress over time, pediatricians can avoid the pitfall of oversimplifying and underestimating the complexity and challenges that these families face. Instead, pediatric primary care providers can play a key role in maximizing the potential of an internationally adopted child and his or her family.


Antibody patterns to herpesviruses in Kaposi's sarcoma. II. Serological association of American Kaposi's sarcoma with cytomegalovirus.
The prominent finding of this extended serologic analysis on American and African Kaposi's sarcoma (KS) patients and appropriately matched control groups is the detection of a specific serologic association of cytomegalovirus (CMV) with American KS patients. All American KS sera contained CMV antibodies and their geometric mean titers (GMT) were significantly higher than those in sera of melanoma patients (GMT ratio k = 5.3 to 7.7 by complement fixation [CF], k = 8.9 by indirect hemagglutination [IHA]) or in sera of age- and sex-matched healthy controls (k = 12.6 to 16.0 by CF, k = 12.6 by IHA). The result is strongly reminiscent of the data obtained previously for European KS. Although the GMT to CMV of African KS patients were similar to the GMT of the American KS groups, their significance cannot be demonstrated due to the high background of CMV infections in the control groups. Complex mechanisms are hypothesized, by analogy with the Epstein-Barr virus (EBV) involvement in Burkitt's lymphoma (BL), for a CMV involvement in the development of KS.


Mapping and regulation of the pifC promoter of the F plasmid.
The pif region of the F plasmid, which causes abortive infection of Escherichia coli by T7 bacteriophage, is autogenously controlled by the product of the pifC gene. Here we describe the identification of the pif operon promoter by S1-nuclease mapping, and show that it is autoregulated at the transcriptional level and that its activity is modulated by integration host factor.


Single amino acid substitutions on the needle tip protein IpaD increased Shigella virulence.
Infection of colonic epithelial cells by Shigella is associated with the type III secretion system, which serves as a molecular syringe to inject effectors into host cells. This system includes an extracellular needle used as a conduit for secreted proteins. Two of these proteins, IpaB and IpaD, dock at the needle tip to control secretion and are also involved in the insertion of a translocation pore into host cell membrane allowing effector delivery. To better understand the function of IpaD, we substituted thirteen residues conserved among homologous proteins in other bacterial species. Generated variants were tested for their ability to surface expose IpaB and IpaD, to control secretion, to insert the translocation pore, and to invade host cells. In addition to a first group of seven ipaD variants that behaved similarly to the wild-type strain, we identified a second group with mutations V314D and I319D that deregulated secretion of all effectors, but remained fully invasive. Moreover, we identified a third group with mutations Y153A, T161D, Q165L and Y276A, that exhibited increased levels of translocators secretion, pore formation, and cell entry. Altogether, our results offer a better understanding of the role of IpaD in the control of Shigella virulence.


Recruitment of the Mint3 adaptor is necessary for export of the amyloid precursor protein (APP) from the Golgi complex.
The amyloid precursor protein (APP) is a ubiquitously expressed single-pass transmembrane protein that undergoes proteolytic processing by secretases to generate the pathogenic amyloid-β peptide, the major component in Alzheimer plaques. The traffic of APP through the cell determines its exposure to secretases and consequently the cleavages that generate the pathogenic or nonpathogenic peptide fragments. Despite the likely importance of APP traffic to Alzheimer disease, we still lack clear models for the routing and regulation of APP in cells. Like the traffic of most transmembrane proteins, the binding of adaptors to its cytoplasmic tail, which is 47 residues long and contains at least four distinct sorting motifs, regulates that of APP. We tested each of these for effects on the traffic of APP from the Golgi by mutating key residues within them and examining adaptor recruitment at the Golgi and traffic to post-Golgi site(s). We demonstrate strict specificity for recruitment of the Mint3 adaptor by APP at the Golgi, a critical role for Tyr-682 (within the YENPTY motif) in Mint3 recruitment and export of APP from the Golgi, and we identify LAMP1(+) structures as the proximal destination of APP after leaving the Golgi. Together, these data provide a detailed view of the first sorting step in its route to the cell surface and processing by secretases and further highlight the critical role played by Mint3.


Setting the maximum ecological potential of benthic communities, to assess ecological status, in heavily morphologically-modified estuarine water bodies.
Investigations on setting benthic macroinvertebrates reference conditions in natural waters have increased recently. Under the European Water Framework Directive, importance is given to research in morphological heavily-modified water bodies (HMWBs), which are very common in countries with high human pressure. However, research has not been undertaken on setting the maximum ecological potential (MEP), as a reference in HMWB. The objective of the present investigation is to set the MEP of two metrics (diversity and richness), used in assessing the ecological status in different benthic indices. The Oiartzun estuary (Basque Country) is used as a case study, which changed morphologically in the 19th Century, following harbour construction. Data obtained from 1874 and the present were used to model changes in currents, water residence time, salinity, volume, and intertidal area. Benthic macroinvertebrate data, from 1995 to 2011, were used to predict 19th Century and present MEP. Changes in the estuary were described: loss of all of the intertidal areas; doubling of the volume; residence time, changing from 2 to 95 days; current velocity reduced by 50%; salinity increase. All these factors have led to changes in the benthic communities and the structural variables. Predicted richness and diversity, for 1874, were lower (48-76%) than those at present. Taking into account the differences between natural and modified waters, it is proposed to utilize 75% of the natural reference conditions, as the MEP values for Basque HMWB.


Expression of matrix metalloproteinase 7 is an unfavorable postoperative prognostic factor in cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts.
Cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts (collectively referred to as the large bile ducts) is an intractable disease, and a papillary phenotype and well-differentiated histologic grade have been proposed as indicators of a favorable prognosis after surgical resection. In this study, we examined the significance of matrix metalloproteinases (MMPs) in cholangiocarcinoma with respect to clinicopathologic features. We subjected 66 surgically resected specimens of cholangiocarcinoma of the large bile ducts to clinicopathologic examination, including postoperative survival, papillary phenotype, and immunohistochemical expression of MMP-2,-7, -9, and membrane type 1 MMP (MT1-MP). Nonneoplastic biliary epithelium did not express these 4 MMPs, whereas cholangiocarcinoma frequently expressed MMP-2 (33.9%), -7 (75.8%), -9 (47.5%), and MT1-MMP (54.5%). In particular, conventional (nonpapillary) cholangiocarcinoma expressed MMP-7 and MT1-MMP more frequently than papillary cholangiocarcinoma. The expression of MMP-7 and MT1-MMP significantly correlated with the nonpapillary phenotype, poorly differentiated histologic grade, perineural invasion, and advanced TNM stage. In contrast, the expression of MMP-2 and -9 was not associated with any of the clinicopathologic features. Univariate analysis of disease-specific survival revealed that a papillary phenotype and expression of MMP-7 were prognostic factors of cholangiocarcinoma, in addition to TNM stage, poorly differentiated histologic grade, perineural invasion, and microscopic margin status. Multivariate analysis showed only TNM stage to be an independent prognostic factor. Expression of MMP-7 in cholangiocarcinoma is an unfavorable postoperative prognostic factor of cholangiocarcinoma arising from the large bile ducts. Underexpression of MMPs in papillary cholangiocarcinoma might be associated with a favorable prognosis.


Degradation of phenanthrene by bacterial strain isolated from soil in oil refinery fields in Shanghai China.
A bacterial strain Pseudomonas stutzeri ZP2 was identified with phenanthrene-degrading ability based on Gram staining, oxydase reaction, biochemical tests, FAME analysis, G+C content and 16S rDNA gene sequence analysis. It is the first time that P. stutzeri is reported to process the capability for phenanthrene degradation. The strain was isolated from soil samples contaminated with polycyclic aromatic hydrocarbon (PAH)-containing waste from an oil refinery field in Shanghai, China. Strain P sp. ZP2 can utilize naphthalene, phenanthrene and Tween 80 as its sole carbon source and can degrade phenanthrene very fast, 6 days for 96% phenanthrene at 250 ppm concentration. The optimal growth conditions of strain ZP2 was determined to be at pH 8.0, 37 degrees C, respectively. The results also indicate that strain ZP2 can remove more than 90% of phenanthrene at any concentrations ranged from 250 to 1000 ppm in 6 days. It suggests that strain ZP2 can endure high concentrations of phenanthrene. Besides, the effects of non-ionic surfactants such as Brij 30, Triton X100 and Tween 80, on the phenanthrene degradation were examined. Therefore, this strain may find great application in bioremediation practices.


Intranasal exposure to amorphous nanosilica particles could activate intrinsic coagulation cascade and platelets in mice.
Nanomaterials with particle sizes <100 nm have been already applied in various applications such as cosmetics, medicines, and foods. Therefore, ensuring the safety of nanomaterials is becoming increasingly important. Here we examined the localization and biological responses of intranasally administered amorphous nanosilica particles in mice, focusing on the coagulation system. We used nanosilica particles with diameters of 30, 70, or 100 nm (nSP30, nSP70, or nSP100 respectively), and conventional microscale silica particles with diameters of 300 or 1000 nm (mSP300 or mSP1000, respectively). BALB/c mice were intranasally exposed to nSP30, nSP70, nSP100, mSP300, or mSP1000 at concentrations of 500 μg/mouse for 7 days. After 24 hours of last administration, we performed the in vivo transmission electron microscopy analysis, hematological examination and coagulation tests. In vivo transmission electron microscopy analysis showed that nanosilica particles with a diameter <100 nm were absorbed through the nasal cavity and were distributed into liver and brain. Hematological examination and coagulation tests showed that platelet counts decreased and that the activated partial thromboplastin time was prolonged in nSP30 or nSP70-treated groups of mice, indicating that nanosilica particles might have activated a coagulation cascade. In addition, in in vitro activation tests of human plasma, nanosilica particles had greater potential than did conventional microscale silica particles to activate coagulation factor XII. In nanosilica-particle-treated groups, the levels of soluble CD40 ligand, and von Willebrand factor which are involved in stimulating platelets tended to slightly increase with decreasing particle size. These results suggest that intranasally administered nanosilica particles with diameters of 30 and 70 nm could induce abnormal activation of the coagulation system through the activation of an intrinsic coagulation cascade. This study provides information to advance the development of safe and effective nanosilica particles.


Scanning laser polarimetry and confocal scanning laser ophthalmoscopy: technical notes on their use in glaucoma.
The mere intraocular pressure (IOP) measurement and the visual field (VF) examination do not allow early primary open-angle glaucoma (POAG) diagnosis. At present, the morphological and morphometric analysis of the optic disk is considered very important for an early diagnosis and follow-up of the disease. The recent introduction of laser systems equipped with new polarimetry techniques (GDx) and confocal tomography (HRT) allows an objective, quantitative, and reproducible evaluation of the morphometry and morphology of the optic disk and retinal nerve fiber layer (RNFL). The GDx, scanning laser polarimetry, studies the RNFL. The HRT, confocal scanning laser tomography, examines several optic disk and peripapillar area parameters. These devices allow obtaining objective and quantitative data concerning RNFL and optic nerve head. They represent complementary and important examinations in case of uncertain POAG diagnosis. The correct evaluation of the parameters studied by these techniques and the knowledge of the instruments' limits are needed for an adequate interpretation of the results obtained.


Hypoxia Suppresses High Fat Diet-Induced Steatosis And Development Of Hepatic Adenomas.
Nonalcoholic fatty liver disease (NAFLD) is considered the most common form of silent liver disease in the United States and obesity is associated with increased risk of NAFLD. Obstructive sleep apnea (OSA) which is common in obese individuals is associated with a greater incidence of NAFLD, which in turn, increases the risk for hepatocellular carcinoma (HCC). It is unclear how obesity, OSA and NAFLD interrelate nor how they collectively contribute to an increased risk for developing HCC. Male BALB/c mice were exposed to diethylnitrosamine and phenobarbital followed by 48 weeks of either standard chow diet (chow), chow with hypoxia, high-fat diet, or a combination of hypoxia and high-fat diet. We noninvasively monitored tumor development using micro-CT imaging. We tracked the total weight gained throughout the study. We evaluated liver histology, fat accumulation, carbonic anhydrase 9 (CA9) and hypoxia-inducible factor 1-alpha (HIF-1α) expression, as well as, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). A high-fat diet without hypoxia led to the development of obesity that induced hepatic steatosis and promoted tumorigenesis. Animals on a high-fat diet and that were also exposed to hypoxia had lower total weight gain, lower steatosis, lower serum AST and ALT levels, and fewer number of hepatic adenomas than a high-fat diet without hypoxia. These findings suggest that hypoxia abrogates obesity, hepatic steatosis, and hepatic tumorigenesis related to a high-fat diet.


Development of an antibody-based diagnostic method for the identification of Bemisia tabaci biotype B.
The whitefly Bemisia tabaci is a very destructive pest. B. tabaci is composed of various morphologically undistinguishable biotypes, among which biotypes B and Q, in particular, draw attention because of their wide distribution in Korea and differential potentials for insecticide resistance development. To develop a biotype-specific protein marker that can readily distinguishes biotypes B from other biotypes in the field, we established an ELISA protocol based on carboxylesterase 2 (COE2), which is more abundantly expressed in biotypes B compared with Q. Recombinant COE2 was expressed, purified and used for antibody construction. Polyclonal antibodies specific to B. tabaci COE2 [anti-COE2 pAb and deglycosylated anti-COE2 pAb (DG anti-COE2 pAb)] revealed a 3-9-fold higher reactivity to biotype B COE2 than biotype Q COE2 by Western blot and ELISA analyses. DG anti-COE2 pAb exhibited low non-specific activity, demonstrating its compatibility in diagnosing biotypes. Western blot and ELISA analyses determined that one of the 11 field populations examined was biotype B and the others were biotype Q, suggesting the saturation of biotype Q in Korea. DG anti-COE2 pAb discriminates B. tabaci biotypes B and Q with high specificity and accuracy and could be useful for the development of a B. tabaci biotype diagnosis kit for on-site field applications.


Hip joint contact forces in normal subjects and subjects with total hip prostheses: walking and stair and ramp negotiation.
To calculate the hip joint contact force in normal subjects and subjects with total hip replacements. An observational study of age matched normal subjects and subjects with hip joint replacements. Hip joint contact forces have been calculated using musculo-skeletal models and measured in vivo using instrumented hip prostheses. There are few examples of studies performed on subjects in the 40-60 year age range. This study characterises the forces in both normal subjects and subjects with hip joint replacements for these 'young' subjects. Motion analysis and force plate data were used as input to a three-dimensional model of the leg. Five male and six female normal subjects and five male subjects with hip prostheses were studied. Each subject was observed walking and negotiating stairs and a ramp. Hip joint contact forces in both thigh and pelvic-based co-ordinate systems are presented. Subjects cadence, speed and stride length are given. In general subjects with hip replacements exhibited lower hip joint contact forces than age matched normal subjects. It is suggested that this was the results of the lower speeds, stride lengths and cadences adopted by the subjects with hip replacements. The characterisation of hip joint contact forces provides essential information for prosthetic joint design and testing. The comparison of hip joint contact forces in normal subjects with those in subjects with prosthetic joints provides evidence of, not only actual use of joints, but also of possible levels of force that might be applied to hip prostheses if subjects returned to normal use.


Comparative trial of continuous nebulization versus metered-dose inhaler in the treatment of acute bronchospasm.
To compare continuous nebulization with the use of a metered-dose inhaler (MDI) with spacer device for delivery of albuterol in acute bronchospastic episodes in the emergency department. Prospective, randomized, double-blinded, placebo-controlled clinical trial. Urban ED with a 28,000 annual census. Patients older than 18 years of age presenting to the ED with an acute bronchospastic episode. After conducting evaluation and collecting baseline data, we treated each patient with a continuous-flow nebulizer set to deliver 15 mg/hour of albuterol or a placebo by face mask. Subsequently, each patient received four puffs (albuterol or placebo) from an MDI with a spacer device. The four MDI puffs were followed by 5 minutes on nebulization, and this sequence was continued until predetermined therapeutic end points were reached or side effects developed. The optimal MDI dose was then determined and repeated each hour for the 3-hour time period of the study. Repeated-measures ANOVA testing revealed statistically and clinically significant improvements over time within each treatment group in peak flow (F = 3.864, P = .0057), Borg score (F = 14.77, P = .0001), pulse (F = 9.642, P = .0001), and respiratory rate (F = 3.081, P = .0093). However, no significant differences could be detected between treatment groups over time except for systolic blood pressure (F = 8.231, P = .0141), and this change was not considered clinically significant. On the basis of the findings of this study, we conclude that continuous nebulization is equally effective as MDI with spacer device for delivery of albuterol to treat acute bronchospastic episodes in the ED. Each method of delivery offers advantages. Each ED should decide which modality to use on the basis of its own resources.


The use of attainment scaling in the evaluation of a regional mental health program.
The general evaluation of the success of a regional mental health program was attempted through the use of the Goal Attainment Scale. There were 278 goal guides scored for 96 sample patients at periods of 6, 12, and 18 months after admission. The interrater reliability between pairs of raters at follow-up interviews was high (.87). The intraclass correlation for goal guides constructed by three independent goal setters was moderate (r=.71). The mean scores of the three raters, when compared to a consensus goal score, attained an intraclass coefficient of .91. Thus the goal-attainment scoring procedure was found to be reliable. However, no evidence could be discerned to support its validity as a measure of a patient's treatment outcome.


Direct observation in a large-scale randomized trial of parent training in children with autism spectrum disorder and disruptive behavior.
A direct observation strategy (Standardized Observation Analogue Procedure, SOAP) was used in a large-scale randomized trial of parent training versus parent education in young children with autism spectrum disorder (ASD) and disruptive behavior. The 16-minute SOAP, modified from an earlier version of this same measure, included parentchild interaction to assess child behavior in a clinical laboratory setting. Despite study entry criteria for all child participants requiring moderate levels of disruptive behavior in this project, 126 of 168 children with complete SOAP data at baseline showed no disruptive behavior on this measure. Although the primary purpose of the study was to determine whether the SOAP could detect differences between the two conditions (i.e.,parent training (PT) and parent education (PE)), baseline observation data was not consistent with parent ratings at baseline or subsequent follow up visits, leaving little room to demonstrate improvement with this observation measure. This and the challenging, time-consuming and resource intensive effort involved in using such a measure in a large randomized scale trial, raises fundamental questions about the validity of the SOAP as an outcome measure in such a study. Further consideration related to the feasibility and practicality of using direct observation as a primary measure in larger scale efforts overall are also discussed.


Noncarious cervical lesions in the aging population analyzed through digital scanning: occlusal risk factors, dimensions, and morphology.
To evaluate noncarious cervical lesions (NCCL) in older adults by analyzing each lesion's morphology, dimension, and occlusal risk factors using intraoral scanning and clinical evaluation. Individuals over 60 treated at the School of Dentistry in Minas Gerais, Brazil, were invited to participate in this cross-sectional study. We clinically evaluated 1245 teeth for the presence of NCCL and dentin hypersensitivity (DH) in 53 individuals. Three-dimensional models were obtained using Omnicam, and occlusal risk factors were evaluated through the presence of wear facets, intense occlusal contacts, and interferences. The 3Shape 3DViewer software was used to classify NCCL morphology and to measure their height. NCCL depth, width, and area measurements were determined using ImageJ. Descriptive analyses were performed. The Kolmogorov-Smirnov test showed that quantitative data exhibited non-normal distribution. For bivariate analyses of quantitative data, the Mann-Whitney test was employed. The results were reported with mean, standard deviation, median, minimum, and maximum. For bivariate analyses of categorical data, the Pearson chi-square test was used. The results were reported with frequencies (counts) and percentages. A regression model evaluating the association between occlusal risk factors and the absence/presence of NCCL was built. Most participants were female (58.5%), with a mean age of 66. The frequency of NCCL was 28.27%, corresponding to 352 teeth. Of these, 68.18% exhibited saucer morphology and 31.82% wedge-shaped morphology. The frequency of DH was 13.92% in teeth with NCCL. Saucer NCCL exhibited significantly greater height (p = 0.02), while wedge-shaped lesions showed greater depth (p < 0.001). Also, teeth with NCCL had a higher proportion of wear facets (66.8%; p < 0.001), intense occlusal contacts (39.8%; p = 0.008), and occlusal interferences (21.9%; p = 0.05). The regression model showed that teeth with wear facets were 1.50 times more likely to exhibit NCCL than teeth without wear facets (p < 0.001). Teeth with intense occlusal contact were 1.22 times more likely to exhibit NCCL than teeth without intense occlusal contact (p = 0.031). NCCL is a common dental condition in the older adults evaluated in this study. Wedge-shaped NCCL exhibited greater depth, while saucer NCCL had more expressive height. Occlusal risk factors may represent a crucial mechanism for the occurrence of NCCL in this population. Understanding the mechanisms involved in developing NCCL is helpful in diagnostic and preventive practices. The study showed the importance of dental occlusion and characteristics of different NCCL morphologies that help the clinician in decision-making.


Prognostic role of epidermal growth factor-like domain 7 protein expression in laryngeal squamous cell carcinoma.
This study aimed to retrospectively analyse the expression of epidermal growth factor-like domain 7 protein in cases of laryngeal squamous cell carcinoma. We studied 116 patients retrospectively. Expression of epidermal growth factor-like domain 7 protein was determined in tumour and nontumour tissue samples, by immunohistochemistry. Expression levels were significantly increased in 94 cases. Increased expression levels correlated well with tumour stage (p = 0.001) and lymph node metastasis (p = 0.002). Log-rank survival testing showed a significant difference between patients with marked versus limited expression levels (p = 0.03). Multivariable Cox regression analysis showed that epidermal growth factor-like domain 7 protein expression level was an independent predictor of laryngeal squamous cell carcinoma prognosis. These findings provide evidence that increased epidermal growth factor-like domain 7 protein expression is associated with laryngeal squamous cell carcinoma stage, lymph node metastasis and poor survival. This suggests that this protein may be a potential marker for laryngeal squamous cell carcinoma.


Marine litter prediction by artificial intelligence.
Artificial intelligence techniques of neural network and fuzzy systems were applied as alternative methods to determine beach litter grading, based on litter surveys of the Antalya coastline (the Turkish Riviera). Litter measurements were categorized and assessed by artificial intelligence techniques, which lead to a new litter categorization system. The constructed neural network satisfactorily predicted the grading of the Antalya beaches and litter categories based on the number of litter items in the general litter category. It has been concluded that, neural networks could be used for high-speed predictions of litter items and beach grading, when the characteristics of the main litter category was determined by field studies. This can save on field effort when fast and reliable estimations of litter categories are required for management or research studies of beaches--especially those concerned with health and safety, and it has economic implications. The main advantages in using fuzzy systems are that they consider linguistic adjectival definitions, e.g. many/few, etc. As a result, additional information inherent in linguistic comments/refinements and judgments made during field studies can be incorporated in grading systems.


PROP taster status and oral fatty acid perception.
Recent studies with rat taste cells treated with polyunsaturated fatty acids suggest that fatty acids may play a role in dietary fat perception. In humans, sensitivity to the textural properties of fat is associated with the genetic ability to taste the bitter compound 6-N-2-propylthiouracil (PROP). However, it has not been shown that PROP tasters are more sensitive in discriminating fatty acids in a high-fat food. Our study with human subjects was designed to test the hypothesis that the ability to orally detect food-grade conjugated linoleic acid added to high-fat vanilla ice cream is associated with the ability to taste PROP. Eighty percent of the PROP tasters in this study, but only 17% of the PROP nontasters correctly discriminated the sample containing the added free fatty acid in a difference test versus unadulterated high-fat vanilla ice cream (Fisher's Exact Test, P=.05). Because most fatty foods contain minute amounts of free fatty acids, further studies with humans examining the contribution of fatty acids to fat perception seem warranted.


Detection of fetal hemorrhage in Rh immune globulin candidates. A rosetting technique using enzyme-treated Rh2Rh2 indicator erythrocytes.
Current serologic tests occasionally fail to identify women needing more than one vial of Rh immune globulin. We compared the indirect antiglobulin test after incubation with anti-D and a rosetting technique using enzyme treated Rh2Rh2 erythrocytes as methods for identifying significant fetal maternal hemorrhage (FMH). Artificial mixtures containing 0.05 to 1.2 percent Rh1rh (CcDe) fetal red blood cells mixed with rh (ce) adult red blood cells were tested. The indirect antiglobulin test of the 0.6 percent mixture (approximately 30 ml FMH) was reported to be microscopically positive by 17/20 technologists; whereas, 20/20 found the rosetting test to be strongly positive. The volume of FMH in 118 postpartum Rh immune globulin candidates was quantified using Kleihauer's test and formula. The results of the rosetting and Kleihauer tests of blood specimens from these patients were negative 1.4 ml for two, and strongly positive rosetting test and FMH of 6.5 ml for one. The rosetting test utilizes routine blood banking skills and requires 5 minutes more "hands on" time than an indirect antiglobulin test. Confirmation and quantification of positive results by an acid-elution test is necessary.


Histiomonocytic malignancy. A spectrum of disease in an 11-month-old infant.
The initial pathologic diagnosis in an 11-month-old girl presenting with a suprarenal mass was true histiocytic lymphoma. The histiocytic nature of the cells was verified by ultrastructural, histochemical, and immunologic studies. The subsequent course featured widespread dissemination as both tumorous masses and diffuse tissue infiltrates, including extensive soft tissue, leptomeningeal, and bone marrow involvement, with a terminal histiomonocytic leukemic phase. Subsequently, this tumor was reclassified as malignant histiocytosis with atypical features, and this case exemplifies the difficulties in classifying some malignant histiomonocytic neoplasms. The overlapping clinical, pathologic, and theoretic features of true histiocytic lymphoma, malignant histiocytosis, and histiomonocytic leukemia are discussed in the context of this case.


Functional training added to intradialytic cycling lowers low-density lipoprotein cholesterol and improves dialysis adequacy: a randomized controlled trial.
Exercise has various positive effects on hemodialysis patients. However, there is no clear evidence which type of exercise yields better results. This study aimed to determine the effects of guided functional training added to the intradialytic cycling on dialysis adequacy and biochemical parameters in hemodialysis patients. Additionally, we aimed to investigate if patients could transfer functional exercise to an unsupervised home environment and retain gained improvements. Randomization was done to a functional training intervention group (INT) (n = 20) or intradialytic cycling control group (CON) (n = 20). The INT attended a pre-dialysis functional training in the first 8 weeks. In the second 8 weeks, they performed functional exercises at unsupervised home environment on non-dialysis days. During the whole study, both groups participated in the intradialytic cycling program. Both groups demonstrated a significant increase in dialysis adequacy (Kt/V) in the eight (0.15, 95% CI 0.06 to 0.24; p = 0.003 for INT and 0.21, 95% CI 0.11 to 0.3; p < 0.001 for CON) and the 16th study week (0.13, 95% CI 0.03 to 0.24; p = 0.017 for INT and 0.13, 95% CI 0.03 to 0.22; p = 0.013 for CON) compared to their baseline values with no significant between-group differences. At week eight, the total cholesterol was significantly lowered in the INT (- 0.34 mmol/L, 95% CI - 0.6 to - 0.07; p = 0.016) and remained lower at week 16 (- 0.32 mmol/L, 95% CI - 0.64 to - 0.01; p = 0.049) with no significant changes in the CON. Low-density lipoprotein levels in the INT were significantly reduced after 8 weeks (- 0.35 mmol/L, 95% CI - 0.64 to - 0.06; p = 0.022) and remained reduced after 16 weeks (- 0.28 mmol/L, 95% CI - 0.52 to - 0.03; p = 0.030). There were no significant differences found for albumin, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, and hemoglobin in both groups. We demonstrated that functional training added to intradialytic cycling improved lipid profile and dialysis adequacy. Additionally, the effects of the unsupervised, home-based program were preserved during the second study phase. This study supports the assumption that combined training is more effective compared to solely intradialytic exercise. ClinicalTrials.Gov, NCT03334123 . Registered 07 November 2017.


Interhemispheric acute subdural hematoma: a computed tomographic manifestation of child abuse by shaking.
Parieto-occipital interhemispheric acute subdural hematomas (IASH) were found in 17 (61%) of 28 abused children examined by computed tomography, presenting with neurologic symptoms. CT demonstration of IASH correlated with injury due to severe shaking, the presence of retinal hemorrhages, and the absence of the stigmata of battering. Subsequent computed tomographic examination in these patients demonstrated infarction in 50%, and cerebral atrophy in 100%.


Altered expression of micro-RNA 199a and increased levels of cardiac SIRT1 protein are associated with the occurrence of atrial fibrillation after coronary artery bypass graft surgery.
Postoperative atrial fibrillation (POAF) is a potentially life-threatening complication after coronary artery bypass graft (CABG) surgery. The expression of the cardioprotective SIRT1 protein with its antioxidant activity is increased in cardiac tissue of patients suffering from POAF. So far, information is lacking about the relationship between SIRT1 regulating micro RNAs (miRs), SIRT1 protein and the occurrence of POAF. A total of 63 patients undergoing CABG were recruited, and biopsies were obtained from the right atrial appendage during cannulation. Postoperative, all patients were rhythm-monitored until discharge and randomized to POAF (n=20) or sinus rhythm (n=43). The expression of the micro RNAs miR-199a and miR-195 was quantified by real-time PCR. SIRT1 protein was detected by western blot analysis. The relative expression of miR-199a in the POAF group was significantly decreased compared to the control group (0.77±0.27 vs. 1.11±0.69, P=.022) Accordingly, SIRT 1 protein was significantly induced in tissue probes of patients with POAF (P<.001). Altered expression of the SIRT1 protein regulating miR-199a in human atrial tissue was found to be related to the occurrence of POAF, indicating its usefulness as a biomarker for cardiac surgery management.


Human genetic basis of interindividual variability in the course of infection.
The key problem in human infectious diseases was posed at the turn of the 20th century: their pathogenesis. For almost any given virus, bacterium, fungus, or parasite, life-threatening clinical disease develops in only a small minority of infected individuals. Solving this infection enigma is important clinically, for diagnosis, prognosis, prevention, and treatment. Some microbes will inevitably remain refractory to, or escape vaccination, or chemotherapy, or both. The solution also is important biologically, because the emergence and evolution of eukaryotes alongside more rapidly evolving prokaryotes, archaea, and viruses posed immunological challenges of an ecological and evolutionary nature. We need to study these challenges in natural, as opposed to experimental, conditions, and also at the molecular and cellular levels. According to the human genetic theory of infectious diseases, inborn variants underlie life-threatening infectious diseases. Here I review the history of the field of human genetics of infectious diseases from the turn of the 19th century to the second half of the 20th century. This paper thus sets the scene, providing the background information required to understand and appreciate the more recently described monogenic forms of resistance or predisposition to specific infections discussed in a second paper in this issue.


Remediation of environmental toxicants using carbonaceous materials: opportunity and challenges.
Adsorption and photocatalytic properties of carbonaceous materials, viz., carbon nanotubes (CNTs), fullerene, graphene, graphene oxide, carbon nanofiber nanospheres, and activated carbon, are the legitimate weapons for the remediation of emerging and persistent inorganic/organic contaminants, heavy metals, and radionucleotides from the environment. High surface area, low or non-toxic nature, ease of synthesis, regeneration, and chemical modification of carbonaceous material make them ideal for the removal of toxicants. The research techniques investigated during the last decade for the elimination of environmental toxicants using carbonaceous materials are reviewed to offer comprehensive insight into the mechanism, efficiency, applications, advantages, and shortcomings. Opportunities and challenges associated with carbon materials have been discussed to suggest future perspectives in the remediation of environmental toxicants.


Activation of hydrocarbons on acidic zeolites: superior selectivity of methylation of ethene with methanol to propene on weakly acidic catalysts.
The study of methylation of ethene with methanol to propene over MFI zeolites with different heteroatoms has found that an efficient catalyst with weak acidities prevented the side reactions related with the formation of ethene oligomers from occurring, as evidenced by in situ IR spectroscopy, leading to superior propene selectivity in the product distribution.


Metallo-supramolecular polymers derived from benzothiadiazole-based platinum acetylide complexes for fluorescent security application.
Metallo-supramolecular polymers with the incorporation of benzothiadiazole-substituted organoplatinum moiety have been successfully constructed. The designed monomer displays intense fluorescence signals, which are severely quenched upon the supramolecular polymerization process. On-off switching of fluorescence can be further exploited for data security materials in response to the chemical stimuli. Accordingly, the resulting supramolecular polymers can be regarded as a novel and efficient candidate toward information processing applications.


Insulin action during pregnancy. Studies with the euglycemic clamp technique.
To assess the mechanisms responsible for the insulin resistance associated with both normal human pregnancy and gestational-onset diabetes, we have measured exogenous glucose disposal using sequential insulin infusions with the euglycemic glucose clamp technique and erythrocyte insulin binding. Three groups of women were studied: nonpregnant women with normal glucose tolerance (N = 7, mean age 32.9 +/- 2.1 yr), pregnant women with normal glucose tolerance (N = 5, mean age 24.8 +/- 3.5 yr), and pregnant women with gestational-onset diabetes (N = 5, mean age 34.6 +/- 2.6 yr). Despite normal plasma glucose levels obtained during a 100-g oral glucose tolerance test, plasma insulin levels were significantly elevated in the pregnant women compared with the nonpregnant control subjects, suggesting a state of insulin resistance. Insulin binding to erythrocytes was similar in all three groups (maximum specific binding being 5.0 +/- 0.6%, 5.5 +/- 1.1%, and 6.0 +/- 0.7% in nonpregnant, nondiabetic pregnant, and gestational-onset diabetic women, respectively). In vivo peripheral insulin action was measured using the euglycemic glucose clamp technique during an insulin infusion of 40 mU/m2 X min, with blood glucose clamped at a concentration of 75 mg/dl using a variable glucose infusion. Glucose infusion rates were 213 +/- 11 mg/m2 X min, 143 +/- 23 mg/m2 X min, and 57 +/- 18 mg/m2 X min in nonpregnant, nondiabetic pregnant, and gestational-onset diabetic women, respectively. This demonstrates that pregnant subjects display a state of insulin resistance, and that this appears to be more marked in gestational-onset diabetic subjects. To further define the possible mechanism of insulin resistance during pregnancy, the insulin infusion rate was increased to 240 mU/m2 X min and further euglycemic clamp measurements performed. Glucose infusion rates were 372 +/- 11 mg/m2 X min, 270 +/- 31 mg/m2 X min, and 157 +/- 26 mg/m2 X min, in nonpregnant, nondiabetic pregnant, and gestational-onset diabetic women, respectively. This demonstrates a shift to the right of the dose-response curve of insulin action and suggests that the insulin resistance of pregnancy may include a decrease in presumed "maximum" insulin responsivity. In four subjects, studies were repeated in the postpartum period, and these demonstrated that the insulin resistance of pregnancy is ameliorated shortly after delivery. These studies suggest that the insulin resistance of pregnancy results from a target cell defect in insulin action beyond the initial step of insulin binding to cellular receptors, a postreceptor (or postbinding) defect in insulin action.


Predictors of rapidly progressive interstitial lung disease and mortality in patients with autoantibodies against melanoma differentiation-associated protein 5 dermatomyositis.
Anti-melanoma differentiation-associated protein 5 (MDA5)-positive DM is associated with rapidly progressive interstitial lung disease (RP-ILD) and high mortality. This multicentre retrospective study aimed to identify predictors of mortality and RP-ILD. Anti-MDA5-positive DM patients were identified from the Hong Kong Myositis Registry and the Clinical Data Analysis and Reporting System. Clinical characteristics were reviewed. Risk factors for mortality and RP-ILD were identified. Among the 116 recruited patients, 100 (86.2%) had ILD, 47 (40.5%) had RP-ILD and 44 (37.9%) patients died. Cox regression analysis revealed RP-ILD [hazard ratio (HR) 9.735 (95% CI 3.905, 24.272)], age >52 years [HR 4.750 (95% CI 1.692, 13.333)], ferritin level >2800 pmol/l [HR 3.042 (95% CI 1.323, 6.997)] and lactate dehydrogenase (LDH) >400 IU/l [HR 2.290 (95% CI 1.009, 5.198)] were independent predictors of mortality. With regard to RP-ILD, analyses showed that potential predictors at baseline included age >50 years [HR 2.640 (95% CI 1.277, 5.455)], LDH >300 IU/l [HR 3.189 (95% CI 1.469, 6.918)], fever [HR 1.903 (95% CI 0.956, 3.790)] and neutrophil:lymphocyte ratio >7.0 [HR 1.967 (95% CI 0.942, 4.107)]. We proposed a prediction model based on fever, LDH, age and white cell count (FLAW) to stratify the risk of development of RP-ILD. The probability of RP-ILD in a patient with a score of 4 was 100%. A small internal validation cohort showed the odds of RP-ILD with FLAW scores of 0, 1, 2 and 3 were 0%, 0%, 42.9% and 75%, respectively. Anti-MDA5-associated RP-ILD is significantly associated with poor survival rates. The FLAW model maybe useful to predict the development of RP-ILD.


Comparing learning performance on the open trial selective reminding test with the California verbal learning test II in traumatic brain injury.
Introduction: Learning and memory deficits are prevalent following moderate to severe traumatic brain injury (TBI), affecting between 54% and 84% of impacted individuals.Objective: The current study examined learning performance on two tests of verbal memory: the OT-SRT and the CVLT-II.Methods: Sixty-eight participants with TBI performed the OT-SRT and the CVLT-II on two different days. Additionally, all participants completed cognitive tests assessing processing speed, working memory and executive functions. By definition, all participants with TBI were identified as having impaired learning on the OT-SRT, however only 38 were also identified as impaired on the CVLT-II. The sample was thus divided into two groups, those who failed both tests (Fail-2) and those who failed only the OT-SRT (Fail-1).Results: The Failed-1 group showed significantly better performance in processing speed, working memory and executive functions compared to the Fail-2 group. On the CVLT-II, the Fail-1 group performed significantly better on the number of words recalled on trials 1 and 5 compared to the Fail-2 group. Both groups performed similarly the OT-SRT.Discussion: The CVLT-II and the OT-SRT are not equivalent tests and should not be used interchangeably.


Interventional radiologic procedures in the management of the renal transplant patient.
Interventional radiologic procedures have become an important adjunct to the management of the renal transplant patient. Numerous problems can be dealt with, and in our experience these have included the diagnosis and treatment of ureteric obstruction, dilatation of renal artery stenoses, drainage of abscesses, hematomas and lymphoceles, management of complications of pancreatitis and treatment of bleeding due to fistulas and pseudoaneurysms.


Emotion processing in the visual brain: a MEG analysis.
Recent functional magnetic resonance imaging (fMRI) and event-related brain potential (ERP) studies provide empirical support for the notion that emotional cues guide selective attention. Extending this line of research, whole head magneto-encephalogram (MEG) was measured while participants viewed in separate experimental blocks a continuous stream of either pleasant and neutral or unpleasant and neutral pictures, presented for 330 ms each. Event-related magnetic fields (ERF) were analyzed after intersubject sensor coregistration, complemented by minimum norm estimates (MNE) to explore neural generator sources. Both streams of analysis converge by demonstrating the selective emotion processing in an early (120-170 ms) and a late time interval (220-310 ms). ERF analysis revealed that the polarity of the emotion difference fields was reversed across early and late intervals suggesting distinct patterns of activation in the visual processing stream. Source analysis revealed the amplified processing of emotional pictures in visual processing areas with more pronounced occipito-parieto-temporal activation in the early time interval, and a stronger engagement of more anterior, temporal, regions in the later interval. Confirming previous ERP studies showing facilitated emotion processing, the present data suggest that MEG provides a complementary look at the spread of activation in the visual processing stream.


Protein accumulation in the endoplasmic reticulum as a non-equilibrium phase transition.
Several neurological disorders are associated with the aggregation of aberrant proteins, often localized in intracellular organelles such as the endoplasmic reticulum. Here we study protein aggregation kinetics by mean-field reactions and three dimensional Monte carlo simulations of diffusion-limited aggregation of linear polymers in a confined space, representing the endoplasmic reticulum. By tuning the rates of protein production and degradation, we show that the system undergoes a non-equilibrium phase transition from a physiological phase with little or no polymer accumulation to a pathological phase characterized by persistent polymerization. A combination of external factors accumulating during the lifetime of a patient can thus slightly modify the phase transition control parameters, tipping the balance from a long symptomless lag phase to an accelerated pathological development. The model can be successfully used to interpret experimental data on amyloid-β clearance from the central nervous system.


A rare case of anterior mid line neck cyst in a child.
Mid line neck swellings are common in paediatric as well as in adults. They can be of three categories; inflammatory, neoplastic, and congenital. A child with history of a nodular swelling over the anterior midline neck, its unusual diagnosis and its management has been discussed here. Many of Non thyroidal lesions can mimic and present like thyroid nodules. Clinical examination with preoperative work-up will help to differentiate such lesions, in planning subsequent surgical intervention and hence avoiding iatrogenic damage to the thyroid gland. Among the diverse and numerous mid line neck lesions, the clinical assessment can only aid in justifying the surgical procedure in these lesions.


Comparative plastome genomics, taxonomic delimitation and evolutionary divergences of Tetraena hamiensis var. qatarensis and Tetraena simplex (Zygophyllaceae).
The Zygophyllum and Tetraena genera are intriguingly important ecologically and medicinally. Based on morphological characteristics, T. hamiensis var. qatarensis, and T. simplex were transferred from Zygophyllum to Tetraena with the least genomic datasets available. Hence, we sequenced the T. hamiensis and T. simplex and performed in-depth comparative genomics, phylogenetic analysis, and estimated time divergences. The complete plastomes ranged between 106,720 and 106,446 bp-typically smaller than angiosperms plastomes. The plastome circular genomes are divided into large single-copy regions (~ 80,964 bp), small single-copy regions (~ 17,416 bp), and two inverted repeats regions (~ 4170 bp) in both Tetraena species. An unusual shrinkage of IR regions 16-24 kb was identified. This resulted in the loss of 16 genes, including 11 ndh genes which encode the NADH dehydrogenase subunits, and a significant size reduction of Tetraena plastomes compared to other angiosperms. The inter-species variations and similarities were identified using genome-wide comparisons. Phylogenetic trees generated by analyzing the whole plastomes, protein-coding genes, matK, rbcL, and cssA genes exhibited identical topologies, indicating that both species are sisters to the genus Tetraena and may not belong to Zygophyllum. Similarly, based on the entire plastome and proteins coding genes datasets, the time divergence of Zygophyllum and Tetraena was 36.6 Ma and 34.4 Ma, respectively. Tetraena stem ages were 31.7 and 18.2 Ma based on full plastome and protein-coding genes. The current study presents the plastome as a distinguishing and identification feature among the closely related Tetraena and Zygophyllum species. It can be potentially used as a universal super-barcode for identifying plants.


Effects of selective removal of the salivary glands on taste bud cells in the vallate papilla of the rat.
The in-block removal of the main salivary glands produced a significant increase in the rate of development of the intermediate type of taste bud cells. Such effect was reproduced by removal of submaxillary-sublingual glands. Removal of parotid glands was not effective.


Percutaneous radiofrequency ablation of renal tumors in high-risk patients: 10 years' experience.
To retrospectively evaluate the efficacy and safety of percutaneous radiofrequency ablation (RFA) done to treat renal tumors in patients with high surgical risk or with the risk of developing multiple renal tumors in the medium term at our center over a period of 10 years. Between 2005 and 2015, we used RFA to treat 89 T1a or T1b tumors in 87 patients (mean age, 73.7±10.87 years) with high surgical risk. We excluded patients treated with radiofrequency and embolization or microwave ablation. The tumors treated were clear cell carcinomas (43.6%), papillary renal carcinomas (17.2%), chromophobe renal cell carcinomas (10.3%), cystic tumors (2.2%), and an angiomyolipoma (1.1%). The mean size of the tumors was 2.6cm. Computed tomography and/or ultrasonography were used to guide the procedure. We analyzed the relation between the efficacy of the procedure and patients' age, the type of needle, the source of the patients, the size and location of the tumor, and the number of sessions required to achieve ablation. We recorded all complications. The RFA procedure was completed in all patients. The mean follow-up period was 32.1 months. The efficacy was 93.7%. A single session was sufficient in 87.5% of patients; 8% required two sessions and 4.5% required three sessions. The only factor associated with worse efficacy was the size of the tumor (p=0.03). The rate of complications was 5.6%. RFA is efficacious and safe, with results comparable to those reported in the literature.


Evaluating enrollment and outcome criteria in trials of biologics for chronic rhinosinusitis with nasal polyps.
Treatment for chronic rhinosinusitis with nasal polyps (CRSwNP) generally involves intranasal corticosteroids (INCS) and saline irrigation, followed by short courses of systemic corticosteroids (SCS) or surgery with postoperative medical therapy for patients who do not respond to INCS. However, both SCS use and surgery are associated with a range of adverse effects or complications, have a high recurrence rate, and are unsuitable for some patients. Biologics targeting the underlying pathophysiology are promising treatment alternatives for these patients. Dupilumab, omalizumab, and mepolizumab are approved for use in patients with severe, uncontrolled CRSwNP. However, the lack of a consistent definition of severe CRSwNP makes the decision to initiate biologic treatment particularly complex. Furthermore, the position of each biologic in the overall management of CRSwNP remains to be clarified. Publications reporting results of phase III trials of dupilumab, omalizumab, mepolizumab, and benralizumab in the treatment of CRSwNP. Randomized, controlled phase III trials of biologics approved for CRSwNP. These trials all used different enrollment criteria. We discuss the complexities of assessing CRSwNP disease severity and highlight how these impact comparisons of the populations and outcomes of the phase III biologic trials. To position biologic agents appropriately within the existing CRSwNP treatment paradigm, future trials will need to include comparable patient populations and standardized outcome measures. Such trials will help to ensure that biologic treatment is targeted appropriately to support optimal clinical outcomes.


Dispersal ability and relative abundance of Boeckella and Calamoecia (Copepoda: Calanoida) in Australian and New Zealand waters.
Two calanoid copepod genera, Boeckella and Calamoecia have broadly similar geographic distributions in Australia but Boeckella is more common than Calamoecia. A field survey and literature search indicate that Boeckella is usually the first calanoid to colonize newly formed bodies of water, and Boeckella is more common in temporary pools and in high altitude environments. Boeckella usually produces larger clutches than Calamoecia, increasing its probability of establishment in lakes and ponds; calculations indicate that Boeckella's probability of establishment is far greater than that of Calamoecia. That Calamoecia is common on the North Island of New Zealand may be due to the presence of planktivorous fish; small species are more likely to survive in such environments. Calamoecia clutches may be able to move more often and farther than those of Boeckella but Calamoecia remains rare because its probability of establishment is low. Boeckella may be able to survive temporary pool environments not only because it can produce larger clutches, but also because many species in this genus are highly pigmented, and as such can survive brightly lighted environments. Patterns of abundance of North American diaptomids appear to be consistent with factors affecting those of Australian and New Zealand centropagids.


Surgical treatment of patients with initially inoperable and/or metastatic gastrointestinal stromal tumors (GIST) during therapy with imatinib mesylate.
The aim of the study was to analyze the surgical possibilities of unresectable and/or metastatic GIST CD117(+) patients during imatinib treatment. We analyzed the results of surgery in 141 patients treated with imatinib for initially inoperable and/or metastatic GIST CD117(+). Median follow-up time was 12 months (range: 3-26). Surgery was performed as subsequent treatment in 24 patients (Group I, 17%) for resection of residual disease after complete/partial response and lack of further response to imatinib and as salvage therapy in eight patients (Group II, 6%), who progressed on initially successful imatinib therapy. In Group I, the viable GIST cells were not detected histologically in only three resection specimens. The first five patients in Group I did not receive imatinib further and we observed four recurrences. In next 19 patients, continuing imatinib after surgery, we observed only one relapse. In Group II, we continued imatinib therapy after high-risk surgical procedures, but in five patients we observed subsequent progression. Surgical removal of residual disease during imatinib treatment may allow for complete remission in selected GIST patients after response to therapy, theoretically prolonging durable remission, but it is necessary to continue imatinib for its maintenance.