Multiple crack detection in 3D using a stable XFEM and global optimization.
A numerical scheme is proposed for the detection of multiple cracks in three dimensional (3D) structures. The scheme is based on a variant of the extended finite element method (XFEM) and a hybrid optimizer solution. The proposed XFEM variant is particularly well-suited for the simulation of 3D fracture problems, and as such serves as an efficient solution to the so-called forward problem. A set of heuristic optimization algorithms are recombined into a multiscale optimization scheme. The introduced approach proves effective in tackling the complex inverse problem involved, where identification of multiple flaws is sought on the basis of sparse measurements collected near the structural boundary. The potential of the scheme is demonstrated through a set of numerical case studies of varying complexity.


Nutritional status and delirium in long-term care elderly individuals.
Delirium is physiologically plausible in elderly individuals with a poor nutritional status. We explored body composition, serum protein levels, and delirium in a multicenter long-term care study using bioelectrical impedance analysis (BIA). Estimates from the BIA procedure included the body cell mass and fat-free mass (FFM) of nursing home elderly residents (N = 312). Increased delirium was identified in men and women who were leaner and had lower FFM. Clinical surveillance for delirium in frail elderly individuals with low serum albumin levels and polypharmacy is recommended because of their increased likelihood of having drug toxicities for medications with protein-binding properties.


Correction to: Evolution of emergency medical services in the Kingdom of Bahrain.
An amendment to this paper has been published and can be accessed via the original article.


Pain memory in patients with chronic pain versus asymptomatic individuals: A prospective cohort study.
The main objective of this study was to assess pain memory as well as long-term episodic memory, both in patients with chronic pain (CP) and in asymptomatic participants (AP). A prospective cohort study design was used. Sixty-eight participants were divided into two groups: CP (n = 34) and AP (n = 34). The protocol consisted of taking eight tests, four painful provocation tests and four distracting tests, and completing a memory test on the order of the tests at the end of the experiment and at 1-month post-experiment. Patients with CP showed acceptable concordance in the classification, in ascending order from lower to higher pain perception, both post-experiment and 1-month post-experiment (κ = 0.41-0.60, p < .001). No differences were found regarding recall of the order of the tests, but differences were found in painful tests isolated only post-experiment in the CP group with a moderate effect size (p < .05, d = 0.77). Patients with CP had a more reliable memory than AP in relation to the memory of the pain caused experimentally until at least 1 month after the experiment. Interspersing distraction tests appeared to result in increased complexity and difficulty in coding and decoding information in patients with CP, leading to similar reliable long-term memory consolidation in comparison with AP. Treatments directed towards chronic pain should consider the influence of painful memories and their establishment towards long-term explicit episodic memories in patients with chronic pain, as well as the influence of cognitive-evaluative and affective-motivational variables on memory. Not causing pain while implementing a treatment whose objective is to reduce pain could reduce the probability of developing new painful memories in patients with chronic pain.


A review of the phytochemistry and pharmacological activities of Magnoliae officinalis cortex.
Magnoliae Officinalis Cortex (the dried bark of Magnolia officinalis), a widely used traditional Chinese medicine, is also known as 'Houpo' (Chinese: ). Magnoliae Officinalis Cortex has a wide range of pharmacological effects and has been used to treat conditions such as abdominal distention, vomiting, diarrhea, food accumulation, Qi stagnation, constipation, phlegm and fluid retention and cough resulting from asthma. The present paper reviews advances in research relating to the botany, ethnopharmacology, phytochemistry, pharmacology and toxicology of Magnoliae Officinalis Cortex. Prospects for future investigation and application of this herb are also discussed. Information on Magnoliae Officinalis Cortex was obtained from published materials, including ancient and modern books; PhD and MSc dissertations; monographs on medicinal plants; the pharmacopoeia of different countries and electronic databases, such as SCI finder, PubMed, Web of Science, ACS, Science Direct, Wiley, Springer, Taylor, AGRIS, Europe PMC, EBSCO host, CNKI, WanFang DATA, J-STAGE and Google Scholar. More than 200 chemical compounds have been isolated from Magnoliae Officinalis Cortex, including lignans, phenylethanoid glycosides, phenolic glycosides, alkaloids, steroids and essential oils. The plant has been reported to have pharmacological effects on the digestive system, nervous system and cardiovascular and cerebrovascular systems, as well as antibacterial, anti-tumour, analgesic, anti-inflammatory and anti-oxidative effects. Magnoliae Officinalis Cortex is an essential traditional Chinese medicine with pharmacological activities that mainly affect the digestive system, nervous system and cardiovascular and cerebrovascular systems. This review summarises its botany, ethnopharmacology, phytochemistry, pharmacology and toxicology. These information suggest that we should focus on the development of new drugs related to Magnoliae Officinalis Cortex, including specific constituents, so that Magnoliae Officinalis Cortex can exert greater therapeutic potential. Meanwhile, it is important to pay attention to the rational use of Magnolia resources, avoiding over-harvesting which could lead to lack of resources. We should also pursue research on Magnolia substitutes and develop resources such as Magnoliae Officinalis Flos and Magnolia Leaf.


Long-term social isolation inhibits autophagy activation, induces postsynaptic dysfunctions and impairs spatial memory.
Social isolation in adolescence leads to lasting deficits in hippocampal-dependent tasks. The reported effects of isolation on learning and memory in the Morris water maze and synaptic-related proteins have been inconsistent. Moreover, the autophagy level and its effect on cognition in the isolation model are also not clear. In the present study, we did an extended isolation period up to six months to establish a stable and appropriate isolation model to investigate the cognitive changes associated with it. The mTOR inhibitor rapamycin was systemically administered to mice to determine the roles of autophagy activation on cognitive changes. We discovered that long-term post-weaning social isolation (L-PWSI) produced marked deficits in spatial learning and memory and inhibited CA1 long-term potentiation (LTP), but paired-pulse facilitation (PPF) and input/output (I/O) curve were unaffected. The results further showed that the L-PWSI significantly decreased the protein expression levels of PSD-95, GluA1, NR1 and NR2B in the hippocampus, and no significant changes in the extracellular release of glutamate and the protein expression levels of synaptophysin, synapsin I, GAP-43, NR2A and GABAA. Moreover, we found that L-PWSI increased the protein expression of p-AKT/AKT, p-mTOR/mTOR and p62, whereas the protein levels of LC3B and Beclin1 were decreased indicating an inhibition in autophagy activity. Intraperitoneal injection of rapamycin significantly potentiated fEPSP slope and cognition-related proteins expression in the L-PWSI mice. These results therefore suggest that L-PWSI induces postsynaptic dysfunction by disrupting the interaction between AMPAR, NMDAR and PSD-95, and inhibit the autophagy activity which led to impaired spatial memory and cognitive function.


Single puncture combined lumbar erector spinae plane and quadratus lumborum block (SEQ block) in acetabular fracture surgeries: randomized clinical trial.
Acetabular fracture surgery can cause severe postoperative pain. A combined lumbar erector spinae plane block and paraspinous sagittal shift quadratus lumborum block may augment analgesia. Fifty two patients undergoing posterior column acetabular surgery were divided into: Group Single puncture combined lumbar Erector spinae and Quadratus lumborum block (SEQ), patients who received SEQ block before anesthesia; and Group morphine (MOR), those who received general anesthesia (GA) and morphine. Demographic characteristics were comparable. The heart rate and mean arterial blood pressure were significantly lower in the SEQ group than in the MOR group between 60 and 180 min intraoperatively (P < 0.001). Postoperative resting and dynamic visual analogue scale scores in the SEQ group were significantly lower than those in the MOR group at all studied periods (P = 0.022-0.001), except at 20 and 24 h postoperatively. Fentanyl was required in all MOR group patients at a mean dose of 110.0 ± 28.42 µg while 18 patients required fentanyl in SEQ group at a mean dose of 60.55 ± 25.54 µg. Postoperative morphine consumption was significantly less in SEQ group (6.33 ± 2.37 mg) than MOR group (17.0 ± 2.55 mg). Postoperative nausea and vomiting were recorded in eight and four patients in MOR and SEQ group, respectively. No complications associated with the block technique were observed. The SEQ block reduces the postoperative opioid consumption and provides stable intra and postoperative hemodynamics without observed complications in posterior column acetabular surgery.


Genome instability in AZFc region on Y chromosome in leukocytes of fertile and infertile individuals following exposure to gamma radiation.
Men are exposed to various doses of ionizing radiation due to living in regions with high natural background radiation, accidentally, occupationally or for cancer treatment. To study genomic instability of AZFc region to gamma radiation, blood samples from normal, oligozoospermia, and azoospermia individuals were irradiated by a Co-60 source. Irradiated cells were kept for 48 h in order to repair initial DNA damages. Real time PCR was performed for three markers (SY 1206, SY 1197, SY 579) for testing copy number variation before and after irradiation. Copy number variations were compared by calculation of cycle threshold comparative method. Copy number variations of studied markers in AZFc region (microdeletion and duplication) in all samples after exposure to radiation increased with a dose dependent fashion. The frequency of instability was significantly higher in samples from infertile men in comparison with fertile ones (p < 0.001). No significant difference was seen between the two infertile groups (p > 0.05). This observation might be a possible explanation for induction of azoospermia and oligozoospermia after radiotherapy. Increased frequency of induced microdeletion and duplication in infertile men compared with normal might be attributed to the deficiency in repair systems and the genetic factors involved in incomplete spermatogenesis of infertile men.


The effect of anchor modality on the reliability of vocal severity ratings.
The purpose of this study was (1) to confirm if anchors (ie, perceptual references) and training affect the inter- and intrarater reliability of perceptual analysis of various voice types and severities compared to receiving training alone, and (2) to determine whether the modality in which the anchor is presented affects rater reliability. In this study, modality refers to whether the anchor is presented auditorily, visually via a written definition (a textual anchor), or a combination of both anchor types. A randomized multigroup comparison was performed. Forty inexperienced judges were selected to rate 36 sustained vowel voice samples of various voice types (ie, normal, breathy, hoarse, and rough) in terms of perceived vocal severity using four different methods (No Anchor, Textual Anchor, Auditory Anchor, and Combined Textual/Auditory Anchors). Subjects were randomly assigned to one of the four conditions. Before the rating task, all subject groups received a brief training sessions (15-20 minutes in duration) in which voice quality type and severity definitions were provided and representative voice samples were listened to. A computer program was developed to present anchors in the form of an auditory sample, written definition, or both. A no anchor condition was also presented. Results indicated that the combination of training and anchors significantly improves the interrater reliability of perceptual voice ratings. In addition, the use of auditory anchors resulted in 95% confidence intervals that were significantly smaller for rating mild voice disorders, and both breathy and hoarse voice qualities. Textual anchors did appear to show some improvement over training alone (ie, no anchors), but were generally not as strong as the use of auditory anchors. However, the combination of textual and auditory anchors resulted in the greatest degree of interrater reliability as assessed via mean correlations. The ratings produced by the Auditory and Combined Anchor groups were also observed to have significantly smaller 95% confidence intervals for the rating of mildly dysphonic voice than the No Anchor or Textual Anchor groups, indicating greater consistency and increased precision of ratings for this level of severity. Anchors were not only useful in improving measures of reliability among judges, but were also able to do so without significantly increasing the amount of time that the judges had to spend on the rating tasks. No significant effect of anchors was observed for measures of intrarater reliability. The use of perceptual anchors (in particular, auditory anchors), in conjunction with training and computerized rating procedures, may provide the consistent methodology necessary to improve the reliability of perceptual judgments. Although textual anchors were not as effective as auditory anchors, the combination of auditory and textual information may result in overall improvements in interrater reliability.


Depression of liver microsomal vitamin K epoxide reductase activity associated with antibiotic-induced coagulopathy.
Hypoprothrombinemic changes in blood coagulation parameters, such as prolongation of prothrombin time, increase in the level of plasma protein induced by vitamin K absence, and decrease in plasma prothrombin level, were detected in rats fed a vitamin K-deficient diet. These changes were enhanced by the administration of beta-lactam antibiotics containing N-methyltetrazolethiol, thiadiazolethiol or methyl-thiadiazolethiol. Microsomal vitamin K epoxide reductase activity was suppressed with the maximum effect at 1-2 days after the treatment and with recovery, thereafter, gradually to the normal level after 5-7 days. Hypoprothrombinemic alterations in blood coagulation parameters following a single administration of antibiotic to vitamin K-deficient rats were somewhat delayed compared with the change in the epoxide reductase activity, but the effects of the antibiotic on both blood coagulation parameters and the enzyme activity disappeared completely 7 days after the antibiotic treatment. Antibiotic-induced depression of the epoxide reductase activity was observed even in the vitamin K sufficient rats, although the hypoprothrombinemic changes in the blood coagulation parameters did not develop. Vitamin K administration could normalize the blood coagulation parameters in the hypoprothrombinemic rats caused by treatment with the antibiotics but without recovery of the decreased epoxide reductase activity. These results suggest that some antibiotics inhibit liver microsomal vitamin K epoxide reductase, which causes hypoprothrombinemia to develop under vitamin K-deficient conditions.


Recalcitrant Palmar-Plantar Atopic Dermatitis Successfully Treated with Dupilumab: A Case Series.
Palmar-plantar atopic dermatitis is a common and debilitating condition with significant diagnostic and management challenges. The paper presents the successful treatment of dupilumab in five female patients with recalcitrant palmar-plantar atopic dermatitis. The Hand Eczema Severity Index (HECSI) and the Foot Eczema Severity Index (FECSI), eosinophils and IgE levels were evaluated before and after the treatment. Five recalcitrant palmar-plantar atopic dermatitis patients had substantial responses to dupilumab and the persistent pruritus was soon alleviated during the therapy. By week 16, all patients' palmar-plantar eczema has been almost clear, with significant decrease of HECSI and FECSI. The count of eosinophils and IgE levels returned to normal in all patients. Dupilumab significantly improves disease severity and reduces eosinophils and IgE in refractory palmar-plantar AD patients.


Recurrent hemolytic uremic syndrome in a renal transplant recipient.
This case report presents clinical, scintigraphic, duplex sonographic, and biopsy findings in a 23-year-old female renal allograft (RAG) recipient, who had transplantation for chronic renal failure secondary to hemolytic uremic syndrome (HUS). She demonstrated acute and rapidly progressing RAG failure at 7 weeks after transplantation.


Creation of an albino squid line by CRISPR-Cas9 and its application for in vivo functional imaging of neural activity.
Cephalopods are remarkable among invertebrates for their cognitive abilities, adaptive camouflage, novel structures, and propensity for recoding proteins through RNA editing. Due to the lack of genetically tractable cephalopod models, however, the mechanisms underlying these innovations are poorly understood. Genome editing tools such as CRISPR-Cas9 allow targeted mutations in diverse species to better link genes and function. One emerging cephalopod model, Euprymna berryi, produces large numbers of embryos that can be easily cultured throughout their life cycle and has a sequenced genome. As proof of principle, we used CRISPR-Cas9 in E. berryi to target the gene for tryptophan 2,3 dioxygenase (TDO), an enzyme required for the formation of ommochromes, the pigments present in the eyes and chromatophores of cephalopods. CRISPR-Cas9 ribonucleoproteins targeting tdo were injected into early embryos and then cultured to adulthood. Unexpectedly, the injected specimens were pigmented, despite verification of indels at the targeted sites by sequencing in injected animals (G0s). A homozygote knockout line for TDO, bred through multiple generations, was also pigmented. Surprisingly, a gene encoding indoleamine 2,3, dioxygenase (IDO), an enzyme that catalyzes the same reaction as TDO in vertebrates, was also present in E. berryi. Double knockouts of both tdo and ido with CRISPR-Cas9 produced an albino phenotype. We demonstrate the utility of these albinos for in vivo imaging of Ca2+ signaling in the brain using two-photon microscopy. These data show the feasibility of making gene knockout cephalopod lines that can be used for live imaging of neural activity in these behaviorally sophisticated organisms.


The NII2 gene of Hansenula polymorpha is involved in nitrite assimilation.
To establish a basis for genetic and molecular studies of nitrite assimilation in the methylotrophic yeast Hansenula polymorpha, we isolated and characterised six nitrite-negative mutants still capable of growing on nitrate. Gene isolation work yielded the NII2 gene, encoding a membrane protein homologous to the Saccharomyces cerevisiae Pho86p. Sequence analysis revealed an ORF of 860 bp encoding a 286-amino-acid protein with a predicted molecular mass of 32.8 kDa. This protein is shorter than its S. cerevisiae homologue, and is predicted to lack an ER-retention signal. Cell suspension work revealed that the null mutant is unable to take up nitrite from the medium.


Location of specific oligosaccharides in heparin in terms of their distance from the protein linkage region in the native proteoglycan.
Studies were conducted to define the location of components and sequences in heparin with respect to their distance from the peptide linkage in the native proteoglycan. A purified heparin-oligopeptide was linked via its amino terminus to a matrix containing an azo bond and an activated carboxyl group. The polysaccharide chain was maximally degraded, either with heparinase or nitrous acid, and the soluble products were removed. The heparin-oligopeptide fragments that remained on the matrix were released by reductive cleavage of the azo linkage and characterized. The fragments, as well as heparin released without prior degradation, contained serine and glycine as the principal amino acids; the ratio of galactose to xylose was 2:1. The ratio of glucosamine to serine of 33:1 in the undegraded heparin was reduced to 6:1 and 1:1 in the heparinase-treated and nitrous acid-treated products, respectively. The undegraded sample and the fragments contained phosphate in equivalent amounts, demonstrating its presence in the heparin-protein linkage region. The heparin-oligopeptide preparation was also fractionated by gel filtration and high and low molecular weight fractions thus obtained were each linked to the insoluble matrix. The products that were subsequently released were subfractionated on a molecular weight-calibrated column of Sephadex G-200, and eluates were assayed for activity in promoting the neutralization of thrombin and factor Xa by antithrombin. The results revealed a sharp decrease in specific activity in heparin-oligopeptide fractions below Mr = 15,000 indicating that the anticoagulant-conferring segment is located at about 20 disaccharide units away from the peptide linkage region.


Surgical Treatment for Toe Deformities in Stiff-Person Syndrome: A Case Report.
Stiff-person syndrome is a rare neurological disorder characterized by rigidity and painful spasms of the trunk and limbs, and patients sometimes have difficulty in walking due to rigid toe deformities. This is a case report of a 76-year-old woman suffering from stiff-person syndrome with painful rigid toe deformities regained walking ability after metatarsal osteotomy and cutting of the toe extensors for all toes in the left foot. For patients with stiff-person syndrome, surgical intervention is a powerful treatment option when they have developed rigid and painful toe deformities despite adequate pharmacological treatment.


How do hospitals engage patients and family members in quality management? A grounded theory study of hospitals in Brazil.
Patient and family engagement (PFE) is considered an essential element of the transformation of the healthcare system. However, it is characterised by its complexity and a small number of institutions that have implemented the mechanisms of engagement. To understand PFE in quality management (QM) in the hospital environment. A qualitative approach was guided by the grounded theory based in Straussian perspective. Data were gathered using semistructured interviews. The coding was performed by excerpts, using an inductive approach and the constant comparison technique. A total of seven Brazilian hospitals were selected based on the theoretical sampling technique. A total of five categories emerged, namely: patient partner, mechanisms of engagement, internal structure for engagement, maturity of the QM system and openness to change. Externally, three contextual factors can impact the engagement: the local health system, the profile of the community and the change in access to the information. At the centre of the change is the balance in power relations between patients and professionals, the sharing of information from the hospital and a proactive attitude towards improving services. The PFE involves a cultural and process change. Cultural change is represented by 'openness', that is, openness to learn, to listen and to consider new perspectives. The change in processes is in turn characterised by the phrase 'test and venture' because the model to be adopted may be different between hospitals. The patient's perspective allows actions to be driven towards what really matters to them, ensuring quality of service and safety, obtaining a new perspective to understand and solve problems, and stimulating a sense of urgency, more empathy and compassion in professionals.


Developmental changes in the expression of GABAA receptor alpha 1 and gamma 2 subunits in human temporal lobe, hippocampus and basal ganglia: an implication for consideration on age-related epilepsy.
Mutations of genes encoding GABA(A) receptor alpha 1 (GABARA1) and gamma 2 subunit (GABARG2) are associated with age-dependent epilepsy. The development of the subunits expression may be related to the age-dependency of epilepsy. Nevertheless, developmental and spatial changes in expression of GABA(A) receptors have not been examined in the human brain. Using immunohistochemistry, we examined the development of GABARA1 and GABARG2 in the human temporal lobe, hippocampus and basal ganglia in specimens obtained from 21 fetuses/subjects who died aged 22 gestation weeks (GW) to 75 years. Unique developmental changes of GABARA1 and GABARG2 were recorded in each region. In hippocampal pyramidal cells, GABARA1 was already found from 22 GW mainly on CA2-3, whereas GABARG2 was expressed later than GABARA1 predominantly in CA3. In the temporal cortex, both subunits appeared in the pyramidal cells layer from 22 GW, while GABARA1 and GABARG2 expression was increased from 29 to 38 GW, respectively. Furthermore, transient increase of GABARA1 was detected in the granular cell layer of the hippocampus from 29 GW to 4 months, in the cortical pyramidal cell layer from 29 to 40 GW, and in the putamen from birth to 5 years of age. Thus gradual or transient increase of GABARA1 and GABARG2 was found in every region at different age. These developmental changes in the expression of these subunits may contribute to the age dependency in some epilepsy syndromes where deficiency of GABARA1 and GABARG2 is involved.


Emergency Inter-Hospital Transfer of Children to PICUs in the United Kingdom: Qualitative Exploration of Parents' Experiences of Retrieval Teams.
Each year in the United Kingdom there are around 5,000 inter-hospital transfers of critically ill children into PICUs. There are few published descriptions of what this experience is like for parents. The objective was to describe parents' experiences of the inter-hospital transfer of their critically ill child to a PICU. Qualitative in-depth interviews. Twenty-four PICUs in England and Wales. Parent interview participants (n = 30) were purposively sampled from a larger pool of parent questionnaire respondents to create a sample diverse in child's age, presenting medical illness, retrieval team and whether a parent traveled in the ambulance. Open-ended semi-structured interviews using topic guides to encourage parents to describe their experiences of transfer. Interviews were audio recorded, transcribed verbatim and thematically analyzed using Framework Analysis. Parents' perceptions of transport staff as confident and competent through observation of clinical care, and positive communication experiences during the transfer process, were related to feelings of trust and being supported, as well as relief from distress. Parents varied in their needs for conversation and support. Parents who did not travel in the ambulance had fewer opportunities to interact with the transport team and experienced different challenges in the period prior to their child's admission to the PICU. Retrieval teams can influence how parents experience their child's emergency transfer to the PICU, offering parents proximity to knowledgeable staff. Satisfaction may be related to matching parents' needs. Understanding parents' needs and optimizing opportunities for effective communication between parents and staff are beneficial to parents.


Highly Efficient Photothermal Conversion and Water Transport during Solar Evaporation Enabled by Amorphous Hollow Multishelled Nanocomposites.
Solar evaporation, which enables water purification without consuming fossil fuels, has been considered the most promising strategy to address global scarcity of drinkable water. However, the suboptimal structure and composition designs still result in a trade-off between photothermal conversion, water transport, and tolerance to harsh environments. Here, an ultrastable amorphous Ta2 O5 /C nanocomposite is designed with a hollow multishelled structure (HoMS) for solar evaporation. This HoMS results in highly efficient photoabsorption and photothermal conversion, as well as a decrease of the actual water evaporation enthalpy. A superfast evaporation speed of 4.02 kg m-2 h-1 is achieved. More importantly, a World Health Organization standard drinkable water can be achieved from seawater, heavy-metal- and bacteria-containing water, and even from extremely acidic/alkaline or radioactive water sources. Notably, the concentration of pseudovirus SC2-P can be decreased by 6 orders of magnitude after evaporation.


Computational Insights into the Binding of Monolayer-Capped Gold Nanoparticles onto Amyloid-β Fibrils.
Amyloids-β (Aβ) fibrils are involved in several neurodegenerative diseases. In this study, atomistic molecular dynamics simulations have been used to investigate how monolayer-protected gold nanoparticles interact with Aβ(1-40) and Aβ(1-42) fibrils. Our results show that small gold nanoparticles bind with the external side of amyloid-β fibrils that is involved in the fibrillation process. The binding affinity, studied for both kinds of fibrils as a function of the monolayer composition and the nanoparticle diameter, is modulated by hydrophobic interactions and ligand monolayer conformation. Our findings thus show that monolayer-protected nanoparticles are good candidates to prevent fibril aggregation and secondary nucleation or to deliver drugs to specific fibril regions.


The effect of piroxicam on platelet aggregation.
Piroxicam inhibited aggregation of human and dog platelets caused by collagen, but not by adenosine diphosphate (ADP). Release of platelet ADP was inhibited by piroxicam.


Genetic susceptibility to keloid disease: mutation screening of the TGFbeta3 gene.
Keloid disease (KD) is a fibroproliferative dermal tumour of unknown aetiology. The increased familial clustering in KD, its increased prevalence in certain races and its presence in identical twins suggest a strong genetic predisposition to keloid formation. Transforming growth factor beta isoforms (TGFbeta) play a central role in wound healing and fibrosis and have been implicated in KD pathogenesis. Recent data has suggested that TGFbeta(3) has an important role in scar formation. There is little known about the genetic variation present within the TGFbeta(3) gene, which contains seven exons and six introns spanning 43,000 base pairs of the human genome. Exons one to seven and the promoter region (1000 bp upstream from exon 1 in the 5'-flanking regions) were screened in 95 Caucasian KD cases and 95 Caucasian controls for the presence of novel mutations using a high throughput DHPLC mutation detection technology. There were no mutations identified in any of the exonic regions, however, multiple nondisease associated mutations were found in the promoter region of the TGFbeta(3) gene. These data demonstrate that there is no association between the exonic and promoter regions of TGFbeta(3) gene and keloid scarring in our cohort of Caucasian patients.


Risk factors for recurrence and regrowth of spinal schwannoma.
Spinal schwannoma recurs after initial surgery at a rate of 4%-6%, with known risk factors including subtotal resection, multilevel involvement, large tumor size, and malignant histopathology. This study examined risk factors for schwannoma recurrence and residual tumor regrowth. Sixty-five patients who underwent resection of spinal schwannoma in our department between July 2010 and December 2018 and were followed up for more than 1 year were retrospectively analyzed for age, sex, follow-up duration, imaging and surgical data, recurrence, reoperation, and Japanese Orthopaedic Association scores before and 1 year after surgery. Patients with postoperative recurrence or residual tumor regrowth of >10% at the final visit (R+ group) were compared with patients without recurrence or regrowth (R- group). Multivariate logistic regression analysis was performed to analyze concurrent effects of risk factors on recurrence and regrowth. The 65 patients (mean age 52.4 years at surgery) had schwannomas involving cervical (n = 14), thoracic (n = 25), and lumbar (n = 26) spinal levels. Mean follow-up duration was 58 months. Location was intradural in 65%, extradural in 17%, and both intradural and extradural in 18%. There were 4 recurrences (6.2%), and the mean interval between surgery and recurrence was 18.8 months. Seven patients (10.8%) experienced regrowth. Comparing group R+ (n = 11) and group R- (n = 54), univariate analysis showed significant differences in Sridhar tumor classification, giant tumor (Sridhar classification II, IVb, and V), left-right and cranial-caudal tumor size, largest diameter, operative time, blood loss, subtotal resection, reoperation, fusion surgery, and follow-up duration. Multivariate logistic regression analysis revealed giant tumor (Sridhar classification types II, IVb, and V) as an independent risk factor for recurrence and regrowth. This retrospective review of 65 consecutive patients with spinal schwannoma in a single institution demonstrated that 16.9% had recurrence or regrowth, demonstrating that this potential risk should be kept in mind.


Mitochondrial dysfunction and cardiac ischemia/reperfusion injury are attenuated by nandrolone: Role of JAK-STAT3 pathway.
To investigate the effect of acute treatment with the anabolic steroid (AS) nandrolone decanoate in mitochondrial homeostasis and JAK-STAT3 signaling during the progression of cardiac ischemia/reperfusion injury (IR). Male Wistar rats (2 months old) were randomly allocated into four experimental groups: Control (CTRL), IR, AS, and AS + AG490. All animals were euthanized 3 days after a single intramuscular injection of nandrolone at 10 mg/kg (AS and AS + AG490 groups) or vehicle (CTRL and IR groups). Baseline mRNA expression of antioxidant enzymes superoxide dismutase (SOD) 1 and 2, glutathione peroxidase, catalase, and myosin heavy chain (MHC) α and β were compared between CTRL and AS groups. Isolated hearts were submitted to ex vivo ischemia and reperfusion, except for hearts from the CTRL group. Before the IR protocol, the JAK-STAT3 inhibitor AG490 was perfused in hearts from the AS + AG490 group. Heart samples were collected during reperfusion to investigate the effects on mitochondrial function. Results Antioxidant enzyme mRNA expression was unaffected, whereas the AS group exhibited decreased β- MHC/α-MHC ratio versus the CTRL group. Compared to the IR group, the AS group exhibited better recovery of post-ischemic left ventricular (LV) end-diastolic pressure and LV-developed pressure levels, while infarct size significantly decreased. Furthermore, mitochondrial production, transmembrane potential, and swelling were improved, whereas ROS formation was decreased versus the IR group. These effects were prevented by the perfusion of JAK-STAT3 inhibitor AG490. These findings suggest that acute nandrolone treatment can provide cardioprotection by recruiting the JAK-STAT3 signaling pathway and mitochondrial preservation.


Interphotoreceptor contacts at the inner segment level in primate retinas.
Just sclerad to the external limiting membrane of the retina of the monkey (M. fasciculata), short processes from some foveolal and foveal cone inner segments made dense contacts with each other and at the same level of peripheral human retina similar rod-cone and rod-rod contacts were observed.


Description of characteristics, management of care and healthcare direct costs of patients with HR+/HER2- early breast cancer in Italy: a real-world study involving administrative and pathological anatomy databases.
Healthcare administrative and pathological anatomy data were used to identify Italian patients with early breast cancer (EBC) with HR+/HER2- status at high risk of recurrence, evaluating drug utilization and other healthcare resource use in clinical practice. This retrospective analysis, based on 9.4 million of Italian National Health Service beneficiaries, included adult patients with hospitalization discharge diagnosis for EBC in 01/2015-12/2020. Those with HR+/HER2- status were selected; among them, patients that underwent removal of lymph nodes (LN) were analyzed. Of 24,137 patients with EBC and HR+/HER2- status, 3619 patients (15%) had documented LN removal. Overall, 4.7% of HR+/HER2- patients and 9.9% of patients with LN removal experienced distant relapse over a median follow-up of 33.2 months (Q1-Q3: 17.0-50.6). Local relapse occurred in approximately 9.1-9.3% of patients in each group. Among the 1,175 patients with LN removal that had available pathological anatomy data, 399 (34.0%) had pathological high-risk characteristics and 13.3% experienced distant relapse. One in ten patients with EBC who underwent LN removal experienced a relapse, highlighting the strong need to prevent early recurrence.


Adipocyte insulin-binding species: the size and subunit composition of the larger binding species.
Several investigators have reported that there are both large and small insulin-binding proteins in plasma membranes; the larger protein demonstrates nonlinear Scatchard binding, and the smaller protein has linear binding. We now present evidence that the larger insulin-binding species consists of four proteins of different sizes. Rat epididymal adipocyte plasma membranes were prebound with 125I-insulin and then exposed to 1 mM disuccinimidyl suberate for 15 min at 2 degrees C. The membranes were solubilized in 0.1% Triton X-100 and applied to a Sepharose 6B column. Peaks of radioactivity from the column were dialyzed, lyophilized, and analyzed by dodecyl-sulphate gel electrophoresis (5%, 100/l; mono/bisacrylamide). Autoradiograms of the gels were scanned with a densitometer. The Sepharose chromatogram revealed four radioactive peaks: peak 1 at column void volume; peak 2, Kav = 0.27; peak 3, Kav = 0.77; and peak 4, Kav = 1.09. Dodecyl sulphate electrophoresis of fractions in peak 2 demonstrated four bands on autoradiography; peak 1 did not enter the gel and peaks 3 and 4 ran with the dye front. Molecular weight estimates of the four insulin-binding species in peak 2 were 600, 500, 420, and 350 K. On dithiothreitol reduction each insulin-binding species yielded subunits of Mr approximately equal to 135 and 18 K. The three largest binding species demonstrated an additional 45-K dalton protein on dithiothreitol reduction, and the 500-K and 420-K binding species also yielded a 49-K dalton protein. These results suggest that the large insulin-binding protein in rat epididymal adipocytes contains several insulin-binding species, and that these insulin-binding species differ in the number of and the type of subunits they contain. In addition, it may be postulated that the nonlinear Scatchard binding associated with the larger binding protein is a consequence of the heterogeneity of the insulin-binding species in this Sepharose peak.


A prospective randomized controlled trial of Psychodermatology on the efficacy of Rilastil Difesa Sterile® cream in the hand eczema of healthcare workers during the COVID-19 pandemic.
Hand eczema is one of the most frequent dermatological diseases, with an incidence increased during the COVID-19 pandemic. The impact on life quality is considerable, giving rise to the need for a psycho-dermatological approach. This is a Randomized Control Trial (RCT) evaluating, either by the dermatological or psychological point of view, the effectiveness of an emollient and rehydrating topical product (Rilastil Difesa Sterile® cream) versus a standard treatment (i.e. moisturizing basic cream) in a group of 51 healthcare workers suffering from hand eczema during the COVID-19 pandemic. The enrolled subjects were randomized into a treatment or a control arm, treated for 8 weeks, and monitored through a clinical score (HECSI) and questionnaires evaluating the impact of the pathology and treatment on quality of life (DLQI and QOLHEQ). A psychometric evaluation was performed using the SCL-90 R, OCI-R, and CPDI scales. Our data, despite not reaching the statistical significance, demonstrated that both the clinical and psychological scores decreased mostly in patients treated with Rilastil Difesa Sterile® cream when compared to those treated with simple topical emollients. Moreover, we observed a high level of psychic suffering in dermatological patients and a parallel change in dermatological and psychological indicators, thus confirming their connection.


Ag Doped Au44 Nanoclusters for Electrocatalytic Conversion of CO2 to CO.
A novel Ag doped Au44 (C10 H9 )28 nanocluster (C10 H10 =1-ethynyl-2,4-dimethylbenzene) was synthesized, that is, Ag4+x Au40-x (C10 H9 )28 (x≤6), where four Ag positions located in the surface staple of the cluster have been determined, while six Au/Ag co-occupying positions have been found in the metal core of the cluster. The electronic configuration of Au44 (C10 H9 )28 cluster is significantly disturbed by doping Ag atoms, hence promoting the electron transport capability. For the two-electron conversion reaction of CO2 to CO in electrochemical reduction of CO2 , Ag doped Ag4+x Au40-x (C10 H9 )28 catalyst exhibited higher effective activity and long-term stability than its counterpart Au44 (C10 H9 )28 catalyst.


Circadian synchronization of hepatocyte proliferation in young rats: the role played by adrenal hormones.
The circadian rhythm of hepatic cell proliferation in rats appears on the 20th day of life, when the hypothalamo-adrenal axis is mature enough for circadian activity to occur. From the 20th day to the 30th day of life, the mitotic rhythm is progressively induced by a reduction in nocturnal values, while diurnal rhythms remain unchanged. Mitotic peaks emerge at 10.00 hours. A labelling index wave occurs 8 hr before the corresponding mitotic wave, with a peak at 02.00 hours and a minimum in the evening, coincidental with the acrophase of plasma corticosterone level (activity phase). Labelled mitoses curves and metaphase accumulation after colchicine injection show that the duration of the S, G2 and M phases remain approximately constant and that the circadian variation is due to a variation in the rate of cells that enter these successive phases. During the synchronization period (from day 20 to 30), the growth fraction decreases progressively. Adrenalectomy at this time is followed by a higher cell proliferation and all rhythms disappear after 2 days. Corticosterone injected before the triggering of the rhythmic activity in 17-day-old rats immediately reduces the labelling index, while the mitotic index is decreased 10 hr later; this delay is equal to the S + G2 duration. The results are discussed. They favour the hypothesis that the circadian variation of corticosterone is responsible for the induction of a circadian variation in developmental cell proliferation by inhibition of the G1-S transition when it is higher in the evening.


Training peers to deliver mental health support to adults with type 1 diabetes using the REACHOUT mobile app.
While peer support research is growing in the Type 1 diabetes (T1D) community, the peer supporter training (PST) process is rarely documented in detail. This study provides a comprehensive description of PST and evaluation for the REACHOUT mental health support intervention, and examines the feasibility and perceived utility of PST. Fifty-three adults with T1D were recruited to participate in a 6-hour, zoom-based PST program for mental health support. The program was structured in three parts: (1) internal motivation, resilience and empathy; (2) mindfulness, emotions and diabetes distress; and (3) active listening and deferring clinical questions to professionals. Candidates were evaluated based on eight pre-established competency criteria during a 5-day support trial with an assigned standardized T1D participant. Perceived usefulness of training skills was also assessed 3 months into the REACHOUT mental health support intervention. Fifty-one of the fifty-three candidates who completed training achieved the criteria to graduate. Mean scores for the eight competency domains were: listens actively (4.55); asks open-ended questions (4.12); expresses empathy (4.42); avoids passing judgment (4.67); sits with strong emotions (4.44); refrains from giving advice (4.38); makes reflections (4.5); and defers medical questions (4.58). Of the skills learned during the PST, 95% rated interpreting and discussing diabetes distress profile and expressing empathy as moderately to extremely useful. Findings demonstrate that it is feasible to recruit and graduate the number of trainees needed using a rigorous process. Only by making training protocols available can the PST be replicated and translated to other T1D populations (e.g. adolescents, parents of children with T1D).


Platelet-albumin (PAL) score as a predictor of perioperative outcomes and survival in patients with hepatocellular carcinoma undergoing liver resection in a Western center.
Preoperative selection of patients with hepatocellular carcinoma (HCC) who will benefit from resection is highly advisable. The Platelet-Albumin (PAL) score was developed as a predictor of survival and morbidity following HCC resection. However, this has never been tested in western populations. The impact of PAL score on perioperative outcomes and survival was evaluated and compared to Child-Pugh, Model for End-Stage Liver Disease (MELD), and albumin-bilirubin (ALBI) scores in patients who underwent HCC resection. A total of 182 patients were included. Postoperative morbidity was higher in patients with PAL grade II-III (P = 0.039), ALBI grade II-III (P = 0.028), and MELD >10 (P = 0.042). Post-hepatectomy liver failure (PHLF) occurred in 36 patients (19.8%) and was significantly higher in the PAL II-III and ALBI score II-III subgroup (P = 0.001). The PAL II-III group was the only one associated with higher perioperative mortality (OR 3.3, P = 0.036). The PAL score was an independent prognostic factor for overall survival in multivariate analysis (P = 0.018) and was the only one with the areas under the curve in ROC analysis significantly different for morbidity, PHLF, and mortality. The PAL score predicts postoperative complications, mortality, PHLF, and survival following liver resection for HCC in western patients.


Clinical implications of continuous measurement of energy expenditure in mechanically ventilated patients.
Energy expenditure was monitored in 20 critically-ill mechanically ventilated patients using the Siemens-Elema Oxygen Consumption Calculator (OCC 980). Energy expenditure was measured continuously over the 24-h period in all patients (altogether, over 2500 patient hours; range 48-288 h). A predicted energy expenditure was calculated for each patient from standard tables for basal metabolic rates modified according to previously published reports on the influence of trauma, infection and elevated body temperature. For all patients combined, the agreement between the predicted and the measured energy expenditure was good. However, in individual patients the measured energy expenditure varied between 48 and 148% of the predicted value. The measured energy expenditure in surviving traumatized and/or septic patients correlated well (95-100%) with the predicted value at the time when weaning off the ventilator could be initiated. On the first day of measurements, the energy expenditure (in % of the predicted value) in the six patients who later died was significantly lower than in surviving patients (84 +/- 6 vs 107 +/- 2%; p < 0.01). Over a 24-h period, energy expenditure, defined as the value noted during a stable 30-40-min period of measurement, varied between 12 and 50% in the individual patients. This study shows that energy expenditure cannot be accurately predicted in the individual patient, that an energy expenditure below predicted values appears to be indicative of a poor prognosis and that short periods of energy expenditure monitoring may fail to reflect 24-h conditions.


Screening practices for identifying type 2 diabetes in adolescents.
To characterize pediatrician and family physician (FP) screening practices for type 2 diabetes among adolescents and to examine the impact of the 2010 American Diabetes Association (ADA) guidelines, recommending use of Hemoglobin A1c (HbA1c). We conducted a cross-sectional mail survey of a random sample of 1,400 U.S. pediatricians and FPs and we received 604 eligible responses. Our main outcome measure was the types of tests ordered by physicians, particularly HbA1c, when presented with a hypothetical scenario. The overall response rate was 52% (57% for pediatricians and 48% for FPs). Fasting glucose and HbA1c were the most commonly ordered tests. Overall, at least 58% of physicians ordered HbA1c; 35% ordered HbA1c in conjunction with fasting tests; and 22% ordered HbA1c alone or with nonfasting tests. Only 38% of providers were aware of the new ADA recommended HbA1c screening guidelines. However, a majority (67%) said they would change their screening practices. In the context of the guidelines, 84% of physicians would now order HbA1c. Furthermore, there was a large increase in the proportion of physicians who would shift to using HbA1c only or with other nonfasting tests. When screening adolescents for type 2 diabetes, providers are more likely to order HbA1c and order fewer fasting tests in response to the new ADA guidelines. HbA1c has lower sensitivity and higher costs than other testing modalities in children, therefore increasing uptake of this test (HbA1c) in children may have implications for both detection rates and healthcare costs.


Causal learning from joint action: Collaboration helps first graders but hinders kindergartners.
This study investigated whether early school-aged children's causal learning from collaborative joint action differs from their learning from their own individual action or observation. Children in a joint condition performed causal interventions with an adult on two causal systems. Children in an independent condition took turns and observed an adult perform the same interventions on one system and performed the same interventions themselves on the other system. Joint action improved first graders' (n = 60) causal inference compared with individual action and observation. However, joint action impaired kindergartners' (n = 60) inference relative to individual action and observation. These findings demonstrate that joint action, as a component of collaborative activity, can help or hinder inductive causal learning depending on features of the learner. Children's abilities to learn from collaborative joint action undergo a developmental shift during the early school years.


[Nurses engaged in the fight against leprosy].
Even now in the 21st century, leprosy is still rife, notably among poor populations. In the regions of the world concerned, nurses specialised in the disease play an essential role in supporting the screening, treatment and reintegration of patients. In more than twenty countries, the Order of Malta France is acting to fight against leprosy.


Use of chiral zwitterionic surfactants for enantiomeric resolutions by capillary electrophoresis.
The enantiomeric resolution of 1,1'-binaphthyl-2,2'-diamine and Tröger's base was investigated using the commercially available zwitterionic surfactants 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulphonate (CHAPS) and 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulphonate (CHAPSO). Resolution of the weakly basic chiral probes was achieved using varying concentrations of surfactant, above their critical micellar concentrations, in a phosphate buffer (pH 2.5; 100 mM) to ensure ionisation of the analytes. Both CHAPS and CHAPSO were employed in the absence of additional coselectors or surfactants as sole micellar-forming agents. The addition of organic modifiers, methanol and acetonitrile (ACN), to the background electrolyte (BGE) was found to have a detrimental effect on enantioselectivity presumably by alteration of the phase polarity.


Role of endogenous nitric oxide in the control of canine pancreatic secretion and blood flow.
Endogenous nitric oxide has been implicated in the control of mesenteric circulation, but its role in the control of pancreatic blood flow and exocrine pancreatic secretion has not been studied. Secretory studies were performed on conscious dogs with chronic pancreatic fistulas, and changes in pancreatic blood flow were measured by laser Doppler flowmetry in anesthetized animals. Infusion of NG-nitro-L-arginine did not affect basal pancreatic protein secretion but suppressed an increase of this secretion induced by L-arginine but not that induced by glyceryl trinitrate. Sham-feeding, meal feeding, and infusion of secretin plus cholecystokinin induced pancreatic protein outputs reaching, respectively, 30%, 74%, and 50% of cerulein maximum in these dogs. Infusion of NG-nitro-L-arginine caused a profound inhibition of these secretions, whereas the addition of L-arginine reversed this inhibition in part. NG-nitro-L-arginine or L-arginine added to the incubation medium of isolated canine pancreatic acini did not affect basal or cholecystokinin-induced amylase release. In anesthetized dogs, infusion of NG-nitro-L-arginine caused a significant reduction in the pancreatic blood flow both while resting and following stimulation with secretin plus cholecystokinin but did not affect this flow in animals treated with glyceryl trinitrate. Addition of L-arginine attenuated the decrease in pancreatic blood flow and the increase in systemic blood pressure caused by NG-L-nitro-arginine. Endogenous NO affects pancreatic secretion probably through the changes in the vascular bed.


The branchial circulation and the gill epithelia in the Atlantic hagfish, Myxine glutinosa L.
The vessels of the branchial circulation of the Atlantic hagfish, Myxine glutinosa, and their relationship with the gill epithelia have been studied by light and electron microscopy. The inner surface of the pouch wall (containing the interconnected radial arteries) and the afferent and efferent unbranched portions (cavernous tissues) of the radially oriented gill folds are covered by a multilayered epithelium. The lamellar portion that is characterized by pillar cells is lined by a thin bilayered epithelium. The thin-walled sinusoid system is part of an arterio-venous circulation. This is demonstrated by the presence of arterio-venous anastomoses and by the connection to the peribranchial sinus. The sinusoid system has a close spatial relationship to the multilayered epithelium. The multilayered epithelium consists of pavement cells, cells of the medial layer and basal cells. Granulated cells are often found in the basal half of the epithelium. The pavement cells are characterized by large vesicles in close apposition to the apical plasma membrane. Ionocytes, which display a cytoplasmic tubular system that is continuous with the intercellular space, a high number of mitochondria, and small apical vesicles, are present. The occurence of the ionocytes in the afferent multilayered epithelium as well as the bilayered lamellar epithelium, the morphology of the ionocyte, and the absence of accessory cells is reminiscent of the freshwater teleost gill, and in part the elasmobranch gill, and is discussed in relation to osmo- and ion regulation.


Novel insights into the biology and physiology of the Ito cell.
Ito cells, perisinusoidal mesenchymal elements with possible pericytic functions within the liver, recently have been shown to play multiple physiological and pathophysiological roles. In particular, several in vivo and in vitro studies have clearly indicated that Ito cells play a relevant role in the progression of liver fibrogenesis. More recently, attention has been focussed on the mechanisms leading to Ito cell activation, proliferation and synthesis of extracellular matrix components. Among other soluble factors potentially involved in these processes, transforming growth factor-beta 1 and platelet-derived growth factor have been shown to act in a paracrine, and possibly autocrine, fashion on Ito cells, thus perpetuating their activated state. Finally, other studies have shown that Ito cells could play an active role in chronic liver tissue inflammation by promoting chemotaxis of infiltrating inflammatory cells.


The Potential of Psychedelics for the Treatment of Episodic Migraine.
This review presents the existing literature of and a framework for how psychedelic drugs might be applied as therapeutic agents in episodic migraine. The therapeutic effects of psychedelics in headache disorders have been reported for decades and controlled investigations are now beginning. In the first and only clinical trial of a psychedelic drug in migraine, the single administration of low-dose psilocybin reduced weekly migraine days and pain intensity for the following 2 weeks in episodic subjects. These transitional effects, along with abortive effects in two subjects and additional findings in cluster headache, offer insight into the potential medicinal use of this and other psychedelic drugs in episodic migraine. The existing evidence supports the continued investigation of psilocybin and other psychedelics as transitional treatments in episodic migraine. Acute and preventive effects also exist, but the risks may outweigh benefits with these applications. Future research of psychedelics in episodic migraine should be tailored for this condition and not modeled after protocols used in other medical or psychiatric conditions.


Ropivacaine and levobupivacaine for bilateral selective ankle block in patients undergoing hallux valgus repair.
A selective ankle block, blocking the tibial, deep and superficial peroneal nerves, can be used successfully for great toe surgery. No comparative information is available on selective ankle block using ropivacaine and levobupivacaine. We compared the onset time and success rate of a selective ankle block using low volumes (12 ml) of ropivacaine 10 mg/ml and levobupivacaine 7.5 mg/ml in 40 patients undergoing elective repair of bilateral hallux valgus. Each patient received an ankle block induced in one foot with ropivacaine and in the contralateral foot with levobupivacaine. The success rate was higher [90% vs. 75%, hazard ratio (95% CI) 0.39 (0.23-0.64)] and anesthesia onset time was shorter (median, 10 vs. 20 min) after ropivacaine than after levobupivacaine. In successful ankle blocks, post-operative pain was similar in the two groups. In this study, ropivacaine 10 mg/ml had a shorter anesthesia onset time and a higher success rate than levobupivacaine 7.5 mg/ml for selective ankle block.


Diagnostic and prognostic value of serum L1-cell adhesion molecule in esophageal squamous cell carcinoma.
L1 cell adhesion molecule (L1CAM) has been found to be dysregulated in several types of human cancers. Here, we aimed to determine the level of soluble L1CAM in serum of patients with esophageal squamous cell carcinoma (ESCC). Serum levels of L1CAM were determined by an enzyme-linked immunosorbent assay (ELISA) in 191 patients with ESCC and 94 normal controls. Receiver operating characteristics (ROC) was employed to calculate diagnostic accuracy. Cumulative survival time was calculated by the Kaplan-Meier method and analyzed by the logrank test. Levels of L1CAM were significantly lower in all ESCC patients than in normal controls (P < 0.001). Detection of serum L1CAM provided a sensitivity of 28.3%, a specificity of 90.4% and an area under the curve (AUC) of 0.644 (95% CI: 0.579-0.710) in diagnosing ESCC. Similar results were observed in the diagnosis of early-stage ESCC (26.2% sensitivity, 90.4% specificity, and an AUC of 0.629). Moreover, decreased level of L1CAM was correlated with depth of tumor invasion (P < 0.05). Kaplan-Meier analysis showed that lower serum L1CAM level was significantly related to shorter overall survival time (P = 0.036) and disease-free survival time (P = 0.021) of ESCC patients. Our study demonstrated that serum L1CAM might serve as a potential biomarker for the diagnosis and prognosis of ESCC.


Transformation of prostacyclin (PGI2) to a biologically active metabolite: 5(6)-oxido-PGI1 by cytochrome P450-dependent epoxygenase.
The renal epoxygenase has been demonstrated to be an active pathway for the conversion of PGI2 to a new, previously unreported, metabolite. This metabolite was isolated and identified by radiogas-chromatography-mass spectrometry as 5-hydroxy-6-keto PGF1 alpha. Its structure was further confirmed by comparison of the mass-spectra to that of the synthetic standard. The formation of 5-hydroxy-6-keto PGF1 alpha in the kidney suggested epoxidation of prostacyclin via the renal epoxygenase as an alternative pathway of PGI2 metabolism.


Serologic comparisons of 4 Anaplasma isolates as measured by the complement-fixation test.
Anaplasma marginale isolated from Virginia ( VAM ), from North Texas ( NTAM ), from Florida (FAM), and Anaplasma ovis from Idaho were used in these trials. Complement-fixation antigens from each of the 4 isolates were used to compare complement-fixing antibody titers of 10 cattle infected with VAM , 17 with FAM, and 6 with NTAM . Strong cross-reactions occurred with all antigens and sera. The homologous system generally showed higher average antibody titers. The serum antibody titers occurring with the A. ovis antigen were significantly lower than those seen with A. marginale antigens. Serum antibody titer differences as measured by FAM and NTAM antigens on sera from VAM , NTAM and FAM failed to reach significance. Serum antibody titer comparisons using VAM antigen were significantly different from those occurring with FAM and NTAM in most instances.


An epigenetically inherited UV hyper-resistance phenotype in Saccharomyces cerevisiae.
Epigenetics refers to inheritable phenotypic changes that occur in the absence of genetic alteration. Such adaptations can provide phenotypic plasticity in reaction to environmental cues. While prior studies suggest that epigenetics plays a role in the response to DNA damage, no direct demonstration of epigenetically inheritable processes have been described in this context. Here we report the identification of an epigenetic response to ultraviolet (UV) radiation in the baker's yeast Saccharomyces cerevisiae. Cells that have been previously exposed to a low dosage of UV exhibit dramatically increased survival following subsequent UV exposure, which we refer to as UV hyper-resistance (UVHR). This phenotypic change persists for multiple mitotic generations, without any indication of an underlying genetic basis. Pre-exposed cells experience a notable reduction in the amount of DNA damage caused by the secondary UV exposure. While the mechanism for the protection is not fully characterized, our results suggest that UV-induced cell size increases and/or cell wall changes are contributing factors. In addition, we have identified two histone modifications, H3K56 acetylation and H3K4 methylation, that are important for UVHR, potentially serving as mediators of UV protective gene expression patterns, as well as epigenetic marks to propagate the phenotype across cell generations. Exposure to UV radiation triggers an epigenetically inheritable protective response in baker's yeast that increases the likelihood of survival in response to subsequent UV exposures. These studies provide the first demonstration of an epigenetically inheritable dimension of the cellular response to DNA damage.


Risk of second primary cancers after malignant mesothelioma and vice versa.
We aimed at investigating risk of specific second primary cancers (SPCs) after malignant mesothelioma (MM) and vice versa, which has not been reported. Among survivors of 3672 pleural MM and 895 peritoneal MM, overall 113 and 28 SPCs were recorded, respectively, while reverse analyses included overall 431 pleural and 88 peritoneal MMs after any first cancers. We found a bidirectional association of pleural MM with kidney cancer for overall [for second kidney cancer after pleural MM: standardized incidence ratios (SIRs) = 4.4, 95% confidence intervals (CIs): 2.0-8.3; for second pleural MM after kidney cancer: 2.3 (1.3-3.9)] and for <1 year follow-up [5.4 (2.0-12) and 4.9 (2.0-10), respectively, according to the 2-way analyses]. In contrast, a bidirectional association of pleural MM with unknown primary cancer was found only for follow-up ≥1 year [3.9 (1.1-10) and 2.8 (1.3-5.1), respectively]. We found a bidirectional association of pleural MM with kidney cancer for overall and for <1 year follow-up, suggesting the involvement of germline BAP1 mutations and increased medical surveillance, while the bidirectional association of pleural MM with unknown primary cancer suggests shared genetic or environmental risk factors.


[Quality of life of older women with dependency and abuse experience].
Quality of life is largely determined by changing biographical contexts of a person's behavioural action. In later age, health and social relationships are major determinants for a "good life". A decline in health status may lead to the need for support which may result in further dependency; thus, social relations play an even more important role for older people. Relationships characterised by strain and tension may increase the risk of exposure to force and violence. This article investigates the influence of dependency and abuse on the subjective quality of life of older people. The dataset was drawn from an Austrian survey of 593 home-dwelling older women aged 60 and over (71.0 ± 8.1 years). Quality of life was assessed by the EUROHIS-QOL Scale, dependency by the degree of need for support with respect to activities of daily living and by the levels of care allowance received by this cohort. Following the Conflict Tactics Scales (CTS), six different types of abuse have been operationalised by 34 indicators. The data were analysed by descriptive statistics, confirmatory factor analysis and structural equation modelling. With increasing dependency the subjective quality of life of older women decreases. At the same time it is reduced by the experience of abuse in the close social environment. Neglect, psychological abuse and the violation of personal liberties and rights can be identified as factors which have a negative impact on quality of life. It is also noted that neglect can be found particularly among women with a greater need for support and a higher level of care allowance, which is a particularly problematic situation. Dependency and abuse are major risk factors for low quality of life in old age. The results stress the importance of raising general awareness on violence and highlight the social taboos around the issue of abuse against older people, especially in the case of increasing dependency. In addition, the results point to an increasing demand for specific measures of health promotion and prevention activities addressing vulnerable older people.


Diagnostic Yield and Safety of Pleural Cryobiopsy during Medical Thoracoscopy to Diagnose Pleural Effusion. A Systematic Review and Meta-Analysis.
Current evidence on the diagnostic yield and safety of pleural cryobiopsy (CB) is based on a series of heterogeneous studies with limited cohorts. A pooled analysis of these studies could improve the evidence and contribute to a better understanding of this new technique. We performed a systematic review and meta-analysis of published studies that included data on the yield and diagnostic safety of pleural CB compared with procedures performed using conventional flexible forceps. The heterogeneity of the analysis was evaluated by determining the I2 index, while study quality was measured with the QUADAS-2 tool. Seven studies involving 356 patients were used for the final evaluation. In 55.6%, the etiology of the pleural effusion was malignant, 61.1% of which were lung cancer. The diagnostic yield of pleural CB was 95% (95% CI 92-97) vs. 91% (95% CI 87-94) with conventional flexible forceps (P = .019). Mild bleeding was reported in 67% of CB procedures (95% CI 62-72) compared with 85% of conventional flexible forceps procedures (95% CI 79-90) (P < .001). CB specimens were larger, and fewer artifacts were detected. A pooled analysis of the detection of molecular changes could not be performed. Heterogeneity was moderate to high, although the quality of the studies was acceptable. Pleural CB is a safe technique with a high yield for etiological diagnosis of pleural effusion, and larger specimens with fewer artifacts are obtained. Molecular determinations should be investigated in more depth.


Soft tissue reconstruction on the very late presenting neglected acromioclavicular dislocation Rockwood type IV. A case report.
Acromioclavicular (AC) joint dislocation Rockwood type IV is a rare condition characterized by the posterior displacement of the distal clavicle and soft tissue damage. The rate of soft tissue healing markedly decreases as time from injury increases. In this case report, we had a very late presenting neglected AC joint dislocation Rockwood type IV successfully treated by AC and coracoclavicular (CC) reconstruction. A 24-year-old female presented with pain around her right shoulder since a motorcycle accident four years prior to current presentation. She was diagnosed with a posterior AC joint dislocation and suggested undergoing surgery, but she refused and chose to seek an alternative treatment. The patient felt pain chronically and could not elevate her shoulder, and she decided to come to our hospital. We performed a physical and radiograph examination that showed an AC joint dislocation Rockwood type IV. The management, suggested to the patient, was AC and CC soft tissue reconstruction. The advantages of using this procedure were to restore effective anatomy and avoid bone-to-bone contact between the clavicle and acromion. The disadvantages were increased cost and needed to be evaluated for long-term results. We considered the idea of maintaining AC joint reduction by biologic soft tissue healing of the graft and augmentation fixation to replace the CC ligaments. We could not rely on biological soft tissues healing themselves due to the chronicity. AC and CC reconstruction can be an option of treatment in neglected AC joint dislocation Rockwood type IV with excellent clinical and radiographic results.


Inhibition of the high-affinity glucose transporter GLUT 1 affects the sensitivity to glucose in a hamster-derived pancreatic beta cell line (HIT).
HIT is a hamster-derived beta-cell line which in contrast to normal beta cells that only express the high Km GLUT-2 glucose transporter, also expresses the low Km glucose transporter GLUT 1. In HIT cells the abnormal glucose transport mechanism is associated with a marked shift to the left of the glucose-induced insulin release dose-response curve. We have used this cell model to investigate whether changes in glucose transport affect the glucose-induced insulin release. HIT cells were first incubated with a concentration of cytochalasin B (0.4 mumol/l) that selectively inhibits the GLUT-1 but not the GLUT-2 transporter. The consequences of blocking glucose phosphorylation and insulin release were studied. Exposure to 0.4 mumol/l cytochalasin B for 1 h caused a selective loss of the low Km transport: the calculated Vmax of GLUT 1 was reduced from 1726 +/- 98 to 184 +/- 14 pmol.mg protein-1 5 min-1 (mean +/- SEM, n = 6, p < 0.005), while no major difference in the high Km (GLUT-2) transport was observed. In cytochalasin B exposed HIT cells the glucose phosphorylating activity (due to hexokinase and glucokinase) was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of chronic ethanol consumption on [14C]deoxyglucose uptake in rat brain in vivo.
The uptake of [14C]deoxyglucose by brains of rats that were given alcohol in drinking water for 7 months was investigated. There was a general, approximately 50%, increase in deoxyglucose uptake in brains of ethanol-treated rats with areas of the limbic system being particularly affected.


Effect of swine manure dilution on ammonia, hydrogen sulfide, carbon dioxide, and sulfur dioxide releases.
Animal manure is a significant source of environmental pollution and manure dilution in barn cleaning and slurry storage is a common practice in animal agriculture. The effect of swine manure dilution on releases of four pollutant gases was studied in a 30-day experiment using eight manure reactors divided into two groups. One group was treated with swine manure of 6.71% dry matter and another with manure diluted with water to 3.73% dry matter. Ammonia release from the diluted manure was 3.32 mg min(-1)m(-2) and was 71.0% of the 4.67 mg min(-1)m(-2) from the undiluted manure (P<0.01). Because the ammonia release reduction ratio was lower than the manure dilution ratio, dilution could increase the total ammonia emissions from swine manure, especially in lagoons with large liquid surface areas. Carbon dioxide release of 87.3 mg min(-1)m(-2) from the diluted manure was 56.4% of the 154.8 mg min(-1)m(-2) from the undiluted manure (P<0.01). Manure dry matter was an important factor for carbon dioxide release from manure. No differences were observed between the treatments (P>0.05) for both hydrogen sulfide and sulfur dioxide releases. Therefore, dilution could also significantly increase the total releases of hydrogen sulfide and sulfur dioxide to the environment because dilution adds to the total manure volume and usually also increases the total gas release surface area.


Low-contrast-dose protocol in cardiac CT: 20% contrast dose reduction using 100 kVp and high-tube-current-time setting in 256-slice CT.
The use of the smallest contrast dose is highly desirable in performing cardiac computed tomography (CT), especially for patients with cardiovascular diseases to prevent contrast-induced nephropathy. To evaluate the feasibility of 20% reduced contrast dose protocol in cardiac CT using 100 kVp and high-tube-current-time product setting. Fifty patients were scanned with our conventional 120 kVp protocol, and the other 50 patients underwent scans using a tube voltage of 100 kVp, a high-tube-current-time product, and a 20% reduced contrast dose. We evaluated estimated effective dose (ED), CT attenuation, image noise, and contrast-to-noise ratio (CNR) of the ascending aorta. We also evaluated CT attenuation of the coronary arteries. Two radiologists independently assessed image quality of coronary arteries. There was no significant difference in the ED between the 100 kVp and 120 kVp protocols (21.7 mSv ± 1.6 vs. 21.8 mSv ± 1.1, P=0.65). There was no significant difference in the CNR of the ascending aorta between the 100 kVp and 120 kVp protocols (18.8 ± 3.5 vs. 18.7 ± 3.8, P=0.98). Mean CT attenuation of the coronary arteries of the 100 kVp protocols was significantly higher than that of 120 kVp protocols (P<0.05). There was no significant difference in the overall image quality of the coronary artery between the 100 kVp and 120 kVp protocols (3.7 ± 0.4 vs. 3.7 ± 0.5, P=0.65). For cardiac CT a voltage setting of 100 kVp and a high-tube-current-time product enable 20% reduction in the contrast dose without affecting the quality of coronary artery images compared with a 120 kVp and standard-contrast-dose CT protocol.


Circ_0000620 acts as an oncogenic factor in gastric cancer through regulating MMP2 expression via sponging miR-671-5p.
Gastric cancer (GC) is one of the most common cancers in the digestive system. Circular RNAs (circRNAs) have been found to function as important regulators in the pathogenesis of GC. This study focused on the biological role and molecular mechanism of circ_0000620 in GC progression. The expression levels of circ_0000620, microRNA-671-5p (miR-671-5p) and Matrix MetalloProteinase 2 (MMP2) were measured by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) assay or western blot. The stability of circ_0000620 was confirmed by Ribonuclease R (RNase R) assay. The protein levels were determined by western blot assay. Cell viability, colony formation, cell migratory ability, cell invasive ability and tube formation capacity were respectively examined by CCK-8 assay, colony formation assay, wound healing assay, transwell invasion assay and tube formation assay. The interaction between miR-671-5p and circ_0000620 or MMP2 was validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay. The role of circ_0000620 in GC undefined was explored by xenograft tumor assay. Circ_0000620 was conspicuously upregulated in GC tissues and cells. Circ_0000620 knockdown reduced cell viability, colony formation, migration, invasion and tube formation capacity of GC cells in vitro. Furthermore, MMP2 was upregulated in GC and MMP2 overexpression reversed the anti-tumor response of circ_0000620 knockdown in GC progression. Moreover, circ_0000620 directly interacted with miR-671-5p and circ_0000620 downregulation regulated malignant behaviors of GC cells by upregulating miR-671-5p. In addition, silencing of circ_0000620 inhibited tumor growth in vivo. Circ_0000620 knockdown inhibited the malignant development of GC partly through modulating the miR-671-5p/MMP2 axis.


Polybrominated diphenyl ethers (PBDEs) and bioaccumulative hydroxylated PBDE metabolites in young humans from Managua, Nicaragua.
Our aim was to investigate exposure to polybrominated diphenyl ethers (PBDEs) in a young urban population in a developing country, with focus on potentially highly exposed children working informally as scrap scavengers at a large municipal waste disposal site. We also set out to investigate whether hydroxylated metabolites, which not hitherto have been found retained in humans, could be detected. We assessed PBDEs in pooled serum samples obtained in 2002 from children 11-15 years of age, working and sometimes also living at the municipal waste disposal site in Managua, and in nonworking urban children. The influence of fish consumption was evaluated in the children and in groups of women 15-44 years of age who differed markedly in their fish consumption. Hydroxylated PBDEs were assessed as their methoxylated derivates. The chemical analyses were performed by gas chromatography/mass spectrometry, using authentic reference substances. The children living and working at the waste disposal site showed very high levels of medium brominated diphenyl ethers. The levels observed in the referent children were comparable to contemporary observations in the United States. The exposure pattern was consistent with dust being the dominating source. The children with the highest PBDE levels also had the highest levels of hydroxylated metabolites. Unexpectedly, very high levels of PBDEs were found in children from an urban area in a developing country. Also, for the first time, hydroxylated PBDE metabolites were found to bioaccumulate in human serum.


Diffusion-weighted MR imaging of the kidneys and the urinary tract.
There is currently a growing interest in applications of diffusion-weighted imaging (DWI) in the abdomen and pelvis. DWI provides original functional information where the signal and contrast are determined by the microscopic mobility of water. DWI can provide additional information over conventional MR sequences, and could potentially be used as an alternative to contrast-enhanced sequences in patients with chronic renal insufficiency at risk of nephrogenic systemic fibrosis. We provide an overview on basic physics background on DWI applied to the kidneys, and we summarize the current available data, including our recent experience.


Rapid identification of bacterial and fungal pathogens from positive blood cultures by MALDI-TOF MS.
Sepsis is a syndrome characterized by a systemic inflammatory response due to severe infection. Early detection of causal agents and appropriate antimicrobial treatment reduce mortality. Conventional microbiological methods often do not provide time critical results for an optimal early management. We used an in-house protocol based on Tween 80 to process 109 positive blood cultures for bacteria and yeast identification by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS), and results were compared to standard reference or automated methods. MALDI-TOF MS correctly identified 91.7% of the isolates. Correct identification was obtained for 57/62 (91.9%) aerobic/facultative anaerobic Gram-positive isolates, 53 (85.5%) at species level, and 4 (6.4%) at the genus level; 32/32 (100%) aerobic/facultative anaerobic Gram-negative isolates, 31 (96.9%) at species level, and 1 (3.1%) at the genus level; 7/7 (100%) obligate anaerobes, all at the genus level; 3/7 (42.8%) fungi, all at genus level. Overall, the median identification time of MALDI-TOF MS vs reference standard methods was significantly shorter: median (interquartile range) 7.1h (4.7-10.2) vs 48.1h (32.5-50.0), p<0.0001. MALDI-TOF MS is a valuable tool for rapid identification of pathogens in septic patients. An in-house protocol based on Tween 80 can be used to process positive blood cultures.


A cost analysis of postoperative management in endometrial cancer patients treated by robotics versus laparoscopic approach.
The purpose of this study is to compare postoperative pain management and costs in endometrial cancer patients who had a robotic-assisted or laparoscopic-assisted hysterectomy. This is a retrospective cohort study of all endometrial cancer patients from 9/2005 to 6/2010 who had a completed robotic-assisted or laparoscopic-assisted hysterectomy. All surgeries were performed by gynecologic oncologists on the da Vinci S surgical system. Demographic data, patient-recorded pain scores, pain-management interventions, and postoperative pain medication costs were compared. Data was analyzed using Student's t-tests and Pearson's χ(2) tests in SPSS. Two-hundred fifteen (101 robotic and 114 laparoscopic) patients met the inclusion criteria. There were no significant differences between the groups in age, BMI, clinical stage, comorbidities, lymph nodes retrieved, and the number of narcotic vs. non-narcotic drug interventions administered. Robotic patients had a lower number of initial drug interventions (21 vs. 52; P<.001) and total drug interventions (162 vs. 219; P<.001) than laparoscopic patients. Robotics had a lower initial pain score (2.1 vs. 3.0; P=.012). There was a 50% reduction in the pain medication cost on the day of surgery for robotic patients ($12.24 vs. $24.45; P<.01), and a 56% cost reduction for the rest of their length of stay ($3.63 vs. $8.17; P<.01). Endometrial cancer patients who have robotic surgery experience less initial postoperative pain and have fewer drug interventions. The cost associated for their pain management represents a savings of greater than 50%. These factors demonstrate the value of robotic surgery in regard to postoperative pain management by delivering higher quality care at a lower cost.


Microsatellite instability in thyroid tumours and tumour-like lesions.
Fifty-one thyroid tumours and tumour-like lesions were analysed for instability at ten dinucleotide microsatellite loci and at two coding mononucleotide repeats within the transforming growth factor beta (TGF-beta) type II receptor (TbetaRII) and insulin-like growth factor II (IGF-II) receptor (IGFIIR) genes respectively. Microsatellite instability (MI) was detected in 11 out of 51 cases (21.5%), including six (11.7%) with MI at one or two loci and five (9.8%) with MI at three or more loci (RER+ phenotype). No mutations in the TbetaRII and IGFIIR repeats were observed. The overall frequency of MI did not significantly vary in relation to age, gender, benign versus malignant status and tumour size. However, widespread MI was significantly more frequent in follicular adenomas and carcinomas than in papillary and Hürthle cell tumours: three out of nine tumours of follicular type (33.3%) resulted in replication error positive (RER+), versus 1 out of 29 papillary carcinomas (3.4%, P = 0.01), and zero out of eight Hürthle cell neoplasms. Regional lymph node metastases were present in five MI-negative primary cancers and resulted in MI-positive in two cases.


Dysregulated expression of miR-101b and miR-26b lead to age-associated increase in LPS-induced COX-2 expression in murine macrophage.
Aging is the natural process of decline in physiological structure and function of various molecules, cells, tissues, and organs. Growing evidence indicates that increased immune genetic diversity and dysfunction of immune system cause aging-related pathophysiological process with the growth of age. In the present study, we observed that LPS-induced higher activation of cyclooxygenase (COX)-2 promoter is associated with the upregulated binding activity of nuclear factor kappa B (NF-κB) in peritoneal macrophages of aged mice than young ones. Additionally, COX-2 is a direct target of miR-101b and miR-26b in the macrophages. Significant upregulation of miR-101b and miR-26b effectively prevented LPS-induced excessive expression of COX-2 in the young mice. Because these negative regulatory factors were unresponsive to LPS stimulation, the levels of COX-2 were markedly higher in the macrophages of aged mice. Further study showed that NF-κB activation contributed to the increase in the expression of miR-101b and miR-26b in the LPS-stimulated macrophages of young mice, but not aged ones. Moreover, histone deacetylase (HDAC) inhibitor trichostatin A (TSA) upregulated expression of miR-101b and miR-26b in the aged mouse macrophages only, but not the young cells. This demonstrated that HDAC suppressed the expression of miR-101b and miR-26b in the LPS-treated macrophages of aged mice and contributed to the aging process. TSA-induced increased expression of miR-101b and miR-26b could further suppress COX-2 expression. These findings provide novel evidence on the regulation of immune senescence and miR-101b and miR-26b, which might be promising targets in treating aged-related inflammatory diseases. Epigenetic regulation of the microRNAs (miRNAs) provides an important evidence for the treatment of innate inflammatory disease with HDAC inhibitors in elderly.


[Arthrodesis of the talonavicular joint].
The talonavicular joint as part of the coxa pedis plays a pivotal role in the overall motion of the foot. The necessity for talonavicular fusion arises from isolated arthritis of posttraumatic, rheumatoid, degenerative, or idiopathic etiology. Posttraumatic arthritis is seen after malunited mid-tarsal (Chopart) fracture-dislocations and is frequently accompanied by malalignment due to an imbalance between the medial and lateral columns of the foot. In these cases a corrective arthrodesis becomes necessary. In cases of poor bone stock or arthritis of the calcaneocuboid joint, a double arthrodesis is preferred over isolated talonavicular fusion. Fusion with mini-plates is biomechanically superior to fusion with screws and especially staples, the latter being associated with non-union rates of up to 37%. Talonavicular fusion allows reproducible pain reduction in isolated arthritis with subjective patient satisfaction of between 86% and 100% in a literature review. The substantial reduction of movement in the triple joint complex leads to overload of the adjacent joints with development of arthritis in about 30% in the medium term.


Report on blind subjects' tactile and auditory recognition for environmental stimuli.
In two related experiments on recognition-on touch and audition-accuracy rates were obtained from congenitally blind subjects and compared with those for normally sighted subjects. In Exp. 1, 5 blind subjects inspected, i.e., handled, 150 common objects and were tested after a delay of 7 days. In Exp. 2, 9 blind subjects listened to 194 naturalistic sounds and were also tested after a 7-day delay. Accuracy of tactile recognition for the blind was 89.4% while it was 87.9% for the normally sighted. Sound recognition by blind subjects was 76.6% and for the normally sighted it was 78.4%. Neither difference was statistically significant.


An improved low order method for corneal reconstruction.
An iterative and cubic arc-step method for corneal reconstruction developed previously, was retested including improved skew-ray compensation. The method was compared with a similar method described by Klein, and also with a least squares based approach using Zernike polynomials. Images of an asphere, a cornea after photorefractive keratectomy (PRK), an ellipsoid and radially keratotomized (RK) cornea were generated. Three reconstruction methods were applied: (i) the cubic method (without skew-ray compensation; with old and improved compensation), (ii) the method due to Klein and (iii) a least squares approach based on Zernike polynomials (order taken up to 25). Errors were recorded for all conditions tested. The root mean square errors for the improved method were well below micron level, and consistently lower than the method of Klein. The Zernike-based method produced lowest errors for aspheric and ellipsoidal surfaces, when order was > or =(10, 8) respectively. However, the improved method produced the lowest errors for the PRK and RK examples. In this case, the Zernike-based method produced submicron errors for orders > or =14 (both surfaces), but errors comparable with the arc-step methods could not be achieved for polynomial orders < or =25. The improved method completed in three to four iterations (abs. height error <1 x 10(-7) mm) in all cases. Compensation for skew-rays was incorporated in a straightforward way, yielding an efficient and effective low-order method. The Zernike method produced the lowest root mean square errors for asphere and ellipsoid, provided order was > or =(10, 8). However, the arc-step methods (the cubic and Klein methods) were more accurate for RK and PRK surfaces, at least for Zernike orders < or =25. The results suggest that low order methods provide a good solution to the reconstruction of corneal shape, at least for Placido disk videokeratography applications.


Targeted Prostate Biopsy in the Era of Active Surveillance.
Targeted prostate biopsy using magnetic resonance imaging (MRI) guidance is improving the accuracy of prostate cancer (CaP) diagnosis. This new biopsy technology is especially important for men undergoing active surveillance, improving patient selection for enrollment and enabling precise longitudinal monitoring. Magnetic resonance imaging/ultrasound fusion biopsy allows for 3 functions not previously possible with US-guided biopsy: targeting of suspicious regions, template-mapping for systematic sampling, and tracking of cancer foci over time. This article reviews the evolving role of the new biopsy methods in active surveillance, including the UCLA Active Surveillance pathway, which has incorporated magnetic resonance imaging/ultrasound fusion biopsy from program inception as a possible model.


Parenteral lipid emulsions induce unique ileal fatty acid and metabolomic profiles but do not increase the risk of necrotizing enterocolitis in preterm pigs.
Necrotizing enterocolitis (NEC) is a manifestation of maladaptive intestinal responses in preterm infants centrally medicated by unattenuated inflammation. Early in the postnatal period, preterm infants develop a deficit in arachidonic and docosahexaenoic acid, both potent regulators of inflammation. We hypothesized that the fatty acid composition of parenteral lipid emulsions uniquely induces blood and intestinal fatty acid profiles which, in turn, modifies the risk of NEC development. Forty-two preterm pigs were randomized to receive one of three lipid emulsions containing 100% soybean oil (SO), 15% fish oil (MO15), or 100% fish oil (FO100) with enteral feedings over an 8-day protocol. Blood and distal ileum tissue were collected for fatty acid analysis. The distal ileum underwent histologic, proteomic, and metabolomic analyses. Eight pigs [3/14 SO (21%), 3/14 MO15 (21%), and 2/14 FO100 (14%)] developed NEC. No differences in NEC risk were evident between groups despite differences in induced fatty acid profiles in blood and ileal tissue. Metabolomic analysis of NEC versus no NEC tissue revealed differences in tryptophan metabolism and arachidonic acid-containing glycerophospholipids. Proteomic analysis demonstrated no differences by lipid group; however, 15 proteins differentiated NEC versus no NEC in the domains of tissue injury, glucose uptake, and chemokine signaling. Exposure to parenteral lipid emulsions induces unique intestinal fatty acid and metabolomic profiles; however, these profiles are not linked to a difference in NEC development. Metabolomic and proteomic analyses of NEC versus no NEC intestinal tissue provide mechanistic insights into the pathogenesis of NEC in preterm infants.NEW & NOTEWORTHY Exposure to parenteral lipid emulsions induces unique intestinal fatty acid and metabolomic profiles; however, these profiles are not linked to a difference in NEC risk in preterm pigs. Metabolomic and proteomic analyses provide mechanistic insights into NEC pathogenesis. Compared with healthy ileal tissue, metabolites in tryptophan metabolism and arachidonic acid-containing glycerophospholipids are increased in NEC tissue. Proteomic analysis differentiates NEC versus no NEC in the domains of tissue injury, glucose uptake, and chemokine signaling.


POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in adults. We have analyzed exome sequencing data from 127 individuals with CLL and Sanger sequencing data from 214 additional affected individuals, identifying recurrent somatic mutations in POT1 (encoding protection of telomeres 1) in 3.5% of the cases, with the frequency reaching 9% when only individuals without IGHV@ mutations were considered. POT1 encodes a component of the shelterin complex and is the first member of this telomeric structure found to be mutated in human cancer. Somatic mutation of POT1 primarily occurs in gene regions encoding the two oligonucleotide-/oligosaccharide-binding (OB) folds and affects key residues required to bind telomeric DNA. POT1-mutated CLL cells have numerous telomeric and chromosomal abnormalities that suggest that POT1 mutations favor the acquisition of the malignant features of CLL cells. The identification of POT1 as a new frequently mutated gene in CLL may facilitate novel approaches for the clinical management of this disease.


Conversion of levoglucosan into glucose by the coordination of four enzymes through oxidation, elimination, hydration, and reduction.
Levoglucosan (LG) is an anhydrosugar produced through glucan pyrolysis and is widely found in nature. We previously isolated an LG-utilizing thermophile, Bacillus smithii S-2701M, and suggested that this bacterium may have a metabolic pathway from LG to glucose, initiated by LG dehydrogenase (LGDH). Here, we completely elucidated the metabolic pathway of LG involving three novel enzymes in addition to LGDH. In the S-2701M genome, three genes expected to be involved in the LG metabolism were found in the vicinity of the LGDH gene locus. These four genes including LGDH gene (lgdA, lgdB1, lgdB2, and lgdC) were expressed in Escherichia coli and purified to obtain functional recombinant proteins. Thin layer chromatography analyses of the reactions with the combination of the four enzymes elucidated the following metabolic pathway: LgdA (LGDH) catalyzes 3-dehydrogenation of LG to produce 3-keto-LG, which undergoes β-elimination of 3-keto-LG by LgdB1, followed by hydration to produce 3-keto-D-glucose by LgdB2; next, LgdC reduces 3-keto-D-glucose to glucose. This sequential reaction mechanism resembles that proposed for an enzyme belonging to glycoside hydrolase family 4, and results in the observational hydrolysis of LG into glucose with coordination of the four enzymes.


Does experimental research support psychoanalysis?
The question of whether a psychodynamic view is compatible with experimental research is still a challenging issue-especially for child and adolescent psychopathology-despite the influence of psychoanalytic theory in this field until the 1980s. In this article, is explored the relationship between psychodynamic theory and experimental research using examples of evidence-based studies in the fields of (i) psychotherapeutic intervention assessment, (ii) placebo response in children and adolescents, (iii) unconscious lasting traumatic effects in children and adolescents, (iv) psychodynamic-oriented psychological testing. There are now a sufficient number of evidence-based studies to support the use of psychodynamic therapy in mental disorders, particularly in personality disorder and anxious/depressive disorder. In addition, placebo responses in children and adolescents with internalizing disorders are significantly higher in major depression compared to obsessive-compulsive disorder or other anxiety disorders, which highlights differential psychopathologies regarding the experience of loss. Also, using an experimental task, psychoanalysts are able to identify, without explicit knowledge and above the level of chance, healthy adults whose siblings had experienced cancer during childhood. This experiment suggests that implicit information regarding a participant's history is conveyed in interpersonal exchanges that can be intuitively perceived by judges experienced in listening to free associations from a psychodynamic perspective. Finally, psychodynamic-oriented psychological testing may predict the transition to schizophrenia in adolescents with a history of manic/mixed episodes. It can be concluded that there are no discrepancies between psychodynamic views and experimental data, whether one tests psychotherapeutic approaches, discusses data from other fields such as psychopharmacology, or designs experiments based on psychodynamic theory.