Dichotic listening by chronic schizophrenic patients.
The hypothesis that schizophrenics show hemispheric dysfunction (e.g., overactivation ) was examined using the dichotic listening test (words). Thirty-three chronic schizophrenic patients and 33 normal controls were tested. Their data were analysed for over-all correct identification of the stimuli presented to the left and the right ears, the magnitude of differences between the ears in recall, and the number of shifts in report from one ear to the other. The overall level of performance was lower for schizophrenics than for the normal controls; between the ears difference were not significant although schizophrenics showed large individual differences. The number of shifts was greater for normals than for the schizophrenics; and there was no sex difference on any index within the two of subjects groups. The results were discussed in relation to the hypothesized hemispheric dysfunction in schizophrenics and other aspects of cognitive activity which may underlie the performance of the task.


Droperidol for treatment of nausea and vomiting in palliative care patients.
This is an updated version of the original Cochrane review published in Issue 10, 2010, on droperidol for the treatment of nausea and vomiting in palliative care patients. Nausea and vomiting are common symptoms in patients with terminal illness and can be very unpleasant and distressing. There are several different types of antiemetic treatments that can be used to control these symptoms. Droperidol is an antipsychotic drug and has been used and studied as an antiemetic in the management of postoperative and chemotherapy nausea and vomiting. To evaluate the efficacy and adverse events (both minor and serious) associated with the use of droperidol for the treatment of nausea and vomiting in palliative care patients. We searched electronic databases including CENTRAL, MEDLINE (1950-), EMBASE (1980-), CINAHL (1981-) and AMED (1985-), using relevant search terms and synonyms. The basic search strategy was ("droperidol" OR "butyrophenone") AND ("nausea" OR "vomiting"), modified for each database. We updated the search on 2 December 2009. We performed updated searches of MEDLINE, EMBASE, CENTRAL and AMED 2009 to 2013 on 19 November 2013 and of CINAHL on 20 November 2013. We also searched trial registers (metaRegister of controlled trials (www.controlled-trials.com/mrct), clinicaltrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (http://apps.who.int/trialsearch/)) on 22 November 2013, using the keyword "droperidol". Randomised controlled trials (RCTs) of droperidol for the treatment of nausea or vomiting, or both, in adults receiving palliative care or suffering from an incurable progressive medical condition. We judged the potential relevance of studies based on their titles and abstracts, and obtained studies that we anticipated might meet the inclusion criteria. Two review authors independently reviewed the abstracts for the initial review and four review authors reviewed the abstracts for the update to assess suitability for inclusion. We discussed discrepancies to achieve consensus. The 2010 search strategy identified 1664 abstracts (and 827 duplicates) of which we obtained 23 studies in full as potentially meeting the inclusion criteria. On review of the full papers, we identified no studies that met the inclusion criteria.The updated searches carried out in November 2013 identified 304 abstracts (261 excluding duplicates) of which we obtained 18 references in full as potentially meeting the inclusion criteria. On review of the full papers, we identified no studies that met the inclusion criteria, therefore there were no included studies in this review.We found no registered trials of droperidol for the management of nausea or vomiting in palliative care. Since first publication of this review, no new studies were found. There is insufficient evidence to advise on the use of droperidol for the management of nausea and vomiting in palliative care. Studies of antiemetics in palliative care settings are needed to identify which agents are most effective, with minimum side effects.


Matched Behavioral and Neural Adaptations for Low Sound Level Echolocation in a Gleaning Bat, Antrozous pallidus.
In active sensing, animals make motor adjustments to match sensory inputs to specialized neural circuitry. Here, we describe an active sensing system for sound level processing. The pallid bat uses downward frequency-modulated (FM) sweeps as echolocation calls for general orientation and obstacle avoidance. The bat's auditory cortex contains a region selective for these FM sweeps (FM sweep-selective region, FMSR). We show that the vast majority of FMSR neurons are sensitive and strongly selective for relatively low levels (30-60 dB SPL). Behavioral testing shows that when a flying bat approaches a target, it reduces output call levels to keep echo levels between ∼30 and 55 dB SPL. Thus, the pallid bat behaviorally matches echo levels to an optimized neural representation of sound levels. FMSR neurons are more selective for sound levels of FM sweeps than tones, suggesting that across-frequency integration enhances level tuning. Level-dependent timing of high-frequency sideband inhibition in the receptive field shapes increased level selectivity for FM sweeps. Together with previous studies, these data indicate that the same receptive field properties shape multiple filters (sweep direction, rate, and level) for FM sweeps, a sound common in multiple vocalizations, including human speech. The matched behavioral and neural adaptations for low-intensity echolocation in the pallid bat will facilitate foraging with reduced probability of acoustic detection by prey.


HPV Vaccination in Correctional Care: Knowledge, Attitudes, and Barriers Among Incarcerated Women.
Incarcerated women are at increased risk of developing cervical cancer and have high rates of human papillomavirus (HPV) infection, an important cause of cervical cancer. However, many correctional facilities do not offer HPV vaccination to female inmates. This pilot survey study, conducted with incarcerated women aged 18 to 26 at a facility that does not offer the vaccine, assessed attitudes and knowledge about HPV and the HPV vaccine, acceptability of and barriers to in-prison HPV vaccination, and self-reported HPV vaccination rates. Most participants reported that they had not received the HPV vaccine but had positive attitudes toward it and would be willing to get it in prison. Correctional facilities should consider offering this preventive service to this vulnerable population.


Molecular strategies to inhibit restenosis: modulation of the vascular myocyte phenotype.
The transduction of vascular myocytes with exogenous genetic material will be a common feature of many gene-based therapies for cardiovascular disorders. Therefore, the successful application of cardiovascular gene therapy will require a thorough understanding of the molecular biology of the smooth muscle cell. Of key importance are the transcriptional regulatory events that coordinate the de-differentiation and proliferation of myocytes in response to vascular injury. The goal of this review is to highlight what is known about the regulators of vascular myocyte transcription that may serve as candidate genes for the development of genetic strategies to manage postinterventional restenosis.


Susceptibility to retinopathy of prematurity in Alaskan Natives.
Threshold retinopathy of prematurity occurred in 11 of 34 Alaskan natives compared with 10 of 93 non-natives. Natives constitute 16% of the state population. This significant Alaskan native preponderance was not explained by differences in prenatal or intensive care unit morbidity except that the intervals from birth to extubation and birth to cryotherapy were shorter for natives.


Intensive rehabilitation in selected hip fracture patients may optimize care efficiency: A retrospective comparison study.
To gather preliminary data on the effectiveness of intensive rehabilitation after hip fracture surgery, as provided in the Transfer Unit (TU) in Leiden, The Netherlands, compared with the effectiveness of rehabilitation in a regular nursing home. Intensive rehabilitation in the TU consists of physical therapy twice daily by dedicated medical staff and aims to shorten hospital stay and duration of rehabilitation, in order to increase the hospital admission capacity and reduce waiting lists for nursing homes. Retrospective cohort study. A total of 173 hip fracture patients, selected postoperatively for intensive rehabilitation in the TU. Of these, 156 received TU rehabilitation (TU+ group), while 17 were rehabilitated in regular nursing homes for logistic reasons (TU- group). Length of hospital stay, rehabilitation duration and survival were compared between TU+ and TU-. Both groups appeared comparable at baseline. TU+ patients had a mean hospital stay of 10.4 vs 12.3 days for TU- patients (p = 0.29), while their rehabilitation duration was 25.2 days shorter: 42.0 vs 67.2 days (p = 0.001). One-year survival was similar (87%). Intensive rehabilitation in selected hip fracture patients may reduce rehabilitation duration by almost 4 weeks. Differentiated aftercare appears to increase care efficiency for hip fracture patients in both hospitals and nursing homes and may result in a significant reduction in costs.


[Dispersive liquid-liquid microextraction coupled with high performance liquid chromatography for the determination of polynuclear aromatic hydrocarbons in environmental water samples].
A simple, rapid and effective method, the dispersive liquid-liquid microextraction coupled with high performance liquid chromatography-fluorescence detection (DLLME-HPLCFLD), has been developed for the extraction and determination of polynuclear aromatic hydrocarbons (PAHs) in environmental water samples. The factors relevant to the microextraction efficiency, such as type and volume of dispersion agent and extraction solvents and the extraction time were investigated and optimized. Under the optimized extraction conditions, the reliability of the proposed method was evaluated. The linear response of this method was in the range of 0.01-10 microg/L (r > or = 0.9913), the relative standard deviations (RSDs) of peak area for 0.05 microg/L PAHs were in the range of 2.3%-4.7% (n = 6). At room temperature, the method exhibited excellent enrichment factors and good recoveries, 674-1032 and 67.4%-103.2% respectively. The detection limits (S/N = 3) were in the range of 0. 000 3 - 0. 002 pg/L. The developed method was applied to the determination of 15 PAHs in the water from Aojiang river, the average recoveries were 79.5% -92.3% with RSD of 4.3%-6.7% (n = 5). The developed method is suitable for the analysis of trace PAHs in environmental water samples.


Acute Management of Traumatic Knee Dislocations for the Generalist.
Acute knee dislocations are an uncommon injury that can result in profound consequences if not recognized and managed appropriately on presentation. Patients presenting with knee pain in the setting of high- or low-energy trauma may have sustained a knee dislocation that spontaneously reduced. Prompt reduction of the dislocated knee and serial neurovascular examinations are paramount. Damage to the popliteal artery is a common associated injury that can be diagnosed on physical examination using ankle brachial indices (ABIs), CT angiography, or standard angiography. After reduction, patients with a normal pulse examination and an ABI ≥0.9 may be observed, with serial examination performed to document vascular status and monitor for compartment syndrome. Patients with asymmetric pulses or an ABI <0.9 in the presence of pulses may be treated urgently depending on the results of additional vascular imaging, and patients with absent pulses and clear signs of vascular compromise should be treated emergently. Some knee dislocations are not reducible and should be taken emergently to the operating room for an open reduction. Persistent joint subluxation or severe soft-tissue injuries after reduction require temporary external fixation before definitive repair or reconstruction of ligaments is performed.


Design and simulation of an imaging neutral particle analyzer for the ASDEX Upgrade tokamak.
An Imaging Neutral Particle Analyzer (INPA) diagnostic has been designed for the ASDEX Upgrade (AUG) tokamak. The AUG INPA diagnostic will measure fast neutrals escaping the plasma after charge exchange reactions. The neutrals will be ionized by a 20 nm carbon foil and deflected toward a scintillator by the local magnetic field. The use of a neutral beam injector (NBI) as an active source of neutrals will provide radially resolved measurements, while the use of a scintillator as an active component will allow us to cover the whole plasma along the NBI line with unprecedented phase-space resolution (<12 keV and 8 cm) and a fast temporal response (up to 1 kHz with the high resolution acquisition system and above 100 kHz with the low resolution one), making it suitable to study localized fast-ion redistributions in phase space.


Aerobic adaptation in yeast. III. Changes in metabolic intermediates during anaerobic-aerobic transitions in exponentially growing cultures.
The changes in mechanism of control and in the mode of metabolism which yeast cells undergo when an anaerobic-aerobic transition is imposed on them has received much attention. One experimental approach to this type of investigation has been a step-down transition. The data from our experiments (cf. papers I and II of this series) has shown that this model is too complex to arrive at meaningful interpretation. We therefore repeated these measurements of glycolytic and citric acid cycle metabolites in cells growing on either glucose or galactose media and exposed to exponential N2 yields 02 transitions. This type of experiment is designed to examine directly the effect of oxygen challenge. Interpretation of this new data shows that the major metabolic control operating in the two hexose cultures are different and suggests that adenine nucleotide controls glucose cells whereas galactose cell metabolism is controlled by the NAD/NADH balance. This concept is discussed.


XRCC1 and PCNA are loading platforms with distinct kinetic properties and different capacities to respond to multiple DNA lesions.
Genome integrity is constantly challenged and requires the coordinated recruitment of multiple enzyme activities to ensure efficient repair of DNA lesions. We investigated the dynamics of XRCC1 and PCNA that act as molecular loading platforms and play a central role in this coordination. Local DNA damage was introduced by laser microirradation and the recruitment of fluorescent XRCC1 and PCNA fusion proteins was monitored by live cell microscopy. We found an immediate and fast recruitment of XRCC1 preceding the slow and continuous recruitment of PCNA. Fluorescence bleaching experiments (FRAP and FLIP) revealed a stable association of PCNA with DNA repair sites, contrasting the high turnover of XRCC1. When cells were repeatedly challenged with multiple DNA lesions we observed a gradual depletion of the nuclear pool of PCNA, while XRCC1 dynamically redistributed even to lesions inflicted last. These results show that PCNA and XRCC1 have distinct kinetic properties with functional consequences for their capacity to respond to successive DNA damage events.


Mobile MUTE specifies subsidiary cells to build physiologically improved grass stomata.
Plants optimize carbon assimilation while limiting water loss by adjusting stomatal aperture. In grasses, a developmental innovation-the addition of subsidiary cells (SCs) flanking two dumbbell-shaped guard cells (GCs)-is linked to improved stomatal physiology. Here, we identify a transcription factor necessary and sufficient for SC formation in the wheat relative Brachypodium distachyon. Unexpectedly, the transcription factor is an ortholog of the stomatal regulator AtMUTE, which defines GC precursor fate in Arabidopsis The novel role of BdMUTE in specifying lateral SCs appears linked to its acquisition of cell-to-cell mobility in Brachypodium Physiological analyses on SC-less plants experimentally support classic hypotheses that SCs permit greater stomatal responsiveness and larger range of pore apertures. Manipulation of SC formation and function in crops, therefore, may be an effective approach to enhance plant performance.


Global epidemiology of dental caries and severe periodontitis - a comprehensive review.
Dental caries and periodontitis are the most common oral diseases and major causes of tooth loss. To perform a review of global prevalence and incidence of dental caries and periodontitis. Inclusion and exclusion criteria were developed. MEDLINE database and EMBASE database were used to search for eligible publications using keywords and MeSH terms. Additionally, WHO databank was used for obtaining dental caries information and PUBMED for a search on trends of dental caries prevalence and severity. Over the last four decades, the prevalence and severity of dentine carious lesions among 5- and 12-year-olds have declined; the decay-component is very high, with the lowest prevalence among 12-year-olds in high-income countries, which also had the lowest prevalence among 35- to 44-year-olds; and the number of retained teeth has increased around the globe. The prevalence of periodontitis is high, with approximately 10% of the global population affected by severe periodontitis. Study heterogeneity and methodological issues hamper comparisons across studies and over time. While the prevalence of dental caries has decreased, the disease is prevalent in all age groups. The prevalence of periodontitis is high. There is insufficient evidence to conclude that the prevalence of periodontitis has changed over time.


A neuroprotective function of NSF1 sustains autophagy and lysosomal trafficking in Drosophila.
A common feature of many neurodegenerative diseases is the accumulation of toxic proteins that disrupt vital cellular functions. Degradative pathways such as autophagy play an important protective role in breaking down misfolded and long-lived proteins. Neurons are particularly vulnerable to defects in these pathways, but many of the details regarding the link between autophagy and neurodegeneration remain unclear. We previously found that temperature-sensitive paralytic mutants in Drosophila are enriched for those exhibiting age-dependent neurodegeneration. Here we show that one of these mutants, comatose (comt), in addition to locomotor defects, displays shortened lifespan and progressive neurodegeneration, including loss of dopaminerigic (DA) neurons. comt encodes N-ethyl-maleimide sensitive fusion protein (NSF1), which has a well-documented role in synaptic transmission. However, the neurodegenerative phenotypes we observe in comt mutants do not appear to depend on defects in synaptic transmission, but rather from their inability to sustain autophagy under stress, due at least in part to a defect in trafficking of lysosomal proteases such as cathepsin-L. Conversely, overexpression of NSF1 rescues α-synuclein-induced toxicity of DA neurons in a model of Parkinson's disease. Our results demonstrate a neuroprotective role for NSF1 that involves mediation of fusion events crucial for degradative pathways such as autophagy, providing greater understanding of cellular dysfunctions common to several neurodegenerative diseases.


Methionine-enkephalin peptides in human teeth.
The presence of the free opioid pentapeptide methionine enkephalin (ME) and of ME-containing peptide(s) was established firmly in decalcified, depulped human teeth by using a combination of methods including RP-HPLC, radioimmunoassay, radioreceptorassay, trypsin, carboxypeptidase B, fast atom bombardment mass spectrometry, and MS/MS methodology. Positive structural identification of ME was made with mass spectrometry. Those data demonstrate the presence of the preproenkephalinergic A system in the human trigeminal sensory termini.


Successful management of small cell neuroendocrine carcinoma of the ureter with neoadjuvant chemotherapy and adjuvant chemoradiation: case report and literature review.
Neuroendocrine tumours (NETs) of the urinary tract are rare, and the urinary bladder is the the most common primary site. Primary ureteric NET is rarer with under 80 cases reported in the literature thus far. Most of these tumours are of the high-grade small cell neuroendocrine carcinoma subtype, which has a worse prognosis. Neoadjuvant chemotherapy has a proven role in the management of NET of the bladder as it downstages the tumour, which may add to significant recurrence-free survival and overall survival. We report the successful management of a patient with locally advanced small cell neuroendocrine carcinoma of the ureter, who had a pathological complete response after neoadjuvant chemotherapy with etoposide and cisplatin. He subsequently received adjuvant chemotherapy followed by radiation and is recurrence-free at a follow-up of 1 year.


Cutting-aspiration instruments.
Cutting-aspiration instruments are discussed in relation to design and principles of action. Experience with the Roto-extractor in over 100 cases is reviewed. Large pupillary openings were achieved in nearly all cases. No vitreous was attached to the wound postoperatively. Retinal detachment has not occurred to date in nontraumatic lenticular opacities.


Spatiotemporal Expression of Bcl-2/Bax and Neural Cell Apoptosis in the Developing Lumbosacral Spinal Cord of Rat Fetuses with Anorectal Malformations.
Fecal incontinence and constipation still remain the major complications after procedures for anorectal malformations (ARMs). Previous studies have demonstrated a decrease of neural cell in lumbosacral spinal cord of ARMs patients and rat models. However, the underlying mechanism remains elusive. In this study, the neural cell apoptosis and Bcl-2/Bax expression were explored during lumbosacral spinal cord development in normal and ARMs fetuses. ARMs rat fetuses were induced by treating pregnant rats with ethylenethiourea on embryonic day 10. TUNEL staining was performed to identify apoptosis, and the expression of Bcl-2/Bax was confirmed with immunohistochemical staining, RT-qPCR and Western blot analysis on E16, E17, E19 and E21. Apoptosis index (AI) in the ARMs group was significantly higher compared to normal group. Our results showed that TUNEL-positive cells were mainly localized in the ventral horn, which is the location of neural cells controlling defecation. And the expression of Bcl-2 decreased, whereas the level of Bax increased in the ARMs fetuses. In addition, there was a significantly negative correlation between protein expression of Bcl-2/Bax ratio and AI in the ARMs group. Abnormal apoptosis might be a fundamental pathogenesis for the number decrease of neural cells in lumbosacral spinal cord, which leads to complications after procedures for ARMs. The negative correlation between the ratio of Bcl-2/Bax and AI manifested that Bcl-2/Bax pathway might be the mechanism for neural cell apoptosis in ARMs.


Heart‑lung crosstalk in pulmonary arterial hypertension following myocardial infarction (Review).
Left heart disease is the main cause of clinical pulmonary arterial hypertension (PAH). Common types of left heart disease that result in PAH include heart failure, left ventricular systolic dysfunction, left ventricular diastolic dysfunction and valvular disease. It is currently believed that mechanical pressure caused by high pulmonary venous pressure is the main cause of myocardial infarction (MI) in individuals with ischemic cardiomyopathy and left ventricular systolic dysfunction. In the presence of decreased cardiac function, vascular remodeling of pulmonary vessels in response to long‑term stimulation by high pressure in turn leads to exacerbation of PAH. However, the underlying pathological mechanisms remain unclear. Elucidating the association between the development of MI and PAH may lead to a better understanding of potential risk factors and better disease treatment. In this article, the pathophysiological effects of multiple systems in individuals with MI and PAH were reviewed in order to provide a general perspective on various potential interactions between cardiomyocytes and pulmonary vascular cells.


Ideology and science in the individual psychotherapy of schizophrenia.
The efficacy of individual psychotherapy for acute schizophrenics has been the source of controversy for many decades. Discussion of the scientific issues, such as design, methodology, and assessment, has been clouded by strong ideological conflicts. The relative value of drugs and psychotherapy for schizophrenics has been the subject of tension and dispute between various psychiatric schools--psychoanalytic, interpersonal, biological, and behavioral. The Psychotherapy of Schizophrenia Project is discussed in terms of the mixture of scientific and ideological issues.


[Hungarian dentists' corporate response to eliminating mandatory membership in the Medical Chamber].
Hungary's recent parliamentary act (Act XCVII. 2006) revoked the mandatory membership in medical chambers as a prerequisite of professional activity in the health service. After 31st of March 2007, members were automatically canceled except having addressed a unilateral declaration to the presidency of the relevant chamber from 1st of January until the above deadline. Dentists and physicians were mandatory members of the Hungarian Medical Chamber. According to the data obtained and analysed from the registry of this Chamber, out of all former dentist members (N = 5878) 5022 (85.44%) volunteered for the reorganized corporation. In cases of immigrant dentists (N = 522, 8.9% of the whole community) nine out of ten decided the same way (88.5%). Using specific distributions and correlations (gender, age groups, geographic location, practices on public financing) this study revealed many remarkable behavioural patterns of dentists' community to the changed legislation.


Disrupted Pediatric Diabetes Trends in the Second Year of the COVID-19 Pandemic.
Increases in incident cases of pediatric type 1 (T1D) and type 2 diabetes (T2D) were observed during the first year of the COVID-19 pandemic. This work aimed to identify trends in incidence and presentation of pediatric new-onset T1D and T2D during the second year of the COVID-19 pandemic. A retrospective chart review was conducted. Demographics, anthropometrics, and initial laboratory results from patients aged 0 to 21 years who presented with new-onset diabetes to a pediatric tertiary care center were recorded. The incident cases of T1D (n = 46) and T2D (n = 46) in 2021-2022 (second year of the pandemic) were consistent with the incident cases of T1D (n = 46) and T2D (n = 53) in 2020 to 2021 (first year of the pandemic). Compared to the incident cases of diabetes in the prepandemic years, in the second year, the incident cases of T1D increased 48%, and the incident cases of T2D increased 188%. In the second year of the pandemic, incident cases of T2D represented half (50%) of all newly diagnosed pediatric diabetes cases. Patients with T2D were more likely to present in diabetic ketoacidosis, though this was not statistically significant (P = .08). The increase in incident cases of pediatric T1D and T2D observed during the first year of the COVID-19 pandemic persisted during the second pandemic year. This suggests that despite pediatric vaccination efforts and return to social in-person activities, we may continue to see effects of the pandemic on pediatric diabetes trends.


Mechanism of Ca2+ increase in myoblasts derived from chicken embryos.
The mechanism of intracellular calcium ions (Ca(2+)) increase in chicken myoblasts was studied using histological, immunohistochemical, immunoblotting and Ca(2+) imaging techniques. Mononuclear myoblasts at embryonic day 12 (E12) contained myofibrils in the peripheral cytoplasm, and the sarcoplasmic reticulum was observed in the cytoplasm. Several Ca(2+)-related receptors, namely acetylcholine (ACh) receptors, dihydropyridine receptors (DHPRs) and ryanodine receptors (RyRs), were detected in the tissue as early as E12. Western blotting analyses detected one band corresponding to RyR subtype 3 (RyR3) at E12 and two bands corresponding to RyR1 and RyR3 after E13. Ca(2+) imaging of mononuclear myoblasts in vitro revealed an intense Ca(2+)-increase response to ACh stimulation, and this effect was abolished after EGTA addition to the culture medium. Nifedipine treatment also led to a lack of Ca(2+) increase in response to ACh stimulation, while ryanodine treatment led to a weak Ca(2+)-increase response. On the other hand, multinuclear myoblasts showed a Ca(2+)-increase response to ACh stimulation in the presence of not only EGTA but also nifedipine, although ryanodine treatment led to a lack of Ca(2+) increase. These results suggest that the mechanism of Ca(2+) increase in mononuclear myoblasts involves extracellular Ca(2+) entry through DHPRs, which is amplified by Ca(2+) release from the cytoplasmic Ca(2+) store, while multinuclear myoblasts mainly depend on Ca(2+) release from the cytoplasmic Ca(2+) store.


Lopromide one-sample clearance as a measure of glomerular filtration rate.
The pharmacokinetics of iopromide were analysed using a two-compartment model. The optimal point of time for blood withdrawal for calculation of a one-sample clearance was determined. Plasma concentration of iodine was measured up to 8 h postinjection (p.i.) in 62 adult patients who received 120 ml iopromide for computed tomography (CT). A two exponential function was fitted by a weighted least error square method. As reference method, clearance was calculated from this function and the injected amount of iodine. Empirical parameters for calculation of one-sample clearance were determined. This one-sample clearance was compared with one-sample clearance calculated according to formulas developed for Tc99m-DTPA by Jacobsson as well as a two sample method. Total distribution volume of iopromide was calculated as 0.242 Lkg(-1)+/- 5.9%. A high correlation of all one-sample method and the two-sample method with reference to clearance was found. Best estimation of iopromide plasma clearance was achieved by determining one-sample clearance 270 or 285 min p. i. with SD(y.x) of 5.8 ml min(-1). After administration of 120 ml iopromide, one-sample plasma clearance can be calculated with low estimation error taking one blood sample at an appropriate time point. Late phase pharmacokinetics of iopromide found in the present study showed to be virtually identical to results published for iohexol and Tc99m-DTPA.


Multidrug resistance after retroviral transfer of the human MDR1 gene correlates with P-glycoprotein density in the plasma membrane and is not affected by cytotoxic selection.
Multidrug resistance (MDR) in mammalian cells is associated with the expression of the MDR1 gene encoding P-glycoprotein (P-gp), an and active efflux pump for various lipophilic compounds. MDR transfectants can be isolated after MDR1 gene transfer and selection with cytotoxic drugs; low levels of drug resistance have also been observed in unselected NIH 3T3 mouse cells after retrovirus-mediated transfer of mouse mdr1 cDNA. MDR cell lines possess multiple phenotypic changes, suggesting that P-gp function could be complemented by some additional mechanisms associated with cytotoxic selection. To determine whether cytotoxic selection contributes to the MDR phenotype of MDR1-expressing cells, NIH 3T3 cells infected with a recombinant retrovirus carrying the human MDR1 gene were selected by two different procedures: (i) noncytotoxic selection for increased P-gp expression on the cell surface by multiple rounds of immunofluorescence labeling and flow sorting or (ii) one or more steps of selection with a cytotoxic drug. The levels of MDR in both types of infectants showed an excellent correlation with the P-gp density in the plasma membrane, expressed as immunoreactivity with a P-gp-specific antibody normalized by reactivity with an antibody against an unrelated antigen. Cytotoxic selection conferred no additional increase in resistance relative to P-gp density. These results indicate that P-gp density in the plasma membrane may be sufficient to determine the level of MDR.


Innate immune biology in age-related macular degeneration.
Age-related macular degeneration (AMD) is a neurodegenerative disease and a leading cause of irreversible vision loss in the developed world. While not classically described as an inflammatory disease, a growing body of evidence has implicated several components of the innate immune system in the pathophysiology of age-related macular degeneration. In particular, complement activation, microglial involvement, and blood-retinal-barrier disruption have been shown to play key roles in disease progression, and subsequent vision loss. This review discusses the role of the innate immune system in age-related macular degeneration as well as recent developments in single-cell transcriptomics that help advance the understanding and treatment of age-related macular degeneration. We also explore the several potential therapeutic targets for age-related macular degeneration in the context of innate immune activation.


Optimization of a retrospective technique for respiratory-gated high speed micro-CT of free-breathing rodents.
The objective of this study was to develop a technique for dynamic respiratory imaging using retrospectively gated high-speed micro-CT imaging of free-breathing mice. Free-breathing C57Bl6 mice were scanned using a dynamic micro-CT scanner, comprising a flat-panel detector mounted on a slip-ring gantry. Projection images were acquired over ten complete gantry rotations in 50 s, while monitoring the respiratory motion in synchrony with projection-image acquisition. Projection images belonging to a selected respiratory phase were retrospectively identified and used for 3D reconstruction. The effect of using fewer gantry rotations--which influences both image quality and the ability to quantify respiratory function--was evaluated. Images reconstructed using unique projections from six or more gantry rotations produced acceptable images for quantitative analysis of lung volume, CT density, functional residual capacity and tidal volume. The functional residual capacity (0.15 +/- 0.03 mL) and tidal volumes (0.08 +/- 0.03 mL) measured in this study agree with previously reported measurements made using prospectively gated micro-CT and at higher resolution (150 microm versus 90 microm voxel spacing). Retrospectively gated micro-CT imaging of free-breathing mice enables quantitative dynamic measurement of morphological and functional parameters in the mouse models of respiratory disease, with scan times as short as 30 s, based on the acquisition of projection images over six gantry rotations.


Pathological and Therapeutic Aspects of Long noncoding RNAs in osteosarcoma.
Osteosarcoma (OS) is a common bone malignant tumor, which is the eighth leading form of pediatric cancer. Despite the modern chemotherapeutic development of OS, a number of patients with OS have a high risk of lung metastasis and local relapse after chemotherapy. This review study focused on the role of long non coding RNAs (lncRNAs) in OS progression, and presented update reports on OS treatment by targeting specific lncRNAs. We have acquired information on OS and lncRNAs from scientific databases like google scholar, pubmed and scopus, and reviewed for this study. The lncRNAs regulate a number of biological processes, and abnormal expression of lncRNAs could play role in many cancers and other human diseases. Interestingly, some lncRNAs can act as oncogenes, while some act as tumor suppressor genes. A number of studies revealed that targeting the specific lncRNAs by RNA interferance technology may provide a novel therapeutic strategy in the treatment of OS. LncRNAs could be a promising biomarker and might be a potential therapeutic target in OS patients.


Dynamins and BAR Proteins-Safeguards against Cancer.
Dynamins and BAR proteins are crucial in a wide variety of cellular processes for their ability to mediate membrane remodeling, such as membrane curvature and membrane fission and fusion. In this review, we highlight dynamins and BAR proteins and the cellular mechanisms that are involved in the initiation and progression of cancer. We specifically discuss the roles of the seproteinsin endocytosis, endo-lysosomal trafficking, autophagy, and apoptosis as these processes are all tightly linked to membrane remodeling and cancer.


Electronic states of neutral and cationic bis(benzene) titanium and vanadium sandwich complexes studied by pulsed field ionization electron spectroscopy.
Ti- and V-bz2 (bz=C6H6) sandwich complexes have been prepared in a laser-ablation cluster beam source and studied by pulsed field ionization-zero electron kinetic energy photoelectron spectroscopy and theoretical calculations. The ground electronic states of the neutral Ti- and V-bz2 complexes are determined to be 1A1g and 2A1g, and their ionization energies are measured to be 5.732+/-0.001 and 5.784+/-0.002 eV, respectively. These neutral complexes have eta6 binding and are in an eclipsed D6h configuration with flat benzene rings. Ionization of the 1A1g and 2A1g neutral states of Ti- and V-bz2 yields the 2B1g and 3B1g ion states, respectively, in a D2h point group with slightly puckered benzene rings. In addition, the binding and structures of these two complexes are compared with other first-row transition metal bis(benzene) sandwiches.


A Novel Microchip Flow Chamber (Total Thrombus Analysis System) to Assess Canine Hemostasis.
Hemorrhagic diseases are common in dogs. Current coagulation assays do not model all aspects of in vivo hemostasis and may not predict bleeding risk. The Total-Thrombus Analysis System (T-TAS) is a novel hemostasis assay system in which whole blood flows through microfluidic channels at defined shear rates to provide qualitative and quantitative evaluation of platelet function (PL-chip) and coagulation function (AR-chip). The present study evaluated the T-TAS in dogs with hereditary bleeding disorders and with acquired hemorrhagic syndromes (Group 1), and healthy controls (Group 2). Hereditary defects included von Willebrand's disease (VWD; n = 4), hemophilia A (n = 2), and canine Scott syndrome (n = 2). Acquired hemorrhagic disorders included neoplastic hemoperitoneum (n = 2) and acute hemorrhagic diarrhea syndrome (n = 1). Citrate anticoagulated samples were collected from diseased dogs (Group 1, n = 11) and controls (Group 2, n = 11) for coagulation screening tests, fibrinogen analyses, D-dimer concentration, antithrombin activity, von Willebrand Factor antigen, PFA-100 closure time (PFA-CT), and thromboelastography (TEG). Citrate and hirudin anticoagulated samples were used for T-TAS analyses at two shear rates. Qualitative thrombus formation in each chip was recorded using the T-TAS video camera. Numeric parameters, derived from the instrument software, included occlusion start time (OST; time to 10 kPa), occlusion time (OT; time to 60 kPa (PL-chip) or 80 kPa (AR-chip)), and area under the pressure curve (AUC). Correlations between continuous variables were evaluated by Spearman's rank. Continuous variables were compared between groups by Student's t-test or the Mann-Whitney U-test. Alpha was set at 0.05. In combined analyses of all dogs, significant correlations were identified between T-TAS variables, between the PFA-CT and PL-chip parameters and between TEG variables and AR-chip parameters. The prothrombin time correlated with the AR-chip AUC at both shear rates. In Group 1 dogs, the AR-chip AUC at low shear was significantly reduced compared with Group 2 dogs. Aberrant thrombus formation was seen in video images recorded from dogs with VWD and hemophilia A. The T-TAS AR-chip analysis distinguished dogs with bleeding risk compared to healthy controls. Initial evaluations of the T-TAS suggest it may aid characterization of hemostasis in patients at-risk of bleeding and assist with delineating bleeding phenotypes.


Quantification and Whole Genome Characterization of SARS-CoV-2 RNA in Wastewater and Air Samples.
Wastewater-based epidemiology has emerged as a promising and efficacious surveillance system for SARS-CoV-2 and other infectious diseases in many nations. The process typically involves wastewater concentration, nucleic acid extraction, amplification of selected genomic segments, and detection and quantification of the amplified genomic segment. This methodology can similarly be leveraged to detect and quantify infectious agents, such as SARS-CoV-2, in air samples. Initially, SARS-CoV-2 was presumed to spread primarily through close personal contact with droplets generated by an infected individual while speaking, sneezing, coughing, singing, or breathing. However, a growing number of studies have reported the presence of SARS-CoV-2 RNA in the air of healthcare facilities, establishing airborne transmission as a viable route for the virus. This study presents a composite of established protocols to facilitate environmental detection, quantification, and sequencing of viruses from both wastewater and air samples.


Quantifying class participation.
Student participation in classroom activities is frequently considered part of the evaluation of a student's performance. However, the quality of a student's contribution can be difficult to assess. The Evaluation of Class Participation tool was developed to quantify expectations of student preparation and participation.


What influences career choices among graduates of a primary care training program?
To identify factors that influence primary care residents to become generalists or specialists. Structured survey and interview. A large university-based, internal medicine residency program in primary care. Of 92 residency graduates who completed training between 1979 and 1993, 88 (96%) participated. Although 82% of the participating graduates reported themselves very committed to primary care at the beginning of residency, only 68% pursued generalist careers. Factors influencing career choice that were more important to generalists than specialists included breadth of knowledge used in primary care practice (p = .04), breadth of clinical problems in practice (p = .001), and opportunity for continuity of care (p = .01). Although salary was rated "not important," 50% of generalists and specialists advocated increased salaries for generalists as a way to increase interest in primary care. Other promoting factors included mentors, increased prestige for generalists, community-based training, lifestyle changes, and decreased paperwork. Seventy-three percent of participants felt it was easier to be a specialist than a generalist. A substantial minority of primary care residents pursue specialty careers. To produce more generalists, graduates recommend addressing income inequities, providing generalist role models, increasing community-based teaching, and increasing prestige for generalists.


Effects of warning validity and proximity on responses to warnings.
The effects of a warning's validity and display characteristics on the responses to binary warnings were studied in a categorization task that resembled the control of a simulated production environment. Students performed a visual signal detection task and were aided by a binary warning indicator. Experimental conditions differed in the validity of the warning and its proximity to the judged stimulus. Participants' performance improved over the course of the experiment, and they partly adjusted their responses to the validity of the warnings but continued to respond to nonvalid warnings throughout the experiment. It was particularly difficult to ignore the nonvalid information when it was integrated with the continuous information. There was evidence for nonoptimal use of the information from the warning system, whether it was valid or not valid. The results indicate a possible distinction between two dimensions of users' trust in warning systems: compliance and reliance. Actual or potential implications of this research include improved warning design based on analysis of system and operator characteristics.


Impact of chronic and acute stressors on daily reports of mood.
This research compares the relative impact of major life events, chronic stressors, and minor daily stressors on daily reports of mood. Analyses are based on daily diary data combined with interview data derived from a longitudinal study of 96 women sampled from the population of persons using the services of a neighborhood health center in Boston. The most important direct determinants of mood were found to be concurrent daily stressors and physical symptoms, and previous levels of psychological well-being. Life events and chronic stressors had indirect effects on mood through these other variables. The results serve to confirm and extend previous studies on the determinants of short-term changes in mood. The advantages and disadvantages of the temporal aggregation of time-series data are discussed.


Characterization of follicular thyroid nodules at fine needle aspiration biopsy using double phase thallium-201 imaging: comparison of visual and semiquantitative analyses.
To compare visual and semiquantitative indices of double phase thallium-201 thyroid scintigraphy (DTS) for differentiation of malignant nodules by indeterminate fine needle aspiration biopsy (FNAB) results. DTS (early; 15 minutes; delayed, 2 hour) were performed after injection of 37MBq of thallium-201 in 60 patients with indeterminate FNAB. With grade 4 and 5, sensitivity and specificity were 51.4% and 78.3%, respectively. With early lesion to nonlesion ratio (L/N) 1.49, sensitivity and specificity were 97.3% and 39.1%, respectively. With delayed L/N 1.89, sensitivity and specificity were 70.3% and 78.3%, respectively. With wash-out rate (WR) 18.93%, sensitivity and specificity were 89.2% and 82.6%. Early L/N was superior to delayed L/N and WR for the detection of malignant thyroid nodules. Visual assessment had a limited value for differentiation of follicular nodules. The optimal semiquantitative indices were 1.49 for early L/N and 1.89 for delayed L/N. Also, optimal WR was 18.93%. The early L/N was superior to delayed L/N and WR for the detection of malignant thyroid nodular lesions. However, visual assessment and early L/N of DTS showed similar results. Visual analysis and semiquantitative indices of DTS could not differentiate follicular carcinoma and follicular variant of papillary thyroid cancer.


Social-ecological factors related to preventive behaviors during the COVID-19 pandemic in South Korea.
Most studies on COVID-19 preventive behaviors have focused on single-level factors such as national policy, community social capital, or individuals' sociodemographic characteristics. Through a social-ecological model, this study attempts to comprehensively examine the multilevel factors associated with COVID-19 preventive practices in South Korea. Accordingly, a web survey involving 1,500 participants was conducted in December 2020. An ordinary least squares (OLS) regression was used to examine the multilevel factors (individual, interpersonal, community, and policy levels) related to COVID-19 preventive measures, which are based on wearing a mask, washing hands, covering the mouth when coughing or sneezing, and social distancing. When factors at each level were investigated, higher scores of COVID-19 fear and correct knowledge at the individual level, COVID-19 information share at the interpersonal level, and better evaluation of the national government policies in regard to COVID-19 at the policy level were positively associated with COVID-19 preventive behaviors. Community-level factors-neighborhood perception and community participation-were negatively significantly related to COVID-19 preventive behaviors. Additionally, older age, being female, and having a graduate-level education were positively related to better preventive behaviors. The findings of the current study suggest that multilevel efforts are needed to promote preventive behaviors. Specifically, more effort to alleviate COVID-19-related fear and disseminate correct knowledge among Korean citizens is needed as the individual-level characteristics explained the preventive behaviors more than the factors at upper levels.


HIV and HIV-Tat inhibit LPS-induced IL-27 production in human macrophages by distinct intracellular signaling pathways.
Monocyte-derived Mϕs (MDMs) from HIV-infected patients and MDM infected in vitro with HIV exhibit a reduced ability to secrete various cytokines, including IL-12. Recently, IL-27, an IL-12 family cytokine, was shown to inhibit HIV replication in Mϕ. Whether HIV infection or HIV accessory protein(s) impact IL-27 production in Mϕs remains unknown. Herein, we show that in vitro HIV infection, as well as intracellular HIV-Tat (Tat) and Tat peptides, inhibit LPS-induced IL-27 production in human MDMs, suggesting impairment of the TLR4 signaling pathway. To understand the signaling pathways governing HIV or Tat-mediated inhibition of LPS-induced IL-27 production, we first demonstrated that p38 MAPK, PI3K, Src-homology region 2 domain-containing tyrosine phosphatase 1 (SHP-1), and Src kinases regulate LPS-induced IL-27 production in MDMs. Tat caused down-regulation of TNFR-associated factor (TRAF)-6 and inhibitor of apoptosis 1 (cIAP-1) and subsequently decreased phosphorylation of downstream PI3K and p38 MAPKs, which were implicated in LPS-induced IL-27 production. Whereas SHP-1 and Src kinases regulated LPS-induced IL-27 production, Tat did not inhibit these kinases, suggesting that they were not involved in Tat-mediated inhibition of LPS-induced IL-27 production. In contrast to Tat, in vitro HIV infection of MDM inhibited LPS-induced IL-27 production via inhibition of p38 MAPK activation. Overall, HIV and Tat inhibit LPS-induced IL-27 production in human macrophages via distinct mechanisms: Tat through the inhibition of cIAP-1-TRAF-6 and subsequent inhibition of PI3K and p38 MAPKs, whereas HIV through the inhibition of p38 MAPK activation.


Primary malignant melanoma of the kidney.
The fourth patient with a solitary malignant melanoma of the kidney with no apparent primary lesion or metastasis is reported.


Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization.
The development of human liver scaffolds retaining their 3-dimensional structure and extra-cellular matrix (ECM) composition is essential for the advancement of liver tissue engineering. We report the design and validation of a new methodology for the rapid and accurate production of human acellular liver tissue cubes (ALTCs) using normal liver tissue unsuitable for transplantation. The application of high shear stress is a key methodological determinant accelerating the process of tissue decellularization while maintaining ECM protein composition, 3D-architecture and physico-chemical properties of the native tissue. ALTCs were engineered with human parenchymal and non-parenchymal liver cell lines (HepG2 and LX2 cells, respectively), human umbilical vein endothelial cells (HUVEC), as well as primary human hepatocytes and hepatic stellate cells. Both parenchymal and non-parenchymal liver cells grown in ALTCs exhibited markedly different gene expression when compared to standard 2D cell cultures. Remarkably, HUVEC cells naturally migrated in the ECM scaffold and spontaneously repopulated the lining of decellularized vessels. The metabolic function and protein synthesis of engineered liver scaffolds with human primary hepatocytes reseeded under dynamic conditions were maintained. These results provide a solid basis for the establishment of effective protocols aimed at recreating human liver tissue in vitro.


Predictive Accuracy of the European Society of Cardiology SCORE Among French People.
Assessment of cardiovascular (CV) risk with a predictive algorithm is recommended for managing CV disease prevention. The aim of this study was to assess the predictive accuracy of the European Society of Cardiology SCORE among French people. Our analysis was based on the Third French MONICA population-based survey (1995-1996) and on a sample of subjects referred (from 1995 to 2000) for a CV checkup in a preventive cardiology unit. Vital status was obtained 10 years after inclusion. The 10-year predicted risk of CV death was calculated using the SCORE equation for low-risk countries and was compared with the 10-year incidence of CV death observed in the cohort. The sample was composed of 6915 participants aged 35 to 64 years, among whom 56 CV deaths occurred during the followup. The median risk SCORE (0.97%) did not differ from the 10-year incidence of CV death observed in the cohort (1.05%; 95% CI, 0.81-1.37). The median risk SCORE calculated for different categories of sex, age, educational level, family history of premature CV disease, physical activity, impaired fasting glucose, smoking, systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol did not differ from the 10-year incidence of CV death observed in these categories. The C-statistic of the SCORE equation was 79% (73-85). Using a 5% threshold to discriminate people at high risk, 93% of participants were correctly classified (subjects with SCORE ≥5% who died from a CV causes during followup and those with SCORE <5% who did not). Among middle-aged French people, the SCORE equation adequately predicts CV death.


Stromal microenvironment of human fetal hematopoiesis: in vitro morphologic studies.
The stromal microenvironment is essential for the proliferation and differentiation of hematopoietic progenitors. The features of stroma which contribute to normal hematopoietic stem cell ontogeny or to observed differences in hematopoiesis between fetal and adult hematopoietic organs remain to be fully characterized. In this study, we used long-term culture conditions to grow human fetal liver, fetal bone marrow and adult bone marrow-derived stroma. The stromal layers in all cultures were observed to support multilineage hematopoiesis. Routine and electron microscopic evaluation of the stromal layers reveal the presence of two distinct cell types: a large cell with extensive cytoplasmic projections, and a smaller cell resembling a macrophage. In contrast to some previous reports from in vitro stromal studies, there were no adipocytes, endothelial cells, or cells which could conclusively be identified as fibroblasts in the stromal layer. These findings were further substantiated by negative findings on sections stained with oil-red-O for fat, trichrome for collagen, and factor VIII-related antigen for endothelial elements. There were no morphological differences in the stromal layers from fetal liver, fetal bone marrow, and adult bone marrow sources. This finding is important because it suggests that differences in the behavior of hematopoietic stem cells, when supported in these various hematopoietic microenvironments, are less likely to be explained by obvious differences in the cytologic architecture of stroma than by differences in stem cell biology or growth factor interactions.


[Knowledge of the employees about biological agents in the work environment and the ways of health protection against occupational exposure to biological hazards. Part II].
The effectiveness of health protection of workers occupationally exposed to biological agents is equally influenced by the workers' knowledge about the risks related to biological agents and the ways they behave at work. In this paper, the authors continue to present the results of the study covering 150 workers employed in health services, forestry, and municipal services. They were interviewed on the basis of a specially designed questionnaire. The majority of the study population used personal protective devices in a proper way and followed the principles of occupational safety and hygiene. Only some of the workers informed occupational medicine physicians about their health problems, which they associated with occupational exposure to biological agents. The interviewed workers are actually able to sufficiently protect their health against biological hazards despite their generally low knowledge of risks related to occupational exposure to biological agents.


[Experimental studies on the rat-model for partial splenectomy and on spleen regeneration].
Partial splenectomy is often preferred to total splenectomy as a method to prevent serious post-operative sepsis. However, most of the previous researches on spleen function following partial splenectomy have failed to provide accurate data on the minimum increase of residual spleen in weight necessary for protection against postoperative sepsis. This is not only to the lack of appropriate model but also to the negligence of the effects of spleen regeneration after partial splenectomy. To produce an accurate model for partial splenectomies, and to know how the spleen regenerates following partial resection, about 500 rats underwent partial splenectomies. From these experiments, the following results were obtained. These partial splenectomies based on length of the spleen were satisfactory models as partial splenectomy. Absolute volume of regenerated spleen was finally almost the same in every model. However, the less the remnant spleen was the longer period was necessary until the spleen regeneration completed.


Expression and localization of cyclooxygenases in the oviduct of laying hens during the ovulatory cycle.
Prostaglandins (PGs) play important roles in regulation of the functions of the hen oviduct. However, little is known about the expression and localization of the rate-limiting cyclooxygenases (COX-1 and COX-2) in the oviduct. The aim of this study was to determine the COXs expression and localization in the different segments of the oviduct and to investigate changes in their expression levels during the ovulatory cycle of laying hens. White Leghorn laying hens were killed at 0, 4, 7, 16 and 24 h after oviposition, and samples from the infundibulum, magnum, isthmus, uterus, and vagina were collected. Gene and protein expressions were examined by real-time PCR and western blot, respectively, for both COX-1 and COX-2. Localization of COX-1 and COX-2 in the hen oviduct was determined by immunohistochemistry and PCR analysis of samples collected by laser capture microdissection (LCM). The expression level of COX-1 was highest in the infundibulum, while that of COX-2 was significantly higher in the uterus than in the other segments. The expression levels of COX-1 in the infundibulum and COX-2 in the uterus were higher at 0 and 24 h after oviposition, just prior to subsequent ovulation and oviposition. Western blot analysis confirmed the presence of COX-1 and COX-2 in all oviductal segments. The density of COX-2 was the highest in the uterus, and did not change during the ovulatory cycle. COX-1 and COX-2 were localized in the surface epithelium of all oviductal segments besides the uterine tubular glands. We conclude that both COXs are differentially expressed in the different oviductal segments with a temporal association to ovulation and oviposition. COX-1 and COX-2 may play an important role in the infundibulum and uterus, respectively, and COX-2 may be one of the factors regulating the induction of oviposition.


Genomic Regions in Local Endangered Sheep Encode Potentially Favorable Genes.
The economic evaluation of farm animal genetic resources plays a key role in developing conservation programs. However, to date, the link between diversity as assessed by neutral genetic markers and the functional diversity is not yet understood. Two genome-wide comparisons, using over 44,000 Single Nucleotide Polymorphisms, identified the markers with the highest difference in allele frequency between the Alpago endangered breed and two clusters, composed of four specialized dairy sheep, and four meat breeds respectively. The genes in proximity of these markers were mapped to known pathways of the Gene Ontology to determine which ones were most represented. Our results indicated that the differences of the Alpago breed from the more productive sheep rely upon genes involved in cellular defense and repair mechanisms. A higher number of different markers and genes were detected in the comparison with the specialized dairy sheep. These genes play a role in complex biological processes: metabolic, homeostatic, neurological system, and macromolecular organization; such processes may possibly explain the evolution of gene function as a result of selection to improve milk yield.


Leukotriene C4 in the rat brain after resuscitation from clinical death.
By means of the radioimmunological method changes of concentration of leukotriene C4 (LTC4) in rat brain cortex and hippocampus have been evaluated during 5-min clinical death and up to 2 h after resuscitation. Wet weight/dry weight methodology was utilized to evaluate brain water content. Ischemia did not produce significant changes of LTC4 concentration in the brain. In the postresuscitation period concentration of LTC4 in both brain regions significantly increased reaching in 5 and 15 min respectively a 4- and 5-fold control values. Later the concentration of LTC4 in the brain decreased reaching in 30 min a 3-fold control level, and in 60 and 120 min after resuscitation control values. Water content after resuscitation did not show significant changes in both brain regions. LTC4 does not seem to play an important role in the development of cerebral edema.


Approaches for applications of physiologically based pharmacokinetic models in risk assessment.
Physiologically based pharmacokinetic (PBPK) models are particularly useful for simulating exposures to environmental toxicants for which, unlike pharmaceuticals, there is often little or no human data available to estimate the internal dose of a putative toxic moiety in a target tissue or an appropriate surrogate. This article reviews the current state of knowledge and approaches for application of PBPK models in the process of deriving reference dose, reference concentration, and cancer risk estimates. Examples drawn from previous U.S. Environmental Protection Agency (EPA) risk assessments and human health risk assessments in peer-reviewed literature illustrate the ways and means of using PBPK models to quantify the pharmacokinetic component of the interspecies and intraspecies uncertainty factors as well as to conduct route to route, high dose to low dose and duration extrapolations. The choice of the appropriate dose metric is key to the use of the PBPK models for the various applications in risk assessment. Issues related to whether uncertainty factors are most appropriately applied before or after derivation of human equivalent dose (or concentration) continue to be explored. Scientific progress in the understanding of life stage and genetic differences in dosimetry and their impacts on variability in susceptibility, as well as ongoing development of analytical methods to characterize uncertainty in PBPK models, will make their use in risk assessment increasingly likely. As such, it is anticipated that when PBPK models are used to express adverse tissue responses in terms of the internal target tissue dose of the toxic moiety rather than the external concentration, the scientific basis of, and confidence in, risk assessments will be enhanced.


[Cryogenic surgery].
Local tumor destruction by cryosurgery was observed clinically and morphologically in 184 patients. If indication is observed strictly this method seems to provide real palliative effect. Complete tumor destruction was observed in 14.1%. Local tumor destruction was followed by tissue inflammation and nonspecific phagocytosis of tumor cells. Immunological reaction and epithelialization was noted only after radical destruction of tumors. Most cases showed immediate relief from stenosing cancer; colostomy could be avoided.


How cadmium could compromise the completion of the European eel's reproductive migration.
The European eel (Anguilla anguilla L.) is severely threatened with extinction. Surprisingly, even though their unusual life cycle makes them particularly vulnerable to pollution, the possible contribution of contamination remains especially poorly known. Here we have investigated the possible effect of cadmium (Cd), a widespread nonessential metal, on eel reproductive capacities. Both control and Cd precontaminated female silver eels were experimentally matured and forced to swim in metal-free conditions to mimic their reproductive migration. Cd pre-exposure was found to strongly stimulate the pituitary-gonad-liver axis of maturing female silver eels leading to early and enhanced vitellogenesis. This was followed by a strong phenomenon of oocyte atresia and eel mortality. These phenomena occurred before oocytes could reach full maturation and were associated with a large entry of both vitellogenin and Cd into the ovaries. Indeed, a redistribution of previously stored cadmium, even from the low Cd levels of control eels, was observed during sexual maturation. Atresia and mortality phenomena were also associated with an overexpression of the pituitary gene encoding the growth hormone, a marker of physiological stress and energy reserves exhaustion. Significantly, these devastating effects of Cd were observed in organisms that presented liver and kidney Cd concentrations still below those observed in eels from Cd contaminated hydrosystems. Our research shows how common levels of cadmium contamination could disrupt endocrine pathways implicated in gonad maturation and subsequently impair reproductive capacity of eel future genitors.


Parental psychopathology and posttraumatic stress in Puerto Ricans: the role of childhood adversity and parenting practices.
Parental psychopathology is associated with their children's posttraumatic stress symptoms (PTSS). However, the mechanisms through which this occurs remain unclear. We hypothesized that exposure to childhood adversities is the mechanism linking parental psychopathology to child PTSS and that parenting practices moderated these associations. Participants (N = 1,402) with an average age of 24.03 years old (SD = 2.20), were all Puerto Ricans (50% Male and 50% Female) from the Boricua Youth Study, which is a four-wave longitudinal study spanning almost 20 years, following individuals from childhood (ages 5-13 at Wave 1) to young adulthood. Measured variables include parental psychopathology at Wave 1, childhood adversities and parenting practices at Waves 2-3, and PTSS at Wave 4. A traditional mediation model estimated the association between parental psychopathology and child PTSS via childhood adversities. A moderated mediation model was used to examine whether parenting practices moderated this mediation model. Results showed that the total effect of parental psychopathology at Wave 1 on PTSS at Wave 4 was fully mediated by childhood adversities at Waves 2-3 (direct effect b = 1.72, 95% CI = [-0.09, 3.83]; indirect effect b = 0.40, 95% CI = [0.15, 0.81]). In addition, the magnitude of this pathway varied by levels of parenting practices (i.e. parental monitoring and parent-child relationship quality). Specifically, the indirect effect of additional adversities in the psychopathology-PTSS link was stronger with higher levels of parental monitoring but weaker with higher parent-child relationship quality scores. Intergenerational continuity of psychopathology may be mitigated through the prevention of additional childhood adversities via upstream interventions, emphasizing providing parents with mental health needs with parenting tools. Family-based interventions focused on providing families with the tools to improve parent-child relationships may reduce the negative impact of childhood adversities on mental health across the life course.


[Clinical practice guideline: 2003 update of Standards, Options et Recommendations for first line palliative chemotherapy in patients with metastatic colorectal cancer (summary report)].
The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centres (FNCLCC), the 20 French Regional Cancer Centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. To update clinical practice guidelines for first line palliative chemotherapy in patients with metastatic colorectal cancer previously validated in 1995, then updated in 1997 and published again in 1998. These recommendations do not cover second line treatment. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines have been developed, they are reviewed by independent reviewers. This article is a summary version of the updated clinical practice guidelines with algorithms. The main questions addressed by the expert group in this update concerned (1) Which patients should be treated? (2) What is the best treatment duration? (3) Which treatment should be administered? The new data identified concerning which patients to treat and the duration of treatment were consistent with the data presented in the initial report and did not modify the original recommendations from 1997. The new data available represent stronger evidence than those in the original report (Two good-quality meta-analyses published since 1997). A new guideline concerning patients who are 75 years old or more has been added. Concerning, the new evidence identified has modified the guidelines for the therapeutic schema to adopt from 1997. These modifications concern irinotecan, oxaliplatin, oral fluoropyrimidines and methotrexate. Treatment with irinotecan or oxaliplatin associated with continuous 5FU infusion, modulated with folinic acid (LV5FU2-like) has become a standard. The use of oral fluoropyrimidines has become an option for patients who refuse hospitalisation or treatment by infusion. The use of methotrexate combined with 5FU is no longer recommended.


Different rotamer states of cytosine nucleobases in heteronuclear PtPd-, PtPd2, and Pt2Pd2Ag complexes derived from [Pt(2,2'-bpy)(1-MeC-N3)2]2+ (1-MeC = 1-methylcytosine): first examples of species with head-head oriented 1-MeC(-) ligands.
[Pt(2,2'-bpy)(1-MeC-N3)(2)](NO(3))(2) (1) (2,2'-bpy = 2,2'-bipyridine; 1-MeC = 1-methylcytosine) exists in water in an equilibrium of head-tail and head-head rotamers, with the former exceeding the latter by a factor of ca. 20 at room temperature. Nevertheless, 1 reacts with (en)Pd(II) (en = ethylenediamine) to give preferentially the dinuclear complex [Pt(2,2'-bpy)(1-MeC(-)-N3,N4)(2)Pd(en)](NO(3))(2)·5H(2)O (2) with head-head arranged 1-methylctosinato (1-MeC(-)) ligands and Pd being coordinated to two exocyclic N4H(-) positions. Addition of AgNO(3) to a solution of 2 leads to formation of a pentanuclear chain compound [{Pt(2,2'-bpy)(1-MeC(-))(2)Pd(en)}(2)Ag](NO(3))(5)·14H(2)O (5) in which Ag(+) cross-links two cations of 2 via the four available O2 sites of the 1-MeC(-) ligands. 2 and 5 appear to be the first X-ray structurally characterized examples of di- and multinuclear complexes derived from a Pt(II) species with two cis-positioned cytosinato ligands adopting a head-head arrangement. (tmeda)Pd(II) (tmeda = N,N,N',N'-tetramethylethylenediamine) and (2,2'-bpy)Pd(II) behave differently toward 1 in that in their derivatives the head-tail orientation of the 1-MeC(-) nucleobases is retained. In [Pt(2,2'-bpy)(1-MeC(-))(2){Pd(2,2'-bpy)}(2)](NO(3))(4)·10H(2)O (4), both (2,2'-bpy)Pd(II) entities are pairwise bonded to N4H(-) and O2 sites of the two 1-MeC(-) rings, whereas in [Pt(2,2'-bpy)(1-MeC(-))(2){Pd(tmeda)}(2)(NO(3))](NO(3))(3)·5H(2)O (3) only one of the two (tmeda)Pd(II) units is chelated to N4H(-) and O2. The second (tmeda)Pd(II) is monofunctionally attached to a single N4H(-) site. On the basis of these established binding patterns, ways to the formation of mixed Pt/Pd complexes and possible intermediates are proposed. The methylene protons of the en ligand in 2 are special in that they display two multiplets separated by 0.64 ppm in the (1)H NMR spectrum.


Histochemical properties of upper airway muscles: comparison of dilator and nondilator muscles.
The upper airway dilator muscles (UADMs) represent a subgroup of muscles in the pharyngeal area which, in addition to their roles in mastication, vocalization, etc., also have an important respiratory function. Failure of these muscles to maintain upper airway patency during sleep is important in the development of the obstructive sleep apnoea syndrome. In the present study, we evaluated the histochemical properties of the UADMs and compared them to those of neighbouring muscles without respiratory functions, and to the diaphragm, to determine whether the UADMs are specifically adapted to their respiratory role. Our results, both in dogs and rats, indicate that the dilator and nondilator upper airway muscles are similar and differ from the diaphragm. In rats, there were significantly less type I fibres (<12% as compared to 42% for the diaphragm) and more type IIb fibres (39-67% as compared to 27% for the diaphragm). A similar pattern was seen in dogs: type I fibres <38% as compared to 46% for the diaphragm, and type IIb fibres, 29-35% as compared to 10% for the diaphragm. These findings suggest that the upper airway dilator muscles are not specifically designed for their respiratory role. They may fail in the presence of increased loads, often encountered in patients with obstructive sleep apnoea, unless appropriate adaptive structural changes take place.


Loss of S100 antigenicity in metastatic melanoma.
Melanoma is a highly malignant disease that may initially present as a poorly differentiated metastatic tumor. Therefore, the S100 immunostain, immunoreactive in 96% to 99% of melanoma, is used to evaluate poorly differentiated malignant tumors. To develop criteria for correctly diagnosing S100-negative melanomas, we studied the immunohistochemical profile of 1553 patients enrolled in ongoing National Cancer Institute clinical trials for melanoma. Seventeen patients (1%) had metastatic melanoma specimens that were negative for S100. Of the 17 S100-negative lesions, 10 (59%) were immunoreactive for both GP100 and MART-1. Of the 17 S100-negative cases, 13 had a documented primary melanoma. Twenty-four percent of the S100-negative cases had an ocular primary, whereas only 6% of all melanomas had an ocular origin. In 11 of the 17 cases with previous surgical specimens, a prior documented S100-immunoreactive specimen was identified in 9 cases (82%). The time interval for loss of S100 immunoreactivity ranged from 3 weeks to 3 years (average, 13.5 months). There was no association between S100-negative status and histological appearance or site of metastasis. We conclude that all S100-negative melanomas could be correctly identified by negative workup for carcinoma, lymphoma, and sarcoma plus (1) GP100/MART-1 immunoreactivity and/or (2) prior documentation of melanoma.


[Early infantile epileptic encephalopathy caused by PACS2 gene variation: three cases report and literature review].
Objective: To explore the clinical features of three early-onset infantile epileptic encephalopathy (EIEE) patients with variations in phosphofurin acidic cluster sorting protein 2 (PACS2) gene and to review related literature. Methods: The clinical data and genetic features of three early infantile epileptic encephalopathy 66 (EIEE66) patients with a PACS2 gene variant diagnosed by the Department of Neurology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2019 to January 2020 were retrospectively analyzed. A literature search with "PACS2 gene" "PACS2" "epileptic encephalopathy, early infantile, 66" and"early infantile epileptic encephalopathy 66" as key words was conducted at PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang Data Knowledge Service Platform (up to July 2020). Case reports of patients with PACS2 gene variants and related clinical data were chosen and reviewed. Results: Case 1, a girl aged 2 years and 2 months was hospitalized because of repetitive seizures within more than two years and 6 convulsions within 2 days due to fever. The seizures occurred at the age of 7 days, characterized by focal seizures and generalized tonic-clonic seizures. Sometimes, the frequency of seizures increased with high fever. Regular treatment had not been implemented in the early stage, later seizures were controlled by valproic acid treatment. Case 2, a female 5 months of age, was admitted due to recurrent convulsions in nearly five months. Focal seizures occured at the age of 5 days. And the brain magnetic resonance imaging (MRI) confirmed abnormal cerebellar hemispheres and cerebellar vermis, as well as cerebellar dysplasia. Several antiepileptic drugs and ketogenic diet were ineffective in the early months, and later seizures were controlled with the treatment with levetiracetam and valproic acid. Case 3, a five-month-old girl, was admitted because of recurrent convulsions for nearly five months. At the age of 3 days, she had tonic seizures, and showed good response to levetiracetam and valproic acid. All the three cases were accompanied by development delay and dysmorphic facial appearance, and got seizure-free with the treatment with valproic acid. All copy-number variant analysis and trio whole exome sequencing revealed a recurrent heterozygous missense variant (c.625G>A) in PACS2 gene. No related reports were found in Chinese journals, while 4 reports were found in English literature, describing 17 patients in total. With these 3 patients included, 20 cases had only two missense PACS2 gene variants, in whom 19 cases carried the variant c. 625G>A (p.Glu209Lys) and 1 case carried the variant c. 631G>A (p.Glu211Lys). Epilepsy was the first reported symptom in all patients, and 17 cases had seizures during the first week of life. Out of the various seizure types observed, focal seizures were the predominant types (13 cases), whereas tonic, clonic, tonic-clonic seizures and non-motor seizures (such as facial flushing) were also reported. Almost all patients showed facial dysmorphism and developmental delay to different degrees. Total of 16 patients had abnormal brain MRI recordings, and 13 cases had cerebellar hypoplasia. More specifically, 7 cases showed inferior vermian hypoplasia, and 3 cases showed hypothalamic fusion anomaly. The treatment was mainly aimed to control the symptoms. And the recommended effective treatment for epilepsy has not been reported yet. Conclusions: PACS2-related early infantile epileptic encephalopathy is an autosomal dominant disease, characterized by seizure onset within the first week of life in most cases, dysmorphic facial appearance, and various degrees of developmental retardation. Treatment with valproic acid showed good effect.


Metamemorial influences in recognition memory: pictorial encoding reduces conjunction errors.
Two experiments are presented that explore the role of the distinctiveness heuristic (e.g., Schacter, Israel, & Racine, 1999) on rates of conjunction errors as a function of encoding condition. The results of Experiment 1 demonstrate a reliable reduction of conjunction errors when participants study pictures relative to both reading words aloud and silently. Experiment 2 demonstrates that the nature of the pictures presented during the study phase is important for reducing conjunction errors. Collectively, the experiments demonstrate that participants can use the distinctiveness heuristic in addition to recall-to-reject strategies to avoid conjunction errors. These findings add to a growing body of literature that suggests that participants are able to use expectations for memory to guide their recognition decisions.


Tyrosinemia type 1 in Spain: mutational analysis, treatment and long-term outcome.
Tyrosinemia type 1 (HT1) is a rare but treatable disease. The aim of the present study was to review the efficacy of long-term treatment of HT1 with nitisinone, expand knowledge about the clinical spectrum of the disease and assess a possible genotype-phenotype correlation. A retrospective multicenter study was carried out based on questionnaires on genotype, phenotype, therapy and outcome in 34 Spanish patients with HT1. The main manifestations that led to the diagnosis were acute liver failure (55.8%), asymptomatic hepatomegaly (44.1%) and renal tubular dysfunction (29.4%). Laboratory analysis indicated a marked increase of α-fetoprotein and coagulopathy. The most common mutation was IVS6-1(G > T; 66.6% of 24/34 patients for whom mutation analysis was available) and these patients presented less nephrocalcinosis and more hepatomegaly at diagnosis; two novel mutations (c.974C>T, c.398A>T) were found. The mean duration of treatment was 6.73 years. Dietary compliance was very good in 47.1% and good in 20.6%; nitisinone treatment adherence was very good in 85.2% of cases. Mean dose of nitisinone was 0.87 mg/kg per day with average plasma levels of 45.67 µmol/L. Only one patient required liver transplantation after nitisinone and none had hepatocellular carcinoma. Treatment with nitisinone has improved the prognosis of HT1, and compliance is good. In Spain, screening for HT1 by plasma tyrosine and urine succinylacetone determination may be implemented with IVS6-1(G > T) mutational analysis. A correlation between low frequency of nephrocalcinosis and IVS6-1(G > T) mutation was observed.


Detection and yield of thyroid cancer surveillance in adults with PTEN hamartoma tumour syndrome.
Thyroid cancer surveillance (TCS) with ultrasound (US) is advised for PTEN hamartoma tumour syndrome (PHTS) patients due to increased thyroid cancer (TC) risk. However, data supporting TCS guidelines are scarce. We aimed to assess the detection and yield of annual TCS with US in adult PHTS patients without a TC history and to evaluate the impact of a reduced US interval on the TCS yield. A retrospective cohort study was conducted, including adult PHTS patients and medical record data between 2005 and 2021. The yield from annual TCS was compared with hypothetical biennial and triennial TCS after two initial US with annual interval by counting delayed detection of nodular growth, thyroid adenoma, and TC. During 279 follow-up years, 84 patients (median age 40 years) underwent 349 US. Thyroidectomy was performed in 6/84 (7%) patients, revealing a minimally invasive follicular TC in one patient aged 22 and a thyroid adenoma in two patients aged 21 and 53. Multiple thyroid nodules were diagnosed in 73/84 (87%) patients (median age 36 years). Nodular growth was detected in 9/56 (16%) patients, and its detection would have been delayed in 4-7% US rounds with biennial TCS, and in 2-6% US rounds with triennial TCS. US-based thyroiditis and indeterminate non-malignant lymph nodes were found in 8/74 (11%) and 7/72 (10%) patients, respectively. Following our findings combined with the literature, we propose starting TCS before age 18 and reducing the follow-up frequency after the initial two US from annual to biennial if no suspicious findings are detected.


Bioactive Hydrogel Marbles.
Liquid marbles represented a significant advance in the manipulation of fluids as they used particle films to confine liquid drops, creating a robust and durable soft solid. We exploit this technology to engineering a bioactive hydrogel marble (BHM). Specifically, pristine bioactive glass nanoparticles were chemically tuned to produce biocompatible hydrophobic bioactive glass nanoparticles (H-BGNPs) that shielded a gelatin-based bead. The designed BHM shell promoted the growth of a bone-like apatite layer upon immersion in a physiological environment. The fabrication process allowed the efficient incorporation of drugs and cells into the engineered structure. The BHM provided a simultaneously controlled release of distinct encapsulated therapeutic model molecules. Moreover, the BHM sustained cell encapsulation in a 3D environment as demonstrated by an excellent in vitro stability and cytocompatibility. The engineered structures also showed potential to regulate a pre-osteoblastic cell line into osteogenic commitment. Overall, these hierarchical nanostructured and functional marbles revealed a high potential for future applications in bone tissue engineering.


Bacterial exploitation of phosphorylcholine mimicry suppresses inflammation to promote airway infection.
Regulation of neutrophil activity is critical for immune evasion among extracellular pathogens, yet the mechanisms by which many bacteria disrupt phagocyte function remain unclear. Here, we have shown that the respiratory pathogen Streptococcus pneumoniae disables neutrophils by exploiting molecular mimicry to degrade platelet-activating factor (PAF), a host-derived inflammatory phospholipid. Using mass spectrometry and murine upper airway infection models, we demonstrated that phosphorylcholine (ChoP) moieties that are shared by PAF and the bacterial cell wall allow S. pneumoniae to leverage a ChoP-remodeling enzyme (Pce) to remove PAF from the airway. S. pneumoniae-mediated PAF deprivation impaired viability, activation, and bactericidal capacity among responding neutrophils. In the absence of Pce, neutrophils rapidly cleared S. pneumoniae from the airway and impeded invasive disease and transmission between mice. Abrogation of PAF signaling rendered Pce dispensable for S. pneumoniae persistence, reinforcing that this enzyme deprives neutrophils of essential PAF-mediated stimulation. Accordingly, exogenous activation of neutrophils overwhelmed Pce-mediated phagocyte disruption. Haemophilus influenzae also uses an enzyme, GlpQ, to hydrolyze ChoP and subvert PAF function, suggesting that mimicry-driven immune evasion is a common paradigm among respiratory pathogens. These results identify a mechanism by which shared molecular structures enable microbial enzymes to subvert host lipid signaling, suppress inflammation, and ensure bacterial persistence at the mucosa.


The Breeding Information Management System (BIMS): an online resource for crop breeding.
In this era of big data, breeding programs are producing ever larger amounts of data. This necessitates access to efficient management systems to keep track of cross, performance, pedigree, geographical and image-based data, as well as genotyping data. In this article, we report the progress on the Breeding Information Management System (BIMS), a free, secure and online breeding management system that allows breeders to store, manage, archive and analyze their private breeding data. BIMS is the first publicly available database system that enables individual breeders to integrate their private phenotypic and genotypic data with public data and, at the same time, have complete control of their own breeding data along with access to tools such as data import/export, data analysis and data archiving. The integration of breeding data with publicly available genomic and genetic data enhances genetic understanding of important traits and maximizes the marker-assisted breeding utility for breeders and allied scientists. BIMS incorporates the use of the Android App Field Book, open-source phenotype data collection software for phones and tablets that allows breeders to replace hard copy field books, thus alleviating the possibility of transcription errors while providing faster access to the collected data. BIMS comes with training materials and support for individual or small group training and is currently implemented in the Genome Database for Rosaceae, CottonGEN, the Citrus Genome Database, the Pulse Crop Database, and the Genome Database for Vaccinium. Database URLs: (https://www.rosaceae.org/), (https://www.cottongen.org/), (https://www.citrusgenomedb.org/), (https://www.pulsedb.org/) and (https://www.vaccinium.org/).


Immobilized enzyme/microorganism complexes for degradation of microplastics: A review of recent advances, feasibility and future prospects.
Environmental prevalence of microplastics has prompted the development of novel methods for their removal, one of which involves immobilization of microplastics-degrading enzymes. Various materials including nanomaterials have been studied for this purpose but there is currently a lack of review to present these studies in an organized manner to highlight the advances and feasibility. This article reviewed more than 100 peer-reviewed scholarly papers to elucidate the latest advances in the novel application of immobilized enzyme/microorganism complexes for microplastics degradation, its feasibility and future prospects. This review shows that metal nanoparticle-enzyme complexes improve biodegradation of microplastics in most studies through creating photogenerated radicals to facilitate polymer oxidation, accelerating growth of bacterial consortia for biodegradation, anchoring enzymes and improving their stability, and absorbing water for hydrolysis. In a study, the antimicrobial property of nanoparticles retarded the growth of microorganisms, hence biodegradation. Carbon particle-enzyme complexes enable enzymes to be immobilized on carbon-based support or matrix through covalent bonding, adsorption, entrapment, encapsulation, and a combination of the mechanisms, facilitated by formation of cross-links between enzymes. These complexes were shown to improve microplastics-degrading efficiency and recyclability of enzymes. Other emerging nanoparticles and/or enzymatic technologies are fusion of enzymes with hydrophobins, polymer binding module, peptide and novel nanoparticles. Nonetheless, the enzymes in the complexes present a limiting factor due to limited understanding of the degradation mechanisms. Besides, there is a lack of studies on the degradation of polypropylene and polyvinyl chloride. Genetic bioengineering and metagenomics could provide breakthrough in this area. This review highlights the optimism of using immobilized enzymes/microorganisms to increase the efficiency of microplastics degradation but optimization of enzymatic or microbial activities and synthesis of immobilized enzymes/microorganisms are crucial to overcome the barriers to their wide application.


Is there hope for chronic pain and headache?
Currently the clinical needs for pain and headache management are not met. Despite the numerous and exciting recent advances in understanding the molecular and cellular mechanisms that originate pain, we cannot yet fully explain the mechanism underlying the biology of chronic pain. Pain is a natural mechanism preserving our species survival; however, when the protective quality is lost, physiologic changes to the peripheral and central nervous systems result in the formation of chronic pain states. Once we understand how this chronic pain state is created, either through genetic, environmental, therapeutic, or other triggers we may be able to enhance our species existence, limiting maladaptive pain and suffering. The future therapeutic targets will need to address the genetics, neurophysiologic changes of the neurons and brain as well as help control immune systems including the glia. The key to successful headache and pain therapy is research aimed at prevention and minimizing the plastic changes triggering chronic pain.


Two-mJ level, high-energy all-passive KGW/Tm:YLF Raman laser.
This paper presents an all-passive external cavity KGW Raman laser in the 2-μm spectral range, pumped by a Tm:YLF laser at 1879.5 nm. The Raman laser emits two lines at 2197 nm and 2263 nm achieving maximum energy outputs of 1.86 mJ and 2.08 mJ, and conversion efficiencies of 40% and 45.3%, respectively. To the best of our knowledge, this laser performance is a new record in terms of energy per pulse and conversion efficiency, surpassing the two-mJ level for the first time by stimulated Raman scattering in the 2-μm range in an all-passive configuration.


Novel Application of Hot Melt Extrusion for the Manufacturing of Vaginal Films Containing Microbicide Candidate Dapivirine.
Polymeric films are safe and effective and can be used for vaginal administration of microbicide drug candidates. Dapivirine (DPV), an investigational and clinically advanced antiretroviral drug, was selected as a model compound for this study. We have previously developed and clinically tested a quick-dissolving DPV film using solvent cast (SC) manufacturing technique. As an alternative to current pharmaceutical film manufacturing techniques, we investigated hot melt extrusion (HME) process in this study because it has several benefits, including its capacity as a continuous manufacturing process, lack of solvents, smaller footprint, and ease of scalability. The goal of this work was to evaluate the feasibility of using HME for DPV vaginal film manufacturing and to develop a robust manufacturing process using HME by evaluating the effect of process parameters on film quality and performance. DPV was successfully incorporated into a vaginal film using HME and maintained acceptable characteristics. Three process parameters (zone temperature, screw speed, and feed rate) had an impact on film quality and performance. Of these, the zone temperature was found to most significantly affect weight, thickness, puncture strength, and dissolution of films. Additionally, film manufacturing using HME was highly reproducible. Finally, the DPV HME film was comparable to films manufactured using SC in terms of physicochemical, biological, and safety characteristics including in vitro drug release, mechanical strength, tissue permeability, compatibility with commensal vaginal Lactobacilli, and in vitro bioactivity. These results demonstrate that HME is an effective, robust, and viable manufacturing method to produce vaginal films.


[Clinical Significance of Neutrophil-to-Lymphocyte Ratio in Patients with Prostate Cancer].
Neutrophil-to-lymphocyte ratio (NLR), a simple marker of systemic inflammatory response, has clinical and prognostic value in patients with cancer. We evaluated the role of NLR prior to biopsy in patients suspected of having cancer prostate cancer. In this retrospective study, we reviewed the records of 204 patients who underwent prostate biopsy in Mizushima Kyodo Hospital between August 2002 and June 2015 and collected the following data : age, C-reactive protein (CRP), prostate volume (PV), clinical cancer staging, prostate-specific antigen (PSA) prior to biopsy , Gleason score (GS), NLR. NLR was calculated by prebiopsy neutrophil and lymphocyte counts. We divided the 83 of 204 patients found to have prostate cancer (PCa) into two or three groups by the results of biopsy, PSA, clinical cancer staging, GS, and D'Amico risk classification. Mann-Whitney U-test and Kruskal-Wallis H-test were used to compare NLR in each group. Significant differences were recognized in NLR between the groups : PSA≧10 ng/ml VS < 10 ng/ml in all patients and in patients with cancer, cT2b≧ VS cT2c≦, GS 6 VS GS 7 VS GS 8≦ in patients with cancer and low risk VS intermediate risk VS high risk in patients with cancer without metastasis. Also we investigated the correlated factor with NLR in patients with cancer without metastasis. On multiple regression analysis including age, CRP, PV, PSA, clinical tumor stage and GS, PSA and GS had a significant association with NLR.


[Architectonics of the vascular bed of the fetal portion of the mature human placenta (based on data of scanning electron microscopy)].
Peculiarities of the microangioarchitectonics in the trunks, intermediate and terminal villi of the placenta have been described at a noncomplicated pregnancy. Signs of neovasculogenesis are demonstrated in the microcirculatory bed of the terminal villi. Possible connection between reduction of the paravasal capillary network, as the intermediate villi become mature, and neovasculogenesis is discussed.


Immunization of children with sickle cell disease with Haemophilus influenzae type b polysaccharide vaccine.
There are limited data concerning safety and immunogenicity of Haemophilus influenzae type b polysaccharide vaccine in children with sickle cell disease. Ninety-eight patients with sickle cell disease (65 with SS phenotype, 23 with SC phenotype, and 10 with S beta-thalassemia) 1.5 to 20 years of age were given 25 micrograms of vaccine subcutaneously. The vaccine was well tolerated; mild side effects were observed in 6 of 98 (6.1%) children. In addition, one patient with a recent vasoocclusive crisis was hospitalized because of fever and vasoocclusive crisis 8 hours after vaccination. Prevaccination anticapsular antibody concentrations (by radioimmunoassay) were less than 0.15 microgram/mL in 7 of 11 children 18 to 24 months of age (geometric mean 0.17 microgram/mL), in 10 of 25 children 2 to 5 years of age (geometric mean 0.36 microgram/mL), and in 3 of 50 patients 6 to 20 years of age (geometric mean 1.03 microgram/mL). Inadequate response (1- to 2-month postvaccination antibody level less than 1 microgram/mL) was found in 3 of 5 children 18 to 24 months of age (geometric mean 1.74 microgram/mL), in 8 of 21 children 2 to 5 years of age (geometric mean 2.20 micrograms/mL), and in 2 of 49 patients 6 to 20 years of age (geometric mean 18.03 micrograms/mL). Six months after vaccination, greater than 1 microgram/mL of antibody was present in the 2 children 6 to 20 years of age with inadequate response but not in the 7 children 2 to 5 years of age with inadequate response.(ABSTRACT TRUNCATED AT 250 WORDS)