Melatonin Lulling Th17 Cells to Sleep.
In this issue, Farez et al. report that the circadian hormone melatonin, whose levels vary with seasonal changes in night length, shifts the immune response toward an anti-inflammatory state that may explain the seasonal variability of multiple sclerosis disease activity.


Light-harvesting complexes from purple sulfur bacteria Allochromatium minutissimum assembled without carotenoids.
Effect of carotenoid (Car) biosynthesis inhibitor diphenylamine (DPA) on purple sulfur bacteria Allochromatium (Alc) minutissimum cell growth has been investigated. Cell growth in the presence of maximum concentration of DPA results in practically complete suppression (∼99%) of carotenoids (Cars) according to the spectrophotometric, HPLC and CD data. Phytoene does not replace the colored carotenoids in these cells. Also Phytoene does not accumulate in large amounts in the cells treated with DPA. A new method for calculating the content of Cars in the complexes from the cells with inhibited Car synthesis including the number of empty Car's "pockets" has been used. Our results together with published data devoted to DPA action on the cell growth of purple bacteria revealed that Phytoene was not accumulated in the cells treated with DPA. We have concluded that (i) DPA completely inhibits or strongly reduces synthesis of the colored Cars in the cells of purple bacteria, (ii) Phytoene is the main one among the trace amounts of the other Cars in the case of significant inhibition of Car biosynthesis (80-90% or higher). The amount of the LH2 complexes presented in the membranes of Alc minutissimum was found to be little dependent on DPA. From DPA-grown cultures it was possible to isolate Car-less both the LH1 (as LH1-RC complex) and the LH2 complexes. Electronic absorption properties of BChl's were very similar to those isolated from the control cells. It is shown by HPLC data that the 100 LH2 complexes from cells of Alc minutissimum, in which the synthesis of Car was depressed, contained ∼9 Car molecules and 5 Phytoene molecules. Thus, only nine (with 1 Car molecule per a complex) or less (if more than one Car molecule per a complex) of the 100 LH2 complexes contain molecules of Cars. It means that 90 or more LH2 complexes from each 100 ones are assembled without any Cars. This is in strong contrast with the previous results obtained with purple non-sulfur bacterium Rhodobacter sphaeroides, where the amount of LH2 presented in the membrane was directly correlated to the amount of the carotenoids synthesized (H.P. Lang, C.N. Hunter, The relationship between carotenoid biosynthesis and the assembly of the light harvesting LH2 complex in Rhodobacter sphaeroides, Biochem. J. 298 (1994) 197-205). Our results show that although the presence of Car molecules is important for the stability of the LH2 complexes the overall native structure can be maintained without any Cars at least in the case of purple sulfur bacteria.


Predictive performance of lipid accumulation product and visceral adiposity index for renal function decline in non-diabetic adults, an 8.6-year follow-up.
Lipid accumulation product (LAP) and visceral adiposity index (VAI) are surrogates for visceral adiposity dysfunction. Our aim was to evaluate potential association of these two indices with the incidence of renal function decline. We included 6693 non-diabetic adults age ≥ 18 years, with estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2, from the Tehran Lipid and Glucose Study 2002-2005 survey. Natural logarithmic transformation (Ln) was applied for LAP and VAI measures. The incidence of renal function decline, defined as eGFR < 60 ml/min/1.73 m2, was evaluated for each gender, across tertiles of Ln LAP, Ln VAI, body mass index (BMI), waist circumference (WC), waist to height ratio (WHtR) and waist to hip ratio (WHR), using Cox-proportional hazard models. Over a median 8.6 years of follow-up, 1670 new cases of renal function decline were identified (incidence rate 3.2%). After multivariable adjustment, the hazard ratios (HRs) with 95% CI across second and third tertiles of Ln LAP were 1.14 (0.86-1.50) and 1.33 (1.00-1.78) in men (P trend = 0.132); and 1.16 (0.90-1.50) and 1.24 (0.96-1.61) in women (P trend = 0.263), respectively. Multivariable adjusted HRs across second and third tertiles of Ln VAI were 1.40 (1.08-1.83) and 1.35 (1.02-1.78) in men (P trend = 0.031); and 0.93 (0.75-1.15) and 1.15 (0.93-1.41) in women (P trend = 0.072), respectively. HRs across tertiles of BMI, WC, WHtR and WHR were not significant for renal function decline among both genders in any adjustment models. Among the adiposity indices assessed in this study, VAI seems to be an independent predictor of renal function decline only in males.


Frequency and impact of suboptimal immune recovery on first-line antiretroviral therapy within the International Epidemiologic Databases to Evaluate AIDS in East Africa.
To describe patterns of suboptimal immune recovery (SO-IR) and associated HIV-related-illnesses during the first 5 years following first-line antiretroviral therapy (ART) initiation across seven ART sites in East Africa. Retrospective analysis of data from seven ART clinical sites (three Uganda, two Kenya and two Tanzania). SO-IR was described by proportions of ART-treated adults with CD4 cell counts less than 200, less than 350 and less than 500 cells/μl. Kaplan-Meier survival analysis techniques were used to assess predictors of SO-IR, and incident rates of HIV-related illnesses at CD4 cell counts less than 200, 200-350, 351-499, and >500 cells/μl, respectively. Overall 80 843 adults initiated non-nucleoside reverse transcriptase inhibitor-based first-line ART; 65% were women and median CD4 cell count was 126 [interquartile range (IQR), 52-202] cells/μl. Cumulative probability of SO-IR <200 cells/μl, <350 cells/μl and <500 cells/μl, after 5 years, was 11, 38 and 63%, respectively. Incidence of HIV-related illnesses was higher among those with CD4 cell counts less than 200 and 200-350 cells/μl, than those who achieved CD4 counts above these thresholds. The most common events, at CD4 < 200 cells/μl, were pulmonary tuberculosis [incident rate 15.98 (15.47-16.51)/100 person-years at risk (PYAR), oral candidiasis [incident rate 12.5 (12.03-12.94)] and herpes zoster [incident rate 6.30 (5.99-6.64)] events/100 PYAR. With attainment of a CD4 cell count level 200-350 cells/μl, there was a substantial reduction in events/100 PYAR - by 91% to 1.45 (1.29-1.63) for TB, by 94% to 0.75 (0.64-0.89) for oral candidiasis, by 84% to 0.99 (0.86-1.14) for Herpes Zoster, and by 78% to 1.22 (1.07-1.39) for chronic diarrhea. The incidence of all events decreased further with CD4 counts above these thresholds. Around 40% of adults initiated on ART have suboptimal immune recovery with CD4 counts <350 cells/μl after five years. Such patients will require closer monitoring for both HIV-related and non-HIV-related clinical events.


[Fulminant coagulopathy after bivalirudin use in a patient diagnosed with heparin-induced thrombocytopenia and subject to cardiac bypass surgery].
Patients with a previous history of heparin-induced thrombocytopenia are at a higher risk for thromboembolic events, and heparin administration is formally contraindicated. Bivalirudin has been reported as an alternative therapy whenever an intervention that requires systemic anticoagulation and cardiopulmonary by-pass pump is needed. We present the case of a patient diagnosed with heparin-induced thrombocytopenia and heparin-PF4 (+) antibodies requiring a triple cardiac valve replacement who developed fulminant coagulopathy after bivalirudin administration. A discussion on the serious difficulties that the management of these types of patients involves, as well as a review of prevention strategies are presented.


Ophthalmoscopic findings in spontaneous carotid cavernous fistula: an analysis of 20 patients.
The pathophysiological influence of spontaneous carotid cavernous fistula (CCF) on retinal/orbital circulation is discussed. Of 20 patients, 1 case of papilloedema, 4 of choroidal detachment (CD), 2 of exudative retinal detachment (ERD) and 3 cases of central venous thrombosis (CVT) were seen, associations that on rarely reported in the literature. An elevation in the episcleral venous pressure was measured that was more than twice the normal, which explains the ophthalmoscopic findings.


Normal outcome of pregnancy in chronic myeloid leukemia treated with interferon-alpha in 1st trimester: report of 3 cases and review of the literature.
Three patients with chronic myeloid leukemia (CML) in chronic phase received interferon-alpha during pregnancy, starting from the 1st trimester. No maternal complications were reported. The 3 patients delivered normal looking babies apart from one baby who was found to have transient mild thrombocytopenia. Subsequently these children were followed for 30, 12, and 4 months and all had normal growth and development.


Toxicogenomics and classic toxicology: how to improve prediction and mechanistic understanding of human toxicity.
The field of toxicogenomics has been advancing during the past decade or so since its origin. Most pharmaceutical companies are using it in one or more ways to improve their productivity and supplement their classic toxicology studies. Acceptance of toxicogenomics will continue to grow as regulatory concerns are addressed, proof of concept studies are disseminated more fully, and internal case studies show value for the use of this new technology in concert with classic testing.


Normobaric oxygen as a sensitizer of hypoxic tumor cells.
A series of experiments have been performed to determine the relative radiosensitivities of a mouse mammary tumor (CA NT) irradiated in 100% normobaric oxygen or in air, using clinically relevant dose-fractionation schedules. The results demonstrate that normobaric oxygen is a potent radiosensitizer, its effect being more marked with smaller size fractions. Enhancement ratios (ER) of 1.23 to 1.45 were obtained. By contrast, no significant benefit was seen with single doses (ER = 1.05 +/- 0.14). The degree of radiosensitization with oxygen, in these fractionated regimens, is greater than that reported for the chemical radiosensitizer, misonidazole. It therefore seems appropriate to re-examine the clinical potential of normobaric oxygen and to consider how the conditions of normobaric radiotherapy achieved in the laboratory can be translated to man.


Synaptic density correlated with maze performance in young and aged rats. A preliminary study.
The aim of this study was to determine the effect of age both on maze performance and upon morphological changes in the brain. Young and senescent rats were differentiated into three groups by use of a complex 14-unit maze: young maze-bright rats, old maze-bright animals and old maze-dull rats. Layer III of the frontal and the occipital cortices of these animals was studied, employing coded electron micrographs, to determine the average number of synaptic profiles per area of thin section. It was observed that the young maze-bright rats had the highest synapse density, the old maze-bright rats had 85% of that amount while the old maze-dull animals had a density that was 54% that of the young animals.


Bile salts in digestion and transport of lipids.
Because of their unusual chemical structure, bile salts (BS) play a fundamental role in intestinal lipid digestion and transport. BS have a planar arrangement of hydrophobic and hydrophilic moieties, which enables the BS molecules to form peculiar self-assembled structures in aqueous solutions. This molecular arrangement also has an influence on specific interactions of BS with lipid molecules and other compounds of ingested food and digestive media. Those comprise the complex scenario in which lipolysis occurs. In this review, we discuss the BS synthesis, composition, bulk interactions and mode of action during lipid digestion and transport. We look specifically into surfactant-related functions of BS that affect lipolysis, such as interactions with dietary fibre and emulsifiers, the interfacial activity in facilitating lipase and colipase anchoring to the lipid substrate interface, and finally the role of BS in the intestinal transport of lipids. Unravelling the roles of BS in the processing of lipids in the gastrointestinal tract requires a detailed analysis of their interactions with different compounds. We provide an update on the most recent findings concerning two areas of BS involvement: lipolysis and intestinal transport. We first explore the interactions of BS with various dietary fibres and food emulsifiers in bulk and at interfaces, as these appear to be key aspects for understanding interactions with digestive media. Next, we explore the interactions of BS with components of the intestinal digestion environment, and the role of BS in displacing material from the oil-water interface and facilitating adsorption of lipase. We look into the process of desorption, solubilisation of lipolysis, products and formation of mixed micelles. Finally, the BS-driven interactions of colloidal particles with the small intestinal mucus layer are considered, providing new findings for the overall assessment of the role of BS in lipid digestion and intestinal transport. This review offers a unique compilation of well-established and most recent studies dealing with the interactions of BS with food emulsifiers, nanoparticles and dietary fibre, as well as with the luminal compounds of the gut, such as lipase-colipase, triglycerides and intestinal mucus. The combined analysis of these complex interactions may provide crucial information on the pattern and extent of lipid digestion. Such knowledge is important for controlling the uptake of dietary lipids or lipophilic pharmaceuticals in the gastrointestinal tract through the engineering of novel food structures or colloidal drug-delivery systems.


Evaluation of bolus cis-platinum and continuous 5-fluorouracil infusion for metastatic and recurrent squamous cell carcinoma of the cervix.
The combination of cis-platinum and 5-fluorouracil has been reported to act synergistically with improved response rates in squamous cell carcinomas of the head and neck. The activity of bolus cis-platinum and continuous infusion of 5-fluorouracil in 24 patients with recurrent and metastatic squamous cell carcinoma of the cervix was evaluated. Twelve patients were stage I, 3 were stage II, 5 were stage III, and 4 were stage IV cervical carcinomas. Among the 24 patients, there were 4 complete and 8 partial responses (50%). The overall median response was 24 weeks. The overall cumulative survival was 55% at 40 weeks and 40% at 1 year after beginning this regimen. Complications included 4 patients who developed leukopenia, 3 thrombocytopenia, 11 stomatitis, 14 nephrotoxicity, 4 peripheral neuropathy, and 6 ototoxicity. The combination of cis-platinum and continuous infusion of 5-fluorouracil appears to have useful activity in patients with recurrent or metastatic squamous cell carcinoma of the cervix.


Antibacterial gas therapy: Strategies, advances, and prospects.
One of the challenges posed by current antibacterial therapy is that the expanded and massive use of antibiotics endows bacteria with the ability to resist almost all kinds of antibiotics. Therefore, developing alternative strategies for efficient antibacterial treatment is urgently needed. Antibacterial gas therapy has attracted much attention in the past decade. Nitric oxide (NO), carbon monoxide (CO), sulfur dioxide (SO2), hydrogen sulfide (H2S), and hydrogen (H2) are not only known as endogenous signaling molecules, but also play critical roles in many pathological processes. These gases are considered as attractive bactericidal agents because they are able to kill bacteria, disperse biofilms, and promote bacteria-infected wound healing while avoiding resistance. In this review, we discuss the bactericidal properties of these gases, as well as the recent advances of gas-involving systems in antibacterial, antibiofilm, and wound treatment applications. Moreover, we summarize various gas donors utilized in antibacterial treatment. We hope this review will shed new light on the future design and applications of advanced antibacterial gas therapy.


Providing an environmental management model with emphasis on ecosystem resilience: a coastal City in Southern Iran.
Urban environmental management is an effective tool which aims at urban development inline with environmental, social and economic values. The present study aims to provide an environmental management model of Bandar Abbas with an emphasis on ecosystem resilience. The research has been conducted in several steps, the first of which includes the assessment and analysis of resilience of Bandar Abbas city in terms of environmental dimensions and components based on the selection of environmental indicators and components in accordance with the opinions of urban issues experts and access to the available data and information resources, estimation and evaluation of the resilience status of indicators and components of the city. The second step presents the regression equation of resilience under the influence of environmental indicators and components. Also, the third step provides a strategy for the resilience, given the frequency of strategies ranking by the experts and the current environmental situation of Bandar Abbas. The results of the overall resilience assessment indicated that Bandar Abbas is of favorable resilience in terms of the climate, water and soil, vegetation, water, air, water quality and air quality indicators and components, while being of unfavorable resilience situation in terms of the institutional-functional index, citizens' culture and awareness, waste, sewage and trash management. In general, the environmental resilience situation of Bandar Abbas city was found to be favorable with an estimated value of 3.29 and in a good situation against environmental crises. Finally, an environmental management model has been presented along with the effective strategies from the perspective of Urban Issues experts to improve the resilience of Bandar Abbas city.


Assessing the economic and ecological viability of generating electricity from oil derived from pyrolysis of plastic waste in China.
The increased plastic waste generation worldwide poses ponderous issues for public health and the environment. China is the highest generator of plastic waste around the world. The current treatment process (incineration) of the increased plastic waste causes dangerous environmental consequences. Pyrolysis has recently surfaced as an ecologically friendly technique for energy and material recovery from plastic waste. The present study assesses the financial and ecological viability of power production from oil derived from the pyrolysis of mixed plastic wastes in China from 2009 to 2028. The prominent findings show that the amount of plastic waste collected in 2020 (24.16 Mt) increased by 53.19% in 2028.The pyrolysis of mixed plastic wastes during the project period yielded 359.29 Mt oil, which has a power potential of 1,060.86 GWh. The economic analysis indicated the project is viable and profitable with a positive net present value (US$8.80 million) and profitability index (1.26) greater than 1. The project has 10.6 y payback period, US$0.0752/kWh levelized cost of energy, 22.5% return on investment, and 13.0% internal rate of return. The life cycle assessment results show that conversion of mixed plastic waste to pyrolysis oil for electricity generation during the project period has a total global warming potential (GWP) of 1,311.4 kt CO2eq. The GWP is mainly from conversion of pyrolysis oil to electricity (73.42%), pyrolysis oil production (15.01%) and upgrading of pyrolysis oil (11.38%). The consumption of power from the project could avoid the combustion of 2,659.0 t coal, minimizing global warming by 11,278.8 kt CO2eq. Sensitivity analysis, which examines the influence of variation in sensitive factors on the success of the project, is presented. This paper provides scientific strategies for optimal investment and decision-making on the environmental sustainability of plastic waste-to-energy pyrolysis projects.


Epithelioid sarcoma of the penis.
A case of epithelioid sarcoma of the penis is reported with a review of the current treatment modalities. A new method of reconstructing the penis involved with malignancy is presented. Pertinent literature is cited. Cases of epithelioid sarcoma should be published to improve the understanding of the potential of different treatments available. This case represents the fifth epithelioid sarcoma of the penis reported in the literature.


Differential recruitment of high frequency wavelets (600 Hz) and primary cortical response (N20) in human median nerve somatosensory evoked potentials.
Human median nerve somatosensory evoked potentials contain a burst of high-frequency (600 Hz) wavelets superimposed on the primary cortical response (N20). These presumably reflect highly-synchronized repetitive thalamic and/or intracortical population spike bursts and are diminished in non-REM sleep with N20 persisting. Here the burst/N20 relation in awake subjects was examined by using eight different intensities of electric median nerve stimuli. In all subjects the amplitude recruitment of both N20 and burst could be modeled adequately as a sigmoidal function of stimulus intensity. While 8/10 subjects showed a parallel recruitment, 2/10 subjects required significantly higher stimulation intensities for burst than for N20 recruitment. This dampened burst recruitment possibly reflects slight vigilance fluctuations in open-eyed awake subjects; a further increase of burst thresholds could explain the burst attenuation when entering shallow sleep.


A retrospective analysis of the care cascades for non-communicable disease and mental health among people living with HIV at a tertiary-care centre in Malaysia: opportunities to identify gaps and optimize care.
The rapidly growing epidemic of non-communicable diseases (NCDs) including mental health among aging people living with HIV (PLWH) has put a significant strain on the provision of health services in many HIV clinics globally. We constructed care cascades for specific NCDs and mental health among PLWH attending our centre to identify potential areas for programmatic improvement. This was a follow-up study of participants recruited in the Malaysian HIV & Aging study (MHIVA) from 2014 to 2016 at the University Malaya Medical Centre (n = 336). PLWH on suppressive antiretroviral therapy (ART) for a minimum of 12 months were invited to participate. At study entry, all participants underwent screening for diabetes (DM), hypertension (HTN) and dyslipidaemia; and completed assessments using the depression, anxiety and stress scale (DASS-21). Screening results were recorded in medical charts and clinical management provided as per standard of care. A subsequent review of medical records was performed at 24 months following study completion among participants who remained on active follow-up. Treatment pathways for NCD treatment and psychiatric referrals were assessed based on local practice guidelines to construct the care cascade. A total of 329 participants (median age = 43 years, 83% male, 100% on ART) completed follow-up at 24 months. The prevalence of diabetes was 13%, dyslipidaemia 88% and hypertension 44%, whereas 23% presented with severe/extremely severe symptoms of depression, anxiety and/or stress. More than 50% of participants with dyslipidaemia and hypertension were not diagnosed until study screening, whereas over 80% with prevalent psychiatric symptoms were not previously recognized clinically. Suboptimal control of fasting lipids, sugar and blood pressure were found in the majority of participants despite optimal HIV treatment outcomes maintained over this same period. Only 32% of participants with severe/extremely severe mental health symptoms received psychiatric referrals and 83% of these attended their psychiatry clinic appointments. Systematic screening must be introduced to identify NCDs and mental health issues among PLWH followed by proper linkage and referrals for management of screen-positive cases. Assessment of factors associated with attrition at each step of the care cascade is critically needed to improve health outcomes in our aging patients.


Biochemical characterization of the proliferation pool of lymphatic cells in the human tonsil and demonstration of the age-dependent pool size reduction.
The DNA and RNA content and also the thymidine and uridine incorporation kinetics were determined in peripheral lymphocytes and lymphatic cells of the tonsil. The existence of a proliferation pool of lymphoid cells in the tonsil could be established by the comparison of all data. An age-conditioned reduction of the pool size was assumed from the uridine incorporation rate which takes place faster than the organo-specific cell decrease likewise conditioned by age in the tonsil. The abscess tonsil could be explained as a pathological state with considerable reduction of proliferation.


Infant eye movement asymmetries: stationary counterphase gratings elicit temporal-to-nasal optokinetic nystagmus in two-month-old infants under monocular test conditions.
Tested monocularly, young infants classically show directional eye movement asymmetries, with optokinetic nystagmus (OKN) being more readily elicited by stimuli moving in the temporal-to-nasal (T-N) than in the nasal-to-temporal (N-T) direction. Since a counterphase grating is physically identical to two superimposed sinusoidal components moving in opposite directions, we wondered whether or not a counterphase grating would elicit T-N OKN in monocularly tested infants. Two-month-old infants were tested in a motion nulling paradigm. Under monocular test conditions, all infants showed T-N OKN in response to the counterphase grating. The results suggest that the young infant's visual system represents the counterphase grating in terms of its T-N and N-T components, and reduces the effective contrast of the N-T component prior to the generation of OKN. The results are discussed in relation to models of OKN asymmetries and the responses of direction-selective neurons to counterphase gratings.


Partitioning of heavy metals in sediments and microplastics from stormwater runoff.
Microplastics could act as vehicles for transporting heavy metals from urban environments to water resources via stormwater runoff. Although the transport of heavy metals by sediments has been widely studied, there is a lack of mechanistic understanding of their competition with microplastics (MPs) for heavy metal uptake. Therefore, this study was conducted to examine the partitioning of heavy metals in microplastics and sediments from stormwater runoff. For this purpose, new low density polyethylene (LDPE) pellets were selected as representative MPs, and accelerated UV-B irradiation experiments were conducted for eight weeks to generate photodegraded MPs. The competition of Cu, Zn, and Pb species for the occupation of available surface sites on sediments and new and photodegraded LDPE MPs was examined through 48 h kinetics experiments. Additionally, leaching experiments were conducted to identify the extent of organics released into the contact water by new and photodegraded MPs. Moreover, 24 h metal exposure experiments were conducted to identify the role of initial metal concentrations on their accumulation onto the MPs and sediments. The photodegradation process altered the LDPE MPs' surface chemistry by creating the oxidized carbon functional groups [>CO, >C-O-C<], and it also enhanced their dissolved organic carbon (DOC) leaching into the contact water. The results showed significantly greater levels of Cu, Zn, and Pb accumulations on photodegraded MPs compared to the new MPs in either absence or presence of sediments. Heavy metal uptake by sediments when photodegraded MPs were present was significantly reduced. This might be due to the organic matter leached by photodegraded MPs into the contact water.


Direct evidence for chloride-dependent volume reduction in macrocytic sheep reticulocytes.
Cytometric analysis of the volume-distribution of macrocytic reticulocytes from 6-8 days acutely anemic sheep of both high and low potassium erythrocyte type revealed hyposmotically induced cell volume reduction in K-free NaCl but not in Na-methane sulfonate (CH3SO3Na) media. Furthermore N-ethylmaleimide, known to stimulate K:Cl efflux in these cells, and low extracellular pH caused cell shrinkage in isosmotic NaCl but not in CH3SO3Na. These data suggest that cell volume reduction, physiologically occurring during reticulocyte maturation, is a Cl-dependent process most likely involving electro-neutral K:Cl transport known to exist in reticulocytes of both sheep cation genotypes.


Histological expression of angiogenic factors: VEGF, PDGFRalpha, and HIF-1alpha in Hodgkin lymphoma.
Angiogenesis is a prerequisite for solid tumor growth, but there is relatively limited data regarding Hodgkin lymphoma. The purpose of this study was to examine the immunohistochemical expression of angiogenic and proliferation markers in Hodgkin biopsies in relation to clinical parameters. Immunostaining was performed on 65 Hodgkin biopsies with vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 alpha (HIF-1alpha), platelet-derived growth factor receptor alpha (PDGFRalpha), Ki-67, and p53. Microvessel density (MVD) was determined by CD31 staining. In all cases, neoplastic cells and reactive background cells were evaluated. The neoplastic population expressed VEGF in 48% of the cases, HIF-1alpha in 54% of the cases, and PDGFRalpha in 95% of the cases. Both Ki-67 and p53 were positive in neoplastic cells in over 60% of the cases. The MVD had a median of 2.6/0.0625mm(2) which was not different from normal lymph nodes. VEGF in the non-neoplastic compartment showed increased staining in Ann Arbor stage I-II versus III-IV. In conclusion, VEGF, HIF-1alpha, and predominantly PDGFRalpha are expressed in neoplastic cells in the majority of Hodgkin lymphomas. As microvessel formation is not increased in Hodgkin, additional functions of these angiogenic molecules should be investigated.


Eye movements induced by microinjection of GABA agonist in the rat substantia nigra pars reticulata.
Injection of muscimol (GABA agonist) in the substantia nigra pars reticulata (SNr) of the alert rat induced a continual repetition of fast eye movements to the contralateral side, each of which was followed by a slow returning movement. The fast eye movements were similar to spontaneous saccades. Larger saccades were accompanied by contralateral neck muscle activity. We suggest that the SNr plays an important role in control of eye movements in the rat.


Shared neural codes for visual and semantic information about familiar faces in a common representational space.
Processes evoked by seeing a personally familiar face encompass recognition of visual appearance and activation of social and person knowledge. Whereas visual appearance is the same for all viewers, social and person knowledge may be more idiosyncratic. Using between-subject multivariate decoding of hyperaligned functional magnetic resonance imaging data, we investigated whether representations of personally familiar faces in different parts of the distributed neural system for face perception are shared across individuals who know the same people. We found that the identities of both personally familiar and merely visually familiar faces were decoded accurately across brains in the core system for visual processing, but only the identities of personally familiar faces could be decoded across brains in the extended system for processing nonvisual information associated with faces. Our results show that personal interactions with the same individuals lead to shared neural representations of both the seen and unseen features that distinguish their identities.


Cardiac Involvement in Granulomatosis with Polyangiitis.
To determine frequency and outcomes of granulomatosis with polyangiitis (GPA)-related cardiac disease in a North American GPA cohort. Analysis was done of all patients in the Vasculitis Clinical Research Consortium Longitudinal Study of GPA. Demographic and clinical characteristics of patients with and without GPA-related cardiac involvement were compared. Of 517 patients with GPA, 3.3% had cardiac involvement. No differences were observed between patients with or without cardiac involvement in terms of demographics, antineutrophil cytoplasmic antibody positivity, or relapse rate. Cardiac involvement in GPA is rare and heterogeneous. In this cohort, cardiac involvement was not associated with a higher rate of relapse or premature death.


Persistence and dynamic structures of diverse cephalosporinase genes in nontyphoidal Salmonella in cross-sectional surveillance in Taiwan.
Nontyphoidal Salmonella (NTS) is a major foodborne pathogen causing from acute gastroenteritis to bacteraemia, particularly in paediatric and elderly patients. Antimicrobial resistance of NTS, especially resistance to extended-spectrum cephalosporins, has emerged over the past decades. Thirteen NTS isolates resistant to ceftriaxone or cefotaxime were collected from a teaching hospital in Taipei, and another three from a tertiary hospital, in New Taipei City, Taiwan, from September 2018 to December 2019. Ten other archived isolates from 2000 to 2017 were also obtained. Complete genomes of the 26 isolates were obtained. Serovars, sequence types, resistomes, genetic relatedness, and sequence comparison of plasmids were analyzed. Serogroups B, C2 and E were significantly associated with ampicillin resistance. Over 90% of these 26 isolates are susceptible to carbapenems and colistin. Genomic epidemiology of these isolates shows that blaCMY-2-harbouring isolates in different serovars were prevalent over two decades, presumably resulting from highly mobile IncI1 plasmid harbouring blaCMY-2. One type of the IncI1 plasmids contained a mobile element, IS26, which might be involved in the acquisition of antimicrobial resistance genes. Two emerging serovars, S. Goldcoast ST358 harbouring blaCTX-M-55 on IncHI2 plasmids and S. Anatum ST64 harbouring blaDHA-1 on IncA/C2 plasmids persisted in Taiwan, possibly through the clonal spread. Integration of complete or partial plasmid sequences into host chromosomes or multiplications of the antimicrobial resistance genes also appears to be mediated by IS26, in the two emerging clones. The dynamic movement of cephalosporinase genes mediated by IS26 in NTS is of great concern.


Permutation-based group sequential analyses for cognitive neuroscience.
Cognitive neuroscientists have been grappling with two related experimental design problems. First, the complexity of neuroimaging data (e.g. often hundreds of thousands of correlated measurements) and analysis pipelines demands bespoke, non-parametric statistical tests for valid inference, and these tests often lack an agreed-upon method for performing a priori power analyses. Thus, sample size determination for neuroimaging studies is often arbitrary or inferred from other putatively but questionably similar studies, which can result in underpowered designs - undermining the efficacy of neuroimaging research. Second, when meta-analyses estimate the sample sizes required to obtain reasonable statistical power, estimated sample sizes can be prohibitively large given the resource constraints of many labs. We propose the use of sequential analyses to partially address both of these problems. Sequential study designs - in which the data is analyzed at interim points during data collection and data collection can be stopped if the planned test statistic satisfies a stopping rule specified a priori - are common in the clinical trial literature, due to the efficiency gains they afford over fixed-sample designs. However, the corrections used to control false positive rates in existing approaches to sequential testing rely on parametric assumptions that are often violated in neuroimaging settings. We introduce a general permutation scheme that allows sequential designs to be used with arbitrary test statistics. By simulation, we show that this scheme controls the false positive rate across multiple interim analyses. Then, performing power analyses for seven evoked response effects seen in the EEG literature, we show that this sequential analysis approach can substantially outperform fixed-sample approaches (i.e. require fewer subjects, on average, to detect a true effect) when study designs are sufficiently well-powered. To facilitate the adoption of this methodology, we provide a Python package "niseq" with sequential implementations of common tests used for neuroimaging: cluster-based permutation tests, threshold-free cluster enhancement, t-max, F-max, and the network-based statistic with tutorial examples using EEG and fMRI data.


TSG-6 in conditioned media from adipose mesenchymal stem cells protects against visual deficits in mild traumatic brain injury model through neurovascular modulation.
Retinal inflammation affecting the neurovascular unit may play a role in the development of visual deficits following mild traumatic brain injury (mTBI). We have shown that concentrated conditioned media from adipose tissue-derived mesenchymal stem cells (ASC-CCM) can limit retinal damage from blast injury and improve visual function. In this study, we addressed the hypothesis that TNFα-stimulated gene-6 (TSG-6), an anti-inflammatory protein released by mesenchymal cells, mediates the observed therapeutic potential of ASCs via neurovascular modulation. About 12-week-old C57Bl/6 mice were subjected to 50-psi air pulse on the left side of the head overlying the forebrain resulting in an mTBI. Age-matched sham blast mice served as control. About 1 μl of ASC-CCM (siControl-ASC-CCM) or TSG-6 knockdown ASC-CCM (siTSG-6-ASC-CCM) was delivered intravitreally into both eyes. One month following injection, the ocular function was assessed followed by molecular and immunohistological analysis. In vitro, mouse microglial cells were used to evaluate the anti-inflammatory effect of ASC-CCM. Efficacy of ASC-CCM in normalizing retinal vascular permeability was assessed using trans-endothelial resistance (TER) and VE-cadherin expression in the presence of TNFα (1 ng/ml). We show that intravitreal injection of ASC-CCM (siControl-ASC-CCM) but not the TSG-6 knockdown ASC-CCM (siTSG-6-ASC-CCM) mitigates the loss of visual acuity and contrast sensitivity, retinal expression of genes associated with microglial and endothelial activation, and retinal GFAP immunoreactivity at 4 weeks after blast injury. In vitro, siControl-ASC-CCM but not the siTSG-6-ASC-CCM not only suppressed microglial activation and STAT3 phosphorylation but also protected against TNFα-induced endothelial permeability as measured by transendothelial electrical resistance and decreased STAT3 phosphorylation. Our findings suggest that ASCs respond to an inflammatory milieu by secreting higher levels of TSG-6 that mediates the resolution of the inflammatory cascade on multiple cell types and correlates with the therapeutic potency of the ASC-CCM. These results expand our understanding of innate mesenchymal cell function and confirm the importance of considering methods to increase the production of key analytes such as TSG-6 if mesenchymal stem cell secretome-derived biologics are to be developed as a treatment solution against the traumatic effects of blast injuries and other neurovascular inflammatory conditions of the retina.


Prox1 mRNA expression in the medial cortex of the turtle (Pseudemys scripta elegans).
The medial cortex of the cerebrum in reptiles is thought to be homologous to the mammalian dentate gyrus, based on cytoarchitectures, fiber connections, and neurochemical profiles. To support this hypothesis, we examined the mRNA expression of vesicular glutamate transporter 1 (vGluT1), a glutamatergic gene marker, and Prox1, a selective gene marker for granule cells of the dentate gyrus, in the turtle medial cortex (zone 2). Reverse transcription-polymerase chain reaction revealed the presence of both mRNAs in the turtle cerebrum. In situ hybridization of zone 2, which is a layer of densely packed neurons in Nissl stains, intensely expressed vGluT1 and Prox1. In zone 3, which is a loosely packed layer, vGluT1 was intensely expressed, whereas Prox1 signals gradated from strong to negative toward zone 4. These findings demonstrate that zone 2 contains glutamatergic neurons and expresses Prox1 mRNA and suggest that zone 2 in the turtle cerebrum is homologous to the mammalian dentate gyrus.


Physiological response and molecular mechanisms against UV-B radiation in Brachionus asplanchnoidis (Rotifera).
Ultraviolet B (UV-B, 280-320 nm) radiation is a major environmental stressor for aquatic organisms on Earth's surface. Its effects on biological systems are well known, but the mechanisms by which organisms respond and adapt to UV-B radiation are still being explored. In this study, we investigated the effects of UV-B radiation on the monogonont rotifer Brachionus asplanchnoidis, focusing on physiological parameters, antioxidant systems, DNA damage, and DNA repair-related molecular mechanism. Our results showed that the LD50 was at 28.53 kJ/m2, indicating strong tolerance to UV-B. However, UV-B radiation caused adverse effects on growth and reproduction, with shortened reproductive period and longevity, decreased fecundity and hatchability, and inhibition of population growth. Biochemical analyses revealed severe oxidative damage and lipid peroxidation, with increased ROS and MDA levels. Activities of antioxidant enzymes were highly induced at low doses but decreased at high doses. DNA damage also occurred in UV-B-exposed rotifers. Furthermore, selected DNA repair-related genes were up-regulated in a dose-dependent manner. These findings provide a comprehensive understanding of the effects of UV-B radiation on rotifers and highlight the importance of considering both ecological and molecular responses in assessing the impact of UV-B radiation on aquatic organisms.


Effects of captopril and losartan on lipid peroxidation, protein oxidation and nitric oxide release in diabetic rat kidney.
Increased oxidative stress has an important role in the pathogenesis of diabetic nephropathy. The aim of this study was to evaluate the effects of renin-anigiotensin system blockage, either by angiotensin-converting enzyme inhibition or angiotensin receptor blockage, on oxidative stress and nitric oxide release in diabetic rat kidneys. After induction of diabetes, six rats were given captopril, six rats were given losartan, and six rats served as diabetic controls. Six healthy rats were also included. At the end of an 8-week period nitric oxide release, lipid peroxidation and protein oxidation were measured in kidney cortices, and urinary albumin excretion (UAE) was determined in 24-h urine samples. Losartan- and captopril-treated diabetic rats had lower levels of UAE than diabetic controls. Diabetic rats had higher levels of lipid peroxidation and protein oxidation compared to healthy rats. NO release was significantly lower in diabetic groups than healthy controls. UAE levels showed a positive correlation with lipid peroxidation and a negative correlation with NO release. Inhibition of lipid peroxidation could be one of the protective mechanisms of renin-angiotensin axis inhibition in diabetic kidney tissues.


Non-HDL cholesterol is strongly associated with coronary artery calcification in asymptomatic individuals.
Growing evidence shows that non-high-density lipoprotein cholesterol (Non-HDL-C) is a strong and independent predictor of cardiovascular disease (CVD). Few studies have assessed the association between traditional lipid measures and subclinical end points. In this study we analyzed the association of Non-HDL-C, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) with coronary artery calcium (CAC), a marker of subclinical atherosclerosis. The study population consisted of 1611 consecutive asymptomatic individuals (67% men, mean age: 53+/-10 years) referred to a single electron beam tomography (EBT) facility for CAC screening. Multivariate logistic regression was used to test the association between increasing quartiles of lipid levels and presence of CAC score (CACS)>0 and CACS>or=100, with the lowest levels (first quartile) of lipid values as reference. Overall CACS of 0, 1-99, 100-399 and >or=400, were observed in 35%, 44%, 12% and 9% of the study subjects, respectively. The prevalence of CAC increased significantly across increasing quartiles of LDL-C, TG and Non-HDL-C (all p<0.0001), whereas CACS was significantly lower across increasing quartiles of HDL-C (p<0.001). In a multivariate model controlling for age, gender, race, cigarette smoking, hypertension, family history of coronary artery disease and obesity, there was a significant increase in the prevalence of CAC with increasing values of each lipid variable. In a multivariate model simultaneously controlling for increasing quartiles of the remaining lipid variables, only the association of Non-HDL-C with CACS>0 remained statistically significant (p=0.002). Similar results were observed with CACS>or=100 (p=0.038). In this study Non-HDL-C was more strongly associated with subclinical atherosclerosis than all other conventional lipid values. These data suggests that Non-HDL-C may be an important treatment target in primary prevention.


Accommodation response to Chinese and Latin characters in Chinese-illiterate young adults.
Differences in accommodation when reading Chinese, as compared to Latin, characters have been suggested to have a role in the higher prevalence of myopia in some Asian countries. Yeo and colleagues (Optom Vis Sci 2013; 90: 156-163) found that, in Chinese-literate children, accommodation was marginally more accurate (by less than 0.05 D), when reading Chinese text. This was attributed to the additional cognitive demand associated with interpreting the more complex Chinese symbols. The present study compared responses to single Chinese and Latin characters, while controlling for cognitive demand. The monocular accommodative response was measured in Chinese-illiterate adults (10 emmetropes, mean spherical equivalent: -0.07 ± 0.42 D, age: 29.9 ± 4.2 years; 11 myopes, mean spherical equivalent: -4.28 ± 2.84 D, age: 31.7 ± 4.6 years) with an open-field autorefractor. Four Chinese and three Latin characters (approximately 1.15 degrees subtense) were individually presented on a display screen one metre away from the subject, while their vergence was varied over the range zero to 5.00 D using spectacle trial lenses. The slope and the accommodative error index (AEI) were calculated from the accommodative stimulus/response curves (ASRC). No statistically significant differences were found between refractive groups or among characters within the same refractive group in ARSC slopes (Latin: 0.87 ± 0.14 for myopes versus 0.81 ± 0.12 for emmetropes; Chinese: 0.84 ± 0.12 for myopes versus 0.85 ± 0.12 for emmetropes). No significant differences were found between characters in accommodative error index either (Latin, 0.78 ± 0.42 D for myopes versus 1.15 ± 0.72 D for emmetropes; Chinese, 0.74 ± 0.37 D for myopes versus 1.17 ± 0.83 D for emmetropes). However, accommodative error indices and accommodative errors were significantly higher for emmetropes. Under controlled cognitive demand, Chinese and Latin characters elicited similar responses in both individual refractive groups. This study fails to support the hypothesis that development of myopia in some Asian populations is associated with larger lags of accommodation when reading or viewing Chinese characters.


On the recognition of order and disorder.
We compare several algorithms for the recognition of ordered and disordered images. As image sources we use waves of the Belousov-Zhabotinskii reaction coupled to convective motion in a petri dish. This device allows reversibly the generation of periodic (ordered) and aperiodic (disordered) patterns. The best match between the parametric description and the observations is obtained by an "autodifference function". This function is computed by summing up intensity differences over all pairs of picture elements having a given distance on the picture plane. Then, the minimum of this function is determined upon variation of the distance. This algorithm is not only efficient for the recognition of order and disorder in "machine vision", but also plausible in biological visual perception.


Potential association between type 1 diabetes mellitus and gender dysphoria.
Multiple factors have been proposed to explain the increasing prevalence of type 1 diabetes mellitus (T1DM), including psychological stress. The prevalence of gender dysphoria (GD) in youth is also growing. Identifying environmental triggers, such as psychological minority stress experienced by youth with GD, that may influence the pathogenesis and management of T1DM could have important clinical implications. The objective of this study was to determine the prevalence of concurrent diagnosis of T1DM and GD in adolescents evaluated at a university-based children's hospital. An electronic data extraction was conducted at the University of Wisconsin Hospital and Clinics from 1 November 2007 to 1 November 2017. Inclusion criteria included age 10 to 21 years and diagnosis of T1DM and/or GD. Prevalence rates were calculated for T1DM and GD. For adolescents with T1DM and GD, information related to diagnosis, treatment, and psychiatric history was collected. The prevalence for T1DM was 2.69 per 1000; the prevalence for GD was 0.42 per 1000. Eight adolescents had T1DM and GD. In adolescents with GD, the prevalence of T1DM was 9.4-fold higher than the prevalence of T1DM alone (24.77 vs 2.68 per 1000). Five adolescents were seen in GD clinic and their glycemic control initially improved after the first GD clinic visit. There was an increased prevalence of a concurrent diagnosis of T1DM in those with GD compared to the general population. Glycemic control improved after the first GD clinic visit in adolescents with T1DM and GD, which may be secondary to stress reduction.


Regulation of osteoclast differentiation.
The osteoclast (OCL) is derived from the cells in monocyte-macrophage lineage. The earliest identifiable OCL precursor is the granulocyte-macrophage colony-forming unit (CFU-GM), which gives rise to granulocytes, monocytes, and OCL. CFU-GM-derived cells then differentiate to committed OCL precursors, which are post-mitotic cells, and fuse to form multinucleated OCL. A variety of factors both positively and negatively regulate OCL formation and activity. These include growth factors, such as macrophage colony-simulating factor, which simulates the proliferation and prevents apoptosis of early OCL precursors, and RANK ligand (RANKL), which is the primary mediator of OCL formation. Most factors that induce OCL differentiation, such as PTHrP, IL-11, and prostaglandins, do so by inducing expression of RANKL on the surface of immature osteoblasts. Osteoprotegerin is a decoy receptor that blocks RANKL activity. In addition, OCL produce autocrine-paracrine factors that regulate OCL formation, such as IL-6, which is produced at high levels by OCL in Paget's disease and increases OCL formation. We screened human and murine OCL cDNA libraries to identify autocrine-paracrine factors that regulate OCL activity. We identified annexin-II, MIP-1alpha, ADAM8, eosinophil chemotactic factor, and OCL inhibitor factors 1 and 2 as factors involved in OCL formation. Most recently, we have identified the receptor for ADAM8, alpha9beta1 integrin, which appears to be critical for normal OCL activity. OCL differentiation is controlled by exogenous hormones and cytokines as well as autocrine-paracrine factors that positively or negatively regulate OCL proliferation and differentiation.


Successful treatment of the HIV-associated Burkitt lymphoma in a three-year-old child.
We report a case of successful treatment of advanced Burkitt lymphoma in a 3-year-old girl with congenitally acquired HIV infection. She was treated with intensive chemotherapy combined with highly active anti-retroviral therapy (HAART). She had not received any anti-retroviral therapy and had stage C3 HIV infection on admission. She was treated with modified BFM 90 and remission was achieved. Simultaneously with chemotherapy, HAART with three drugs was carried out, resulting in improvements in HIV parameters. Our report suggests chemotherapy combined with HAART is feasible in children and may favorably change the outcomes in pediatric patients with AIDS-NHL.


EPR steering of polar molecules in pendular states and their dynamics under intrinsic decoherence.
Einstein-Podolsky-Rosen (EPR) steering gives evidence for the phenomenon called "spooky action at a distance" in quantum mechanics, and provides a useful resource for the implementation of quantum information tasks. In this paper, we consider a pair of ultracold polar molecules trapped in an external electric field as a promising quantum information carrier, and analyze the evolution behavior of EPR steering for the two coupled polar molecules in pendular states. Our results show that the steering of the two linear dipoles is remarkably reliant upon the Stark effect and dipole-dipole interaction. To be specific, the steerability degree is inversely associated with the intensity of the electric field while it is positively correlated with the coupling strength between the two polar molecules. Moreover, it is found that high ambient temperature can lead to a rapid loss of the steerable resource in thermal equilibrium. Further, we put forward an effective strategy to enhance the steerability using the technique of weak measurement reversal (WMR). By taking into account the influence of intrinsic decoherence on the steering dynamics, we found that robust EPR steering preservation can be realized for the initial state being in the Bell state . Our findings may shed some new light on molecular quantum information processing with pendular states.


Novel technologies combined with traditional metabolic engineering strategies facilitate the construction of shikimate-producing Escherichia coli.
Shikimate is an important intermediate in the aromatic amino acid pathway, which can be used as a promising building block for the synthesis of biological compounds, such as neuraminidase inhibitor Oseltamivir (Tamiflu®). Compared with traditional methods, microbial production of shikimate has the advantages of environmental friendliness, low cost, feed stock renewability, and product selectivity and diversity, thus receiving more and more attentions. The development of metabolic engineering allows for high-efficiency production of shikimate of Escherichia coli by improving the intracellular level of precursors, blocking downstream pathway, releasing negative regulation factors, and overexpressing rate-limiting enzymes. In addition, novel technologies derived from systems and synthetic biology have opened a new avenue towards construction of shikimate-producing strains. This review summarized successful and applicable strategies derived from traditional metabolic engineering and novel technologies for increasing accumulation of shikimate in E. coli.


The spectrum of magnetic resonance imaging proton density fat fraction (MRI-PDFF), magnetic resonance spectroscopy (MRS), and two different histopathologic methods (artificial intelligence vs. pathologist) in quantifying hepatic steatosis.
The grade of hepatic steatosis is assessed semi-quantitatively and graded as a discrete value. However, the proton density fat fraction (PDFF) measured by magnetic resonance imaging (MRI) and FF measured by MR spectroscopy (FFMRS) are continuous values. Therefore, a quantitative histopathologic method may be needed. This study aimed to (I) provide a spectrum of values of MRI-PDFF, FFMRS, and FFs measured by two different histopathologic methods [artificial intelligence (AI) and pathologist], (II) to evaluate the correlation among them, and (III) to evaluate the diagnostic performance of MRI-PDFF and MRS for grading hepatic steatosis. Forty-seven patients who underwent liver biopsy and MRI for nonalcoholic steatohepatitis (NASH) evaluation were included. The agreement between MRI-PDFF and MRS was evaluated through Bland-Altman analysis. Correlations among MRI-PDFF, MRS, and two different histopathologic methods were assessed using Pearson correlation coefficient (r). The diagnostic performance of MRI-PDFF and MRS was assessed using receiver operating characteristic curve analyses and the area under the curve (AUC) were obtained. The means±standard deviation of MRI-PDFF, FFMRS, FF measured by pathologist (FFpathologist), and FF measured by AI (FFAI) were 12.04±6.37, 14.01±6.16, 34.26±19.69, and 6.79±4.37 (%), respectively. Bland-Altman bias [mean of MRS - (MRI-PDFF) differences] was 2.06%. MRI-PDFF and MRS had a very strong correlation (r=0.983, P<0.001). The two different histopathologic methods also showed a very strong correlation (r=0.872, P<0.001). Both MRI-PDFF and MRS demonstrated a strong correlation with FFpathologist (r=0.701, P<0.001 and r=0.709, P<0.001, respectively) and with FFAI (r=0.700, P<0.001 and r=0.690, P<0.001, respectively). The AUCs of MRI-PDFF for grading ≥S2 and ≥S3 were 0.846 and 0.855, respectively. The AUCs of MRS for grading ≥S2 and ≥S3 were 0.860 and 0.878, respectively. Since MRS and MRI-PDFF demonstrated a strong correlation with each other and with the two different histopathologic methods, they can be used as an alternative noninvasive reference standard in nonalcoholic fatty liver disease (NAFLD) patients. However, these preliminary results should be interpreted with caution until they are validated in further studies.


Using simulated fluorescence cell micrographs for the evaluation of cell image segmentation algorithms.
Manual assessment and evaluation of fluorescent micrograph cell experiments is time-consuming and tedious. Automated segmentation pipelines can ensure efficient and reproducible evaluation and analysis with constant high quality for all images of an experiment. Such cell segmentation approaches are usually validated and rated in comparison to manually annotated micrographs. Nevertheless, manual annotations are prone to errors and display inter- and intra-observer variability which influence the validation results of automated cell segmentation pipelines. We present a new approach to simulate fluorescent cell micrographs that provides an objective ground truth for the validation of cell segmentation methods. The cell simulation was evaluated twofold: (1) An expert observer study shows that the proposed approach generates realistic fluorescent cell micrograph simulations. (2) An automated segmentation pipeline on the simulated fluorescent cell micrographs reproduces segmentation performances of that pipeline on real fluorescent cell micrographs. The proposed simulation approach produces realistic fluorescent cell micrographs with corresponding ground truth. The simulated data is suited to evaluate image segmentation pipelines more efficiently and reproducibly than it is possible on manually annotated real micrographs.


PPy coated nanoflower like CuCo2O4based onin situgrowth of nanoporous copper for high-performance supercapacitor electrodes.
General CuCo2O4electrodes suffer a very low reversible capacity and poor cycling stability because of easily fading phenomena and volume change during cycling. To optimize the electrode, a facile method is conducted to fabricate a novel electrode of Cu@CuCo2O4@polypyrrole nanoflowers. Due to larger specific surface area and more electrochemical reactive areas of CuCo2O4@polypyrrole nanoflowers, the pseudocapacitance of thein situgrown CuCo2O4@polypyrrole (912 F g-1at 2 A g-1) is much higher than the pristine CuCo2O4(618 F g-1at 2 A g-1). Remarkably, the CuCo2O4@polypyrrole (cathode) and active carbon (anode) are used to assemble an asymmetric supercapacitor, which exhibits a relatively high energy density of 90 Wh kg-1at a power density of 2519 W kg-1and 35 Wh kg-1at a high-power density of 9109 W kg-1, and excellent cycling stability (about 90.4% capacitance retention over 10 000 cycles). The prominent performance of CuCo2O4@polypyrrole makes it as a potential electrode for supercapacitor.


Identification of antigenic components of Toxoplasma gondii by an immunoblotting technique.
Proteins of Toxoplasma gondii were separated by SDS-polyacrylamide gel electrophoresis with subsequent transfer to a nitrocellulose sheet by electrophoretic blotting. Immunologically reactive polypeptides were detected by human sera with previously known toxoplasma antibody levels. Heavy chain-specific, peroxidase-conjugated anti-human immunoglobulins were used as the indicator antibodies for the separate identification of IgG and IgM reactive polypeptides. IgG toxoplasma antibodies reacted with several antigens of Mr approximately 27 000-67 000, while toxoplasma-specific IgM seemed to detect only a few polypeptides. The Mr of 35 000 for the dominating IgM reactive polypeptide was observed.


Catheterization and superselective angiography of the cerebral vessels.
The technique of catheterization and superselective angiography of the cerebral arteries is described. The balloon can be introduced safely into any of the cerebral arteries including the anterior communicating artery and the peripheral branches of the middle cerebral artery. The superselective angiography seems to be suitable for the study of the regional venous circulation of the brain.


Mechanical thrombectomy of right internal carotid artery terminus occlusion using the ADAPT technique: impact of aspiration on parent vessel.
The impact of ADAPT-"a direct aspiration first pass technique"-on intracranial vasculature is not well understood, since the change of arterial diameter is often not visible during aspiration. We present a unique case in which the impact of aspiration on the parent vessel was visualized due to a previously deployed Neuroform Atlas stent and a Pipeline embolization device. The patient presented with right internal carotid artery occlusion. An aspiration catheter was advanced over the microcatheter system and corked into the clot, located within the stents in proximal M1. The stents were seen to collapse both during electronic pump and hand aspiration with no evidence of stent migration. This demonstrates that it is crucial to engage the clot interface with the tip of the aspiration catheter while performing ADAPT. Placing the aspiration catheter remote from the clot may result in collapse of the artery proximal to the clot with subsequent ADAPT failure.(video 1) neurintsurg;12/11/1148/V1F1V1video 1.


Symposium on chemical information utilization by FDA bureau of drugs chemists. Introductory remarks.
This symposium was organized to acquaint the scientific community with the manner in which Bureau of Drugs chemists utilize available chemical information as it pertains to the various areas in which they are involved.


Tyrosine/tyrosinate fluorescence at 700 MPa: a pressure unfolding study of chicken ovomucoid at pH 12.
The utility of tyrosine/tyrosinate fluorescence for pressure-unfolding studies of Trp-lacking proteins has been explored for the first time, with chicken ovomucoid (OVM) as target. A newly developed fluorescence spectrometer working in the range 0.1-700 MPa is employed for this purpose. At 25 °C at pH 12, all six Tyr residues give tyrosine emission at 306 nm, implying that all five Tyr residues are well buried at pH 12 in the folded OVM, except one giving "half-tyrosinate" emission at 325 nm. Upon increasing pressure, however, a distinct intermediate state, in which domains 1 and 2 are selectively unfolded, appears and increases up to 700 MPa. Extrapolated to 0.1 MPa, this intermediate lies 8.8±2.6 kJ mol(-1) above the native state, characterized with a partial molar volume smaller by -28.9±7.4 ml mol(-1). At 5 °C at 700 MPa, even domain 3 gives a sign of cold denaturation.


[Diagnostic and therapeutic problems of bladder endometriosis. Apropos of 5 cases].
Five cases of bladder endometriosis are reported with special emphasis on diagnostic methods and therapeutic possibilities. In all five cases a large resection of the lesion have been necessary without the need for postoperative hormonal management.


Homologous prostatic fluid added to frozen-thawed dog spermatozoa prior to intravaginal insemination of bitches resulted in better fertility than albumin-free TALP.
The aim of this study was to determine whether canine prostatic fluid has intrinsic effects resulting in higher fertility than albumin-free Tyrode's albumin lactate pyruvate (afTALP) when added to thawed semen prior to intravaginal insemination. Twenty-four German shepherd bitches were inseminated intravaginally with frozen-thawed spermatozoa to which either homologous prostatic fluid (Group P; 12 bitches) or afTALP (Group T; 12 bitches) was added to give a final insemination volume of 7mL. Each bitch was inseminated daily starting when the vaginal folds first became angular and continuing until the day before a diestrus vaginal smear was first seen. Bitches were spayed about 3 weeks after the onset of diestrus and the number of corpora lutea and the number of conceptuses counted. Group P and Group T bitches were, respectively, inseminated 5.3+/-1.0 and 5.8+/-2.1 times with 48.9+/-8.6 and 50.4+/-8.3 million progressively motile spermatozoa per insemination. Eight Group P bitches and 10 Group T bitches conceived with totals of 76 and 45 conceptuses and 126 and 117 corpora lutea, respectively. Odds of conception were taken as the number of conceptuses divided by (the number of corpora lutea minus the number of conceptuses). After adjustment for the number of progressively motile spermatozoa per day and the random effect of bitch, the addition of prostatic fluid resulted in an increased odds of conception compared to afTALP. This effect decreased as the number of progressively motile spermatozoa per day increased.


What is the Molecular Basis of Nonhost Resistance?
This article is part of the Top 10 Unanswered Questions in MPMI invited review series.Nonhost resistance is typically considered the ability of a plant species to repel all attempts of a pathogen species to colonize it and reproduce on it. Based on this common definition, nonhost resistance is presumed to be very durable and, thus, of great interest for its potential use in agriculture. Despite considerable research efforts, the molecular basis of this type of plant immunity remains nebulous. We here stress the fact that "nonhost resistance" is a phenomenological rather than a mechanistic concept that comprises more facets than typically considered. We further argue that nonhost resistance essentially relies on the very same genes and pathways as other types of plant immunity, of which some may act as bottlenecks for particular pathogens on a given plant species or under certain conditions. Thus, in our view, the frequently used term "nonhost genes" is misleading and should be avoided. Depending on the plant-pathogen combination, nonhost resistance may involve the recognition of pathogen effectors by host immune sensor proteins, which might give rise to host shifts or host range expansions due to evolutionary-conditioned gains and losses in respective armories. Thus, the extent of nonhost resistance also defines pathogen host ranges. In some instances, immune-related genes can be transferred across plant species to boost defense, resulting in augmented disease resistance. We discuss future routes for deepening our understanding of nonhost resistance and argue that the confusing term "nonhost resistance" should be used more cautiously in the light of a holistic view of plant immunity.


Gradually increased Golgi protein 73 expression in the progression of benign liver diseases to precancerous lesions and hepatocellular carcinoma correlates with prognosis of patients.
Serum Golgi protein 73 (sGP73) is a novel biomarker for hepatocellular carcinoma (HCC). However, there are few reports on the pattern of GP73 expression in the progression of benign liver diseases to precancerous lesions and HCC. This study aimed to investigate GP73 expression and its correlation with clinicopathological parameters. Tissue GP73 (tGP73) levels were detected in specimens of group A (n = 186) including HCC, peritumoral tissue (PTL), high/low-grade hepatic atypical hyperplasia (AH), chronic hepatitis B (CHB) and normal controls (NC) by immunohistochemistry, and GP73 expression in group B (n = 159) and group C (n = 16) were detected by reverse transcription polymerase chain reaction and western blot, respectively. sGP73 levels were detected in subjects of group D (n = 287) by enzyme-linked immunoassay. GP73 expression increased gradually from NC, CHB, PTL to high-grade AH and HCC at both protein and mRNA levels (P < 0.05), while sGP73 in the HCC group was lower than in the liver cirrhosis (LC) group (P < 0.001). Both tGP73 and sGP73 levels were negatively associated with tumor size and tumor-node-metastasis stage, and tGP73 levels were positively associated with tumor differentiation. The high-tGP73 group showed significantly better overall and disease-free survival than the low-tGP73 group (P = 0.008, P = 0.018). Multivariate analysis revealed that the tGP73 level was an independent prognostic factor for HCC, but not sGP73. GP73 expression pattern suggests that the regulatory mechanism of GP73 is related to the progression of chronic liver diseases. Furthermore, a high level of tGP73 is a favorable prognostic factor for HCC.


Introducing the thyroid gland as another victim of the insulin resistance syndrome.
Insulin is a thyroid growth factor that stimulates proliferation of thyroid cells in culture. In order to evaluate the effects of insulin resistance (IR) on the thyroid gland, we developed a prospective study in euthyroid women. One hundred eleven women (mean age 32.2 +/- 7 years) were evaluated by a thyroid ultrasound (US) and basal and postprandial serum insulin. Subjects were divided into four groups as follows: G1 (n = 42), subjects with IR and obesity; G2 (n = 21), subjects with obesity without IR; G3 (n = 17), subjects with IR and normal weight; and G4 (n = 31) control group (without IR and obesity). The thyroid volume (TV), measured by US, showed the following values: G1, 17 +/- 3 mL; G2, 13.8 +/- 2.8 mL; G3, 16.2 +/- 2.1 mL; and G4,12.1 +/- 2.4 mL. There was no significant difference in TV between G1 and G3, but differences between G1 and G2, and between G3 and G4 were significant at p < 0.05. The percentage of nodular thyroid glands observed by US in each group was as follows: G1, 50%; G2, 23.8%; G3, 61%; G4, 16.1%. Again, the differences between G1 and G2 and between G3 and G4 were statistically significant (p < 0.005 and p < 0.001, respectively, for each comparison). It is concluded that the higher circulating levels of insulin cause increased thyroid proliferation. The clinical manifestations are the larger thyroid volume and the formation of nodules. Thus, the thyroid gland appears to be another victim of the insulin resistance syndrome.


Loss of microRNAs in thymus perturbs invariant NKT cell development and function.
microRNAs (miRNAs) are small noncoding RNAs that mediate RNA interference to suppress protein expression at the translational level. Accumulated evidence indicates that miRNAs play critical roles in various biological processes and disease development, including autoimmune diseases. Invariant natural killer T (iNKT) cells are an unusual CD1d-restricted subset of thymus-derived T cells that are potent regulators of diverse immune responses. Our previous studies with the mouse model of bone marrow-specific Dicer deletion suggest the involvement of Dicer-dependent miRNAs in the development and function of iNKT cells. In the present study, to further dissect the functional levels of Dicer-dependent miRNAs in regulating iNKT cell development, we generated a mouse model with the Dicer deletion in the thymus. Our data indicate that lack of miRNAs following the deletion of Dicer in the thymus severely interrupted the development and maturation of iNKT cells in the thymus and significantly decreased the number of iNKT cells in the peripheral immune organs. miRNA-deficient peripheral iNKT cells display profound defects in activation and cytokine production upon α-galactosylceramide (α-GalCer) stimulation. Our results demonstrate a critical role of the miRNA-dependent pathway in the thymus in the regulation of iNKT cell development and function.


Detection of endogenous circadian rhythms of clock gene mRNA expression in mouse lung tissue using slice cultures.
Detection of endogenous circadian rhythms in clock gene mRNA expression requires that mice be sacrificed at regular time intervals over one or more days. This protocol uses culture tissue slices obtained from a single mouse to collect time-course samples. We describe the procedure from preparation of lung slices to rhythmicity analysis of mRNA expression, including details to create handmade culture inserts. This protocol is useful for many mammalian biological clock researchers because it allows a decrease in animal sacrifice. For complete details on the use and execution of this protocol, please refer to Matsumura et al. (2022).1.


Objective Evaluation of Otoscopy Skills Among Family and Community Medicine, Pediatric, and Otolaryngology Residents.
The objective of this study is to evaluate and compare the perceived need for otolaryngology training and otoscopy diagnostic skills in primary care (Family and Community Medicine, Pediatric Medicine), and Otolaryngology Head and Neck Surgery (OTO-HNS) postgraduate trainees. Participant otoscopy skills were evaluated using the OtoSim simulator. Family and Community Medicine, Pediatric, and OTO-HNS residents were recruited. Each resident participated in 3 separate otoscopy training and assessment sessions. The ability to correctly identify middle ear pathology was objectively evaluated using OtoSim™. Pretest, posttest, and 3-month retention test results were compared among residents in a paired comparison paradigm. Survey data assessing exposure to OTO-HNS during undergraduate and postgraduate training were also collected. A total of 57 residents participated in the study. All residents reported limited exposure to OTO-HNS during undergraduate medical training. Primary care trainees performed poorly on pretest assessments (30% ± 7.8%; 95% CI). Significant improvement in diagnostic accuracy was demonstrated following a single 1-hour teaching session (30%-62%; p < 0.001). Primary care residents demonstrated a significant decrease in diagnostic accuracy at a 3-month follow-up assessment (62%-52%, p < 0.001). Self-perceived comfort with otology was poorly correlated to pretest performance among primary care trainees (r = 0.26) and showed a stronger positive correlation among OTO-HNS trainees (r = 0.56). A single teaching session with an otoscopy simulator significantly improved diagnostic accuracy in primary care and OTO-HNS trainees. Improved performance is susceptible to deterioration at 3 months if acquired skills are not frequently used. Self-perceived comfort with otology may not be an accurate predictor of otoscopic diagnostic skill.


High-throughput screening and selection of mammalian cells for enhanced protein production.
The production of recombinant proteins for biotherapeutic use is a multibillion dollar industry, which has seen continual growth in recent years. In order to produce the best protein with minimal cost and time, selection methods are utilized during the cell line development process in order to select for the most desirable clonal cell line from a heterogeneous transfectant pool. Today, there is a vast array of potential selection methods available, which vary in cost, complexity and efficacy. This review aims to highlight cell line selection methods that exist for the isolation of high-producing clones, and also reviews techniques that can be used to predict, at a small scale, the performance of clones at large, industrially-relevant scales.


Biochemical characterization of a specific phosphate acceptor of nuclear cyclic AMP-independent protein kinase.
The regulatory mechanism of transcription involved in the phosphorylation of a 13 kDa non-histone chromatin protein from calf thymus, which is the most effective phosphate acceptor for cyclic AMP-independent protein kinase purified from the nuclei of mouse spleen cells, by the kinase has been studied in vitro. An analytical study of the circular dichroism (CD) spectra of the 13 kDa protein under different conditions showed that it underwent a major conformational change when incubated with DNA. The presented data suggest that the DNA-induced conformational change may result in a great increase of the 13 kDa protein phosphorylation by the kinase in vitro. Mg2+ (8-10 mM) enhanced the binding of the protein to DNA. Furthermore, the phosphorylated 13 kDa protein stimulated elongation of RNA synthesis by RNA polymerase II from calf thymus. However, neither the 13 kDa protein nor the phosphorylated 13 kDa protein had any affect on DNA synthesis. The available evidence suggests that the 13 kDa protein may play a role in the regulation of transcription through its phosphorylation by the kinase in vitro.


[Main areas and results of research at the Institute of Biomedical Problems in 1963-1998].
The paper features the history of the Institute of Biomedical Problems (IBMP), the Russian leading institution in space biology and medicine, and the advances achieved by researchers over 35 years since its foundation. Special attention is devoted to the contribution of the Institute to the establishment of international co-operation in human space flight and space life sciences. Future of the space life sciences and humans in space is outlined.


Detection of human papillomavirus in esophageal and gastroesophageal junction tumors: A retrospective study by real-time polymerase chain reaction in an instutional experience from Turkey and review of literature.
Esophageal cancer is a poor-prognosis malignancy that ranks eighth among all cancer types, and its prevalence shows differences among geographical regions. Although the most important risk factors for esophageal carcinoma are alcohol and smoking, viral infections, particularly HPV infection, are also considered among etiological agents. Our study aims to detect the presence of HPV in esophageal cancers in our patient population and to investigate its correlation with clinico-pathological parameters. We investigated the presence of HPV-DNA by real-time polymerase chain reaction in a total of 52 patients with esophageal cancer. Subtype analysis was performed in positive cases and was correlated with selected clinico-pathological parameters. Five (9.6%) of 52 tumor samples, 3 squamous cell carcinomas (3/33 cases) and 2 adenocarcinomas (2/19 cases), were HPV-DNA-positive. Subtype analysis could be performed in four HPV-DNA-positive cases, of which three were HPV type-39 and 1 was type-16. The Marmara region, where the present study was carried out, is a region with low-moderate risk for esophageal cancer, and the prevalence of HPV-DNA in these tumors is similar to the prevalence of HPV-DNA reported in the literature for regions with similar risk. In conclusion, we detected HPV DNA in a subset of esophageal and gastroesophageal junction tumors. HPV infection may have a role in esophageal carcinogenesis and high-risk HPV subtypes can particularly be considered among risk factors since the prevalence of high risk HPV infection has also been found to be increased in regions with a high risk for esophageal cancer compared to low-moderate risk regions.


Persistence of antibodies to West Nile virus nonstructural protein 5.
Because IgM antibody against West Nile virus (WNV) pre-membrane/envelope (preM/E) recombinant protein may persist for more than 1 year, an assay distinguishing recent from past WNV infection would be useful. Published findings for a single patient suggest that the presence of antibody against WNV nonstructural protein 5 (NS5) indicates recent infection. To compare the persistence of WNV NS5 antibodies and preM/E IgM using plasma samples from blood donors who were viremic at the time of donation. Follow-up plasma samples from 35 viremic donors were tested for WNV NS5 antibodies using a microsphere immunoassay, and compared to WNV preM/E IgM antibodies determined on the same samples using an enzyme-linked immunosorbent assay (ELISA). At 90+/-14 days of follow-up, 20/26 donors (77%) were positive for NS5 antibodies; 6/25 (24%) were positive at 180+/-27 days, and 3/23 (13%) were positive at 365+/-55 days. The comparable values for preM/E IgM antibodies were 77%, 32% and 17%, respectively. Persistence of WNV NS5 antibody in plasma is similar to that of preM/E IgM antibody. WNV NS5 antibody cannot be used to distinguish recent from past WNV infection.


A novel host-protective antigen from Trichostrongylus colubriformis.
The detergent-soluble fraction from Trichostrongylus colubriformis third-stage larvae contained a simple set of antigens, one of which (molecular weight 41,000) induced 43-51% protection in guinea pigs following immunization. Isolation and partial amino acid sequence analysis of this protective antigen showed it was parasite tropomyosin.


Polymorphism of XRCC1 (at codon 399) and susceptibility to breast cancer, a meta-analysis of the literatures.
The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair. Several polymorphisms in the XRCC1 gene have been described, including Arg399Gln. Previous studies investigating the association between genetic polymorphism of Arg399Gln XRCC1 and risk of breast cancer have provided inconsistent results. A meta-analysis was conducted to investigate the association between common genetic variant in the XRCC1 gene (exon 10, Arg399Gln) with breast cancer risk. We identified 36 eligible studies, in relation to the Arg399Gln polymorphism of XRCC1 and risk of breast cancer. These studies comprised of 43,716 subjects (20,837 patients and 22,879 controls). We first estimated the risk of the genotypes Arg/Gln and Gln/Gln compared with the wild-type Arg/Arg homozygote, and then evaluated the risk of Gln/Gln versus (Arg/Gln+Arg/Arg) and (Gln/Gln+Arg/Gln) versus Arg/Arg, which assumed recessive and dominant effects, respectively, of the variant 399Gln allele. There was significant heterogeneity between studies. The overall ORs showed that the breast cancer risk were not associated with the XRCC1 genotypes. The heterogeneity between studies decreased dramatically when studies stratified into Asian and Western countries. There was significant association between the polymorphism of XRCC1 and breast cancer risk among studies of Asian countries. In Asian countries the Arg/Gln versus Arg/Arg (OR = 0.98, 95% CI: 0.88-1.10) and Gln/Gln+Arg/Gln versus Arg/Arg (OR = 1.05, 95% CI: 0.95-1.18) were not associated with increased risk of breast cancer. On the other hand, both Gln/Gln versus Arg/Arg (OR = 1.46, 95% CI: 1.19-1.79) and Gln/Gln versus Arg/Gln+Arg/Arg (OR = 1.49, 95% CI: 1.22-1.81) increased the risk. Therefore, it could be concluded that 399Gln allele might act as a recessive allele in its association with breast cancer risk.


The Δ133p53 Isoforms, Tuners of the p53 Pathway.
The TP53 gene is a critical tumor suppressor and key determinant of cell fate which regulates numerous cellular functions including DNA repair, cell cycle arrest, cellular senescence, apoptosis, autophagy and metabolism. In the last 15 years, the p53 pathway has grown in complexity through the discovery that TP53 differentially expresses twelve p53 protein isoforms in human cells with both overlapping and unique biologic activities. Here, we summarize the current knowledge on the Δ133p53 isoforms (Δ133p53α, Δ133p53β and Δ133p53γ), which are evolutionary derived and found only in human and higher order primates. All three isoforms lack both of the transactivation domains and the beginning of the DNA-binding domain. Despite the absence of these canonical domains, the Δ133p53 isoforms maintain critical functions in cancer, physiological and premature aging, neurodegenerative diseases, immunity and inflammation, and tissue repair. The ability of the Δ133p53 isoforms to modulate the p53 pathway functions underscores the need to include these p53 isoforms in our understanding of how the p53 pathway contributes to multiple physiological and pathological mechanisms. Critically, further characterization of p53 isoforms may identify novel regulatory modes of p53 pathway functions that contribute to disease progression and facilitate the development of new therapeutic strategies.


Effects of macromolecular crowding on the folding and aggregation of glycosylated MUC5AC.
To investigate the effects of macromolecular crowding on the folding and aggregation of MUC5AC with different levels of glycosylation during refolding. Part 1:An in vitro catalytic reaction comprising the ppGalNAc T2 enzyme, uridine-5'-diphospho-N-galactosamine (UDP-GalNAc) and an 11-amino acid peptide substrate, was used to assess the enzyme activity of the ppGalNAc T2 enzyme in macromolecular crowding environment respectively with bovine serum albumin (BSA), polyethylene glycol (PEG2000), Dextran70 and Ficoll70 at different concentration and temperature. Part 2: The recombinant MUC5AC was expressed in HEK293 cells and purified by nickel column chromatography. The purified protein was treated with PNGase F, and the degree of glycosylation was analyzed by SDS-PAGE. Macromolecular crowding was simulated using PEG2000 at the concentrations of 50, 100, and 200 g/L. Deglycosylated-MUC5AC (d-MUC5AC) and glycosylated MUC5AC (g-MUC5AC) were denatured by GdnHCl and renatured by dilution in a refolding buffer. Protein aggregation was monitored continuously by absorbance reading at 488 nm using a UV spectrophotometer at 25 °C. The refolded proteins were centrifuged, the protein concentration of the supernatant was measured, and refolding yield in different refolding buffers was determined. Enzyme activityof ppGalNAc T2 was observed to increase with increasing crowding agent concentration, with highest enzyme activity at 200 g/L. Compared with the group in the absence of crowding reagent, the refolding yield of g-MUC5AC and d-MUC5AC were reduced significantly in the presence of different concentrations of PEG2000 (200, 100, and 50 g/L). Compared with the dilute solution, aggregation increased significantly in the presence of PEG2000, especially at 200 g/L. Moreover, in the crowded reagent with the same concentration, the refolding yield of d-MUC5AC was higher than that of g-MUC5AC, whereas the degree of aggregation of d-MUC5AC was lower than that of g-MUC5AC. The crowded intracellular environment reduces the refolding rate of MUC5AC and strongly induces the misfolding and aggregation of glycosylated MUC5AC.


Retropharyngeal Parathyroid Glands: Important Differences.
In primary hyperparathyroidism (PHPT), parathyroid ectopia is seen in up to 22% leading to more difficult surgery. We aimed to determine the rate and characteristics of retropharyngeal (RP) parathyroid glands. A prospective database was queried for patients with sporadic PHPT who had surgery from 1997 to 2016. The data of RP patients were compared to those who had surgery for sporadic PHPT over the same time period with hyperfunctioning parathyroids in anatomically normal positions (N). RP glands occurred in 47/3006 (1.6%) patients and were more common at reoperative than initial surgery (5.5 vs 1.4%, p < 0.01). RP patients had prior failed surgery more often than N patients (17 vs 3.1%, p < 0.01). Preoperative calcium levels (p = 0.06), PTH levels (p = 0.15), and mean gland weights (p = 0.07) were similar among groups. For RP glands, ultrasound imaging was negative in all but one patient, while 99mTc-sestamibi accurately indicated a posterior midline position in only 13/47 (28%) and was negative in 21%. All RP glands were anatomically superior. RP patients more often required > 1 post-resection intraoperative PTH level (36 vs 21%, p = 0.02). Failure due to persistent PHPT was more likely in RP patients (4.7 vs 2.1%, p = 0.2). In PHPT, hyperfunctioning RP glands are seen in 1.6% of cases and often associated with initial failure (17%). At reoperation, RP ectopia is 4X more common. RP glands are associated with a high rate of negative imaging, but imaging results suggestive of a midline abnormality can guide exploration. The RP space should be evaluated prior to ending an otherwise unfruitful surgery.


Diagnostic Value of White Blood Cell and C-Reactive Protein in Pediatric Appendicitis.
Background. Acute appendicitis (AA) associated with acute phase reaction is the most prevalent disease which requires emergency surgery. Its delayed diagnosis and unnecessarily performed appendectomies lead to numerous complications. In our study, we aimed to detect the role of WBC and CRP in the exclusion of acute and complicated appendicitis and diagnostic accuracy in pediatric age group. Methods. Appendectomized patient groups were constructed based on the results of histological evaluation. The area under a receiver operating characteristic (ROC) curve (AUC) was performed to examine diagnostic accuracy. Results. When WBC and CRP were used in combination, based on cut-off values of ≥13.1 × 10(3)/μL for WBC counts and ≥1.17 mg/dL for CRP level, diagnostic parameters were as follows: sensitivity, 98.7%; specificity, 71.3%; PPV, 50.6%; NPV, 99.5%; diagnostic accuracy, 77.6%; LR(+), 3.44; LR(-), 0.017. AUC values were 0.845 (95% CI 0.800-0.891) for WBC and 0.887 (95% CI 0.841-0.932) for CRP. Conclusions. For complicated appendicitis, CRP has the highest degree of diagnostic accuracy. The diagnosis of appendicitis should be made primarily based on clinical examination, and obviously more specific and systemic inflammatory markers are needed. Combined use of cut-off values of WBC (≥13100/μL) and CRP (≥1.17 mg/L) yields a higher sensitivity and NPV for the diagnosis of complicated appendicitis.


Complexes of Li, Na, and Mg with 2D allotropies of second and third period: a theoretical study.
Complexes of Li, Na, and Mg with graphene, silicene, phosphorene nanoflakes (NFs), and their 2D allotropies have been studied at dispersion corrected TPSS/def-TZVP level of theory. The energy partition analysis of the complexes revealed that for most of the complexes exchange and correlation energies represent dominant contributions to the binding with strong charge transfer from the metal atom to a NF. The exceptions are Mg complexes of graphene and phosphorene NFs where binding is due to dispersion and correlation terms. This difference is also reflected in large Mg-NF distances suggesting weak intermolecular interactions in these complexes. The calculated activation energies for metal hopping are easily achievable at room temperatures for carbon and silicon allotropies. However, they are significantly higher for phosphorus allotropies reaching almost 18 kcal/mol. Generally, activation energies for hopping increase with binding energies for graphene, silicene, and phosphorene NFs. This trend does not observe however for graphene, silicene, and phosphorene 2D allotropies.


Endoscopic ultrasound for staging esophageal cancer, with or without dilation, is clinically important and safe.
To fully evaluate patients with esophageal cancer by endoscopic ultrasonography (EUS), the transducer must pass through the entire tumor to the cardia to scan the celiac axis. Dilation may be necessary. Published information suggests that dilation with EUS carries a sizeable risk. In order to assess the complication rate associated with dilation prior to EUS in patients with esophageal cancer and the clinical significance of dilation for complete EUS staging, we reviewed the records of all patients who had undergone EUS for esophageal cancer. Sixty-three patients underwent EUS staging of esophageal cancer. Thirty-nine (62%) had lesions through which the EUS scope was passable (Group I). Ten (16%) patients (Group II) had lesions through which an EUS scope (diameter 13 mm) was unable to pass even after dilation. Fourteen patients (22%) had lesions that were dilated to allow passage of the EUS scope (Group III). All patients in Groups II and III had confirmation of EUS staging by CT and/or surgery. In Group II, five patients had tumors defined as T4 (50%) and five as T3 (50%). In Group III, nine (64%) had T4 tumors, four (29%) had T3, and one (7.7%) had T2. No complications were encountered in any group. EUS, either alone or after dilation, is a safe procedure and the complete EUS examination with celiac node visualization adds prognostically significant information.


Maternal hyponatremia and the syndrome of hemolysis, elevated liver enzymes, and low platelet count.
A patient with the syndrome of hemolysis, elevated liver enzymes, and low platelet count and hyponatremia is described. Hyponatremia could explain the central nervous system symptoms sometimes seen in cases of toxemia.


Impact of gastrointestinal lipolysis on oral lipid-based formulations and bioavailability of lipophilic drugs.
Oil-in-water emulsions are common vehicles for lipids as nutrients and for the delivery of poorly water-soluble drugs. Enhancing oral bioavailability of these drugs using lipid-based formulations (LBF) or self-emulsifying drug delivery systems is one of the current challenges in pharmaceutical industry. Many of the compounds found in LBF (acylglycerols, surfactants with esterified fatty acids, …) are however potential substrates for digestive enzymes. Their digestion (or lipolysis) in the gastrointestinal (GI) tract is critical for drug dissolution and absorption: it can be beneficial (drug solubilization/dispersion) or deleterous (drug precipitation) depending on the drug-LBF association. A better understanding of the fate of LBF in the GI tract is therefore required to engineer efficient lipid-based drug delivery systems. In vitro models for testing simultaneously LBF digestion and drug dispersion are in development to predict drug solubilization and bioavailability, select the best drug-LBF association and obtain better in vitro-in vivo correlations. So far, research in this area has focused on LBF lipolysis under intestinal conditions because the small intestine is the main target for drug delivery and absorption, as well as the main site of digestion by pancreatic enzymes. Lipolysis however starts within the stomach through the action of gastric lipase, the first enzyme involved in fat digestion in humans. In vitro digestion experiments show that most LBFs are submitted to gastric lipolysis, and therefore, both intragastric and intestinal digestions are critical for the fate of LBF and drug solubility.


Evaluation of the effect of umbilical hernias on play behaviors in growing pigs.
Umbilical hernias (UH) are common in pigs and are an animal welfare concern. This study used an assessment of play behavior to evaluate the welfare of pigs with UH. Twenty-one grower pigs with UH and 17 without hernias (WUH) were assigned to 16 playing groups (PG) of 2 or 3 pigs (with at least 1 UH pig per PG). The time each animal was engaged in any of the defined playing behaviors for locomotor/social or toy play behaviors was recorded. Mixed Poisson or negative binomial and linear models were used to determine the effect of UH and day of session, accounting for the cluster of pigs within groups, on the frequency of each play behavior, and playing times. Pigs with UH had the same frequency of most play behaviors and playing times as pigs without hernias. There was no indication that the presence of UH-affected play behavior or performance in pigs.


Interprofessional Intervention to Support Mature Women: A Case Study.
Understanding the impact interprofessional teamwork has on patient outcomes is of great interest to health care providers, educators, and administrators. This article describes one clinical team, Women's Health Specialists, and their implementation of an interprofessional health intervention course: "Mindfulness and Well-being: The Mature Woman" (MW: MW) to support mature women's health needs in midlife (age 40-70 years) and empower patient involvement in self-care. The provider team works to understand how their interprofessional education and collaborative practice (IPECP) interventions focused on supporting midlife women are associated with improved quality and clinical outcomes. This case study describes the work of the Women's Health Specialists clinic in partnership with the National Center for Interprofessional Education and Collaborative Practice to study the impact an interprofessional team has on the health needs of women in midlife. This article summarizes the project structure, processes, outputs, and outcomes. Data collection, analysis, strategy, and next steps for future midlife women's projects are also discussed.


Effects of hTERT immortalization on osteogenic and adipogenic differentiation of dental pulp stem cells.
These data relate to the differentiation of human dental pulp stem cells (DPSC) and DPSC immortalized by constitutively expressing human telomerase reverse transcriptase (hTERT) through both osteogenic and adipogenic lineages (i.e. to make bone producing and fat producing cells from these dental pulp stem cells). The data augment another study to characterize immortalized DPSC for the study of neurogenetic "Characterization of neurons from immortalized dental pulp stem cells for the study of neurogenetic disorders" [1]. Two copies of one typical control cell line (technical replicates) were used in this study. The data represent the differentiation of primary DPSC into osteoblast cells approximately 60% more effectively than hTERT immortalized DPSC. Conversely, both primary and immortalized DPSC are poorly differentiated into adipocytes. The mRNA expression levels for both early and late adipogenic and osteogenic gene markers are shown.