Preserving advanced practice nurse role integrity: One hospital's journey.
Specialists in nursing have existed since the turn of the century. The term denoted a nurse with extensive experience in a particular area of nursing who performed with technical expertise. The modern advanced practice nurse (APN) is a master's degree-prepared clinical expert who has a high level of expertise in the assessment, diagnosis, and treatment of the complex responses of individuals or populations to health problems. The APN delivers comprehensive, cost-effective care and has a recognized role in the multidisciplinary world of healthcare. Despite these advancements, the role of the hospital-based APN is poorly understood. Other hospital positions such as "nurse educator" or "nurse clinician" add to the role confusion. The APN practice in a large urban hospital will be examined. The journey of preserving the role integrity of the hospital-based APN will be explored.


Oestrogenic metabolite equol negatively impacts the functionality of ram spermatozoa in vitro.
Oestrogenic pastures are known to cause infertility in the ewe, due primarily to the oestrogen-like actions of the metabolite equol. Despite strong evidence that phytoestrogens and their metabolites compromise male reproductive function in many other species, there is little information concerning the effect of oestrogenic pastures on ram sperm quality and function. To investigate this, ram spermatozoa were exposed in vitro to physiologically relevant concentrations of either 0, 0.001, 0.01, 0.1 and 1 μM equol and incubated over 6 h. Sperm motility, viability, DNA integrity, membrane lipid disorder, mitochondrial superoxide production, lipid peroxidation and intracellular reactive oxygen species were assessed via computer assisted sperm analysis and flow cytometry at 0.5, 3 and 6 h post-equol exposure. Whilst sperm viability was decreased only at 1 μM equol at 0.5 h post-exposure, exposure to equol at concentrations of 0.1 and 1 μM reduced sperm total and progressive motility (P < 0.001), increased sperm membrane fluidity (P < 0.001), increased mitochondrial superoxide production (P < 0.001) and promoted lipid peroxidation (P < 0.001) across all timepoints. At 6 h post-exposure to 0.1 and 1 μM equol, DNA fragmentation was greater compared that of non-exposed spermatozoa (P = 0.045). Intracellular reactive oxygen species did not change between treatment groups throughout the study (P > 0.05). It is concluded that even low concentrations of equol negatively impact the functionality of ram spermatozoa, these effects likely driven through increased mitochondrial superoxide production. This work indicates that equol may exert oestrogen-like actions upon ram spermatozoa, bringing into question as to whether oestrogenic pastures could influence ram fertility.


Use of spent irrigation water for microbiological analysis of alfalfa sprouts.
Numerous outbreaks of foodborne illness have been linked to the consumption of raw sprouts. Sprout producers have been advised by the Food and Drug Administration to include microbiological testing of spent irrigation water during production as part of an overall strategy to enhance the safety of sprouts. Alfalfa sprouts and irrigation water were analyzed to show the feasibility of using irrigation water for monitoring the microbiological safety of sprouts. Sprouts and water were produced and harvested from both commercial-scale (rotary drum) and consumer-scale (glass jars) equipment. Rapid increases of aerobic mesophiles occurred during the first 24 h of sprouting, with maximum levels achieved after 48 to 72 h. The counts in irrigation water were on average within approximately 1 log of their respective counts in the sprouts. Similar results were obtained for analysis of Escherichia coli O157:H7 in irrigation water and sprouts grown from artificially inoculated seeds. Testing of spent irrigation water indicated the contamination status of alfalfa sprouts grown from seeds associated with outbreaks of Salmonella infection.


Diallyl Disulfide (DADS) Ameliorates Intestinal Candida albicans Infection by Modulating the Gut microbiota and Metabolites and Providing Intestinal Protection in Mice.
Diallyl disulfide (DADS), a garlic extract also known as allicin, has been reported to have numerous biological activities, including anticancer, antifungal, and inflammation-inhibiting activities, among others. Although many studies have assessed whether DADS can treat Candida albicans infection in vitro, its in vivo function and the underlying mechanism are still not clear. Accumulated evidence has implicated the gut microbiota as an important factor in the colonization and invasion of C. albicans. Thus, this study aimed to identify the mechanism by which DADS ameliorates dextran sulfate (DSS)-induced intestinal C. albicans infection based on the systematic analysis of the gut microbiota and metabolomics in mice. Here, we determined the body weight, survival, colon length, histological score, and inflammatory cytokine levels in the serum and intestines of experimental mice. Fecal samples were collected for gut microbiota and metabolite analysis by 16S rRNA gene sequencing and LC-MS metabolomics, respectively. DADS significantly alleviated DSS-induced intestinal C. albicans infection and altered the gut microbial community structure and metabolic profile in the mice. The abundances of some pathogenic bacteria, such as Proteobacteria, Escherichia-Shigella, and Streptococcus, were notably decreased after treatment with DADS. In contrast, SCFA-producing bacteria, namely, Ruminiclostridium, Oscillibacter, and Ruminococcaceae_UCG-013, greatly increased in number. The perturbance of metabolites in infectious mice was improved by DADS, with increases in secondary bile acids, arachidonic acid, indoles and their derivatives, which were highly related to the multiple differentially altered metabolic pathways, namely, bile secretion, arachidonic acid metabolism, and tryptophan metabolism. This study indicated that DADS could modulate gut microbiota and metabolites and protect the gut barrier to alleviate DSS-induced intestinal C. albicans infection in mice. Moreover, this work might also provide novel insight into the treatment of C. albicans infection using DADS.


Processive phosphorylation of p130Cas by Src depends on SH3-polyproline interactions.
Many in vivo substrates of Src family tyrosine kinases possess sequences conforming to Src homology 2 and 3 (SH2 and SH3) domain-binding motifs. One such substrate is p130Cas, a protein that is hyperphosphorylated in v-Src transformed cells. Cas contains a substrate domain consisting of 15 potential tyrosine phosphorylation sites, C- and N-terminal polyproline regions fitting the consensus sequence for SH3 domain ligands, and a YDYV motif that binds the Src SH2 domain when phosphorylated. In an effort to understand the mechanisms of processive phosphorylation, we have explored the regions of Cas necessary for interaction with Src using the yeast two-hybrid system. Mutations in the SH2 domain-binding region of Cas or the Src SH2 domain have little effect in Cas-Src complex formation or phosphorylation. However, disruption of the C-terminal polyproline region of Cas completely abolishes interaction between the two proteins and results in impaired phosphorylation of Cas. Kinetic analyses using purified proteins indicated that multisite phosphorylation of Cas by Src follows a processive rather than a distributive mechanism. Furthermore, the kinetic studies show that there are two properties of the polyproline region of Cas that are important in enhancing substrate phosphorylation. First, the C-terminal polyproline serves to activate Src kinases through the process of SH3 domain displacement. Second, this region aids in anchoring the kinase to Cas to facilitate processive phosphorylation of the substrate domain. The two processes combine to ensure phosphorylation of Cas with high efficiency.


A new method for determining 236U/238U isotope ratios in environmental samples by means OF ICP-MS/MS.
The 236U/238U isotope ratio is a widely used tracer, which provides information on source identification for safeguard purposes, nuclear forensic studies and environmental monitoring. This paper describes an original approach to determine 236U/238U ratios, below 10-8, in environmental samples by combination of ICP-MS/MS for 236U/238U ratio and multiple collector ICPMS measurements for 235U/238U and 234U/235U isotope ratios. Since the hydride form of UO+ (UOH+) is less prone to occur than UH+, we were focused on the oxidised forms of uranium in order to reduce hydride based-interferences in ICP-MS/MS. Then, in-cell ion-molecule reactions with O2 and CO2 were assessed to detect the uranium isotopes in mass-shift mode (Q1: U+ → Q2: UO+). The performances in terms of UO+ sensitivity and minimisation of hydride form of UO+ were evaluated using five different desolvating systems. The best conditions, using an Apex Ω or an Aridus system, produced uranium oxide hydride rate (235U16O1H+/235U16O+) of about 10-7 with O2 in the collision cell. The method was validated through measurements of two certified IRMM standards with 236U/238U isotope ratio of 1.245 × 10-7 and 1.052 × 10-8, giving results in agreement with certified reference values. The relative standard deviations on seven independent measurements for each standard were respectively of 1.5% and 6.2%. Finally, environmental samples corresponding to sediments from the radioactive contamination plume emitted by the Fukushima Daiichi Nuclear Power Plant accident were analysed after a well-established uranium chemical separation procedure. 236U/238U atomic ratios between 1.5 × 10-8 and 7 × 10-9 were obtained with a level accuracy lower than 20%.


Tandem directed lithiations of N-Boc-1,2-dihydropyridines toward highly functionalized 2,3-dihydro-4-pyridones.
[chemical reaction: see text]. Sequential tandem directed lithiations of an N-Boc-4-methoxy-1,2-dihydropyridine have been achieved, leading to C-5,C-6 disubstituted dihydropyridones on acidic workup. The chlorine atom of the dihydropyridone products can in turn be substituted giving rise to diverse substituents at C-6.


Relationship of personal authoritarianism with parenting styles.
This research investigated the relationship between the personality construct of right-wing authoritarianism and Baumrind's 1971 proposed parenting styles of authoritarian, authoritative, and permissive parenting. 68 youth ages 12-18 along with one of their parents participated. The children rated both parents on Buri's 1991 Parental Authority Questionnaire. One of the parents responded to Altemeyer's Right-Wing Authoritarian Scale. People with higher scores on Altemeyer's scale were more likely to prefer the authoritarian parenting style as their offspring reported (r = .33). Permissive parenting correlated negatively with the measure of authoritarianism as a personality variable (r = -.56).


Developmental biology teaching - the importance of a practical approach.
The huge growth in knowledge in many areas of biological sciences over the past few decades has created a major dilemma for those of us in higher education, for not only must we adequately and efficiently convey these new facts and concepts to our students, we must also ensure that they understand and appreciate them. The field of developmental biology has witnessed such a massive growth in knowledge since the mid-1980s, driven mainly by advances in cell and molecular biology, and the development of new imaging techniques and tools. Ensuring that students fully appreciate the four-dimensional nature of embryonic development and morphogenesis is a particular issue, and one that I argue can only be properly learned via direct exposure to embryos via laboratory practicals.


Treatment of scleroderma skin ulcers using becaplermin gel and hydrocolloid membrane.
Skin ulcers can be very painful and detrimental in patients with systemic sclerosis, or systemic scleroderma. A brief review of scleroderma skin ulcers is presented, as well as a case study that demonstrates the effectiveness of becaplermin gel supplemented by oral immunosuppressive agents in the treatment of ulcers resulting from systemic sclerosis. The time to healing (approximately 3 months) was comparable to that associated with the oral agents and surgical interventions specifically designed to help heal scleroderma ulcers. Except for incisional biopsy, no surgical procedures were performed.


Pathways of Risk and Resilience: Impact of a Family Resilience Program on Active-Duty Military Parents.
Over the past decade, studies into the impact of wartime deployment and related adversities on service members and their families have offered empirical support for systemic models of family functioning and a more nuanced understanding of the mechanisms by which stress and trauma reverberate across family and partner relationships. They have also advanced our understanding of the ways in which families may contribute to the resilience of children and parents contending with the stressors of serial deployments and parental physical and psychological injuries. This study is the latest in a series designed to further clarify the systemic functioning of military families and to explicate the role of resilient family processes in reducing symptoms of distress and poor adaptation among family members. Drawing upon the implementation of the Families Overcoming Under Stress (FOCUS) Family Resilience Program at 14 active-duty military installations across the United States, structural equation modeling was conducted with data from 434 marine and navy active-duty families who participated in the FOCUS program. The goal was to better understand the ways in which parental distress reverberates across military family systems and, through longitudinal path analytic modeling, determine the pathways of program impact on parental distress. The findings indicated significant cross-influence of distress between the military and civilian parents within families, families with more distressed military parents were more likely to sustain participation in the program, and reductions in distress among both military and civilian parents were significantly mediated by improvements in resilient family processes. These results are consistent with family systemic and resilient models that support preventive interventions designed to enhance family resilient processes as an important part of comprehensive services for distressed military families.


Neonicotinoid metabolism: compounds, substituents, pathways, enzymes, organisms, and relevance.
Neonicotinoids are one of the three principal insecticide chemotypes. The seven major commercial neonicotinoids are readily biodegraded by metabolic attack at their N-heterocyclylmethyl moiety, heterocyclic or acyclic spacer, and N-nitroimine, nitromethylene, or N-cyanoimine tip. Phase I metabolism is largely dependent on microsomal CYP450 isozymes with situ selectivity in hydroxylation, desaturation, dealkylation, sulfoxidation, and nitro reduction. Cytosolic aldehyde oxidase is a nitroreductase for some neonicotinoids. Phase II metabolism involves methylation, acetylation, and formation of glucuronide, glucoside, amino acid, and sulfate- and glutathione-derived conjugates. Some neonicotinoids act as proinsecticides with metabolism to more potent nicotinic agonists. Pest resistance is more commonly due to synergist-reversible CYP450 detoxification than to nAChR mutants or variants. Metabolites in some cases contribute to mammalian hepatotoxicity and carcinogenesis and in others to enhanced plant vigor and stress shields. These relationships explain much of neonicotinoid comparative toxicology and provide the basis for continued and improved safety and effectiveness of this chemotype.


Oral administration of the Aureobasidium pullulans-derived β-glucan effectively prevents the development of high fat diet-induced fatty liver in mice.
Aureobasidium pullulans-derived β-glucan (AP-PG) consisting of a β-(1,3)-linked glucose main chain and β-(1,6)-linked glucose branches is taken as a supplement to improve health. This study demonstrates that oral administration of AP-PG is effective to prevent the development of high-fat diet (HFD)-induced fatty liver in mice. Here, C57BL/6N mice were fed with a normal diet or HFD, and AP-PG diluted in drinking water was administered orally. After 16 weeks, the serological analysis showed that HFD-induced high blood cholesterol and triglyceride levels were reduced by the oral administration of AP-PG. Further, HFD induced-fatty liver was significantly reduced by the oral administration of AP-PG. The triglyceride accumulation in the liver was also significantly reduced in mice administered AP-PG. Liver injury as indicated by an increase in serum alanine aminotransferase (ALT) in the HFD-fed mice was significantly reduced in the mice administered AP-PG orally, and the gene expression of cholesterol 7 alpha-hydroxylase (CYP7A1) which is known to be involved in cholesterol degradation in the liver was significantly increased in the AP-PG administered mice. These results suggest the possibility that the oral administration of AP-PG is effective to prevent the development of non-alcoholic fatty liver disease (NAFLD).


Improving valid and deficient body segment coordination to improve FES-assisted sit-to-stand in paraplegic subjects.
We investigated dynamic optimization as a tool to improve functional electrical stimulation (FES) assisted sit to stand transfers of paraplegic subjects. The objective would be to find optimal strategy for voluntary trunk movement, which would minimize hip, knee and ankle torques and demand minimal upper limb participation during the motion. Motion of the knee and the ankle were constrained by electrical stimulation. Motion capture (MOCAP) data, and signals from handle force sensors were acquired during FES-assisted rising motion of one paraplegic subject. Based on a 3 DOF dynamic model, we used an optimization algorithm in order to determine optimal trajectories in terms of minimizing joint torques for various conditions of force level applied to handles. Motion computed using the optimization process is compared with the one recorded during the experiment. Our results suggest that in order to minimize the sum of joint torques and arm effort participation, paraplegic patients should bend their body forward in order to use linear momentum of the trunk in sit off phase. This information can be used to design controller for closed-loop FES-assisted standing-up. The controller could use trunk motion to trigger legs stimulation in order to optimize body segment coordination.


Effects of estrogen and gender on cataractogenesis induced by high-LET radiation.
Planning for long-duration manned lunar and interplanetary missions requires an understanding of radiation-induced cataractogenesis. Previously, it was demonstrated that low-linear energy transfer (LET) irradiation with 10 Gy of (60)Co gamma rays resulted in an increased incidence of cataracts in male rats compared to female rats. This gender difference was not due to differences in estrogen, since male rats treated with the major secreted estrogen 17-beta-estradiol (E2) showed an identical increase compared to untreated males. We now compare the incidence and rate of progression of cataracts induced by high-LET radiation in male and female Sprague-Dawley rats. Rats received a single dose of 1 Gy of 600 MeV (56)Fe ions. Lens opacification was measured at 2-4-week intervals with a slit lamp. The incidence and rate of progression of radiation-induced cataracts was significantly increased in the animals in which estrogen was available from endogenous or exogenous sources. Male rats with E2 capsules implanted had significantly higher rates of progression compared to male rats with empty capsules implanted (P = 0.025) but not compared to the intact female rats. These results contrast with data obtained after low-LET irradiation and suggest the possibility that the different types of damage caused by high- and low-LET radiation may be influenced differentially by steroid sex hormones.


Study on a negative hydrogen ion source with hot cathode arc discharge.
A negative hydrogen (H(-)) ion source with hot cathode arc discharge was designed and fabricated as a primary injector for a 10 MeV PET cyclotron at IMP. 1 mA dc H(-) beam with ɛ N, RMS = 0.08 π mm mrad was extracted at 25 kV. Halbach hexapole was adopted to confine the plasma. The state of arc discharge, the parameters including filament current, arc current, gas pressure, plasma electrode bias, and the ratio of I(e(-))/I(H(-)) were experimentally studied. The discussion on the result, and opinions to improve the source were given.


[A case of recurrent IgA nephropathy following renal transplantation under tacrolimus (FK506)].
We report a case of recurrent IgA nephropathy following renal transplantation under tacrolimus (FK506). A 23-year-old female who had been diagnosed with IgA nephropathy was transplanted from her HLA two-mismatched mother under tacrolimus, prednisolone and azathioprine. Two years after transplantation, suddenly she noticed macroscopic hematuria. At that time, functional renal deterioration (serum creatinine: 2.3 mg/dl) and mild proteinuria were observed. Allograft biopsy disclosed acute cellular rejection. She was administered a bolus injection of methylprednisolone, 15-deoxyspergualin and anti-lymphocyte globulin. However, the response to the treatment was poor. A transplant biopsy revealed focal segmental glomerulosclerosis by PAS staining and granular IgA and C3 deposits on immunofluorescence examination. There was no sign of acute rejection and toxicity by tacrolimus. We diagnosed recurrent IgA nephropathy. At the present time, she has normal urinalysis and renal function is stable (serum creatinine: 1.9 mg/dl). No proteinuria was observed after total dosage of immunosuppressants was increased. Although recurrence of IgA nephropathy in renal allograft is frequent, allograft dysfunction is rare. However, IgA nephropathy has several types with different prognosis. For functional renal deterioration after renal transplantation, we should consider not only an acute rejection or the toxicity of immunosuppressants but also recurrent nephropathy.


Cluster analysis of accelerated molecular dynamics simulations: A case study of the decahedron to icosahedron transition in Pt nanoparticles.
Modern molecular-dynamics-based techniques are extremely powerful to investigate the dynamical evolution of materials. With the increase in sophistication of the simulation techniques and the ubiquity of massively parallel computing platforms, atomistic simulations now generate very large amounts of data, which have to be carefully analyzed in order to reveal key features of the underlying trajectories, including the nature and characteristics of the relevant reaction pathways. We show that clustering algorithms, such as the Perron Cluster Cluster Analysis, can provide reduced representations that greatly facilitate the interpretation of complex trajectories. To illustrate this point, clustering tools are used to identify the key kinetic steps in complex accelerated molecular dynamics trajectories exhibiting shape fluctuations in Pt nanoclusters. This analysis provides an easily interpretable coarse representation of the reaction pathways in terms of a handful of clusters, in contrast to the raw trajectory that contains thousands of unique states and tens of thousands of transitions.


[Somatic diseases of the schizophrenic patient].
Cardiovascular diseases and metabolic disorders such as obesity, diabetes and metabolic syndrome that increase their risk, are common in schizophrenic patients. Psychiatric therapy of the schizophrenic patient should from the beginning also include examination of somatic status, support towards a healthy lifestyle and appropriate treatment of somatic diseases. Psychiatrists should update their knowledge of diagnostics of somatic diseases, and other medical profession should be aware of the substantial associated somatic morbidity.


Auditory evoked responses in a comparison between schizophrenia patients with and without premorbid history of drug abuse: report of pilot results.
Evidence for a role for drugs of abuse in the development of chronic psychotic syndromes is scattered throughout 40 years of literature. Electrophysiological studies examining groups believed to have chronic drug-induced psychotic symptoms yielded interesting findings. To our knowledge, no studies directly compared schizophrenia patients whose drug use preceded and those whose drug use followed the onset of psychotic symptoms. Twenty-six schizophrenia patients and 10 healthy control subjects were recruited for the study. Based on the SCID interview, schizophrenia subjects were classified into a Psychosis First (Psy 1st) group (N=11), Drugs First (Drugs 1st; N=8), and No Drug Use (No Drugs; N=7). Schizophrenia subjects were administered the Positive and Negative Symptoms Scale (PANSS). The P300 evoked response and sensory gating were measured for all subjects. Despite the small sample sizes significant differences were found between the groups. Most significantly, the P300 amplitude was smallest in the Drugs 1st as compared to the No Drugs groups, while sensory gating deficit was worst in the Psy 1st group. The data suggest that significant clinical and electrophysiological differences between these groups can be identified. Further research to better define these differences seems warranted.


Ring opening of methylcyclohexane over platinum-loaded zeolites.
The activity of different platinum-loaded zeolites (Mordenite, ZSM-12, ZSM-5, ZSM-23) was investigated in the hydroconversion of methylcyclohexane (MCH), in the context of upgrading highly aromatic distillates for fuel blending. In all cases, conversion of MCH proceeds according to a pathway where the primary products are a mixture of dimethylcyclopentanes and ethylcyclopentane formed by isomerization and ring contraction of MCH. The primary products undergo consecutive ring-opening reactions with formation of n- and isoheptanes. The latter further react to form lower-molecular-weight n- and isoalkanes. The selectivity and distribution of products deriving from ring-contraction and ring-opening reactions are strongly affected by the pore size and topology of the zeolites. ZSM-5 exhibits a strong reactant shape-selectivity effect on ring-opening products. The evaluated zeolites show the following order of activity in the conversion of methylcyclohexane: Mordenite>ZSM-12>ZSM-5>ZSM-23.


The Role of Primary School Composition in the Trajectories of Internalising and Externalising Problems across Childhood and Adolescence.
There is little research on the role of school and its composition in explaining individual children's psychological outcomes. This study examined for the first time the role of several primary-school compositional characteristics, and their interactions with individual level characteristics, in the development of two such outcomes, internalising and externalising problems, at ages 7, 11 and 14 years in 4794 children in England participating in the Millennium Cohort Study. Using hierarchical (multilevel) linear models, we found that, even after adjusting for individual and family characteristics, children in schools with higher proportions of pupils eligible for free school meals had more externalising problems. In general, children with special educational needs, lower academic performance, more distressed mothers, and those in non-intact families had more internalising and externalising problems. Our results underline the importance of targeting schools with less affluent overall intakes, but also highlight the key role of individual and family characteristics in the development of their pupils' psychological functioning.


Bilateral chylothorax.
A 2.5-kg female developed bilateral chylothoraces 10 days after surgery for coarctation of the aorta. Initial conservative management consisted of intermittent positive pressure ventilation, drainage of chylous fluid and enteral feeding, but there was no diminution in loss of chyle. Ligation of the thoracic duct and pleurectomy were performed subsequently to reduce the large daily losses of chyle, amounting to nearly three times the child's circulating blood volume. Brawny oedema of the right upper quadrant of the body developed rapidly after the duct ligation and right pleurectomy. A further period of conservative treatment was required before the latter complication resolved. The literature relating to this iatrogenic complication and to fluid and nutritional losses in paediatric chylothorax is reviewed and discussed.


The Minimally Invasive-Guided Genioplasty Technique using Piezosurgery and 3D printed surgical guide: An innovative technique.
Mental nerve injuries with neurosensory deficits, asymmetries, and intra-operative bleeding are the main immediate complications of genioplasty. Following a recent systematic review, three-dimensional (3D)-printed cutting guide could improve the predictability and accuracy of this surgical technique avoiding postoperative asymmetries. Furthermore, anatomical structures in the surgical area (mental nerve and teeth roots) are better protected, reducing the morbidity and providing safer results. Ultrasonic piezoelectric osteotomy allows by its intrinsic characteristics, a selective cut of mineralized structure with a lower risk of vascular and nervous damage (microvibrations), intra-operative precision (thin cutting scalpel and no macro-vibrations), and blood-free site (cavitation effect). The aim of this article is to present a new minimally invasive technique: the minimally invasive-guided genioplasty technique (aka MIGG technique). This technique combines the advantages of piezosurgery and of a space-saving 3D-printed cutting guide, requiring open-source programs and an affordable 3D printing technology. All the steps of this technique are described: preoperative surgical planning (CT scanner, segmentation with 3D slicer®, and design of the cutting guide with Blender®) and 3D printing of the guide and sterilization of it. The surgical procedure is presented in detail as well as the postoperative care. The MIGG technique offers, according to the authors, a better postoperative recuperation, a reduction in operating time, less complications, and protection of the anatomical structures (mental nerve, teeth, lingual soft tissue and vessels). This minimally invasive technique for genioplasty is a promising approach to perform a chin osteotomy.


[THERANOSTIC TARGETED DRUG DELIVERY - NEW INSIGHTS INTO DIAGNOSIS AND TREATMENT OF CANCER].
Monoclonal antibodies (mAbs) have become a novel therapeutic modality against cancer due to their specificity, affinity and serum stability. These incredible tools capable of linking variable payload, generate antibody drug conjugates (ADCs) that preserve targeting properties and therefore, specifically deliver drugs to the cancer cells. The drugs should exhibit sub-nano to picomolar cytotoxicity usually affecting fundamental oncogenic mechanisms via mitotic inhibition, DNA alkylation and topoisomerase poisoning. The linkers play a pivotal role in ADC design as they link the cytotoxic payload to the antibody. Linkers maintain the stability of the ADCs in the blood circulation securing their delivery to the cancer cell intact but cleaved when internalized to release the payload. Recently, a more advanced version of ADC, namely theranostic (therapeutic and diagnostic) ADC has emerged. These conjugates allow visualization of targeted drug delivery (TDD) vastly impacting the therapeutic index in cancer treatment. Among diagnostic probes, NIR fluorescent dyes provide important real-time information on the efficacy of drug delivery. A two-dye system comprising one switchable and one constantly light emitting cyanine (Cy) linkers provides the ratiometric quantification of the drug released in the tumor. Due to the enormous repertoire of mAbs, the theranostic ADCs can change the future of cancer diagnosis and treatment.


Sporadic superficial diffuse neurofibromas with repeated local recurrence over many years and a tendency toward malignant change: a report of 3 cases.
Sporadic superficial (cutaneous/subcutaneous) neurofibromas are normally small tumors that do not recur after excision or undergo malignant change. In contrast to this, I have encountered 3 cases in which a solitary sporadic superficial diffuse neurofibroma was large, recurred locally on multiple occasions extending over 30 years, and exhibited malignant change at least once. The first patient was a 44-year-old black woman who had a superficial diffuse neurofibroma with a focus of epithelioid malignant peripheral nerve sheath tumor (MPNST) excised from her left upper arm. The tumor recurred locally 14 times over a period of 38½ years; most specimens demonstrated only neurofibroma, but the 11th and 14th recurrences also had areas of epithelioid MPNST (extensive in the latter recurrence). There was no follow-up information after the last recurrence was excised except that the patient died of an unknown cause 3 years later. The second patient was a 39-year-old white woman who had a superficial neurofibroma excised from her scalp. A local recurrence was excised 30 years later and demonstrated a small focus of spindle cell MPNST in addition to neurofibroma. There were 6 further recurrences over the ensuing 14 years, of which the last 3 had components of spindle cell MPNST that extended into the skull bone and skeletal muscle. For these, radiotherapy was performed in addition to excision, and the patient had no evidence of tumor when last seen 1 year after the last recurrence was excised (she died 2 mo later of an unknown and presumably incidental cause). The third patient was a 28-year-old black woman who had a mass excised from her back that she was told was benign. A local recurrence was excised from the same area about 10 years later, again with a benign diagnosis (no details were available about these 2 specimens). Another recurrence was excised 36 years after the original excision; this demonstrated an extensive superficial diffuse neurofibroma with at least 2 small foci of spindle cell MPNST. A further recurrence was excised slightly >1 year later and showed superficial diffuse neurofibroma with some cellular areas but no definite MPNST. The patient was lost to follow-up after this. In addition to their diffuse infiltrative nature, a distinctive finding in the neurofibromas in all 3 cases was the presence of a focal to patchy lymphocytic chronic inflammatory infiltrate. Despite the difference in the character of the MPNST components (epithelioid in the first case, spindle cell in the other 2), the cases had sufficient histologic and clinical similarities to suggest that they represent a distinctive type of superficial neurofibroma.


Inhibition by lead of production and secretion of transthyretin in the choroid plexus: its relation to thyroxine transport at blood-CSF barrier.
Long-term, low-dose Pb exposure in rats is associated with a significant decrease in transthyretin (TTR) concentrations in the CSF. Since CSF TTR, a primary carrier of thyroxine in brain, is produced and secreted by the choroid plexus, in vitro studies were conducted to test whether Pb exposure interferes with TTR production and/or secretion by the choroid plexus, leading to an impaired thyroxine transport at the blood-CSF barrier. Newly synthesized TTR molecules in the cultured choroidal epithelial cells were pulse-labeled with [35S]methionine. [35S]TTR in the cell lysates and culture media was immunoprecipitated and separated by SDS-PAGE, and quantitated by autoradiography and liquid scintillation counting. Pb treatment did not significantly alter the protein concentrations in the culture, but inhibited the synthesis of total [35S]TTR (cells + media), particularly during the later chase phase. Two-way ANOVA of the chase phase revealed that Pb exposure (30 microM) significantly suppressed the rate of secretion of [35S]TTR compared to the controls (p < 0.05). Accordingly, Pb treatment caused a retention of [35S]TTR by the cells. In a two-chamber transport system with a monolayer of epithelial barrier, Pb exposure (30 microM) reduced the initial release rate constant (kr) of [125I]T4 from the cell monolayer to the culture media and impeded the transepithelial transport of [125I]T4 from the basal to apical side of epithelial cells by 27%. Taken together, these in vitro data suggest that sequestration of Pb in the choroid plexus hinders the production and secretion of TTR by this tissue. Consequently, this may alter the transport of thyroxine across this blood-CSF barrier.


Autopsy analysis of the safety, efficacy and cartography of electrical stimulation of the central gray in humans.
Electrical brain stimulation is effective in controlling certain intractable chronic pain syndromes in humans, but the specific target site(s) for stimulation producing a maximal analgesic effect is (are) not well defined. This prospective study correlates the clinical results of chronic stimulation of the periaqueductal gray (PAG) and periventricular gray (PVG) matter in humans with the anatomic site of electrode placement as determined at autopsy, and documents the histologic reactions to electrode implantation and electrical stimulation of the area. Seven patients underwent electrode implantation to control their chronic pain; two had electrodes implanted bilaterally. All patients obtained complete analgesia with stimulation, although 3 subsequently found the stimulation to have diminished efficacy. The opiate antagonist naloxone reversed the analgesia in the 4 patients so tested. All 7 patients later died of causes unrelated to electrode implantation or stimulation. Postmortem analysis showed that, for 6 of the 9 electrodes implanted, the electrode tip was located in the ventrolateral PAG at the level of the posterior commissure; the other 3 electrodes were found in the white matter adjacent to the PAG. No evidence of gliosis or parenchymal reaction was observed along the tracts and tips of the electrodes. The results indicate that the ventrolateral PAG and PVG matter at the level of the posterior commissure is the optimal site for therapeutic electrical brain stimulation for opiate-responsive pain in humans.


Role of alcohol in liver carcinogenesis.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and contributes significantly to cancer-related morbidity and mortality. Chronic alcohol consumption has long been associated with progressive liver disease toward the development of hepatic cirrhosis and the subsequent increased risk for developing HCC. In assessing the role of alcohol during hepatic disease, and as a carcinogen, many of the deleterious effects of alcohol can be attributed to alcohol metabolism in hepatocytes. In addition to the direct effects of alcohol/alcohol metabolism on hepatocyte transformation, increasing evidence indicates that other intrahepatic and systemic effects of alcohol are likely to play an equally significant role in the process of hepatic tumorigenesis.


[Gestational diabetes mellitus : management in 2020 and long-term risk].
Gestational diabetes mellitus is a frequent complication of pregnancy. Its diagnosis and management tend now to a better uniformization than in the past years, even if some guidelines still remain debated. Nevertheless, useful actions in GDM's management, as well as the follow-up regarding the long-term metabolic risk for women who underwent this dysglycaemia in a limited time are now quite well described in the literature. In this review, we aim to discuss recent data related to this very particular metabolic disease.


The Structure of Mental Elasticity Education for Children in Plight Using Deep Learning.
The purpose is to solve the problem that the current research on the impact of the microstructure of mental elasticity and its constituent factors on the development of the mental elasticity of children is not comprehensive, and the traditional artificial analysis method of mental problems has strong subjectivity and low accuracy. First, the structural equation model is used to study the microstructure of poor children's mental elasticity, and to explore the structural relationship and functional path between the mental elasticity of children and the self-efficacy of their mental health, psychological anxiety, and attachment. Second, a prediction model of mental problems of children in plight based on the backpropagation neural network (BPNN) is constructed. Finally, middle schools in the representative areas of Northwest China are selected as the research unit. The relevant research data are collected by issuing questionnaires, and the data set is constructed to verify the performance of the model. The experimental results show that the average prediction errors of the BPNN model and the support vector regression (SVR) model are 1.87 and 5.4, respectively. The error of BPNN is 65.4% lower than that of SVR, so BPNN has a better performance. The prediction results of the test set show that the actual error and the relative error of the BPNN model are controlled in the range of 0.01, and the prediction accuracy is high. The structural equation model has a high fitting degree. The results of the questionnaire analysis show that attachment, self-efficacy, and psychological anxiety exert a significant direct impact on mental elasticity. This exploration aims to conduct a micro investigation on the relationship among the three core variables (attachment, self-efficacy, and mental health) in the resilience research of children in plight, and analyze their resilience, to provide a theoretical basis for the resilience intervention design of vulnerable groups.


[Participation of 5-HT 1A receptors in the decrease by serotonin of activation of locus coeruleus neurons by glutamate].
The serotonin-induced decrease of glutamate-evoked activation of noradrenergic locus coeruleus neurons is mimicked by agonists of 5-HT 1 and 1A but not by 5-HT 1B or by 5-HT 2 agonists. Moreover, this effect is reversed by a broad-spectrum 5-HT antagonist but not by a 5-HT 2 antagonist, indicating that this effect is mediated primarily through 5-HT 1A receptors.


Quality of life in melanoma patients during adjuvant treatment with pegylated interferon-α2b: patients' and doctors' views.
Treatment of malignant melanoma with IFN-α has been associated with significant side-effects. The aim of this retrospective monocentric non-randomized study was first to evaluate the impact on quality of life (QOL) in 30 melanoma patients treated with once weekly 2 μg/kg PEG-IFN-α2b for 18 months, and second to examine whether there is a difference in patients' and physicians' perception of QOL. Data on QOL were collected by means of the EORTC QLQ-C30 questionnaire completed by the patient before consultation at baseline and every three months during treatment. A second questionnaire was filled out independently by the physician, based on the consultation and patient file. All data were routinely collected in an outpatient care unit. At baseline, patients had more favorable mean values on almost all dimensions of the EORTC QLQ-C30 than follow-up assessments. In comparison to published low-dose IFN-α2a data, once weekly 2 μg/kg PEG-IFN-α2b was associated with stronger impairment in most QOL single dimensions but with almost no differences regarding the global health status. QOL documented by physicians was significantly higher than QOL from the patients' questionnaires in all QOL dimensions (p<0.05). PEG-IFN-α2b has measurable effects on QOL. Measuring QOL based only on physicians' patient files without explicitly determining patients' assessments leads to a profound underestimation of impairment of QOL.


Adolescents murderers: abuse and adversity in childhood.
With rising rates of juvenile violence, an improved understanding of its causes is much needed. The relative absence of controlled studies based on British populations of murderers further increases the need for information in this area. This case control study examines a group of 21 imprisoned males, convicted of murder whilst aged 18 years or less, and compares them on a range of psychosocial variables to 21 convicted non-violent burglars. The groups were matched for age at interview and race. Results showed that lower socio-economic status, harsh parenting from both mother and father, and exclusion from school were significantly more common for murderers. Harsh parenting from the mother than from the father appeared to contribute more strongly. When factors were combined in a general adversity index, a significant difference was found between the two groups. The study confirms that multiple environmental factors are associated with murderous behaviour in young men.


Perceptions of voice disorders: a survey of Arab adults.
A disordered voice may lead to social stigma as well as reduced occupational opportunities. Much of the research on this topic has investigated the effects of voice disorders from a Western perspective. The societal attitudes of international populations toward people with voice disorders (PWVD) are less well known. The purpose of this study was to investigate the attitudes of adults living in Kuwait toward PWVD. Participants completed a questionnaire that addressed social, educational, and occupational aspects of life for PWVD. The results indicated that while Kuwaiti adults hold generally positive attitudes toward PWVD, they may also perceive PWVD as more likely to be emotionally disturbed, have difficulty making friends or getting married, and experience trouble in finding a good job.


The protective role of erdosteine on testicular tissue after testicular torsion and detorsion.
Testicular torsion and detorsion are important clinical problems for infertile man and oxidative stress may have a role in this clinical situation. The aim of this study was to investigate the protective role of erdosteine, an antioxidant, on unilateral testicular reperfusion injury in rats. The rats were divided into four groups including seven rats in each group: control, torsion, torsion/detorsion and torsion/detorsion+erdosteine. Rats, except the sham operation group, were subjected to left unilateral torsion (720( composite function) rotation in the clockwise direction) without including the epididymis. The experiments were finished after sham operation time for control, 120 min torsion for torsion group and 120 min torsion and 240 min detorsion for torsion/detorsion groups. Bilateral orchiectomy was performed for all groups of rats. The ipsilateral and controlateral testis were divided into two pieces to analyse biochemical parameters and to investigate the light microscopic view. Malondialdehyde level of ipsilateral testis was increased in torsion and torsion/detorsion groups in comparison with the other groups (p < 0.05). Erdosteine treatment ameliorated lipid peroxidation after torsion/detorsion in ipsilateral testis (p < 0.05). Also, xanthine oxidase activity of ipsilateral testis was increased in torsion/detorsion group in comparison with the others (p < 0.05). Nitric oxide (NO) level of ipsilateral testis was higher in all experimental groups than sham operated control group (p < 0.05). Also, NO level of torsion group was increased in comparison with detorsion groups (p < 0.05). Erdosteine treatment caused increased glutathione peroxidase activity in comparison with torsion and torsion/detorsion groups and catalase activity in comparison with the other groups in ipsilateral testis (p < 0.05). Superoxide dismutase activity of ipsilateral testis was higher in torsion/detorsion and torsion/detorsion+erdosteine groups than control and torsion groups (p < 0.05). The biochemical parameters were not affected in controlateral testis in all groups. Torsion, torsion/detorsion and torsion/detorsion+erdosteine groups showed ipsilateral testicular damage in the histological examination, but the specimens from torsion/detorsion had a significantly greater histological injury than those from the other groups (p < 0.05). Control rats showed normal seminiferous tubule morphology. Rats in torsion group had slight-to-moderate disruption of the seminiferous epithelium. Rats in torsion/detorsion group displayed moderate-to-severe disruption of the seminiferous epithelium. In all animals from torsion/detorsion+erdosteine group, the testicular tissues were affected with slight-to-moderate degenerative changes of the seminiferous epithelium. Administration of erdosteine resulted in a significantly reduced histological damage associated with torsion of the spermatic cord compared with torsion/detorsion. In all groups, the contralateral testes were histologically normal. In conclusion, the results clearly displayed that erdosteine treatment may have a protective role on testicular torsion/detorsion injury.


Histone Arginine Methylation by PRMT7 Controls Germinal Center Formation via Regulating Bcl6 Transcription.
B cells are the center of humoral immunity and produce Abs to protect against foreign Ags. B cell defects lead to diseases such as leukemia and lymphomas. Histone arginine methylation is important for regulating gene activation and silencing in cells. Although the process commonly exists in mammalian cells, its roles in B cells are unknown. To explore the effects of aberrant histone arginine methylation on B cells, we generated mice with a B cell-specific knockout of PRMT7, a member of the methyltransferases that mediate arginine methylation of histones. In this article, we showed that the loss of PRMT7 led to decreased mature marginal zone B cells and increased follicular B cells and promoted germinal center formation after immunization. Furthermore, mice lacking PRMT7 expression in B cells secreted low levels of IgG1 and IgA. Abnormal expression of germinal center genes (i.e., Bcl6, Prdm1, and Irf4) was detected in conditional knockout mice. By overexpressing PRMT7 in the Raji and A20 cell lines derived from B cell lymphomas, we validated the fact that PRMT7 negatively regulated Bcl6 expression. Using chromatin immunoprecipitation-PCR, we found that PRMT7 could recruit H4R3me1 and symmetric H4R3me2 to the Bcl6 promoter. These results provide evidence for the important roles played by PRMT7 in germinal center formation.


Antifungal, Repellency, and Insecticidal Activities of Cymbopogon distans and Ruta graveolens Essential Oils and Their Main Chemical Constituents.
Essential oils produced by Cymbopogon distans and Ruta graveolens with a similar Chinese name could be explained as book fragrance in the Chinese idiom 'shu xiang men di', namely, a wealthy intellectual family according to ancient Chinese. Therefore, volatile oils from these two plants and their main compounds were tested to explore their antifungal, repellent, and insecticide actions. In this study, the essential olis (EO) of C. distans exhibited significant antifungal activity against Rhizopus stolonifera (97 %), Mucor racemosus (97 %), and Trichoderma viride (84 %); its main compounds exhibit interesting activity, such as methyleugenol (87 %) and elemicine (85 %) against T. viride and butyl hydroxytoluene against M. racemosus (90 %) and R. stolonifera (95 %). The EO of R. graveolens and other major chemical constituents showed weak inhibitory effects against other fungi (Aspergillus flavus and Fusarium oxysporum). Then, EO (C. distans and R. graveolens) and its main compounds exhibited obvious repellent activity (more than 85 %) at a concentration of 16 nL/cm2 , which was consistent with the repellency of the positive control (DEET). In terms of insecticidal activity, the mortality of C. distans volatile oil against R. padi (56.4 %) was lower than that of R. graveolens volatile oil (92.4 %), and all compounds showed weak lethal effects. These results provide a natural substance for controlling fungi and insects when storing books and that can be used as a biological pesticide for industrial production. Through our study, the book fragrance in the Chinese idiom 'shu xiang men di' was speculated to be the EO odor of C. distans.


Combined anti-angiogenic therapy targeting PDGF and VEGF receptors lowers the interstitial fluid pressure in a murine experimental carcinoma.
Elevation of the interstitial fluid pressure (IFP) of carcinoma is an obstacle in treatment of tumors by chemotherapy and correlates with poor drug uptake. Previous studies have shown that treatment with inhibitors of platelet-derived growth factor (PDGF) or vascular endothelial growth factor (VEGF) signaling lowers the IFP of tumors and improve chemotherapy. In this study, we investigated whether the combination of PDGFR and VEGFR inhibitors could further reduce the IFP of KAT-4 human carcinoma tumors. The tumor IFP was measured using the wick-in-needle technique. The combination of STI571 and PTK/ZK gave an additive effect on the lowering of the IFP of KAT-4 tumors, but the timing of the treatment was crucial. The lowering of IFP following combination therapy was accompanied by vascular remodeling and decreased vascular leakiness. The effects of the inhibitors on the therapeutic efficiency of Taxol were investigated. Whereas the anti-PDGF and anti-VEGF treatment did not significantly inhibit tumor growth, the inhibitors enhanced the effect of chemotherapy. Despite having an additive effect in decreasing tumor IFP, the combination therapy did not further enhance the effect of chemotherapy. Simultaneous targeting of VEGFR and PDGFR kinase activity may be a useful strategy to decrease tumor IFP, but the timing of the inhibitors should be carefully determined.


[Histomorphometric and quantitative histochemical analysis of periimplantation zone in patients with different bone mineral density within dental implantation].
The aim of the work is to study histomorphometric and histochemical properties of jaw bone loss in patients with full or partial edentulism, need to restoring their dentition integrity by dental implantation. Cytological studies were carried out in 83 patients, among which normal bone mass was observed in 28 patients (17 women and 11 men), osteopenia in 26 patients (17 women and 9 men), osteoporosis in 29 (19 women and 10 men) patients. Histological examination of bone biopsies were performed in 76 patients, among which normal bone mass was observed in 22 (16 women and 6 men, osteopenia in 26 patients (17 women and 9 men), osteoporosis in 28 (19 women and 9 men) patients. Histomorphometric analysis of "implant-bone" contact in the entire length of the joint in patients with normal bone mass was 61.8 +/- 3.7%, with osteopenia was 51.6+/- 3.0%, with osteoporosis was 46.1 +/- 2.8%. The intensity of bone remodeling in patients with normal bone mass was 2.7 +/- 0.19, in patients with osteopenia was 2.2 +/- 0.14, in patients with osteoporosis was 1.8 +/- 0.11. This demonstrates the significant difference between the patients with normal bone mass and osteoporotic patients. The "implant-bone" interface in osteoporotic patients was significantly lower than in patients with normal bone mass. Histomorphometric studies and quantitative histochemical analysis revealed that the decrease of bone mineral mass in patients often combined with a decrease of the "implant surface-bone" site contact area, with atrophy and with hypoplasia of perimplant tissues.


Role of Histone Deacetylases in Skeletal Muscle Physiology and Systemic Energy Homeostasis: Implications for Metabolic Diseases and Therapy.
Skeletal muscle is the largest metabolic organ in the human body and is able to rapidly adapt to drastic changes during exercise. Histone acetyltransferases (HATs) and histone deacetylases (HDACs), which target histone and non-histone proteins, are two major enzyme families that control the biological process of histone acetylation and deacetylation. Balance between these two enzymes serves as an essential element for gene expression and metabolic and physiological function. Genetic KO/TG murine models reveal that HDACs possess pivotal roles in maintaining skeletal muscles' metabolic homeostasis, regulating skeletal muscles motor adaptation and exercise capacity. HDACs may be involved in mitochondrial remodeling, insulin sensitivity regulation, turn on/off of metabolic fuel switching and orchestrating physiological homeostasis of skeletal muscles from the process of myogenesis. Moreover, many myogenic factors and metabolic factors are modulated by HDACs. HDACs are considered as therapeutic targets in clinical research for treatment of cancer, inflammation, and neurological and metabolic-related diseases. This review will focus on physiological function of HDACs in skeletal muscles and provide new ideas for the treatment of metabolic diseases.


Fluorodeoxyuridine-mediated cytotoxicity and radiosensitization require S phase progression.
The role of cell cycle redistribution in fluoropyrimidine-mediated radiosensitization remains unresolved. To determine if radiosensitization resulted from the redistribution of cells into a sensitive phase of the cell cycle, we assessed fluorodeoxyuridine (FdUrd)-mediated radiosensitization in flow-sorted mid-S phase HT29 human colon cancer cells. We hypothesized that if FdUrd-mediated radiosensitization were strictly the result of cell cycle redistribution, FdUrd-treated mid-S phase cells would remain as radioresistant as mid-S phase cells cultured in the absence of drug. However, we found that the mid-S phase cells from FdUrd-treated populations were markedly radiosensitized. To assess the role of S phase progression in radiosensitization, we exposed FdUrd-treated cells to aphidicolin, an inhibitor of DNA polymerase alpha, prior to irradiation. We found that aphidicolin blocked the radiosensitizing (and cytotoxic) effects of FdUrd. These results, combined with our previous observations that FdUrd-treated cells at the G1/S boundary are minimally sensitized, appear to disprove the hypothesis that sensitization results strictly from cell cycle distribution. Furthermore, they suggest that a key aspect of both FdUrd-mediated radiosensitization and cytotoxicity is S phase progression on a damaged DNA template.


[Delirium: Concepts, Etiology, and Clinical Management].
Delirium is a common condition: up to 35 percent of non-ICU- and 80 percent of ICU-patients experience delirium - particularly the elderly suffering from cerebral dysfunction accompanied by acute infection, surgery, or change of medication. Medical staff should be alert for decrease (within hours) of concentration, memory, orientation, and consciousness - especially when agitation appears and symptoms are fluctuating. Vegetative lapses and seizures may complicate the course, in particular in delirium in withdrawal (of alcohol or drugs). Treatment comprises neuroleptic and sedative medication (be careful with benzodiazepines because of their delirogenic potential) as well as alpha-2-agonists for vegetative derangements and anti-epileptics in case of seizures. As usual: start with low doses, and keep the medical treatment as short as possible. Additionally, take care in the · search and solution of delir-causes,. · termination of unnecessary medication (in particular, anticholinergic agents),. · comfort, intimacy and orientation,. · cognitive training and mobilization.. Avoiding a delirium is the best medicine. For that reason, identification of patients at risk, early detection of signs of delirium and prevention are most important. Beside factors 2 to 4, personalized treatment has been proved to be very helpful.


Dose response of monoclonal tumor induction with 3-methylcholanthrene in mosaic mice.
Inductions of monoclonal tumors, as judged by their single phenotype of phosphoglycerate kinase, in mice with X-chromosome inactivation mosaicism, were observed after s.c. injection of doses of 3-methylcholanthrene of 0.005 to 2 mg/mouse. The tumors induced (79% fibrosarcomas) exhibited the single-enzyme phenotype with 93% frequency at the lowest dose and with 57% frequency at the highest dose, indicating the dependence of monoclonal tumor induction on the dose of carcinogen.


The Ellis Jones Method of Treating Chronic Peroneal Subluxation: Revisited and Colorized After 87 Years.
Chronic cases of peroneal subluxation typically call for surgical treatment; however, research on current surgical procedures suggests nonuniformity. The purpose of this study is to remind surgeons of the efficacy of an older surgical method by using the case of a selected patient. In this study, the Ellis Jones procedure was performed on a patient who had been suffering from a chronic peroneal subluxation for 22 years, since, in this particular case, other approaches were deemed likely to be unsuccessful. The patient had hypertrophied, frayed, and swollen tendons, which were unsuitable to be rerouted, whereas the superior peroneal retinaculum was diminished and deepening procedures would not be able to establish sufficient volume for retaining the hypertrophied tendons. After the debridement and repair of the peroneal tendons, ¼ of the lateral Achilles tendon was split, passed through a hole in the fibula, and sutured onto itself, and the subluxation path of the peroneal tendons was closed with an effective tendon barrier. The patient returned to work after 8 weeks of the surgery and was followed up for 4 years postoperatively. On selected patients, the Ellis Jones surgical method might therefore still be applied.Levels of Evidence: Level V.


Delayed urethral obstruction after uterine torsion in a pregnant dog.
A 4 yr old pregnant female shih tzu was presented with abdominal discomfort and bloody vulvar discharge. The nongravid uterine horn was reflected caudally over the trigone, obstructing urine outflow. A cesarian section and ovariohysterectomy were performed. Postoperatively, the hematuria and pollakiuria resolved. Seventeen days later, the pelvic urethra was completely obstructed by a soft tissue mass that was identified by rectal palpation, blocked catheterization attempts, contrast radiography, ultrasonography, and surgery. Management included temporary cystostomy tube and definitive prepubic urethrostomy. Histologic diagnosis was severe, multifocal, necrosuppurative urethritis with fibroplasia, fibrosis, and cellulitis, apparently secondary to ischemia. Delayed urethral obstruction is a potential complication of canine uterine torsion.


Randomised trial of ganciclovir and acyclovir in the treatment of herpes simplex dendritic keratitis: a multicentre study.
This study was designed to assess the relative efficacy of topical ganciclovir 0.15% gel and acyclovir 3% ointment in the treatment of herpes simplex dendritic keratitis. Both treatment modalities were administered on a five times daily basis to patients suffering from herpes simplex keratitis. Patients were assigned randomly to one of the two treatment groups for the purpose of the trial. They were then examined on days 2, 7, 10, and 14 to assess the rate of healing of the dendritic ulceration. There was no statistically significant difference detected in the rate of healing between the two treatment groups over the course of the trial. Review of the relative efficacy of topical ganciclovir and acyclovir in the treatment of herpes simplex dendritic keratitis showed that both treatment modalities were equally effective in their ability to heal the viral induced corneal ulceration. There were no significant side effects or adverse effects reported for either treatment modality.


Intraoperative autotransfusion in reconstructive hip joint surgery of patients with rheumatoid arthritis and ankylosing spondylitis.
The efficacy of a simple, low-cost device designed for intraoperative blood salvage and reinfusion, known as the Sorensen system, was studied during 24 hip joint operations in adult patients suffering from rheumatoid arthritis or ankylosing spondylitis. The total need for homologous blood was reduced to 28%, compared with a matched control group of patients who had previously undergone hip surgery by homologous blood replacement. In primary hip-replacement operations, the need for blood was met either completely by autotransfused blood or by the addition of 1 or 2 units of homologous blood. In revision arthroplasties, the maximal need for homologous blood was 6 units owing to a greater blood loss during operation. Postoperative changes in several hematologic variables measured were all very small. The autotransfusion system proved easy and safe to operate. No patients manifested complications. In our experience, the system may be considered an underutilized resource in rheumatological surgery.


Effects of metoclopramide and domperidone on cholinergically mediated contractions of human isolated stomach muscle.
The experiments examine the actions of metoclopramide and domperidone on the responses evoked by electrical field stimulation or by acetylcholine, in longitudinal muscle strips obtained from human stomach. Electrical field stimulation evoked contractions which were predominantly cholinergically mediated; metoclopramide 0.28-28 microM caused a concentration-dependent increase in the height of these contractions. In the presence of atropine and barium chloride, electrical stimulation evoked relaxations of the stomach muscle, probably by stimulating non-adrenergic, non-cholinergic inhibitory nerves; metoclopramide 28 microM had no effect on these relaxations. Metoclopramide 0.003-2.8 microM had no effect on contractions evoked by exogenous acetylcholine, although higher concentrations of the drug increased the contractions. The results suggest that in human isolated stomach, low concentrations of metoclopramide may increase electrically evoked cholinergic activity by increasing the release of neuronal acetylcholine. Stimulation by metoclopramide of cholinergic activity in the gut may therefore be an important mechanism by which the drug increases gastrointestinal motility during therapy. Cholinergically mediated contractions were not increased by domperidone, and other mechanism(s) of action may therefore be important for this drug.


The Schizophrenia-Related Protein Dysbindin-1A Is Degraded and Facilitates NF-Kappa B Activity in the Nucleus.
Dystrobrevin-binding protein 1 (DTNBP1), a gene encoding dysbindin-1, has been identified as a susceptibility gene for schizophrenia. Functioning with partners in synapses or the cytoplasm, this gene regulates neurite outgrowth and neurotransmitter release. Loss of dysbindin-1 affects schizophrenia pathology. Dysbindin-1 is also found in the nucleus, however, the characteristics of dysbindin in the nucleus are not fully understood. Here, we found that dysbindin-1A is degraded in the nucleus via the ubiquitin-proteasome system and that amino acids 2-41 at the N-terminus are required for this process. By interacting with p65, dysbindin-1A promotes the transcriptional activity of NF-kappa B in the nucleus and positively regulates MMP-9 expression. Taken together, the data obtained in this study demonstrate that dysbindin-1A protein levels are highly regulated in the nucleus and that dysbindin-1A regulates transcription factor NF-kappa B activity to promote the expression of MMP-9 and TNF-α.


A cluster of transcribed sequences between the Pb and Ob genes of the murine major histocompatibility complex.
The region of the murine major histocompatibility complex (MHC) between the Pb (A beta 3) and Ob (A beta 2) genes controls the expression of an intracellular complex named the LMP (low molecular weight polypeptide) complex. DNA probes for at least seven different genes mapping to this region were isolated. These hybridize to a minimum of eight different transcripts ranging from approximately 1.3 to 3.7 kilobases (kb). The deduced amino acid sequences of the corresponding cDNAs indicate that three of these genes are new members of the MHC class II gene family. These genes are transcribed in a tissue-specific pattern similar to that of the traditional class II genes. Two of the remaining four genes, HAM1 and HAM2, are homologous to one another and to a family of eukaryotic and prokaryotic transport proteins and may be involved in antigen processing. The tissue distribution of HAM1 transcripts is consistent with its proposed role in class I-restricted antigen processing, whereas HAM2 transcription appears more restricted and may be involved in antigen processing for class II-restricted T cells. The HAM2 gene may produce two differentially spliced transcripts. The identity of the remaining two genes is not known. Analyses of transcript sizes, tissue distribution, sequence, and genetic mapping data suggest that none of these genes code for LMP antigens.


Standardizing optic nerve crushes with an aneurysm clip.
Despite the widespread use of optic nerve injury models to simulate central nervous system injury, model protocols vary from laboratory to laboratory, making it difficult to directly compare findings between studies. To standardize the optic nerve crush injury model, the commercially available Yasargil aneurysm clip, which provides a consistent clamping force, was used to produce a crush injury to the rat optic nerve. Histology was verified with hematoxylin-eosin. The number of retinal ganglion cells (RGCs) was counted by fluorescent gold dye labeling. Following nerve crush injury, the density of RGCs was substantially reduced in the aneurysm clip-operated group relative to the normal and sham-operated groups, and no discernable difference was noted between the latter two control groups. The present findings suggest that Yasargil aneurysm clip effectively produces permanent injury to the optic nerve with evidence from retrograde tracing of RGCs and may provide a standard technique for optic nerve crush studies.


The Phenomenology of Healing: Eight Ways of Dealing With the Ill and Impaired Body.
Encounters with illness, impairment, and aging can disrupt one's experiential relationship with self, body, others, and world. "Healing" takes place when the individual is able to re-integrate his or her world, even if the condition is not medically curable. Drawing on work in the phenomenology of the body, this article examines a series of eight "healing strategies" individuals employ, each representing a different way of orienting toward the painful or impaired body. One may lean into freeing oneself from the body, through strategies of "refusing," "ignoring," "objectifying," or "transcending" its problems. Conversely, one may choose to embrace the body, through strategies such as "accepting," "listening," "befriending," or "witnessing." It can be beneficial to have a good number of such coping strategies at one's disposal, enhancing flexible response to chronic challenges. They also are often used in synergistic or complementary combinations.


Effect of an Acute High Carbohydrate Diet on Body Composition Using DXA in Young Men.
The aim of this study is to investigate the effect of a 3-day high-carbohydrate diet (≥75% of total calories) on body composition using dual-energy X-ray absorptiometry (DXA). Twenty non-obese young men (age 22.7 ± 2.6 years, BMI 23.5 ± 2.1 kg/m(2)) completed the study. Two DXA tests were performed for the measurement of total body weight, body mass index (BMI), body fat percentage as well as total, appendicular and central lean body mass (LBM) before and after a high-carbohydrate diet for 3 days. In addition, the participants completed a food diary during the 3-day high-carbohydrate diet to determine the mean percentage of carbohydrates consumed from total kilocalories. The mean percentage of carbohydrate intake over 3 days was 83.7 ± 8.4%. Our results showed a significant increase in total body weight, BMI as well as total and appendicular LBM after the high-carbohydrate diet (p < 0.01). In addition, we observed a strong tendency for lower body fat percentage values after the intervention (p = 0.05). No significant difference was observed for central LBM. These results indicate that the effect of an acute high carbohydrate diet seems to affect body composition values using DXA, such as total LBM. This study may lead to the need of standardizing a diet prior to using DXA.


NMR determination of total carbonyls and carboxyls: a tool for tracing the evolution of atmospheric oxidized organic aerosols.
Nuclear magnetic resonance (NMR) spectroscopy is used to investigate the chemical composition of organic aerosol in terms of functional group distribution with a special focus on secondary organic aerosol (SOA) formation. The knowledge of the functional group composition is a benchmark for understanding how SOA components partition into the particulate phase and undergo chemical transformation. The paper presents a new chemical derivatization procedure coupled to proton NMR (1H NMR) analysis for the specific determination of total carbonylic groups in atmospheric aerosol samples, which couples with the procedure for determination of total carboxylic acid groups described in a previous work. A first deployment of the combined techniques for the analysis of PM10 samples collected in the Po Valley in the warm season shows that the concentration in the particulate phase of total carbonyls varies and covaries with respect to those of carboxylic acids and of less-oxidized functional groups. The proposed methodology provides the breakdown of the oxygenated fraction of the organic aerosol into major functional groups through well-established chemical methods and can be used to benchmark the more sensitive and widely used aerosol mass spectrometric techniques.


Update in Müllerian anomalies: diagnosis, management, and outcomes.
Müllerian anomalies include a fascinating constellation of congenital malformations. There is significant diversity in anatomic variants and their respective long-term sexual and reproductive outcomes. We review the current controversies in classification and management of vaginal, uterine, and fallopian tube anomalies. Comparative trials of preoperative magnetic resonance imaging (MRI) and laparoscopic intraoperative evaluation have demonstrated a moderately well correlated prediction of anatomic description. Three-dimensional ultrasound technology appears to be equivalent to MRI in detecting uterine anomalies; however MRI is a consistently superior method of evaluating the vaginal and cervical anatomy. Despite advances in both modalities, care at an experienced center is most highly associated with an accurate preoperative diagnosis and a decrease in the number of inappropriate surgical procedures.Large case series continue to be the main vehicle by which treatment and surgical management of these unique anomalies are described and recommended. Case reports continue to provide information on novel approaches to improve operative techniques. In the absence of prospective studies, these series provide the only emerging information on the long-term sexual and reproductive function of women with vaginal and uterine anomalies. Recent developments in three-dimensional ultrasonography and MRI improve our ability to accurately describe and diagnose female reproductive tract anomalies. With the description of new complex malformations, which do not fall into the recognized American Society of Reproductive Medicine, formerly American Fertility Society (AFS) classification system, questions arise regarding embryologic development upon which this classification system is based and support attempts to devise a new, comprehensive classification. Advances in surgical correction have expanded the options for the reconstructive surgeon when approaching a patient with an anomaly of the reproductive tract.


The Effect of Surface Substrate Treatments on the Bonding Strength of Aluminium Inserts with Glass-Reinforced Poly(phenylene) Sulphide.
Materials composed of a polymer matrix reinforced with carbon/glass fibres providing lightweight and superior mechanical properties are widely used as structural components for automotive and aerospace applications. However, such parts need to be joined with various metal alloys to obtain better mechanical performance in many structural elements. Many studies have reported enhancements in polymer-metal bonding using adhesives, adhesive/rivet combined joints, and different surface treatments. This study investigated the influences of various surface treatments on the adhesion between glass-reinforced poly(phenylene) sulphide (PPS) and aluminium alloy during the injection over-moulding process. Adhesion strength was evaluated via the shear test. Correlations for the shear strength of the polymer-metal with different metal-substrate treatments were studied. Since the strongest bonding was attained in the treatment with the highest roughness, this value, as it determines the level of micromechanical interlocking of connected materials, seems to be a critical factor affecting the adhesion strength. Three-dimensional (3D) topographic images characterized with a 3D optical microscope indicated that there was a meaningful influence exerted by the interface topologies of the aluminium substrates used for the over-moulding process. The results further indicated that increases in a substrate's surface energy in connection with atmospheric plasma treatments negatively influence the final level of the bonding mechanism.


Topical 'Sydney' propolis protects against UV-radiation-induced inflammation, lipid peroxidation and immune suppression in mouse skin.
Propolis is a honeybee product that has been used in traditional medicine for antioxidant, immune-stimulating, anti-inflammatory and anti-cancer effects. Here, the potential of the topical application of a crude ethanolic extract of Sydney propolis to protect against UV-radiation-induced impairments associated with an increased risk of photocarcinogenesis has been tested in the hairless mouse. Solutions providing between 10 and 200 mg/kg propolis were applied to the skin following UV irradiation. The inflammation from exposure to UV (290-400 nm) was quantitated by measurement of increased skinfold thickness; lipid peroxidation was assayed by the induction of thiobarbituric acid reactive species in the skin; immune function was measured by the contact hypersensitivity (CHS) reaction and supported by the changes in epidermal cytokine expression. Propolis protected significantly and dose-dependently against both sunburn oedema and the suppression of CHS, and (at 100 mg/kg) against lipid peroxidation. The overexpression of IL-10 and the depletion of IL-12 characteristic of photoimmune suppression were markedly reduced by propolis. Further, the upregulation of IL-6 was decreased, and the associated induction of haem oxygenase was shown to play a role in propolis skin protection. Sydney propolis was able to effectively reduce cutaneous inflammation, immunosuppression and lipid peroxidation induced by UV exposure. It is concluded that Sydney propolis might have strong beneficial protective effects against photodamage and skin cancer development in humans.


Using Cluster Analysis to Identify Patient Factors Linked to Differential Functional Gains After Total Knee Arthroplasty.
The basis of poor outcomes following total knee arthroplasty (TKA) is multifactorial. Previous research aimed at predicting outcome following TKA focuses largely on outcomes measured between two specific time points (pre-to post-TKA). Analysis of outcomes measured over multiple time points (trajectory) may expose relationships between patients' characteristics and longitudinal outcome patterns that may otherwise remain obscured. The current study analyzed Short Form 36 Physical Component Score (PCS) trajectories of 656 patients composed of 3 time points over a 1-year period. Clusters were constructed utilizing MultiExperiment Viewer hierarchical clustering algorithm. Statistical significance of these clusters was assessed using MeV's built-in bootstrapping method. Patient characteristics of the resulting statistically conserved clusters were summarized and compared using Wilcoxon rank-sum test or chi-squared test as appropriate. Two distinct clusters of outcome trajectory were identified. Cluster 1 included 550 patients (84%) who demonstrated persistent PCS improvement at 6 and 12 months. Cluster 2 included 106 patients (16%) who demonstrated decline in PCS at 6 months followed by improvement at 12 months. Cluster 1 achieved earlier success, greater absolute mental and physical health scores as compared to Cluster 2 (P < .05), and demonstrated higher baseline mental health scores, lower baseline PCS, and a significantly higher proportion of non-Hispanic Whites (P ≤ .05). Cluster analysis identified distinct functional outcome trajectories following TKA. Specific differentiating patient factors were associated with differing trajectories. Future studies should focus on this method's ability to inform predictive models regarding patient outcomes.


Effects of polymer architecture and composition on the adhesion of poly(tetrafluoroethylene).
Poly(glycidyl methacrylate), PGMA, chains in linear and arborescent structures were incorporated onto surfaces of poly(tetrafluoroethylene), PTFE, films by hydrogen plasma and ozone treatment and atom transfer radical polymerization. The epoxide groups of the PGMA chains were further reacted with acetic acid (AAc), oxalic acid (XAc), allyl amine (AA), and ethylenediamine (EDN) to introduce hydroxyl and amine groups to the surfaces of the PTFE films. Surface characterizations performed by Fourier Transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy and X-ray photoelectron spectroscopy (XPS) confirmed the surface modification and the chemical structure. The PGMA chains in arborescent structures show a high effectiveness for the enhancement of the adhesion of PTFE films. The adhesion of PTFE films was also significantly enhanced by ring-opening reactions of the PGMA epoxide groups with acetic acid and amine compounds. A high value of 9.5 N cm(-1) in the optimum 180 degrees peel strength test was observed with PTFE/copper assemblies.


Introduction.
Quantum noise reduction in optical systems and the determination of quasi-distribution functions, in particular Wigner functions, to describe quantum optical states, have been central issues in quantum optics for a number of years. The generation of sources of squeezed light has opened very exciting possibilities of ultrahigh precision measurements beyond the standard quantum limit, by either interferometric or spectroscopic means. In the present issue, the paper by Mundarain and Orszag discusses the interferometric detection of ultrasmall signals, in particular gravitational waves, when one injects a squeezed state in the unused port of the interferometer. The authors find that the sensitivity of the system is very strongly affected by the quantum efficiency of the non-ideal photodetectors, when the squeezed signal is injected, as opposed to the ordinary vacuum case where the effects are rather small. This imposes strong conditions on the quality of those photodetectors. The standard quantum limit and the corresponding minimum detectable gravitational amplitude is also discussed in general, for short time measurements.


Indications and limitations of percutaneous cholecystostomy for acute cholecystitis.
Percutaneous cholecystostomy (PC) was used as an alternative to operative therapy in 21 elderly or critically ill patients with suspected acute cholecystitis. All had associated disabling diseases, ten (48 percent) were older than 65 years, nine (43 percent) were in the intensive care unit and eight (38 percent) were recovering from recent operations. Among the 21 patients, 18 had cholecystitis (eight calculous and ten acalculous); in three patients, the procedure was only diagnostic. In 16 of 18 patients with acute cholecystitis, immediate relief of symptoms and significant improvement of laboratory signs of cholecystitis occurred. Persistent signs of peritonitis and uncertainty of diagnosis led to cholecystectomy without complication in one patient. Colonic perforation, as a result of technical complications, necessitated laparotomy in another patient. No other complication of PC was noted. Mortality rate of a patient with cholecystitis, treated by PC, was 5.5 percent (one of 18). Among ten patients with acalculous cholecystitis, only one patient underwent cholecystectomy because of a direct complication of PC. The other nine patients are alive and symptom-free with an intact gallbladder after a mean follow-up period of 16 months. Among eight patients with calculous cholecystitis, four later underwent cholecystectomy, three died from underlying disease, and one patient had stones extracted percutaneously. These results indicate that PC is an effective temporary measure in elderly or critically ill patients with acute cholecystitis and, under close clinical supervision, a safe alternative to surgical intervention. In patients with acalculous cholecystitis, PC can be used as an immediate and definitive therapy, and cholecystectomy can be avoided.


Autophagy regulates homeostasis of pluripotency-associated proteins in hESCs.
The pluripotency of embryonic stem cells (ESCs) is maintained by intracellular networks of many pluripotency-associated (PA) proteins such as OCT4, SOX2, and NANOG. However, the mechanisms underlying the regulation of protein homeostasis for pluripotency remain elusive. Here, we first demonstrate that autophagy acts together with the ubiquitin-proteasome system (UPS) to modulate the levels of PA proteins in human ESCs (hESCs). Autophagy inhibition impaired the pluripotency despite increment of PA proteins in hESCs. Immunogold-electron microscopy confirmed localization of OCT4 molecules within autophagosomes. Also, knockdown of LC3 expression led to accumulation of PA proteins and reduction of pluripotency in hESCs. Interestingly, autophagy and the UPS showed differential kinetics in the degradation of PA proteins. Autophagy inhibition caused enhanced accumulation of both cytoplasmic and nuclear PA proteins, whereas the UPS inhibition led to preferentially degrade nuclear PA proteins. Our findings suggest that autophagy modulates homeostasis of PA proteins, providing a new insight in the regulation of pluripotency in hESCs.


Expression of RGS2, RGS4 and RGS7 in the developing postnatal brain.
The abundant expression of RGS (regulator of G-protein signalling) proteins in neurons, together with their modulatory function on G-protein-dependent neurotransmission, provides the basis for cellular adaptation to sensory inputs. To identify the molecular mechanism involved in the sensory experience-induced neural development, we performed a systematic survey of the localization of mRNAs encoding three subtypes of the RGSs (RGS2, RGS4 and RGS7) in developing rat brains by in situ hybridization through postnatal day 2 (P2), P10 and P18 to adult. The most dramatic changes of expression patterns were observed in the discrete neuronal cell layers of the cerebral neocortex (for RGS2 and 4), the hippocampus (for RGS2, 4 and 7), the thalamus (for RGS4) and the cerebellum (for RGS2 and 7). In the neocortex, RGS2 mRNA was enriched in the superficial cortical plate at P2, in contrast to RGS4, which was enriched in more mature neurons of the deeper layer V and VI. In the hippocampus, the neuronal cell layer-specific expression pattern of RGS2 developed from P2 to P18. RGS4 expression was temporarily confined to the CA pyramidal cell layer and not detectable in the dentate gyrus at P10 and P18. Similarly, a high level of expression of RGS7 was observed in the CA area, but not in the dentate gyrus at P2 and P10. In the cerebellum, the maturation of laminar expression patterns for the three RGSs correlated with neuronal maturation and synaptogenesis at P18. The most characteristic temporal pattern among the three RGSs was observed for RGS4 mRNA, which was highly enriched in the thalamocortical regions. The peaks of RGS4 expression were seen in the following regions with distinct onset and duration: the neocortex (from P2 onward), the hippocampus (P10 and P18) and the thalamus (from P18 onward). The divergent temporal and spatial expression of RGS subtypes and their dynamic control in the cortex, the hippocampus and the thalamus suggest that the RGS family could play multiple distinct roles in experience-dependent brain development.


Do children really eat what they like? Relationships between liking and intake across laboratory test-meals.
Liking plays a primary role in determining what and how much children eat. Despite this, the relationship between liking and intake of foods and beverages served as part of a meal is not often reported, even though pediatric feeding studies frequently collect such data. In addition, few studies have reported on the test-retest reliability of both hedonic ratings and laboratory intake among children. To address these gaps, this study was designed to assess the relationship between children's liking of items at a meal and subsequent intake. 61, 4-6 year-olds were recruited to participate in two identical laboratory sessions where liking of 7 foods (i.e., chicken nuggets, ketchup, potato chips, grapes, broccoli, cherry tomatoes, cookie) and 2 beverages (i.e., fruit punch, milk) was assessed (5-point hedonic scale) prior to ad libitum consumption of the same items at a meal. Spearman's correlations tested the relationship between liking and intake and intra-class correlations assessed inter-session reliability of both measures. Liking for potato chips (p < 0.01), grapes (p < 0.05), cherry tomatoes (p < 0.001), and fruit punch (p < 0.001) was positively associated with amount consumed, but no associations were found between liking and intake of other meal items. For the majority of meal items, test-retest reliability of liking and intake were significant (ranging from 0.34 for cookies to 0.93 for tomatoes). At a multi-component meal, children's hedonic ratings were both reliable and modestly predictive of subsequent intake, and the relationships were stronger for lower energy, less well-liked foods. Rather than eating what they like, these data are more consistent with the notion that children do not eat what they dislike.


Topical nipradilol: effects on optic nerve head circulation in humans and periocular distribution in monkeys.
To investigate the effects of topical nipradilol on blood velocity in the optic nerve head (ONH) in normal humans and the ocular and periocular distribution of topically instilled nipradilol in monkeys. In normal humans, 0.25% nipradilol was instilled in one eye and vehicle in the other twice daily for 7 days, and blood velocity in the ONH was measured by the laser speckle method. In monkeys, after a single instillation of 1% [(14)C]nipradilol in one eye, distribution of radioactivity was evaluated by whole-head autoradiography. Twice-daily 7-day instillation of nipradilol temporarily but significantly increased human ONH blood velocity, in the ipsilateral eye only (P = 0.005), independent of a reduction in the intraocular pressure. In monkeys, equivalent nipradilol concentration in the periocular tissue around the optic nerve insertion was higher on the ipsilateral side than on the contralateral side (140 +/- 25 ng/g and 42 +/- 10 ng/g, P = 0.022, n = 5). Radioactivity was higher in the periocular tissue behind the equator than around the optic nerve insertion on the ipsilateral side (P = 0.004), but not on the contralateral side. The equivalent nipradilol concentration in the ipsilateral posterior retina-choroid was 636 +/- 92 ng/g, which was significantly higher than that on the contralateral control side (521 +/- 92 ng/g, P < 0.001). The ipsilateral increase in ONH blood velocity induced by topical nipradilol in humans was attributed to drug that penetrated locally. Whole-head autoradiographic study suggests that topically instilled nipradilol can rapidly reach the posterior periocular tissue at pharmacologic concentrations.


How I do it: the stapled ileal J pouch at restorative proctocolectomy.
Ileal pouch-anal anastomosis (IPAA) following proctocolectomy is the preferred option for patients with medically refractory ulcerative colitis, indeterminate colitis, and familial adenomatous polyposis. However, it remains a procedure associated with morbidity and mortality. Pelvic sepsis, pouch fistulae, and anastomotic dehiscence predispose to pouch failure. We report our experience with an adaptation for the formation of the stapled ileal J pouch using the GIA™ 100 stapling device (Covidien, Mansfield, Massachusetts, USA). When creating the J pouch, we remove the bevelled plastic protector from the thin fork of the stapling device, allowing the staple line to be completed to the tip of the stapled efferent limb of the pouch, thereby minimizing potential blind ending in the efferent limb and injury to the transverse staple line. Patients undergoing elective IPAA at our institution over a 5-year period using this adapted stapling technique for creation of the ileal J pouch were reviewed. Data were collected from a prospectively maintained inflammatory bowel disease database, theater records, and patient chart review. Forty-one patients underwent IPAA using this technique at our institution during the study period. Postoperative morbidity was encountered in 11 of 41 patients including pelvic sepsis, pouch fistulae, anastomotic stricture, or leak. There was no morbidity observed related to a blind efferent limb or transverse staple line disruption. No mortality was observed in this series. Maximizing the length of the efferent fork of the GIA stapling device can reduce the length of redundant efferent J limb of the ileal J pouch. This may reduce the incidence of torsion, volvulus, distension, fistulae/sinuses, and pelvic sepsis/anastomotic leak following IPAA.


The potential global distribution of the papaya mealybug, Paracoccus marginatus, a polyphagous pest.
The papaya mealybug, Paracoccus marginatus, is a highly polyphagous invasive pest that affects more than 200 plants, many of which are of economic importance. We modelled the potential distribution of P. marginatus using CLIMEX, a process-oriented, climate-based niche model. We combined this model with spatial data on irrigation and cropping patterns to increase the real-world applicability of the model. The resulting model agreed with known distribution points for this pest and with broad areas where P. marginatus has been reported, but for which no GPS data were available. Our model highlights the potential expansion of P. marginatus into novel areas in Central and East Africa, as well as further expansion in Central America and Asia, as these areas are highly climatically suitable, and have large expanses of suitable crop hosts. It also highlights areas, such as the central and eastern states of the USA as well as the western provinces of China, that are suitable for seasonal invasions of P. marginatus. Our results offer refined resolution on areas with high potential for invasion by P. marginatus. © 2020 Society of Chemical Industry.


Obesity and heart failure as a mediator of the cerebrorenal interaction.
The obesity epidemic is contributing substantially to the burden of cardiovascular disease including heart disease and congestive heart failure, in the United States and the rest of the world. Overnutrition as a driver of obesity, promotes alterations in fatty acid, lipid, and glucose metabolism that influence myocardial function and progression of heart failure from diastolic to systolic failure. The association of progressive heart failure and progressive chronic kidney disease is well documented and often referred to as the cardiorenal syndrome, as well as a prognosticator for cerebrovascular disease (e.g. stroke). Whether the relationship between obesity, heart disease/failure and risk for chronic kidney disease and stroke is direct or a confluence of risk factors is poorly understood.


Cellular localisation of a water-soluble fullerene derivative.
Fullerenes are a new class of compounds with potential uses in biology and medicine and many insights were made in the knowledge of their interaction with various biological systems. However, their interaction with organised living systems as well as the site of their potential action remains unclear. In this work, we have demonstrated that a fullerene derivative could cross the external cellular membrane and it localises preferentially to the mitochondria. We propose that our finding supports the potential use of fullerenes as drug delivery agents as their structure mimics that of clathrin known to mediate endocytosis.


Detrimental kinematics of a flat on flat total condylar knee arthroplasty.
Fourteen subjects having a flat on flat condylar posterior cruciate retaining total knee arthroplasty were evaluated under different in vivo weightbearing conditions, with six performing a deep knee bend and eight walking at normal gait. An interactive model fitting algorithm was used to convert two-dimensional fluoroscopic images into three-dimensional computer aided design solid model images. The femorotibial contact positions for the medial and lateral condyle started posterior at full extension. With a deep knee bend the lateral condyle acted as a pivot, and the medial condyle slid in the anterior direction. Five of six had lateral condyle liftoff (maximum 1.6 mm) and abnormal positive screw home motion was seen from 0 degree to 90 degrees flexion. During gait, all femorotibial contact positions were posterior in extension and throughout the cycle. Six of eight patients experienced lateral condyle liftoff (maximum 3.5 mm), but minimal screw home motion was seen. Abnormal medial condyle posteroanterior sliding, lateral condyle liftoff, and erratic screw home motion may be related to abnormal wear characteristics of this flat on flat condylar design.


[Pharmacological study on levofolinate in intraperitoneal leucovorin-5-FU chemotherapy].
We report the pharmacological findings on levofolinate after the intraperitoneal administration of leucovorin-5-FU. Levofolinate 300 mg/saline 500 ml and 5-FU 750 mg/saline 500 ml were administered intraperitoneally over 1.5 h. The plasma and intraperitoneal concentrations of levofolinate at 0, 0.5, 1, 2, 4, 8, 22(20) h after the administration were evaluated at 6 points with HPLC analysis. The intraperitoneal levofolinate concentration went up as high as 100 micrograms/ml and remained above 10 micrograms/ml over 8 hours. This suggested that intraperitoneal administration elevated the portal vein and abdominal lymphatic levofolinate levels. Intraperitoneal levofolinate-5-FU is a promising protocol for gastro-intestinal cancers.