PIV measurements of the flow field just downstream of an oscillating collapsible tube.
We probed the time-varying flow field immediately downstream of a flexible tube conveying an aqueous flow, during flow-induced oscillation of small amplitude, at time-averaged Reynolds numbers (Re) in the range 300-550. Velocity vector components in the plane of a laser sheet were measured by high-speed ("time-resolved") particle image velocimetry. The sheet was aligned alternately with both the major axis and the minor axis of the collapsing tube by rotating the pressure chamber in which the tube was mounted. The Womersley number of the oscillations was approximately 10. In the major-axis plane the flow fields were characterized by two jets that varied in lateral spacing. The rapid deceleration of flow at maximal collapse caused the jets momentarily to merge about one diameter into the downstream pipe, and strengthened and enlarged the existing retrograde flow lateral to each jet. Collapse also spread the jets maximally, allowing retrograde flow between them during the ascent from its minimum of the pressure at the end of the flexible tube. The minor-axis flow fields showed that the between-jet retrograde flow at this time extended all the way across the pipe. Whereas the retrograde flow lateral to the jets terminated within three diameters of the tube end at Re=335 at all times, it extended beyond three diameters at Re=525 for some 25% of the cycle including the time of maximal flow deceleration. Off-axis sheet positioning revealed the lateral jets to be crescent shaped. When the pressure outside the tube was increased, flattening the tube more, the jets retained a more consistent lateral position. These results illuminate the flows created by collapsible-tube oscillation in a laminar regime accessible to numerical modeling.


Procaspase-3 Overexpression in Cancer: A Paradoxical Observation with Therapeutic Potential.
Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.


A 'molecular guillotine' reveals the interphase function of Kinesin-5.
Motor proteins are important for transport and force generation in a variety of cellular processes and in morphogenesis. Here, we describe a general strategy for conditional motor mutants by inserting a protease cleavage site into the 'neck' between the head domain and the stalk of the motor protein, making the protein susceptible to proteolytic cleavage at the neck by the corresponding protease. To demonstrate the feasibility of this approach, we inserted the cleavage site of the tobacco etch virus (TEV) protease into the neck of the tetrameric motor Kinesin-5. Application of TEV protease led to a specific depletion and functional loss of Kinesin-5 in Drosophila embryos. With our approach, we revealed that Kinesin-5 stabilizes the microtubule network during interphase in syncytial embryos. The 'molecular guillotine' can potentially be applied to many motor proteins because Kinesins and myosins have conserved structures with accessible neck regions.This article has an associated First Person interview with the first author of the paper.


Little reason to call them small noncoding RNAs.
Hundreds of different species of small RNAs can populate a bacterial cell. This small transcriptome contains important information for the adaptation of cellular physiology to environmental changes. Underlying cellular networks involving small RNAs are RNA-RNA and RNA-protein interactions, which are often intertwined. In addition, small RNAs can function as mRNAs. In general, small RNAs are referred to as noncoding because very few are known to contain translated open reading frames. In this article, we intend to highlight that the number of small RNAs that fall within the set of translated RNAs is bound to increase. In addition, we aim to emphasize that the dynamics of the small transcriptome involve different functional codes, not just the genetic code. Therefore, since the role of small RNAs is always code-driven, we believe that there is little reason to continue calling them small noncoding RNAs.


Size-exclusion chromatography-based extracellular vesicle size subtyping and multiplex membrane protein profiling for differentiating gastrointestinal cancer prognosis.
Extracellular vesicles (EVs), as a type of subcellular structure, have been extensively researched for their potential for developing advanced diagnostic technologies for various diseases. However, the biomolecular and biophysical heterogeneity of EVs has restricted their application in clinical settings. In this article, we developed a size-exclusion chromatography-based technique for simultaneous EV size subtyping and protein profiling. By eluting fluorescent aptamer-treated patient plasma through a size-exclusion column, the mixture can be classified into 50 nm aptamer-bound EVs, 100 nm aptamer-bound EVs and free-floating aptamers, which could further enable multiplex EV membrane protein profiling by analyzing the fluorescence intensities of EV-bound aptamers. Using this technique, we successfully identified EV size subtypes for differentiating gastrointestinal cancer prognosis states. Overall, we developed a rapid, user-friendly and low-cost EV size subtyping and protein profiling technique, which holds great potential for identifying crucial EV size subtypes for disease diagnosis in the clinic.


Hearing Protection Outcomes of Analog Electrode Arrays Coated with Different Drug-Eluting Polymer Films Implanted into Guinea Pig Cochleae.
To investigate the hearing protection outcomes of different drug-eluting analog electrode arrays implanted into guinea pig cochleae. Sixty guinea pigs were randomly divided into a negative control group and five experimental groups implanted separately with blank (drug carrier), dexamethasone (DXM), aracytine (Ara-C), Ara-C+DXM, and nicotinamide adenine dinucleotide (NAD+) eluting analog electrode arrays. Micro CT was used to supervise the surgical procedure. Auditory brainstem response (ABR) thresholds of the guinea pigs were measured and analyzed. Compared with the negative control, all other groups showed a significant increase in ABR threshold (p<0.001) after surgery. Among them, there was no obvious difference between the blank (0 vs 90 days: 59.70±10.57 vs 64.60±9.47 dB SPL) and the NAD+ group (0 vs 90 days: 59.90±9.87 vs 64.70±8.65 dB SPL). On the other hand, the ABR thresholds in the DXM (0 days: 58.10±10.73 dB SPL; 90 days: 51.70±9.07 dB SPL) and the Ara-C group (0 days: 59.00±10.05 dB SPL; 90 days: 51.60±8.48 dB SPL) decreased significantly compared with the former two groups (p<0.001). However, the Ara-C+DXM group showed no further benefit (p>0.05). In addition, a significantly higher survival rate of spiral ganglion neurons in cochleae was observed in the Ara-C and/or DXM groups.


Analysis of novel RUNX2 mutations in Chinese patients with cleidocranial dysplasia.
Cleidocranial dysplasia (CCD) is an autosomal dominant inheritable skeletal disorder characterized by cranial dysplasia, clavicle hypoplasia and dental abnormalities. This disease is mainly caused by heterozygous mutations in RUNX2, a gene that encodes an osteoblast-specific transcription factor. In the present study, mutational analyses of RUNX2 gene were performed on four unrelated Chinese patients with CCD. Four different RUNX2 mutations were detected in these patients, including one nonsense mutation (c.199C>T p.Q67X) and three missense mutations (c.338T>G p.L113R, c.557G>C p.R186T and c.673C>T p.R225W). Among them, two mutations (c.199C>T p.Q67X and c.557G>C p.R186T) were novel and the other two had been reported in previous literatures. Except for Q67X mutation located in the Q/A domain, other three mutations were clustered within the highly conserved Runt domain. Green fluorescent protein (GFP) and RUNX2 fusion protein analyses in vitro showed that nuclear accumulation of RUNX2 protein was disturbed by Q67X mutation, while the other two mutations (c.338T>G p.L113R and c.557G>C p.R186T) had no effects on the subcellular distribution of RUNX2. Luciferase reporter assay demonstrated that all the three novel RUNX2 mutations significantly reduced the transactivation activity of RUNX2 on osteocalcin promoter. Our findings enrich the evidence of molecular genetics that the mutations of RUNX2 gene are responsible for CCD.


Beyond two worlds: Identity narratives and the aspirational futures of Alaska Native youth.
Indigenous communities across the Alaskan Arctic have experienced profound revisions of livelihood, culture, and autonomy over the past century of colonization, creating radical discontinuities between the lives of young people and those of their parents and Elders. The disrupted processes of identity development, access to livelihoods, and cross-generational mentorship associated with colonialism have created complex challenges for youth as they envision and enact viable paths forward in the context of a rapidly changing Arctic home. In this study, we consider the meanings associated with different constructions of culture and selfhood, and the ways in which these identity narratives position Inupiaq Alaskan Native youth in relation to their personal and collective futures. Through an intergenerational and participatory inquiry process, this study explores how representations of shared heritage, present-day struggles, resilience, and hope can expand possibilities for youth and thus impact individual and community health.


The potential for misuse and abuse of medications in ADHD: a review.
This article reviews the literature concerning attention-deficit/hyperactivity disorder (ADHD) medication misuse, abuse, dependence, diversion, and malingering. The review covers nonmedical use (NMU) of both stimulant (methylphenidate and amphetamine) and nonstimulant (α-adrenergic agonists and atomoxetine) prescription medications, and provides a discussion on the relevance for ADHD treatment today. The neural basis for ADHD medication mechanisms of action (increased norepinephrine and dopamine signaling) and their neurobiochemical relationship to the abuse potential is explored. Regionally-specific, stimulant-induced elevations in brain dopamine appear to be integral to both efficacy in ADHD and potential for abuse. In addition to the prevalence of misuse and diversion, additional topics discussed include the potential safety concerns associated with NMU of prescription ADHD medications and the cost to payers of prescription drug diversion (eg, increased emergency department visits associated with misuse). The evidence describing the difficulty in detecting malingering for the purpose of illicit access to ADHD medications for subsequent misuse or diversion is also summarized. Moreover, the effect of ADHD medications in patients with comorbid substance use disorder and the controversial potential linkage of stimulant prescription use with subsequent substance use disorder are explored. Overall, the data suggest that ADHD medication misuse and diversion are common health care problems for stimulant medications, with the prevalence believed to be approximately 5% to 10% of high school students and 5% to 35% of college students, depending on the study. Stimulant effectiveness and speed of action are deemed desirable to enhance attention and focus performance for activities like studying, but stimulants are also misused recreationally. Conversely, the data suggest a lack of abuse potential and lack of actual medication misuse for the nonstimulant medications. Although they can be efficacious for the treatment of ADHD, the nonstimulants lack a mechanism of action linked to the abuse potential and they lack the desirable effects (speed of action, stimulant feel) that make stimulants susceptible to NMU. In light of these findings, the data suggest a need for close screening and therapeutic monitoring of ADHD medication use. In addition, nonstimulants might be an appropriate alternative for patients with concern about abuse and physicians concerned with general misuse and diversion.


Model-based exploration of the variability in lake trout (Salvelinus namaycush) bioaccumulation factors: The influence of physiology and trophic relationships.
Because dietary consumption of fish is often a major vector of human exposure to persistent organic pollutants (POPs), much effort is directed toward a quantitative understanding of fish bioaccumulation using mechanistic models. However, many such models fail to explicitly consider how uptake and loss rate constants relate to fish physiology. We calculated the bioaccumulation factors (BAFs) of hypothetical POPs, with octanol-water partition coefficients ranging from 104.5 to 108.5 , in lake trout (Salvelinus namaycush) with a food-web bioaccumulation model that uses bioenergetics to ensure that physiological parameters applied to a species are internally consistent. We modeled fish in 6 Canadian lakes (Great Slave Lake, Lake Ontario, Source Lake, Happy Isle Lake, Lake Opeongo, and Lake Memphremagog) to identify the factors that cause the BAFs of differently sized lake trout to vary between and within lakes. When comparing differently sized lake trout within a lake, larger fish tend to have the highest BAF because they allocate less energy toward growth than smaller fish and have higher activity levels. When comparing fish from different lakes, the model finds that diet composition and prey energy density become important in determining the BAF, in addition to activity and the amount of total energy allocated to growth. Environ Toxicol Chem 2019;38:831-840. © 2019 SETAC.


Alcoholic denial: a biopsychological interpretation.
A theory of the origins and mechanisms of denial, which is frequently characteristic of alcoholics, is proposed on the basis of a biopsychological rather than a psychodynamic model of emotion. The biopsychological approach views denial as a consequence of a developmental defect in the apperception of interoceptive stimuli and in the appraisal of the significance of environmental events. Three hypotheses must be substantiated in order to support this theory: (1) alcoholics were physiologically unstable in arousal regulation; (2) alcoholics cannot cognitively discriminate interoceptive cues and physiological states; and (3) alcoholics cognitively underestimate emotion-laden events in their lives. Research which demonstrates the validity of these hypotheses is reviewed and implications for future research and treatment strategies are discussed.


Synthetic cannabinoids and acute kidney injury.
Synthetic cannabinoids (SCB) are a family of chemicals that bind to cannabinoid receptors and cause psychoactive effects. Over the past few years, they have been increasingly used for recreational purposes, especially by young adults, and have been reported to have many adverse effects. Acute kidney injury (AKI) has been recently reported; the pathophysiology of SCB-induced AKI is unknown. We report three cases of AKI in the setting of SCB use. The peak serum creatinine levels ranged from 3.0 to 5.7 mg/dL; one patient required hemodialysis. SCB can induce AKI.


An approach to the question of relevance of medical physiology courses.
One of the problems of designing basic science courses is to define objectives relevant to the future needs of the graduates. A simple approach is described whereby a series of clinical problems were identified by physiologists and practising physicians. Priority areas were then identified to provide a basis for defining objectives for the medical physiology courses and for the selection of materials and methods. It is argued that the question of relevance, emotional involvement and effective facilitation of learning will be served by the approach described. Finally, the usefulness of this exercise to the selection and orientation of appropriate evaluation tools is discussed.


[Applications of 1H nuclear magnetic resonance spectroscopy and nuclear magnetic resonance-based metabonomics in tumour studies].
1H nuclear magnetic resonance (1H NMR) spectroscopy has found widespread applications in tumour studies. Several complementary NMR techniques have provided valuable information concerning tumours, including in vivo localized 1H NMR spectroscopy, ex vivo high-resolution 1H NMR spectroscopy of extracts of intact tissue biopsy samples, high-resolution magic angle spinning 1H NMR spectroscopy of intact tissue biopsy samples, and in vitro high-resolution 1H NMR spectroscopy of body fluids. On the basis of the combination of NMR measurements with multivariate data analysis, 1H NMR-based metabonomics has become a promisingly novel approach in the studies of tumour early diagnosis, processes and prognosis estimate.


Photochemotherapy (PUVA) in the tumour stage of mycosis fungoides: a report from the Scandinavian Mycosis Fungoides Study Group.
Twenty-five patients with mycosis fungoides in the tumour stage were treated with oral 8-Methoxypsoralen followed by UVA (PUVA), sometimes in combination with topical or systemic chemotherapy. In 17 patients the disease was confined to the skin, in 7 lymph nodes also were involved, and one had visceral involvement. Complete and partial remission was achieved in 14/17 patients with the disease limited to the skin (82%), and partial remission of the skin lesions in 5/8 patients with extracutaneous location.


The Seroprevalence of Some Pathogen Specific IgM in Children with Acute Respiratory Tract Infections in Guangzhou Region, 2011 - 2012.
Acute respiratory tract infections (ARTIs) are the leading cause of morbidity and death in children < 5 years worldwide. The aim of this study is to analyze the seroprevalence of nine pathogen specific IgMs in children with ARTIs with respect to gender, age, and seasonality in the Guangzhou region. Serum samples were collected from 20160 children with ARTIs admitted to the Guangzhou Women and Children's Medical Center between 2011 and 2012. Serum-specific IgM antibodies to nine respiratory pathogens, Mycoplasma pneumonia (MP), Legionella pneumophila (LP), Coxiella burnetii (C. burnetii), Chlamydophila pneumonia (CP), adenovirus (ADV), respiratory syncytial virus (RSV), type A and type B influenza virus (IVA and IVB), and parainfluenza virus (PIV), were detected using immunofluorescence assay. The male-to-female ratio of all patients was 1.9:1. The median age was 3 years and 8 months with a significant difference in seropositivity to respiratory tract pathogens between children from different age groups. Seropositivity was detected in 43.53% of the children with the top three pathogens being MP (33.15%), RSV (10.27%), and ADV (6.63%), followed by IVB (2.63%), LP (2.25%), IVA (1.59%), PIV (1.57%), CP (0.27%), and C. burnetii (0.13%). The prevalence of single, double, and triple seropositivity was 70.20% (6160/8775), 25.22% (2213/8775), and 4.57% (401/8775), respectively. The total IgM seropositivity for any kind of pathogen in the nine kinds of pathogens peaked in winter (46.53%), while the nadir was observed in summer (41.97%). The top three seroprevalence of nine kinds of pathogen specific IgM was MP, followed by RSV and ADV. The epidemic pathogen specific IgM had a season-specific seropositivity distribution. Seroprevalence of the pathogen should be a focus of attention.


[Response of dental pulp to self-etching adhesive systems used in indirect capping. A literature review].
To review the literature on dental pulp responses to self-etching adhesive systems used in indirect capping. Many studies in vitro and in vivo focused on biocompatibility of the self-etching adhesive system used in deep defects. Clinical and radiographic findings from animal and human studies are compared and discussed. Self-etching adhesive systems may be useful when applied to dentin. The results in animal studies cannot be extrapolated directly to humans. Many studies in vitro have shown that components of self-etching adhesive systems exhibit cytotoxic effects in contact with cell cultures. The reaction of dental pulp to self-etching bonding agents depends on the depth of defect, type of agent, and method of application.


Synthesis of Polycyclic Tetrahydroisoquinolines and Tetrahydrobenzo[d]azepines from Polymer-Supported Allylglycine.
Herein, we report a multistep synthesis of polycyclic tetrahydroisoquinolines and tetrahydrobenzo[d]azepines starting from Wang resin-immobilized allylglycine. After sulfonylation with 2/4-nitrobenzenesulfonyl chlorides, Mitsunobu alkylation with various phenylalkynols yielded the corresponding (phenylprop-2-yn-1-yl)-sulfonamides. "Interior" ring-closure enyne metathesis (RCEM) using a Grubbs catalyst second generation (Ru2) yielded functionalized tetrahydroisoquinoline/tetrahydrobenzo[d]azepine intermediates. "East-side" [4 + 2] cycloaddition with representative dienophiles was followed by the "west-side" construction of different heterocycles using various electrophiles to finally furnish a set of novel molecular frameworks bearing fused [6 + 6] or [6 + 7] rings. The developed methodology enables the facile parallel synthesis of novel, pharmacologically promising compounds derived from privileged scaffolds.


The integration of occupational- and household-based chronic stress among South African women employed as public hospital nurses.
Nurses are a critical part of healthcare delivery systems, especially in under-resourced environments. Compared to other female-dominated professions in South Africa, nurses are securely employed and relatively well-paid. However, they are often drawn from complex, poor communities where they are responsible for many dependents and must accommodate community and family expectations of financial, health, and other forms of support. The aim of the study was to explore public hospital-employed, black women nurses' lived experiences to better understand their stressors and consider interventions that may reduce psychological distress. In 2015, we conducted semi-structured life history interviews with 71 nurses in Johannesburg. Using grounded theory and social network mapping, we trace complex, interrelated stressors and networks of familial dependency. Every participant experienced high levels of stress. Nurses described daily lives of chronic distress, with extreme pressures on their incomes, time, and resources. Much of the pressure on nurses comes from familial and partner dependency, both in absolute number of dependents and intensity, and related financial obligations and debt. Dependency is a function of social and cultural norms which assign women primary responsibility for unpaid work, yet nurses characterized their efforts as unsustainable and anxiety-inducing; their pay and paid work schedules made meeting that responsibility virtually impossible. The structure of the nursing occupation contributes to stress outside the workplace, while the structure of nurses' households contributes to stress and emotional exhaustion. The integrated nature of their chronic stress suggests that occupationally-oriented interventions are unlikely to adequately address it. To fully alleviate chronic stress, the gender norms that place responsibility for unpaid work on nurses with already full-time employment need to shift. A better understanding of the extensive networks dependent on nurses should inform interventions designed to improve their wellbeing. Assistance addressing childcare, mental health, and financial planning may be especially useful.


Subjective fatigue and stress hormone levels in urine according to duration of shiftwork.
To determine the associations between urinary catecholamines and cortisol and subjective complaints of fatigue in shiftworkers, we conducted a field survey of 113 male shiftworkers at a manufacturing company in South Korea from late October to late November in 1999. The shiftwork system in the company was the backward rapidly rotating 4-crew 3-shift, with the morning shift starting at 7:30 AM. Using a self-report questionnaire, we assayed demographic characteristics, past medical history and working hours, as well as subjective complaints of fatigue in 3 categories of questionnaire. We found that, among workers with less than 5 yr of shiftwork experience, the concentrations of norepinephrine, epinephrine (Epi), and dopamine during the afternoon shift were positively correlated with Set II (difficulties in concentration) and Set III (projection of disintegration) of subjective fatigue symptoms. In addition, Epi concentrations were positively correlated with Set I (drowsiness and dullness), II, and III of subjective fatigue symptoms during the night shift. However, among workers with 5 or more years of shiftwork experience, there was no significant positive correlation between urinary catecholamine and subjective fatigue symptoms. In the long term shiftwork experience group, only the complaints scores of Set II fatigue symptoms (difficulties in concentration) during the morning shift were significantly higher than those of the short-term shiftwork experience group within the same shift.


Efficacy, safety, predictability, aberrations and corneal biomechnical parameters after SMILE and FLEx: Meta-analysis.
To identify possible differences of efficacy, safety, predictability, higher-order aberrations and corneal biomechnical parameters after small-incision lenticule extraction (SMILE) and femtosecond lenticule extraction (FLEx). A systematic literature retrieval was conducted in Medline, Embase and the Cochrane Library, up to October, 2015. The included studies were subject to a Meta-analysis. Comparison between SMILE and FLEx was measured as pooled odds ratio (OR) or weighted mean differences (WMD). Of 95% confidence intervals (CI) were used to analyze data. A total of seven studies were included. Firstly, there were no differences in uncorrected distance visual acuity (UDVA) 20/20 or better (OR, 1.37; 95% CI, 0.69 to 2.69; P=0.37) and logMAR UDVA (WMD, -0.02; 95% CI, -0.05 to 0.01; P=0.17) after SMILE versus FLEx. We found no differences in corrected distance visual acuity (CDVA) unchanged (OR, 0.98; 95% CI, 0.46 to 2.11; P=0.97) and logMAR CDVA (WMD, -0.00; 95% CI, -0.01 to 0.01; P=0.90) either. Secondly, we found no differences in refraction within ±1.00 D (OR, 0.98; 95% CI, 0.13 to 7.28; P=0.99) and ±0.50 D (OR, 1.62; 95% CI, 0.62 to 4.28; P=0.33) of target postoperatively. Thirdly, for higher-order aberrations, we found no differences in the total higher-order aberrations (WMD, -0.04; 95% CI, -0.09 to 0.01; P=0.14), coma (WMD, -0.04; 95% CI, -0.09 to 0.01; P=0.11), spherical (WMD, 0.01; 95% CI, -0.02 to 0.03; P=0.60) and trefoil (WMD, -0.00; 95% CI, -0.04 to 0.03; P=0.76). Furthermore, for corneal biomechanical parameters, we also found no differences (WMD, 0.08; 95% CI, -0.17 to 0.33; P=0.54) after SMILE versus FLEx. There are no statistically differences in efficacy, safety, predictability, higher-order aberrations and corneal biomechnical parameters postoperative between SMILE and FLEx.


The Surface of Protein λ6-85 Can Act as a Template for Recurring Poly(ethylene glycol) Structure.
PEGylated proteins play an increasingly important role in pharmaceutical drug delivery. We recently showed that short poly(ethylene glycol) (PEG) chains can affect protein structure, even when they are not making extensive contact with the protein surface. In contrast, PEG is generally thought to form a relatively unstructured coil, and its compactness depends on solvent conditions. Here we test whether a host protein could allow PEG to form recurrent structural motifs while the PEG chain is in contact with the protein surface. We link a PEG oligomer (n = 45) to one of two nearly opposite locations on the small α-helical protein λ6-85 to investigate this question. We first demonstrate experimentally that in these particular positions, PEG does not significantly affect the thermodynamic stability or folding kinetics of λ6-85. We then use several all-atom molecular dynamics (MD) simulations 1 μs in duration to show how PEG equilibrates between states extending into the solvent and states packed onto the protein surface. The packing reveals recurring structures, including persistent hydrogen bond and hydrophobic contact patterns that appear multiple times. Some interactions of PEG with surface lysines are best described as an "intermittent slithering" motion of the PEG around the side chain, as seen in short MD movies. Thus, PEG achieves a variety of metastable organized structures on the protein surface, somewhere between a random globule and true folding. We also investigated the PEG-protein interaction in the unfolded state of the protein. We find that PEG has a propensity to stabilize certain helices of λ6-85, no matter which of the two positions it was attached to. Thus, sufficiently long PEG chains are organized by the protein surface and in turn interact with certain elements of protein structure more than others, even when PEG is attached to very different sites.


Development of an Immunochromatographic Strip for Rapid Detection of Mink Enteritis Virus.
Although mink enteritis virus (MEV) is an acute, virulent, and highly contagious pathogen in minks, there is currently a lack of a quick diagnostic method. By conjugating colloidal gold nanoparticles with the MEV-specific monoclonal antibody, monoclonal antibody (MAb) 14, we developed a single-step competitive immunochromatographic strip (ICS) assay for simple determination of MEV. The optimal concentrations of the colloidal gold-coupled MAb 14 (coating antibody), the capture protein (MEV VP2 protein), and the goat anti-mouse antibody were 1.0, 0.8, and 1.0 mg/ml, respectively. The limit of detection was approximately 512 hemagglutination units/100 μl of MEV B strain. Other common viruses of mink were tested to evaluate the specificity of the ICS, and the results showed no cross-reactivity for other pathogens. In comparison with the Anigen Rapid canine parvovirus (CPV) Ag Test Kit (BioNote, Korea) in testing 289 samples, the percentage of agreement and relative sensitivity and specificity of the MEV ICS assay were 94.1, 93.2, and 97.1%, respectively. The ICS test was found to be a sufficiently sensitive and specific detection method for the convenient and rapid detection of MEV.


Delayed behavioral effects of postnatal exposure to corticosterone in the zebra finch (Taeniopygia guttata).
Early developmental conditions can significantly influence the growth and survival of many animal species. We studied the consequences of exposure to corticosterone (CORT), a stress hormone, during the nestling stage on two behavioral traits (neophobia, social dominance) measured when the birds had reached independence. Nestling zebra finches (Taeniopygia guttata) were exposed twice daily to exogenous CORT via oral administration for a 12-day period up until fledging. Experimental CORT administration depressed nestling growth rates, confirming results previously obtained in this species. Our data on neophobic behavior revealed a significant interaction between sex and treatment, with CORT-dosed males showing reduced latencies to approach a novel object, while there was little effect of corticosterone treatment on female neophobia. There was no significant effect of age (30 or 50 days), however, there was a non-significant trend towards an interaction between treatment and age, with neophobia increasing with age in the CORT-dosed birds, but decreasing in controls. At 50 days of age previous exposure to corticosterone resulted in reduced success in competitions for a non-food-based resource (a perch) in both sexes. There were no effects of brood size on any behavioral traits measured here, but this may be due to the small range in brood size used. Our results show that elevated levels of stress hormones during postnatal development can have significant effects on important behavioral traits, i.e., neophobia and dominance. Moreover, they confirm the importance of rearing conditions in shaping adult phenotypes.


Scouting out the neighborhood in AIDS-related lymphoma.
In this issue of Blood, Liapis et al investigate the characteristics of the tumor microenvironment as well as the role of viral components in AIDS-related diffuse large B-cell lymphoma (AR-DLBCL) and compare these findings with sporadic cases of DLBCL.


[How to enhance the efficacy of radiotherapy].
Radiation therapy is one of the most effective treatment for cancer patients. Many developments in radiotherapy have resulted from new technologies or have been made empirically by clinicians. Radiobiology, which provides a conceptual basis for radiotherapy, identifying mechanisms and processes that underlie the response of tumors and normal tissues to irradiation, is the best research way to enhance the therapeutic index of radiation therapy. Raising the standards of radiation dose using multiple fractions per day, treating patients with accelerated radiotherapy to reduce the effect of tumor-cell repopulation during treatment, overcoming hypoxic cell radioresistance, using biological response modifiers, combining radiation and chemotherapy are principal ways to enhance radiation results. Some of them are now in the clinical practice, other are still under evaluation.


The locus of fixation and the foveal cone mosaic.
High-resolution retinal imaging with adaptive optics was used to record the position of a light stimulus on the cone mosaic, with an error at least five times smaller than the diameter of the smallest foveal cones. We discuss the factors that limit the accuracy with which absolute retinal position can be determined. In five subjects, the standard deviation of fixation positions measured in discrete trials ranged from 2.1 to 6.3 arcmin, with an average of 3.4 arcmin (about 17 microm), in agreement with previous studies (R. W. Ditchburn, 1973; R. M. Steinman, G. M. Haddad, A. A. Skavenski, & D. Wyman, 1973). The center of fixation, based on the mean retinal position for each of three subjects, was displaced from the location of highest foveal cone density by an average of about 10 arcmin (about 50 microm), indicating that cone density alone does not drive the location on the retina selected for fixation. This method can be used in psychophysical studies or medical applications requiring submicron registration of stimuli with respect to the retina or in delivering light to retinal features as small as single cells.


Sensible drinking.
Although it is rare to find people willing to talk seriously about sensible smoking or sensible heroin-injection, the concept of sensible drinking is now sufficiently well established to merit debate beyond the specialists who have so far been interested in promoting or opposing it. The purpose of this article is to take a fresh look at sensible drinking as a stimulus to encouraging that wider debate.


HIV-1 is spreading out of former high-risk population through heterosexual transmission in Hebei, China.
Multiple specific populations, including MSMs, IDUs, and FPDs, are involved in HIV epidemic in China. In the recent years, HIV transmission due to heterosexual transmission also contributed greatly to HIV epidemic in China. Very few studies have been fulfilled to characterize relationships of HIV-1 strains prevalent in different populations. In this study, the phylogenetic relationships of HIV-1 spreading in different populations were investigated. HIV-1 sero-positive patients infected through different routes were enrolled into the study. Nested RT-PCR was used to amplify HIV gag and pol genes followed by sequencing. Multiple subtypes, including subtype B (52.1%), CRF01_AE (34.4%), CRF07_BC (6.3%), subtype C (4.2%), CRF02_AG (1.0%), CRF08_BC (1.0%) and unique recombination forms (1.0%) were identified. Phylogenetic analysis showed that strains from MSM, IDU, and FPDs grouped into clusters separately. However, strains identified in heterosexual transmitted population intermixed with all of other high risk populations. The genetic data supposed that HIV-1 was spreading out of MSMs, IDUs, and FPDs through heterosexual transmission in Hebei, China. Urgent prevention and behavior intervention in the population will be necessary. Furthermore, the detailed sequence data will help the design of HIV-1 vaccines in China. Sequence Data: All of sequences have been deposited into the GenBank with the accession number: KJ820007-KJ820144.


TLR signaling inhibitor, phenylmethimazole, in combination with tamoxifen inhibits human breast cancer cell viability and migration.
Heightened co-expression and dysregulated signaling associated with Toll-like receptor 3 (TLR3) and Wnt5a is an integral component of solid tumors and hematological malignancies. Our previous findings in pancreatic cancer and melanoma suggest that inhibition of these pathways by a TLR3 signaling inhibitor, phenylmethimazole (C10), results in significantly decreased IL-6 levels, STAT3 phosphorylation, minimal cancer cell migration and reduced cancer cell growth in vitro and in vivo. In this study, we extended our earlier observations by performing studies in human breast cancer cells. We found that human MCF-7 breast cancer cells express high basal levels of TLR3 and Wnt5a RNA. C10 treatment resulted in significantly decreased TLR3 and Wnt5a expression levels. This functionally translated into significantly reduced IL-6 levels and STAT3 phosphorylation in vitro. In addition, the inhibition of this signaling cascade by C10 further resulted in decreased cell viability and migration of MCF-7 cells. Strikingly, the combination of C10 and tamoxifen, the standard of care therapy for breast cancer, further decrease cancer cell growth better than either agent alone. These data support the novel finding that inhibition of TLR3 signaling in combination with tamoxifen, may increase the effectiveness of current treatments of breast cancer.


Idiopathic multicentric osteolysis: report of two new cases and a review of the literature.
Idiopathic multicentric osteolysis is a rare skeletal disorder, usually presenting in early childhood with a clinical picture mimicking juvenile rheumatoid arthritis. Progressive destruction of the carpal and tarsal bones usually occurs and other bones may also be involved. Chronic renal failure is a frequent component of this syndrome. Mental retardation and minor facial abnormalities have been noted in some patients. We report on 2 unrelated, sporadic cases, one with facial anomalies and the other with nephropathy. Our second patient is the first black child to be diagnosed with this disease. The mode of presentation, differential diagnosis, and natural history of this disorder are briefly reviewed.


Invasive keratinizing squamous cell carcinoma of the left external auricular canal and the middle ear - case report.
The rather low incidence of auricular neoplasms irrespective of localization is likely to cause confusion of diagnosis with the more frequent benign ear pathology. Because of this, the elapsed time until confirmation of the diagnosis facilitates the evolution of the disease to the detriment of the patient's health. The diagnosis of an ear neoplasm can hide under the ordinary appearance of external otitis, chronic otorrhea or episodes of various types of ear pain. Evolution of such a malignant pathology is quite rapid and highly aggressive locoregional complications are the subject of discussions regarding the interpretation of the results of paraclinical tests and the medical-surgical treatment approach that must take into account the histological structure, the size of the tumor, and the invasion of neighboring tissue.


Selective activation of the superior frontal gyrus in task-switching: an event-related fNIRS study.
In the task-switching paradigm, reaction time is longer and accuracy is worse in switch trials relative to repetition trials. This so-called switch cost has been ascribed to the engagement of control processes required to alternate between distinct stimulus-response mapping rules. Neuroimaging studies have reported an enhanced activation of the human lateral prefrontal cortex and the superior frontal gyrus during the task-switching paradigm. Whether neural activation in these regions is dissociable and associated with separable cognitive components of task switching has been a matter of recent debate. We used multi-channel near-infrared spectroscopy (fNIRS) to measure brain cortical activity in a task-switching paradigm designed to avoid task differences, order predictability, and frequency effects. The results showed a generalized bilateral activation of the lateral prefrontal cortex and the superior frontal gyrus in both switch trials and repetition trials. To isolate the activity selectively associated with the task-switch, the overall activity recorded during repetition trials was subtracted from the activity recorded during switch trials. Following subtraction, the remaining activity was entirely confined to the left portion of the superior frontal gyrus. The present results suggest that factors associated with load and maintenance of distinct stimulus-response mapping rules in working memory are likely contributors to the activation of the lateral prefrontal cortex, whereas only activity in the left superior frontal gyrus can be linked unequivocally to switching between distinct cognitive tasks.


Epitaxy of Ferroelectric P(VDF-TrFE) Films via Removable PTFE Templates and Its Application in Semiconducting/Ferroelectric Blend Resistive Memory.
Ferroelectric polymer based devices exhibit great potentials in low-cost and flexible electronics. To meet the requirements of both low voltage operation and low energy consumption, thickness of ferroelectric polymer films is usually required to be less than, for example, 100 nm. However, decrease of film thickness is also accompanied by the degradation of both crystallinity and ferroelectricity and also the increase of current leakage, which surely degrades device performance. Here we report one epitaxy method based on removable poly(tetrafluoroethylene) (PTFE) templates for high-quality fabrication of ordered ferroelectric polymer thin films. Experimental results indicate that such epitaxially grown ferroelectric polymer films exhibit well improved crystallinity, reduced current leakage and good resistance to electrical breakdown, implying their applications in high-performance and low voltage operated ferroelectric devices. On the basis of this removable PTFE template method, we fabricated organic semiconducting/ferroelectric blend resistive films which presented record electrical performance with operation voltage as low as 5 V and ON/OFF ratio up to 105.


Segregation of human immunodeficiency virus type 1 subtypes by risk factor in Australia.
The aim of this study was to determine which human immunodeficiency virus type 1 (HIV-1) subtypes were circulating in Australia and to correlate the subtypes with risk factors associated with the acquisition of HIV-1 infection. DNA was extracted from peripheral blood mononuclear cells, and HIV-1 env genes were amplified and subtyped using heteroduplex mobility analysis, with selected samples sequenced and phylogenetic analysis performed. The HIV-1 env subtypes were determined for 141 samples, of which 40 were from female patients and 101 were from male patients; 13 samples were from children. Forty-seven patients were infected by homosexual or bisexual contact, 46 were infected through heterosexual contact, 21 were infected from injecting drug use (IDU), 13 were infected by vertical transmission, 8 were infected from nosocomial exposure, and 6 were infected by other modes of transmission, including exposure to blood products, ritualistic practices, and two cases of intrafamilial transmission. Five subtypes were detected; B (n = 104), A (n = 5), C (n = 17), E (CRF01_AE; n = 13), and G (n = 2). Subtype B predominated in HIV-1 acquired homosexually (94% of cases) and by IDU (100%), whereas non-subtype B infections were mostly seen in heterosexually (57%) or vertically (22%) acquired HIV-1 infections and were usually imported from Africa and Asia. Subtype B strains of group M viruses predominate in Australia in HIV-1 transmitted by homosexual or bisexual contact and IDU. However, non-B subtypes have been introduced, mostly acquired via heterosexual contact.


Promoting protective factors for young adolescents: ABCD Parenting Young Adolescents Program randomized controlled trial.
This study examined the efficacy of a program for parents of young adolescents combining behavioral family intervention with acceptance-based strategies. 180 parents were randomly allocated to a 6-session group ABCD Parenting Young Adolescent Program or wait-list condition. Completer analysis indicated parents in the intervention reported significantly higher adolescent prosocial behaviors (p = 0.020), lower conduct problems (p = 0.048) and total difficulties (p = 0.041). These parents also reported lower stress associated with adolescent moodiness (p = 0.032), parent life-restriction (p < 0.001), adult-relations (p < 0.001), social isolation (p = 0.012), incompetence/guilt (p < 0.001), lower stress in the parenting domain (p < 0.001) and lower overall stress (p = 0.003) relative to the control condition following the intervention period. No other statistically significant differences were evident (p < 0.05). Results of intention-to-treat analyses were similar. Greater reliable clinically significant change was also achieved for the intervention condition. Participants reported high satisfaction with all elements of the ABCD program. Results suggest the program may assist parents of young adolescents to promote or maintain protective factors in their families. Australian and New Zealand Clinical Trials Registry: ANZCTRN12609000194268.


Controllable dark-hollow beams and their propagation characteristics.
A new mathematical model called "controllable dark-hollow beams" is introduced to describe hollow beams. The central dark size of this beam can be controlled easily by the beam order N and parameter epsilon. An analytical formula is derived for the propagation of a controllable dark-hollow beam through a paraxial optical system, and some numerical calculations are carried out. Some important propagation characteristics of this beam, such as the beam propagation factor and the kurtosis parameter, are studied in detail, and their variation rules versus the beam order N and parameter epsilon are presented and plotted.


Occlusion revisited.
The evaluation of occlusion is of utmost importance, when planning for dental and orthodontic treatment. The occlusal characteristics of normal occlusion change according to the dentoalveolar maturation stages. In primary dentition, flush terminal plane relationship of the second primary molars is desired for a normal molar relationship. In the early mixed dentition stage, cusp to cusp molar relationship is the normal occlusal feature, when posterior primary teeth are in place and leeway space is preserved.


Facets of the geography of population in the Midwest.
"This paper explores four selected facets of the geography of population in the [U.S.] Midwest that are related to the movement of people: (1) the spread of occupance across the land; (2) the growth of the population of counties once they had been occupied; (3) the distribution of the foreign-born population; and (4) the distribution of retired people who have migrated after they have retired."


Kinetic Model for Two-Step Nucleation of Peptide Assembly.
Intermediate dynamic assemblies are increasingly seen as necessary for the initial desolvation and organization of biomaterials to achieve their final crystalline order. Here we present a general peptide assembly model for two-step nucleation. The model predicts the phase transitions and equilibria between different phases by employing a combination of the Flory-Huggins parameter, the particle growth constant, and the binding energy to assemblies. Monte Carlo simulations are used to demonstrate how the system evolves from pure solution phases to the final thermodynamic assembly phase via an intermediate metastable particle phase. The final state of the system is determined by the solubility of the particle and assembly phases, where the phase with the lower solubility accumulates. A rare three-phase equilibrium exists when the solubilities of the particles and assemblies are similar. Experimental support for this model is achieved with assembly of the amyloid peptide Ac-KLVFFAE-NH2 (Aβ(16-22)) in mixed acetonitrile/water systems. Increasing the acetonitrile concentration decreases the number of particles, increases the particle size, and accelerates the assembly rate, all consistent with acetonitrile increasing the Aβ(16-22) peptide's solubility of particles but with little influence on the stability of the assemblies. Taken together, our model captures the transition from the metastable particle phase to the higher order peptide assembly through two-step nucleation.


Psoriasis strikes back! Epicardial adipose tissue: another contributor to the higher cardiovascular risk in psoriasis.
For many years psoriasis was considered an inflammatory condition restricted to the skin. However, nowadays it is considered an immune-mediated, systemic inflammatory condition associated with numerous medical comorbidities, particularly cardiometabolic diseases, and overall cardiovascular mortality. Several studies have suggested that psoriasis may be an independent risk factor for atherosclerosis, indicating that psoriasis itself poses an intrinsic risk for cardiovascular disease, probably due to the disease's inflammatory burden. However, other causes beyond systemic inflammation and traditional cardiovascular risk factors may be implicated in cardiovascular disease in psoriasis. Recently, epicardial adipose tissue, an emerging cardiovascular risk factor, has been shown to be increased in psoriasis patients and to be associated with subclinical atherosclerosis, providing another possible link between psoriasis and atherosclerosis. The reason for the increase in epicardial adipose tissue in patients with psoriasis is unknown, but it is probably multifactorial, with genetic, immune-mediated and behavioral factors having a role. Thus, along with the increased prevalence of cardiometabolic risk factors and systemic inflammation in psoriasis, epicardial adipose tissue is probably another important contributor to the higher cardiovascular risk observed in psoriasis.


Manipulating Peierls Distortion in van der Waals NbOX2 Maximizes Second-Harmonic Generation.
Two-dimensional (2D) van der Waals (vdW) materials, featuring relaxed phase-matching conditions and highly tunable optical nonlinearity, endow them with potential applications in nanoscale nonlinear optical (NLO) devices. Despite significant progress, fundamental questions in 2D NLO materials remain, such as how structural distortion affects second-order NLO properties, which call for advanced regulation and in situ diagnostic tools. Here, by applying pressure to continuously tune the displacement of Nb atoms in 2D vdW NbOI2, we effectively modulate the polarization and achieve a 3-fold boost of the second-harmonic generation (SHG) at 2.5 GPa. By introducing a Peierls distortion parameter, λ, we establish a quantitative relationship between λ and SHG intensity. Importantly, we further demonstrate that the SHG enhancement can be achieved under ambient conditions by anionic substitution to tune the distortion in NbO(I1-xBrx)2 (x = 0-1) compounds, where the chemical tailoring simulates the pressure effects on the structural optimization. Consequently, NbO(I0.60Br0.40)2 with λ = 0.17 exhibits a giant SHG of over 2 orders of magnitude higher than that in monolayer WSe2, reaching the record-high value among reported 2D vdW NLO materials. This work unambiguously demonstrates the correlation between Peierls distortion and SHG property and, more broadly, opens new paths for the development of advanced NLO materials by manipulating the structure distortions.


The Link between Hypersensitivity Syndrome Reaction Development and Human Herpes Virus-6 Reactivation.
Background. There are challenges in the clinical diagnosis of drug-induced injury and in obtaining information on the reactivation of human herpes viruses (HHV) during idiosyncratic adverse drug reactions. Objectives. (i) To develop a unified list of drugs incriminated in drug-induced hepatotoxicity and severe cutaneous reactions, in which drug hypersensitivity leads to HHV-6 reactivation and further complication of therapy and recovery and (ii) to supplement the already available data on reporting frequencies of liver- or skin-induced cases with knowledge of individual case reports, including HHV-6 reactivation and briefly introducing chromosomally integrated HHV-6. Data Sources and Extraction. Drugs identified as causes of (i) idiosyncratic reactions, (ii) drug-induced hypersensitivity, drug-induced hepatotoxicity, acute liver failure, and Stevens-Johnson syndrome, and (iii) human herpes virus reactivation in PubMed since 1997 have been collected and discussed. Results. Data presented in this paper show that HHV-6 reactivation is associated with more severe organ involvement and a prolonged course of disease. Conclusion. This analysis of HHV-6 reactivation associated with drug-induced severe cutaneous reactions and hepatotoxicity will aid in causality assessment and clinical diagnosis of possible life-threatening events and will provide a basis for further patient characterization and therapy.


Purification, characterization, and cDNA cloning of a novel alpha-galactosidase from Mortierella vinacea.
A novel alpha-galactosidase, designated alpha-galactosidase II, was isolated from the culture filtrate of Mortierella vinacea. The molecular size of the purified enzyme estimated by gel filtration was 60 kDa, which agreed with that, 51-62 kDa, estimated by SDS-PAGE. The enzyme was thermolabile at neutral pH, but the addition of BSA to the enzyme solution at the concentration of 0.01% increased its stability considerably. The enzyme appears to be novel because it showed a distinct substrate specificity from other microbial alpha-galactosidases on galactomanno-oligosaccharides, prepared from galactomannan, that is, the enzyme liberated not only side-chain alpha-galactosyl residue from 6(3)-mono-alpha-D-galactopyranosyl-beta-1,4-D-mannotetraose but also terminal alpha-galactosyl residue from 6(3)-mono-alpha-D-galactopyranosyl-beta-1,4-D-mannotriose. In addition, the enzyme acted on galactomannans effectively. alpha-Galactosidase II cDNA was cloned and its nucleotides sequenced. The deduced amino acid sequence showed that the mature enzyme consisted of 376 amino acid residues with a molecular mass of 41,334 Da. The derived amino acid sequence of the enzyme showed 31-49% sequence similarity with those of alpha-galactosidases from other origins.


Effect of angiotensin II on arteriovenous shunting assessed by hepatic arterial perfusion scintigraphy.
Angiotensin II (AT II) has been reported to improve drug delivery in intraarterial chemotherapy for hepatic tumors. We studied the effect of this agent on arteriovenous (AV) shunting in the liver. Eleven patients with hepatic tumors and an indwelling catheter in the hepatic artery underwent hepatic arterial perfusion scintigraphy with and without AT II infusion. At baseline, following the administration of technetium-99m macroaggregated albumin (Tc-99m MAA) through the catheter, static images of the upper abdomen and whole-body anterior and posterior images were obtained. Two to 14 days later, AT II was infused via the catheter one minute prior to Tc-99m MAA injection, and imaging was performed in the same way as the baseline study. Visual interpretation of the static images showed improvement of drug delivery to the hepatic tumors in eight of 11 patients and no changes in the remaining patients. The percent injected dose in the lungs assessed quantitatively using the whole-body images increased in all patients, suggesting enhancement of AV shunt flow. It was concluded that intraarterial infusion of AT II increases AV shunting in the liver with better targeting to hepatic tumors.


Mass transfer in electromembrane extraction--The link between theory and experiments.
Electromembrane extraction was introduced in 2006 as a totally new sample preparation concept for the extraction of charged analytes present in aqueous samples. Electromembrane extraction is based on electrokinetic migration of the analytes through a supported liquid membrane and into a μL-volume of acceptor solution under the influence of an external electrical field. To date, electromembrane extraction has mostly been used for the extraction of drug substances, amino acids, and peptides from biological fluids, and for organic micropollutants from environmental samples. Electromembrane extraction has typically been combined with chromatography, mass spectrometry, and electrophoresis for analyte separation and detection. At the moment, close to 125 research papers have been published with focus on electromembrane extraction. Electromembrane extraction is a hybrid technique between electrophoresis and liquid-liquid extraction, and the fundamental principles for mass transfer have only partly been investigated. Thus, although there is great interest in electromembrane extraction, the fundamental principle for mass transfer has to be described in more detail for the scientific acceptance of the concept. This review summarizes recent efforts to describe the fundamentals of mass transfer in electromembrane extraction, and aim to give an up-to-date understanding of the processes involved.


A scoping review of the nurse practitioner workforce in oncology.
The quality of cancer care may be compromised in the near future because of work force issues. Several factors will impact the oncology health provider work force: an aging population, an increase in the number of cancer survivors, and expansion of health care coverage for the previously uninsured. Between October 2014 and March 2015, an electronic literature search of English language articles was conducted using PubMed(®) , the Cumulative Index to Nursing and Allied Health Sciences (CINAHL(®) ), Web of Science, Journal Storage (JSTOR(®) ), Google Scholar, and SCOPUS(®) . Using the scoping review criteria, the research question was identified "How much care in oncology is provided by nurse practitioners (NPs)?" Key search terms were kept broad and included: "NP" AND "oncology" AND "workforce". The literature was searched between 2005 and 2015, using the inclusion and exclusion criteria, 29 studies were identified, further review resulted in 10 relevant studies that met all criteria. Results demonstrated that NPs are utilized in both inpatient and outpatient settings, across all malignancy types and in a variety of roles. Academic institutions were strongly represented in all relevant studies, a finding that may reflect the Accreditation Council for Graduate Medical Education (ACGME) duty work hour limitations. There was no pattern associated with state scope of practice and NP representation in this scoping review. Many of the studies reviewed relied on subjective information, or represented a very small number of NPs. There is an obvious need for an objective analysis of the amount of care provided by oncology NPs.


Leaching behavior of lead from ultrasonically treated MSWI fly ash.
This study was conducted to evaluate the effect of ultrasound widely used for extraction of contaminants and for synthesis of complexes, on extraction and stabilization of heavy metals in MSWI fly ash. Ten grams of fly ash was treated at 10 of liquid--solid (L/S) ratio with and without ultrasonic irradiation of 20 kHz. The extractability of Pb from fly ash was enhanced by ultrasound at the acidic condition. At neutral and alkaline conditions, however, ultrasound did not affect the enhancement of extractability. The results of the maximum availability leaching test (MALT) of the residues treated under various pH conditions with or without ultrasound indicated that the stability of Pb in the fly ash residues was enhanced after ultrasonic irradiation irrespective of treated pH conditions. However, there was a critical point on the enhancement of lead stability in the residues even though the extraction efficiency of Pb decreased gradually with increasing ultrasonic intensity during fly ash treatment. Ultrasonic irradiation was effective for phosphate stabilization of Pb in fly ash. Irrespective of leaching tests, less amount of Pb was leached out from the phosphate stabilized residues treated with ultrasound than without ultrasound. The extraction efficiency of Pb from fly ash decreased with increasing treatment time but the fractions available for leaching at MALT increased with increasing treatment time. Conclusively, although the effect of ultrasound on the extraction of Pb from fly ash highly depends on the pH condition of solvent, the stability of lead in the fly ash residues can be enhanced with ultrasonic irradiation.


Critical role of the epithelial Ca2+ channel TRPV5 in active Ca2+ reabsorption as revealed by TRPV5/calbindin-D28K knockout mice.
The epithelial Ca(2+) channel TRPV5 facilitates apical Ca(2+) entry during active Ca(2+) reabsorption in the distal convoluted tubule. In this process, cytosolic Ca(2+) remains at low nontoxic concentrations because the Ca(2+) influx is buffered rapidly by calbindin-D(28K). Subsequently, Ca(2+) that is bound to calbindin-D(28K) is shuttled toward the basolateral Ca(2+) extrusion systems. For addressing the in vivo role of TRPV5 and calbindin-D(28K) in the maintenance of the Ca(2+) balance, single- and double-knockout mice of TRPV5 and calbindin-D(28K) (TRPV5(-/-), calbindin-D(28K)(-/-), and TRPV5(-/-)/calbindin-D(28K)(-/-)) were characterized. These mice strains were fed two Ca(2+) diets (0.02 and 2% wt/wt) to investigate the influence of dietary Ca(2+) content on the Ca(2+) balance. Urine analysis indicated that TRPV5(-/-)/calbindin-D(28K)(-/-) mice exhibit on both diets hypercalciuria compared with wild-type mice. Ca(2+) excretion in TRPV5(-/-)/calbindin-D(28K)(-/-) mice was not significantly different from TRPV5(-/-) mice, whereas calbindin-D(28K)(-/-) mice did not show hypercalciuria. The similarity between TRPV5(-/-)/calbindin-D(28K)(-/-) and TRPV5(-/-) mice was supported further by an equivalent increase in renal calbindin-D(9K) expression and in intestinal Ca(2+) hyperabsorption as a result of upregulation of calbindin-D(9K) and TRPV6 expression in the duodenum. Elevated serum parathyroid hormone and 1,25-dihydroxyvitamin D(3) levels accompanied the enhanced expression of the Ca(2+) transporters. Intestinal Ca(2+) absorption and expression of calbindin-D(9K) and TRPV6, as well as serum parameters of the calbindin-D(28K)(-/-) mice, did not differ from those of wild-type mice. These results underline the gatekeeper function of TRPV5 being the rate-limiting step in active Ca(2+) reabsorption, unlike calbindin-D(28K), which possibly is compensated by calbindin-D(9K).


Influence of solution phase environmental heterogeneity and fluctuations on vibronic spectra: Perylene diimide molecular chromophore complexes in solution.
Ensembles of ab initio parameterized Frenkel-exciton model Hamiltonians for different perylene diimide dimer systems are used, together with various dissipative quantum dynamics approaches, to study the influence of the solvation environment and fluctuations in chromophore relative orientation and packing on the vibronic spectra of two different dimer systems: a π-stacked dimer in aqueous solution in which the relative chromophore geometry is strongly confined by a phosphate bridge and a side-by-side dimer in dichloromethane involving a more flexible alkyne bridge that allows quasi-free rotation of the chromophores relative to one another. These entirely first-principles calculations are found to accurately reproduce the main features of the experimental absorption spectra, providing a detailed mechanistic understanding of how the structural fluctuations and environmental interactions influence the vibronic dynamics and spectroscopy of solutions of these multi-chromophore complexes.


Noncoordinate regulation of myelinogenic parameters in primary cultures of dissociated fetal rat brain.
The developmental regulation of sulfogalactosylceramide (sulfatide) synthesis, 2', 3'-cyclic nucleotide-3'-phosphohydrolase activity (CNP), and myelin basic protein (MBP) accumulation, three markers characteristic of myelinogenesis, were observed in dispersed cultures of fetal rat brain in spite of the absence of the formation of compact, multilamellar myelin. Sulfatide synthetic rate and CNP activity began to increase by 8 days in vitro (DIV) (approximately comparable to days post-natal) and reached their maxima by 20 DIV. MBP began to accumulate after 14 DEV and reached a maximum by 38 DIV. Thus, the temporal regulation of the onset of expression of these parameters, which is coordinate in vivo, has been dissociated into two sequential periods in vitro. Similarly, the regulatory mechanisms controlling the subsequent decline of the net expression of these three parameters were dissociated. Whereas, the increase in the net CNP activity ceased on schedule, the decline of sulfatide synthetic rate was delayed 20 days, and the accumulation of MBP underwent a net loss. These data suggest that there are multiple parallel but separate mechanisms of temporal regulation controlling myelinogenic gene expression, and that, among them, those factors that control MBP accumulation are more sensitive to disruption by the rigors of dissociated culture.


Interventions to prevent occupational noise-induced hearing loss.
This is the second update of a Cochrane Review originally published in 2009. Millions of workers worldwide are exposed to noise levels that increase their risk of hearing disorders. There is uncertainty about the effectiveness of hearing loss prevention interventions. To assess the effectiveness of non-pharmaceutical interventions for preventing occupational noise exposure or occupational hearing loss compared to no intervention or alternative interventions. We searched the CENTRAL; PubMed; Embase; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; and OSH UPDATE to 3 October 2016. We included randomised controlled trials (RCT), controlled before-after studies (CBA) and interrupted time-series (ITS) of non-clinical interventions under field conditions among workers to prevent or reduce noise exposure and hearing loss. We also collected uncontrolled case studies of engineering controls about the effect on noise exposure. Two authors independently assessed study eligibility and risk of bias and extracted data. We categorised interventions as engineering controls, administrative controls, personal hearing protection devices, and hearing surveillance. We included 29 studies. One study evaluated legislation to reduce noise exposure in a 12-year time-series analysis but there were no controlled studies on engineering controls for noise exposure. Eleven studies with 3725 participants evaluated effects of personal hearing protection devices and 17 studies with 84,028 participants evaluated effects of hearing loss prevention programmes (HLPPs). Effects on noise exposure Engineering interventions following legislationOne ITS study found that new legislation in the mining industry reduced the median personal noise exposure dose in underground coal mining by 27.7 percentage points (95% confidence interval (CI) -36.1 to -19.3 percentage points) immediately after the implementation of stricter legislation. This roughly translates to a 4.5 dB(A) decrease in noise level. The intervention was associated with a favourable but statistically non-significant downward trend in time of the noise dose of -2.1 percentage points per year (95% CI -4.9 to 0.7, 4 year follow-up, very low-quality evidence). Engineering intervention case studiesWe found 12 studies that described 107 uncontrolled case studies of immediate reductions in noise levels of machinery ranging from 11.1 to 19.7 dB(A) as a result of purchasing new equipment, segregating noise sources or installing panels or curtains around sources. However, the studies lacked long-term follow-up and dose measurements of workers, and we did not use these studies for our conclusions. Hearing protection devicesIn general hearing protection devices reduced noise exposure on average by about 20 dB(A) in one RCT and three CBAs (57 participants, low-quality evidence). Two RCTs showed that, with instructions for insertion, the attenuation of noise by earplugs was 8.59 dB better (95% CI 6.92 dB to 10.25 dB) compared to no instruction (2 RCTs, 140 participants, moderate-quality evidence). Administrative controls: information and noise exposure feedbackOn-site training sessions did not have an effect on personal noise-exposure levels compared to information only in one cluster-RCT after four months' follow-up (mean difference (MD) 0.14 dB; 95% CI -2.66 to 2.38). Another arm of the same study found that personal noise exposure information had no effect on noise levels (MD 0.30 dB(A), 95% CI -2.31 to 2.91) compared to no such information (176 participants, low-quality evidence). Effects on hearing loss Hearing protection devicesIn two studies the authors compared the effect of different devices on temporary threshold shifts at short-term follow-up but reported insufficient data for analysis. In two CBA studies the authors found no difference in hearing loss from noise exposure above 89 dB(A) between muffs and earplugs at long-term follow-up (OR 0.8, 95% CI 0.63 to 1.03 ), very low-quality evidence). Authors of another CBA study found that wearing hearing protection more often resulted in less hearing loss at very long-term follow-up (very low-quality evidence). Combination of interventions: hearing loss prevention programmesOne cluster-RCT found no difference in hearing loss at three- or 16-year follow-up between an intensive HLPP for agricultural students and audiometry only. One CBA study found no reduction of the rate of hearing loss (MD -0.82 dB per year (95% CI -1.86 to 0.22) for a HLPP that provided regular personal noise exposure information compared to a programme without this information.There was very-low-quality evidence in four very long-term studies, that better use of hearing protection devices as part of a HLPP decreased the risk of hearing loss compared to less well used hearing protection in HLPPs (OR 0.40, 95% CI 0.23 to 0.69). Other aspects of the HLPP such as training and education of workers or engineering controls did not show a similar effect.In three long-term CBA studies, workers in a HLPP had a statistically non-significant 1.8 dB (95% CI -0.6 to 4.2) greater hearing loss at 4 kHz than non-exposed workers and the confidence interval includes the 4.2 dB which is the level of hearing loss resulting from 5 years of exposure to 85 dB(A). In addition, of three other CBA studies that could not be included in the meta-analysis, two showed an increased risk of hearing loss in spite of the protection of a HLPP compared to non-exposed workers and one CBA did not. There is very low-quality evidence that implementation of stricter legislation can reduce noise levels in workplaces. Controlled studies of other engineering control interventions in the field have not been conducted. There is moderate-quality evidence that training of proper insertion of earplugs significantly reduces noise exposure at short-term follow-up but long-term follow-up is still needed.There is very low-quality evidence that the better use of hearing protection devices as part of HLPPs reduces the risk of hearing loss, whereas for other programme components of HLPPs we did not find such an effect. The absence of conclusive evidence should not be interpreted as evidence of lack of effectiveness. Rather, it means that further research is very likely to have an important impact.


Masked-backlighter technique used to simultaneously image x-ray absorption and x-ray emission from an inertial confinement fusion plasma.
A method to simultaneously image both the absorption and the self-emission of an imploding inertial confinement fusion plasma has been demonstrated on the OMEGA Laser System. The technique involves the use of a high-Z backlighter, half of which is covered with a low-Z material, and a high-speed x-ray framing camera aligned to capture images backlit by this masked backlighter. Two strips of the four-strip framing camera record images backlit by the high-Z portion of the backlighter, while the other two strips record images aligned with the low-Z portion of the backlighter. The emission from the low-Z material is effectively eliminated by a high-Z filter positioned in front of the framing camera, limiting the detected backlighter emission to that of the principal emission line of the high-Z material. As a result, half of the images are of self-emission from the plasma and the other half are of self-emission plus the backlighter. The advantage of this technique is that the self-emission simultaneous with backlighter absorption is independently measured from a nearby direction. The absorption occurs only in the high-Z backlit frames and is either spatially separated from the emission or the self-emission is suppressed by filtering, or by using a backlighter much brighter than the self-emission, or by subtraction. The masked-backlighter technique has been used on the OMEGA Laser System to simultaneously measure the emission profiles and the absorption profiles of polar-driven implosions.


[Not Available].
Based on hardly accessible archive documents as well as other original sources and literature data, the author traces the life of the Russian physician K. Yuriev, and more particularly the years of his sojourn in Bulgaria. The emigrant-populist has merits towards Bulgarian surgery in the period of antisepsis. Dr. Yuriev was in contact with the leftists of the liberal party, led by Zahari Stoyanov, he was in charge of the Russe revolutionary circle "1st March", a good friend to the well known Bulgarian populist Spiro Gulabchev and to the outstanding Bulgarian physician Dr. Paraskev Stoyanov.


[Drug clinics. How I treat cutaneous melanoma].
Skin melanoma is one of the rare cancers whose prevalence has increased over the past decades. Its treatment is based on a classification into four anatomoclinical stages. Surgical excision is the mainstay of therapy. However, several protocols of chemotherapy, radiotherapy and immunotherapy also have specific indications in the therapeutic or palliative approach to the disease.


Fetus papyraceus: congenital pulmonary anomalies associated with congenital aplasia cutis on the surviving twin.
Aplasia cutis congenita (ACC) can be associated with fetus papyraceus. We report here the first case of ACC linked to fetus papyraceus with pulmonary anomalies. At birth, the patient presented with skin lesions of the trunk consisting of well-defined, symmetrically distributed, bilateral atrophic ulcerations. Physical examination was otherwise normal. Persistent bronchospasm occurred at the age of 7 months; computed tomography images showed small bilateral pulmonary bullae. At the age of 5 years, skin and pulmonary lesions had not extended. Although the mechanisms of ACC linked to fetus papyraceus are unclear, vascular ischemia is strongly suggested, and could explain the bilateral and symmetric congenital skin and lung aplasia.


Genomic Characterization of a Metastatic Alveolar Rhabdomyosarcoma Case Using FISH Studies and CGH+SNP Microarray Revealing FOXO1-PAX7 Rearrangement with MYCN and MDM2 Amplification and RB1 Region Loss.
Rhabdomyosarcomas (RMS) are rare, heterogeneous, soft tissue sarcomas and a common type of childhood malignancy with a distinct histomorphology. At the molecular level, alveolar rhabdomyosarcoma (ARMS), a subtype of RMS, harbors a signature genetic makeup characterized by specific translocations. The type of translocation and associated genetic aberrations correlate with disease progression, hence we used multiple molecular modalities including high-resolution array comparative genomic hybridization to explore the oncogenic gene fusion and associated copy number variations in a case of metastatic ARMS. We describe a case where traditional cytogenetic and molecular methods yielded inconclusive results in detecting the FOXO1 gene rearrangement. However, microarray analysis identified the essential FOXO1-PAX7 aberration and additional submicroscopic genomic alterations, including amplification of MYCN and MDM2 and deletion of RB1.


General well-being of intensive care nurses: A prototype analysis.
Prototype analyses of well-being have identified central characteristics and prototypicality for New Zealand teachers, lawyers, adolescents, and work well-being of nurses. What has not yet been explored is the broad construct of well-being in intensive care nurses. To identify intensive care nurses' conceptions of general well-being and investigate whether their general well-being is prototypically organized. Prototype analysis. Three linked studies conceptualize well-being in this prototype analysis. In study 1, nurses reported features of well-being. Study 2 investigated the organization of these features. Study 3 sought confirmation of prototypical organization. Sixty-five New Zealand nurses participated. For study 1 (n = 23), the most frequently reported elements of well-being included physical health (n = 26), work-life balance (n = 20), and personal relationships (n = 18). For study 2 (n = 25), the highest rated elements included mental and emotional health, [general] health, work-life balance, and love. Work-life balance, physical health, and personal relationships were in the top five most frequently reported and were rated in the top 12 most central. Overall, ratings of centrality and the number of times reported were positively correlated (r = 0.33, P < .005). For study 3 (n = 17), confirmatory analyses did not reach statistical significance (P = .15). Physical health, work-life balance, and personal relationships are key characteristics of well-being for intensive care nurses. Mental, emotional, and general health and work-life balance were considered most important for well-being. Physical health, work-life balance, and personal relationships are key characteristics of well-being for intensive care nurses. These characteristics of the broad construct of well-being are helpful in both defining and identifying conceptual models of well-being that may be used to inform the development and measurement of well-being programmes.


Student Nurse Knowledge of and Attitudes Toward Pressure Injury Prevention: How Sufficient Is Undergraduate Education?
To assess the knowledge and attitudes of student nurses regarding evidence-based guidelines for preventing pressure injuries. This study used a descriptive research design. The participants included second-, third-, and fourth-year nursing students completing their bachelor's degrees at a faculty of nursing in Turkey. Data collection forms consisted of a student nurse information form, the Pressure Ulcer Prevention Knowledge Assessment Instrument, and the Attitude Towards Pressure Ulcer Prevention Instrument. The overall mean score for knowledge was 49.9% (11.7/26). The highest scores for the instrument's subthemes were for nutrition (72%), and the lowest were for etiology and development (40.1%). The overall mean attitude score was 42.20 ± 2.40, although a statistically significant difference among grades was found (P < .001). The highest mean scores showed agreement among students that pressure injury prevention should be a priority (10.50 ± 1.43). A significant difference was found in the competence subscale according to the number of dressing changes observed and sense of competence in pressure injury care (P = .003). A weak but statistically significant positive relationship was found between knowledge and attitude scores (r = 0.158; 95% confidence interval, .040-.269; P < .001). This study revealed that certain revisions are needed in the nursing curriculum to improve the knowledge and attitudes of nursing students toward the prevention and care of pressure injuries. More details should be covered in the classroom and laboratories through simulation or clinical practice for improved management of pressure injuries.


Radiation-induced cerebellar chondrosarcoma. Case report.
The authors report a case of chondrosarcoma arising in the cerebellum 16 years after treatment of a cerebellar malignant astrocytoma by subtotal resection and irradiation. It is thought that the chondrosarcoma arising within the intracranial cavity was a probable consequence of previous ionizing radiation.


Giant spin-phonon bottleneck effects in evaporable vanadyl-based molecules with long spin coherence.
Vanadium(iv) complexes have recently shown record quantum spin coherence times that in several circumstances are limited by spin-lattice relaxation. The role of the environment and vibronic properties in the low temperature dynamics is here investigated by a comparative study of the magnetization dynamics as a function of crystallite size and the steric hindrance of the β-diketonate ligands in VO(acac)2 (1), VO(dpm)2 (2) and VO(dbm)2 (3) evaporable complexes (acac- = acetylacetonate, dpm- = dipivaloylmethanate, and dbm- = dibenzoylmethanate). A pronounced crystallite size dependence of the relaxation time is observed at unusually high temperatures (up to 40 K), which is associated with a giant spin-phonon bottleneck effect. We model this behaviour by an ad hoc force field approach derived from density functional theory calculations, which evidences a correlation of the intensity of the phenomenon with ligand dimensions and the unit cell size.


Characterization of a mouse amelogenin [A-4]/M59 cell surface receptor.
Amelogenin proteins comprise up to 90% of the organic matrix of developing enamel in the vertebrate tooth. Alternative splicing of mouse amelogenin pre-mRNA leads to the production of more than 14 protein isoforms, the functions of which are not totally understood. The smaller splice products, [A + 4] or M73 and [A - 4] or M59, have been shown to act differently as signaling molecules affecting odontogenic and other cell types. The mechanisms of these signaling processes, beginning with receptor identification, are not well understood. Utilizing radiolabeled [A - 4], we show here that 3H[A - 4] binds in a saturable fashion to the cell surface of C2C12 mouse fetal myoblasts at 4 degrees C, and not only binds at the surface but is internalized at 37 degrees C. "Far Western" immunohistochemistry performed on sections of E18 mouse incisors and molars with biotin-labeled [A - 4] as the primary ligand demonstrates [A - 4]-biotin binding to polarizing ameloblasts and odontoblasts, cells of the dental follicle, and along the stratum intermedium. Using [A - 4] affinity column chromatography and [A - 4]-biotin label transfer reaction, we have identified a 95 kDa C2C12 cell surface protein which bound [A - 4]. Utilizing Tandem MS (MS/MS) sequencing, we report the novel finding of the 95 kDa murine transmembrane protein, LAMP-1, originally identified as a lysosomal membrane protein that is also found at the cell surface, as an [A - 4] cell binding protein.


[Habekacin: a new aminoglycoside. Study of nephrotoxicity in rats in comparison with gentamicin, netilmicin and amikacin].
Habekacin is a new aminoglycoside antibiotic. In this study we want to know the effect of increasing dose of habekacin on renal function and on renal morphology. We decide to compare the renal alterations induced by habekacin to these provoked by gentamicin, netilmicin and amikacin. Female Wistar rats received intraperitonally a single injection daily of 10, 30, 50, 150 mg/kg of habekacin for seven days. Wistar rats received also 50 mg/kg gentamicin, 50 mg/kg netilmicin and 150 mg/kg amikacin. No mortality was observed in groups treated with 10, 30, 50 mg/kg habekacin but 50 per cent of rats died with 150 mg/kg habekacin. Habekacin--30 mg/kg seven days--induced a decrease of cortical enzymatic activities, an increase of the number of lysosomes, a great accumulation of myeloid bodies, an alteration of lysosomal membranes Habekacin--50 mg/kg seven days and 150 mg/kg--induced a decrease of creatinine clearance and ultrastructural alterations of renal tubular cells. Comparative studies with other aminoglycosides showed that amikacin--150 mg/kg was the lesser nephrotoxic drug. With a same dose of 50 mg/kg, gentamicin appeared lesser nephrotoxic than habekacin and habekacin seemed to induce a same degree of renal modifications than netilmicin. With the dose of 150 mg/kg habekacin this drug was higher nephrotoxic than 50 mg/kg gentamicin. In conclusion, if it could be necessary to use habekacin and to prefer this aminoglycoside to gentamicin from an antibacterial activity point of view it is necessary to keep in mind that this drug is potentially nephrotoxic and that the dosage had to be strictly respected.(ABSTRACT TRUNCATED AT 250 WORDS)


Safety and efficacy study of laparoscopic or robotic radical surgery using an endoscopic stapler for inhibiting tumour spillage of cervical malignant neoplasms evaluating survival (SOLUTION): a multi-centre, open-label, single-arm, phase II trial protocol.
The Laparoscopic Approach to Cervical Cancer trial and Surveillance, Epidemiology, and End Results program database study demonstrated that minimally invasive radical hysterectomy was inferior to abdominal radical hysterectomy in terms of disease recurrence and survival. Among risk factors related to poor prognosis after minimally invasive surgery (MIS), tumour spillage during intracorporeal colpotomy became a significant issue. Thus, we designed this trial to evaluate the efficacy and safety of minimally invasive radical hysterectomy using an endoscopic stapler for early-stage cervical cancer. This trial is a prospective, multi-centre, open-label, single-arm, non-inferiority phase II study. The nine organisations will participate in this trial after the approval of the institutional review board. Major eligibility criteria include women aged 20 years or older with cervical cancer stage IB1 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma according to the revised 2009 FIGO staging system who will undergo type B2 or C hysterectomy by MIS. The primary endpoint is the 4.5-year disease-free survival (DFS) rate between abdominal radical hysterectomy and MIS using an endoscopic stapler. For calculating the sample size, we hypothesised that the 4.5-year DFS rate after MIS using an endoscopic stapler is assumed to be the same after abdominal radical hysterectomy at 90.9%, and the non-inferiority margin was 7.2%. When we consider a three-year accrual and 4.5-year follow-up, at least 13 events must happen, requiring a total of 111 patients assuming a statistical power of 80% and the one-tailed test of 5% significance. A total of 124 patients is needed, considering a drop-out rate of 10%. We expect intracorporeal colpotomy using an endoscopic stapler may prevent tumour spillage during MIS for stage IB1 cervical cancer, showing a comparable prognosis with abdominal radical surgery. ClinicalTrials.gov ; NCT04370496 ; registration date, May 2020.


The Future of Biobanking: A Conceptual Look at How Biobanks Can Respond to the Growing Human Biospecimen Needs of Researchers.
Biobanking of human biological specimens has evolved from the simple private collection of often poorly annotated residual clinical specimens, to well annotated and organized collections setup by commercial and not-for-profit organizations. The activities of biobanks is now the focus of international and government agencies in recognition of the need to adopt best practices and provide scientific, ethical and legal guidelines for the industry. The demand for more, high quality and clinically annotated biospecimens will increase, primarily due to the unprecedented level of genomic, post genomic and personalized medicine research activities going on. Demand for more biospecimens provides new challenges and opportunities for developing strategies to build biobanking into a business that is better able to supply the biospecimen needs of the future. A paradigm shift is required particularly in organization and funding, as well as in how and where biospecimens are collected, stored and distributed. New collection sites, organized as Research Ready Hospitals (RRHs) and new public-private partnership models are needed for sustainability and increased biospecimen availability. Biobanks will need to adopt industry-wide standard operating procedures, better and "non-destructive" methods for quality assessment, less expensive methods for sample storage/distribution, and objective methods to manage scarce biospecimens. Ultimately, the success of future biobanks will rely greatly on the success of public-private partnerships, number and diversity of available biospecimens, cost management and the realization that an effective biobank is one that provides high quality and affordable biospecimens to drive research that leads to better health and quality of life for all.


Who are the most affected by Bothrops snakebite envenoming in Brazil? A Clinical-epidemiological profile study among the regions of the country.
Snakebite envenoming represents an important Neglected Tropical Disease (NTD) that mainly affects tropical and subtropical developing countries according to the World Health Organization (WHO). As a priority issue in the tropics, it is estimated that accidental encounter between snakes and humans is the leading cause of morbidity and mortality among all NTDs in the world. In Brazil, an extremely diverse country with continental dimensions, snakebite envenoming is the second leading cause of reported human envenoming. Treating the disease has been an unprecedented challenge for Brazilian Health Systems for decades. Despite access to Antivenom therapy and distributing it free of charge across the country, Brazil faces numerous issues regarding the notification process and accurate treatment targeting for at-risk populations. Thus, this study aimed to identify the temporal epidemiological dynamics of accidents caused by Bothrops snakes in Brazil, the country's major group of venomous snakes, based on secondary information from the online database provided by The Brazilian Notifiable Diseases Information System (SINAN). For this purpose, reported Bothrops snakebites between 2012 and 2021 were counted, then the data were analyzed. We looked at the frequency, occurrence, mortality rates, case fatality rate (CFR), age and gender distribution, and the time lapse between the incident and the initiation of Antivenom therapy. The data were also organized considering regional variations of the country. Throughout the studied period, a total of 202,604 cases of envenoming caused by Bothrops spp. were notified, resulting in 766 fatalities. These accidents were found to occur in variable proportions across different regions in Brazil, with notable concentrations observed in the North, Northeast, and Southeast regions. The epidemiological profile of patients varied greatly between the regions, revealing that snake envenoming is much more a social, economic, and ecological problem than a medical one. In conclusion, our study provides an overview of the clinical and epidemiological profile of envenoming by Bothrops snakes in Brazil. Notably, this is the first study to present such information in a country as vast and diverse as Brazil, encompassing a comparative analysis of its regions using SINAN data, that proves to be a very useful national tool to improve the control and management of envenoming.


A Modified Enucleation and Deflation to Treat Large Ameloblastoma in the Mandible.
Treatment of large ameloblastoma with a conservative method. Case Presentation. Ameloblastomas are benign tumors of odontogenic origin. These tumors are locally invasive with a high recurrence rate. This case report will present a conservative approach to treating large ameloblastoma in the mandible using modified enucleation and deflation technique. The patient presents with a recurrence of large unicystic ameloblastoma. The following patient is treated with the two-stage enucleation and deflation technique. One-year post-treatment follow-up shows satisfactory healing, with good bone regeneration in the defected area, showing no signs of recurrence. The technique that will be discussed in this case report provides an alternative treatment for ameloblastomas of the mandible. This approach can avoid radical operative procedures, such as jaw resection and bone reconstruction.


In-hospital Mortality after Surgical Resection in Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus.
Background: Survival benefit of surgical resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) has been approved recently. However, risk factors for in-hospital mortality in these patients remain unclear. We aimed to determine risk factors and reduce the mortality of these patients. Methods: We analyzed data for 521 of all 1531 HCC patients with PVTT underwent surgery. The primary outcome measure was in-hospital mortality after surgical resection. Univariate and Multivariate cox-regression were performed to identify independent predictors of in-hospital mortality. The methods of Kaplan-Meier, bootstrap and ten-fold-cross validation were applied to validate the risk factors. Results: 521 of 1531 patients in 2004-2012 occurred for the diagnosis of HCC associated with PVTT and underwent surgical resection as a training cohort. Other 325 patients in 2013-2016 were included as a validation cohort. Overall mortality of postoperative in-patients was 3.3% (17/521) and 2.8 % (9/325), respectively. Univariate analysis of mortality revealed that frequency of hospitalization, total albumin, different types of PVTT, bleeding volume, blood transfusion, resection volume, and tumor volume were related with mortality. Therefore, the bootstrap validation reflected that the risk factors of multivariate cox regression in model1(frequency of hospitalization, bleeding volume, and tumor volume) and model 2 (frequency of hospitalization, bleeding volume and total albumin) were stable with mortality in hospital. Ten-fold cross-validation of cox regression analysis showed that the mean C-statistic with 95%CI of model1 and model2 respectively were 0.887(0.779-0.976) and 0.867(0.789-0.966) for predicting in-hospital mortality. Consistency results of models were in the training cohort and validation cohort. Conclusion: Total albumin, tumor volume, intraoperative bleeding and frequency of hospitalization were independent predictive factors for in-hospital mortality in HCC patients with PVTT under surgery. Further study is warranted to utilize these factors to lower in-hospital mortality.


Winter weather versus group thermoregulation: what determines survival in hibernating mammals?
For socially hibernating mammals, the effectiveness of huddling as a means of energy conservation should increase with group size. However, group size has only been linked to increased survival in a few hibernating species, and the relative importance of social structure versus winter conditions during hibernation remains uncertain. We studied the influence of winter weather conditions, social group composition, age-structure, and other environmental factors and individual attributes on the overwinter survival of hoary marmots (Marmota caligata) in the Yukon Territory, Canada. Juvenile hoary marmot survival was negatively correlated with the mean winter (November to May) Pacific Decadal Oscillation (PDO) index. Survival in older age-classes was negatively correlated with PDO lagged by 1 year. Social group size and structure were weakly correlated with survival in comparison to PDO. The relationship between winter PDO and survival was most likely due to the importance of snowpack as insulation during hibernation. The apparent response of hoary marmots to changing winter conditions contrasted sharply with those of other marmot species and other mammalian alpine herbivores. In conclusion, the severity of winter weather may constrain the effectiveness of group thermoregulation in socially hibernating mammals.


[The usefulness of the 6-minute walk test in patients with chronic heart failure in 6-month observation].
The severity of chronic heart failure (CHF) is usually evaluated by using the New York Heart Association (NYHA) classification. However this method is not good to assess the efficacy of therapy. There is no correlation between the severity of CHF measured by echocardiographic examination of left ventricular ejection fraction (LVEF) and NYHA classification. We investigated the usefulness of the 6-minute walk test to determinate the physical activity in patients with CHF. Studies were performed in 50 patients with symptomatic CHF and LVEF no more than 45%. Six-minute walk test, assessment of NYHA class and LVEF were performed. Changes in the treatment were done between first and second part of the investigation. We observed some changes in LVEF value (between the 1st and the 2nd stage of our study) as well as in NYHA classification (between the 1st and the 2nd stage and between the 2nd and the 3rd stage). We did not noticed essential changes in 6-minute walk tests results. We observed negative correlation between the distance walked in six-minute walk test and the NYHA class in examined patients through all study time. There was some dependence indicated between the LVEF and the 6-minute walk test distance in the first stage. The severity of CHF graded with NYHA classification correlates with the 6-minute walk test distance in patients with CHF. The dependence between LVEF, NYHA class and 6-minute walk test results in treated patients with CHF diminish.