Preserved complex emotion-based learning in amnesia.
An important role for emotion in decision-making has recently been highlighted by disruptions in problem solving abilities after lesion to the frontal lobes. Such complex decision-making skills appear to be based on a class of memory ability (emotion-based learning) that may be anatomically independent of hippocampally mediated episodic memory systems. There have long been reports of intact emotion-based learning in amnesia, arguably dating back to the classic report of Claparede. However, all such accounts relate to relatively simple patterns of emotional valence learning, rather than the more complex contingency patterns of emotional experience, which characterise everyday life. A patient, SL, who had a profound anterograde amnesia following posterior cerebral artery infarction, performed a measure of complex emotion-based learning (the Iowa Gambling Task) on three separate occasions. Despite his severe episodic memory impairment, he showed normal levels of performance on the Gambling Task, at levels comparable or better than controls-including learning that persisted across substantial periods of time (weeks). Thus, emotion-based learning systems appear able to encode, and sustain, more sophisticated patterns of valence learning than have previously been reported.


Effects of koumine, an alkaloid of Gelsemium elegans Benth., on inflammatory and neuropathic pain models and possible mechanism with allopregnanolone.
Crude alkaloidal extraction from Gelsemium elegans Benth. produces analgesic property. However, its clinical utility has been obstructed by its narrow therapeutic index. Here, we investigated the potential of koumine, a monomer of Gelsemium alkaloids, to reduce both inflammatory and neuropathic pain. Interestingly, allopregnanolone, a neurosteroid, appeared to mediate the reduction of neuropathic pain. The potential anti-inflammatory pain effects of koumine were evaluated by acetic acid-, formalin- and complete Freund's adjuvant (CFA) -induced nociceptive behaviors in mice. Chronic constriction injury (CCI) and L5 spinal nerve ligation (L5 SNL), inducing thermal hyperalgesia and mechanical allodynia in rats, were used to test whether repeated treatment of koumine ameliorated neuropathic pain. Finally, we explored if koumine altered the level of neurosteroids in rat spinal cord of CCI neuropathy using liquid chromatography-tandem mass spectrometry. Koumine dose-dependently reduced the acetic acid-induced writhes and formalin-induced licking/biting time of Phase II in mice. Repeated administrations of koumine also dose-dependently reversed the CFA-, CCI- and L5 SNL-induced thermal hyperalgesia, as well as, CCI- and L5 SNL-induced mechanical allodynia in rats. The level of allopregnanolone, but not pregnenolone, in the L5-6 spinal cord was elevated by repeated treatment of koumine in CCI-induced neuropathic rats. These results demonstrate that koumine has a significant analgesic effect in rodent behavioral models of inflammatory and neuropathic pain, and that the reduction in neuropathic pain may be associated with the upregulation of allopregnanolone in the spinal cord.


Influence of surface preparation on the strength and surface microstructure of a cast dental ceramic.
The effect of three surface preparations on the flexural strength of a cast glass-ceramic (Dicor) was studied. The microstructure of the external and fracture surfaces was evaluated using electron microscopy. It was found that there was no difference in strength for the "as-cast/cerammed," acid-etched, or glazed shading porcelain specimens. A significant increase in strength (twofold) was observed when the "ceram layer" was mechanically removed from the surface of the ceramic. Scanning electron microscopy revealed that the "ceram layer" was 25 to 100 microns thick and consisted of crystal "whiskers" oriented perpendicular to the external surfaces. It was observed in both the laboratory and the clinically failed specimens that a zone of strength-limiting porosity was associated with this "ceram layer." Potential origins of the crystal "whiskers" and the porosity were discussed.


Evaluation of earlier versus later dietary management in long-chain 3-hydroxyacyl-CoA dehydrogenase or mitochondrial trifunctional protein deficiency: a systematic review.
Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies are rare fatty acid β-oxidation disorders. Without dietary management the conditions are life-threatening. We conducted a systematic review to investigate whether pre-symptomatic dietary management following newborn screening provides better outcomes than treatment following symptomatic detection. We searched Web of Science, Medline, Pre-Medline, Embase and the Cochrane Library up to 23rd April 2018. Two reviewers independently screened titles, abstracts and full texts for eligibility and quality appraised the studies. Data extraction was performed by one reviewer and checked by another. We included 13 articles out of 7483 unique records. The 13 articles reported on 11 patient groups, including 174 people with LCHAD deficiency, 18 people with MTP deficiency and 12 people with undifferentiated LCHAD/MTP deficiency. Study quality was moderate to weak in all studies. Included studies suggested fewer heart and liver problems in screen-detected patients, but inconsistent results for mortality. Follow up analyses compared long-term outcomes of (1) pre-symptomatically versus symptomatically treated patients, (2) screened versus unscreened patients, and (3) asymptomatic screen-detected, symptomatic screen-detected, and clinically diagnosed patients in each study. For follow up analyses 1 and 2, we found few statistically significant differences in the long-term outcomes. For follow up analysis 3 we found a significant difference for only one comparison, in the incidence of cardiomyopathy between the three groups. There is some evidence that dietary management following screen-detection might be associated with a lower incidence of some LCHAD and MTP deficiency-related complications. However, the evidence base is limited by small study sizes, quality issues and risk of confounding. An internationally collaborative research effort is needed to fully examine the risks and the benefits to pre-emptive dietary management with particular attention paid to disease severity and treatment group.


Hematologic and immunologic studies in dogs given nitrogen mustard (hn3).
Hematologic and immunosuppressive effects of single doses of nitrogen mustard (HN3) were evaluated in 20 dogs. HN3 caused profound depression of peripheral blood counts in all animals. Recovery of total white blood cell counts in dogs surviving the acute gastrointestinal toxicity of HN3 was complete by day 15. Recovery of platelet and lymphocyte counts to initial levels took a more prolonged course. Granulopoietic progenitor cells (CFU-C) in the bone marrow were assayed by an in vitro culture system. Concentrations of CFU-C were markedly decreased one day after HN3-treatment, but showed at near-lethal doses rapid restoration to normal values within 4 to 7 days. Cellular immune function of HN3-treated dogs was impaired for prolonged periods as indicated by the reduced capacity of canine lymphocytes to proliferate in vitro in response to stimulation with mitogens. Humoral immune function was similarly affected as determined by the depressed and delayed antibody formation against an intravenous challenge with sheep red blood cell. In conclusion, our results suggest a different effect of HN3 on lymphoid and myeloid precursor cells.


A comparative study on the effects of acute and chronic downhill running vs uphill running exercise on the RNA levels of the skeletal muscles PGC1-α, FNDC5 and the adipose UCP1 in BALB/c mice.
The purpose of this study was to investigate the effect of a single bout and 8 weeks of downhill running versus uphill running exercise on expression of PGC1-α, FNDC5 and UCP1 in mice. Forty-eight BALB/c male mice weighing 25-30 g were randomly assigned into 8 groups: 1) acute downhill running (ADR) on a -15° slope; 2) acute uphill running (AUR) on a +15° slope; 3) acute running without inclination (AWI), 4) acute without exercise as control (ACtrl), 5) chronic downhill running (CDR) on a -15° slope; 6) chronic uphill running (CUR) on a +15°slope; 7) chronic running without inclination (CWI), 8) chronic without exercise as control (CCtrl). Twenty four hours after the last training session, the mice were sacrificed and Calf muscles (including soleus and gastrocnemius) and quadriceps muscles (including Rectus femoris and vastus intermedius) were obtained and expression levels of PGC1-α and FNDC5 in crus and quadriceps muscles and UCP1 in visceral and subcutaneous adipose tissues were measured and compared between the groups. PGC-1α and FNDC5 mRNA levels increased after treadmill exercise training in all acute and chronic exercise groups in both skeletal muscle groups. Furthermore mRNA level of UCP1 in subcutaneous adipose tissue but not in visceral adipose tissue increased both after acute and chronic exercise. Collectively, data showed that downhill running exercise to be more effective than other exercises, as downhill running has led to a greater improvement in metabolism may be considered more effective for browning of fat tissue.


Prevalence of glucose-6-phosphate dehydrogenase deficiency and diagnostic challenges in 1500 immigrants in Denmark examined for haemoglobinopathies.
Similar to the thalassaemia syndromes, glucose-6-phosphate dehydrogenase (G6PD) deficiency is highly prevalent in areas historically exposed to malaria. In the present study, we used quantitative and molecular methods to determine the prevalence of G6PD deficiency in a population of 1508 immigrants in Denmark. We found the allele frequency to be between 2.4 and 2.9% in the female immigrants. Furthermore, the mutation pattern in the studied population showed a high prevalence of the G6PD A-(202A) variant in African and African-American immigrants, a high prevalence of the G6PD Mediterranean variant in Mediterranean European and Western Asian immigrants, and substantial heterogeneity in the variants found in the Eastern Asian/Pacific immigrants. Inasmuch as many of the patients included in this investigation had various thalassaemic syndromes, we were able to evaluate the effects of the interaction between a low mean corpuscular haemoglobin (MCH) value and G6PD activity, particularly in heterozygous females. The activity level was markedly influenced by the MCH value in females with normal G6PD activity, but not in heterozygous and homozygous females. Comparison of patients with normal G6PD activity and heterozygous females indicated considerable overlap in activity levels. To help separating heterozygous females from females with wild-type genes, a DNA analysis is necessary when the female activity level is between 4.0 and 4.9 U/g hgb corresponding to 50-60% of the median activity of unaffected males.


Rank comparisons amongst teenagers and suicidal ideation.
We study how competition amongst known peers at the highest-stakes exam in Korea impacts students' mental health and induces them to express suicidal ideation. Using panel data on Korean students from 2003 to 2007, we exploit a randomization of students' peers (upon entering middle school) to uncover a relationship between students' rank at the CSAT (highest-stakes exam in Korea) and their mental health, more particularly their suicidal thoughts. We find that (i) students' rank amongst peers from middle school affects their suicidal ideation: the farther down in the classification, the more prone to have suicidal thoughts they are; (ii) this association is not capturing the impact of the national ranking at CSAT, which is controlled for in all our specifications; (iii) when reestimating separately our regressions for male and female students, we find all of this association is driven by female students. Male students are more prone to experience other negative feelings such as anxiety or loneliness, but these only appear one year later. Our results confirm that social comparisons with peers matter a lot for individual well-being and mental health. They contribute to building a case against extreme levels of competition at younger ages, as teenagers -especially young girls- suffer deeply from comparing themselves to their peers.


Optoelectronic performance of indium tin oxide thin films structured by sub-picosecond direct laser interference patterning.
A route to increase the efficiency of thin film solar cells is improving the light-trapping capacity by texturing the top Transparent Conductive Oxide (TCO) so that the sunlight reaching the solar absorber scatters into multiple directions. In this study, Indium Tin Oxide (ITO) thin films are treated by infrared sub-picosecond Direct Laser Interference Patterning (DLIP) to modify the surface topography. Surface analysis by scanning electron microscopy and confocal microscopy reveals the presence of periodic microchannels with a spatial period of 5 µm and an average height between 15 and 450 nm decorated with Laser-Induced Periodic Surface Structures (LIPSS) in the direction parallel to the microchannels. A relative increase in the average total and diffuse optical transmittances up to 10.7% and 1900%, respectively, was obtained in the 400-1000 nm spectral range as an outcome of the interaction of white light with the generated micro- and nanostructures. The estimation of Haacke's figure of merit suggests that the surface modification of ITO with fluence levels near the ablation threshold might enhance the performance of solar cells that employ ITO as a front electrode.


Brown adipose tissue: endocrine determinants of function and therapeutic manipulation as a novel treatment strategy for obesity.
Recent observation of brown adipose tissue (BAT) being functional in adult humans provides a rationale for its stimulation to increase energy expenditure through 'adaptive thermogenesis' for an anti-obesity strategy. Many endocrine dysfunctions are associated with changes in metabolic rate that over time may result in changes in body weight. It is likely that human BAT plays a role in such processes. In this brief review article, we explore the endocrine determinants of BAT activity, and discuss how these insights may provide a basis for future developments of novel therapeutic strategies for obesity management. A review of electronic and print data comprising original and review articles retrieved from PubMed search up to December 2013 was conducted (Search terms: brown adipose tissue, brown fat, obesity, hormone). In addition, relevant references from the articles were screened for papers containing original data. There is promising data to suggest that targeting endocrine hormones for BAT modulation can yield a cellular bioenergetics answer for successful prevention and management of human obesity. Further understanding of the physiological link between various endocrine hormones and BAT is necessary for the development of new therapeutic options.


Evaluation of Analytical Performance of Variant II Turbo HbA1c Analyzer According to Sigma Metrics.
Hemoglobin A1c, (HbA1c) which is the major constituent of glycated hemoglobin, has been used in the follow-up of retrospective glycemia for years and in the diagnosis of diabetes mellitus nowadays. Since the analytical performance of HbA1c should be high likewise all laboratory tests, various quality control measures are used. Sigma metrics is one of these measures and it is the combination of bias, precision and total allowable error that ensures a general evaluation of analytical quality. The aim of our study was to evaluate the analytical performance of Bio-Rad's Variant Turbo II HbA1c analyzer according to sigma metrics. Sigma levels were calculated using the data obtained from two levels of internal and 12 external quality control materials (Bio-Rad) of Variant II Turbo HbA1c analyzer according to σ = (TEa% - Bias%) / CV% formula. The mean sigma levels for low and high quality control materials were found to be 3.0 and 4.1, respectively. The annual mean analytical performance of Variant II Turbo HbA1c analyzer was found to be acceptable according to sigma metrics. In order to be sure of the difference in HbA1c results indicating the success or failure in treatment but not arise from analytical variation, it is thought that more stringent quality control measures should be applied to reach higher sigma levels.


Prevalence of serum IgE to storage mites in a southwestern Ohio population.
Storage mites of the families Chortoglyphidae, Glycyphagidae, Echimyopodidae, and Acaridae are commonly found in agricultural and nonagricultural environments. The prevalence of sensitization to these storage mites in the general population in the United States is unknown. To determine the prevalence of serum IgE to the storage mites Lepidoglyphus destructor and Acarus siro and to evaluate the degree of co-sensitization to various other astigmatid mites in a population in southwestern Ohio. Serum samples from 600 people randomly selected from a 1-day submission of approximately 3,000 samples to a clinical diagnostic laboratory were screened for IgE to allergens of L destructor and A siro. Proteins in the extracts of each mite were electrophoretically separated, transferred to membranes, and incubated in the serum samples, and the slot blots were probed for IgE binding using radiolabeled anti-human IgE and autoradiography. Thirty-two (5.3%) of the 600 serum samples screened had IgE to allergens from at least 1 of the 2 mite species; 14 (2.3%) and 20 (3.3%) had serum IgE to proteins of the mites A siro and L destructor, respectively. Additional analysis revealed that most serum samples also had IgE that bound to proteins in extracts prepared from a variety of other astigmatid mite species, but IgE binding profiles suggested little cross-reactivity. Sensitization to the mites L destructor and A siro is significant in this region of southwestern Ohio. Further studies are needed to determine the importance of these and other storage mites in occupationally exposed and urban populations of the United States.


Isolation of highly purified yeast nuclei for nuclease mapping of chromatin structure.
Probing chromatin structure with nucleases is a well-established method for determining the accessibility of DNA to gene regulatory proteins and measuring competency for transcription. A hallmark of many silent genes is the presence of translationally positioned nucleosomes over their promoter regions, which can be inferred by the sensitivity of the underlying DNA to nucleases, particularly micrococcal nuclease. The quality of this data is highly dependent upon the nuclear preparation, especially if the digestion products are analyzed by high-resolution detection methods such as reiterative primer extension. Here we describe a method to isolate highly purified nuclei from the budding yeast Saccharomyces cerevisiae and the use of micrococcal nuclease to map the positions of nucleosomes at the RNR3 gene. Nuclei isolated by this procedure are competent for many of the commonly used chromatin mapping and detection procedures.


Teenage Neurologic Manifestation of a Complex Brain Malformation Consisting of Gray Matter Heterotopia, Schizencephaly and Absent Septum Pellucidum.
Teaching point: Since some minor congenital brain defects manifest long after birth, even in adults they should be kept in the differential of new epileptic seizures or focal neurologic deficits.


Public health development in the Baltic countries (1992-2005): from problems to policy.
The focus of the article is on organizational reform measures in public health in Estonia, Latvia and Lithuania from 1992 to 2005 and the associated changes in population health. The study draws on published reports and analyses official statistics over time and cross-nationally. Changes in population health are measured by indicators of population health status and indicators of primary prevention or avoidable mortality, which reflect performance of national health policy. Our study shows some similarities and some important differences in terms of public health development in the Baltic countries since beginning of the 1990s. This study highlights the importance of political stability and support in achieving public health improvements and the pervasive influence of socio-demographic factors on several key health indicators in Baltic countries. It points to the need to introduce evidence-based public health interventions, enhance social trust, address corruption and tackle poverty.


Nonoperative management of minimally displaced lateral compression type 1 (LC1) injuries with comminuted rami fractures is associated with late displacement.
Rami comminution has been found to be predictive of lateral compression type 1 (LC1) injury instability on examination under anesthesia (EUA) and lateral stress radiographs (LSR). The purpose of this study was to evaluate how rami comminution and subsequent operative vs. nonoperative management impact the late displacement of these injuries. Retrospective review of a prospectively collected LC1 database was performed to identify all patients with minimally displaced LC1 injuries (< 1 cm) and follow-up radiographs over a four-year period (n = 125). Groups were separated based on the presence of rami comminution and subsequent management, including rami comminution/operative (n = 49), rami comminution/nonoperative (n = 54), and no comminution/nonoperative (control group, n = 22). The primary outcome was late fracture displacement, analyzed as both a continuous variable and as late displacement ≥ 5 mm. As a continuous variable, late fracture displacement was lower in the comminuted rami/operative group as compared to the comminuted rami/nonoperative group (PD: -3.0 mm, CI: -4.8 to -1.6 mm, p = 0.0002) and statistically non-different from control. Late displacement ≥ 5 mm was significantly more prevalent in the comminuted rami/nonoperative group than in the comminuted rami/operative and no comminution/nonoperative groups (control)(PD: -33.9%, CI: -49.0% to -16.1%, p = 0.0002 and PD: -30.0%, CI: -48.2% to -6.5%, p = 0.02, respectively). Late fracture displacement was greatest in the group with rami comminution/nonoperative management. Rami comminution, which has been previously associated with dynamic displacement on EUA and LSR, is also associated with a higher incidence of late displacement when managed nonoperatively. Level III, prognostic retrospective cohort study.


Transforaminal Endoscopic Surgical Treatment for Posterior Migration of Polyetheretherketone Transforaminal Lumbar Interbody Fusion Cage: Case Series.
This study aims to report the clinical outcome of treating lumbar radiculopathy in the setting of retropulsed polyetheretherketone (PEEK) transforaminal lumbar interbody fusion (TLIF) cages with transforaminal endoscopic spine surgery. A retrospective study of 8 patients with lumbar radiculopathy in the setting of a retropulsed PEEK TLIF cage were included from January 2014 to January 2019. The inclusion criteria were 1) lumbar radiculopathy in the setting of a retropulsed PEEK TLIF cage causing nerve compression and 2) follow-up at least 1 year. Patients were asked to complete the following questionnaires for outcome evaluation: visual analog scales (VAS) for leg pain and the Oswestry Disability Index (ODI). Eight patients underwent transforaminal endoscopic surgery for treatment of radiculopathy in the setting of a retropulsed PEEK TLIF cage in the 5-year period evaluated. One year after surgery, the VAS and ODI scores showed a significant decrease: average preoperative VAS and ODI scores were 6.9 ± 1.2 and 50.5 ± 10.9, and 1-year postoperative VAS and ODI scores were 2.3 ± 1.3 and 17.3 ± 5.1. Transforaminal endoscopic spine surgery for the treatment of a retropulsed PEEK TLIF cage is a safe and effective approach with low morbidity and acceptable complication rates for patients with radiculopathy secondary to a retropulsed PEEK TLIF cage. Compared with a more invasive approach to removing or drilling the PEEK TLIF cage, endoscopic spine surgery could achieve a similar improvement in the patient-reported outcomes with possibly fewer complications.


The role of photoperiod in the timing of reproduction in the Dasyurid Marsupial Antechinus stuartii.
Antechinus stuartii has one highly synchronized mating period which occurs at the same time each year. An analysis of the time of reproduction in 162 populations of A. stuartii shows that the onset of the mating period is correlated with the rate of change of photoperiod, rather than with critical photoperiodic length. The rate of change of photoperiod is different for two designated forms of this species and can be used as a predictor of these animals' reproductive timing. A rate of change model further explains the rigid and highly sunchronized nature of the mating period and, by providing a mechanism for reproductive isolation, offers an explanation for the evolution of the two forms of this species.


Characteristics of endothelin receptors in the cerebral cortex and spinal cord of aged rats.
Characteristics of endothelin receptors were studied in male Fischer 344 rats at 4-, 15- and 24-months of age and [125I]ET-1 binding showed a single high affinity binding site in their cerebral cortex and spinal cord membranes. The density and affinity of ET binding sites were found to be similar in rats of various age groups. To determine the affinity of ET isotypes to ET-1 binding sites in cerebral cortex and spinal cord, competition studies were performed and K(i) values of ET-1, ET-2 and ET-3 for [125I] ET-1 binding sites were determined. It was found that ET-1 had 100 and ET-2 had 25-100 times lower K(i) values as compared to ET-3, indicating that ET receptors in cerebral cortex and spinal cord are of ETA type. In spinal cord, the K(i) values of ET-1 and ET-2 for ET receptor were found to be similar. However, in cerebral cortex the K(i) values of ET-1 were found to be at least 6 times lower than ET-2. It is inferred that there are two subtypes of ET(A) receptors, ET(A1) which have higher affinity for ET-1 in comparison to ET-2, as found in cerebral cortex and ET(A2) which have higher affinity for ET-2, as found in spinal cord. The K(i) and IC50 values of ET-1, ET-2, and ET-3 for [125I]ET-1 binding sites in cerebral cortex and spinal cord were found to be similar in 4-, 15- and 24-month-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Factoring semi-primes with (quantum) SAT-solvers.
The computational difficulty of factoring large integers forms the basis of security for RSA public-key cryptography. The best-known factoring algorithms for classical computers run in sub-exponential time. The integer factorization problem can be reduced to the Boolean Satisfiability problem (SAT). While this reduction has proved to be useful for studying SAT solvers, large integers have not been factored via such a reduction. Shor's quantum factoring algorithm factors integers in expected polynomial time. Large-scale fault-tolerant quantum computers capable of implementing Shor's algorithm are not yet available, preventing relevant benchmarking experiments. Recently, several authors have attempted quantum factorizations via reductions to SAT or similar NP-hard problems. While this approach may shed light on algorithmic approaches for quantum solutions to NP-hard problems, in this paper we study and question its practicality. We find no evidence that this is a viable path toward factoring large numbers, even for scalable fault-tolerant quantum computers, as well as for various quantum annealing or other special purpose quantum hardware.


Drug-induced aseptic meningitis in suspected central nervous system infections.
This study presents eight patients with drug-induced aseptic meningitis (DIAM) admitted to our centre with an initial suspicion of central nervous system (CNS) infection. In all patients clinical findings, cerebrospinal fluid (CSF) examination, a cause-effect relationship according to the Naranjo adverse drug reactions probability scale and other diagnostic criteria required for DIAM recognition, were fulfilled. Nonsteroidal anti-inflammatory drugs were the most frequent cause of DIAM. In two cases, there was previous antimicrobial use. The time between use of the causative drug and onset of the symptoms ranged from 2 to 7 days. Clinical symptoms and CSF findings in patients with DIAM are indistinguishable from the early stage of infections of the CNS. Detailed anamnesis is essential, particularly related to medication use immediately prior to the appearance of symptoms of CNS impairment. In conclusion, the differential diagnosis of CNS infections should include DIAM.


Pediatric esophageal foreign body with minimal symptomatology.
Presented is the case of a child who swallowed a large plastic button that required endoscopic removal from the esophagus. A 5 1/2-year-old girl was seen in the emergency department on two occasions after having told her parents of the ingestion. There were no clinical findings. Results of AP roentgenogram were negative. Six days after the initial visit, the child developed a fever and mild anterior neck discomfort on palpation and flexion. A barium swallow clearly revealed the impacted foreign body. Removal under general anesthesia and subsequent course were uneventful.


Molecular cloning, structural analysis, and expression of a human IRLB, MYC promoter-binding protein: new DENN domain-containing protein family emerges.
IRLB was originally identified as a partial cDNA clone, encoding a 191-aa protein binding the interferon-stimulated response element (ISRE) in the P2 promoter of human MYC. Here, we cloned the full-size IRLB using different bioinformatics tools and an RT-PCR approach. The full-size gene encompasses 131 kb within chromosome 15q22 and consists of 32 exons. IRLB is transcribed as a 6.6-kb mRNA encoding a protein of 1865 aa. IRLB is ubiquitously expressed and its expression is regulated in a growth- and cell cycle-dependent manner. In addition to the ISRE-binding domain IRLB contains a tripartite DENN domain, a nuclear localization signal, two PPRs, and a calmodulin-binding domain. The presence of DENN domains predicts possible interactions of IRLB with GTPases from the Rab family or regulation of growth-induced MAPKs. Strongly homologous proteins were identified in all available vertebrate genomes as well as in Caenorhabditis elegans and Drosophila melanogaster. In human and mouse a family of IRLB proteins exists, consisting of at least three members.


A comparison of the morbidity associated with occlusive and non-occlusive dressings applied to peripheral intravenous devices.
In a non-randomized controlled study of the effects of an occlusive polymer dressing on the morbidity associated with intravenous (iv) cannulation, it was found that the polymer dressing adversely affected the rate of cannula tip colonization, but that this could not be generally related to an increased risk of thrombophlebitis. A strong association was found between Staphylococcus aureus colonization and thrombophlebitis. It is proposed that the materials, method of manufacture and the use to which the cannula is put are more important in the genesis of the minor complications of iv cannulation than the type of dressing.


Identification and expression of a ferritin homolog in amphioxus Branchiostoma belcheri: evidence for its dual role in immune response and iron metabolism.
Ferritin plays a key role in cellular iron metabolism including iron storage and detoxification, which has been identified in a wide range of organisms including bacteria, fungi, plants and animals. However, little information is available regarding ferritin in the protochordates to date. Here we demonstrate the presence of a ferritin gene homolog, BbFRT, in amphioxus Branchiostoma belcheri. Analysis of the BbFRT 5'-UTR indicated the existence of a putative iron-responsive element (IRE) with a predicated stem-loop structure. BbFRT encoded a deduced protein of 172 amino acids with the conserved motif for ferroxidase center typical of heavy chains of vertebrate ferritins. Sequence comparison showed that BbFRT shared more identity to H-chains (68%) of vertebrate ferritins than to the L-chains (46-51%). Both in situ hybridization histochemistry and immunohistochemical staining revealed that BbFRT was ubiquitously expressed in B. belcheri. In addition, BbFRT expression was up-regulated by 1.6-fold and 1.5-fold, respectively, following exposure to LPS at both transcriptional and translational levels. Similarly, exposure to iron resulted in about 1.6-fold increase in BbFRT in the humoral fluids. These suggest that BbFRT seems a protein with a dual function functioning in both immune response and iron metabolism.


Revisiting the paradigm of silica pathogenicity with synthetic quartz crystals: the role of crystallinity and surface disorder.
Exposure to some - but not all - quartz particles is associated to silicosis, lung cancer and autoimmune diseases. What imparts pathogenicity to any single quartz source is however still unclear. Crystallinity and various surface features are implied in toxicity. Quartz dusts used so far in particle toxicology have been obtained by grinding rocks containing natural quartz, a process which affects crystallinity and yields dusts with variable surface states. To clarify the role of crystallinity in quartz pathogenicity we have grown intact quartz crystals in respirable size. Quartz crystals were grown and compared with a fractured specimen obtained by grinding the largest synthetic crystals and a mineral quartz (positive control). The key physico-chemical features relevant to particle toxicity - particle size distribution, micromorphology, crystallinity, surface charge, cell-free oxidative potential - were evaluated. Membranolysis was assessed on biological and artificial membranes. Endpoints of cellular stress were evaluated on RAW 264.7 murine macrophages by High Content Analysis after ascertaining cellular uptake by bio-TEM imaging of quartz-exposed cells. Quartz crystals were grown in the submicron (n-Qz-syn) or micron (μ-Qz-syn) range by modulating the synthetic procedure. Independently from size as-grown quartz crystals with regular intact faces did not elicit cellular toxicity and lysosomal stress on RAW 264.7 macrophages, and were non-membranolytic on liposome and red blood cells. When fractured, synthetic quartz (μ-Qz-syn-f) attained particle morphology and size close to the mineral quartz dust (Qz-f, positive control) and similarly induced cellular toxicity and membranolysis. Fracturing imparted a higher heterogeneity of silanol acidic sites and radical species at the quartz surface. Our data support the hypothesis that the biological activity of quartz dust is not due to crystallinity but to crystal fragmentation, when conchoidal fractures are formed. Besides radical generation, fracturing upsets the expected long-range order of non-radical surface moieties - silanols, silanolates, siloxanes - which disrupt membranes and induce cellular toxicity, both outcomes associated to the inflammatory response to quartz.


Peptidoglycan from Staphylococcus aureus increases MUC5AC gene expression via RSK1-CREB pathway in human airway epithelial cells.
Respiratory tract exposure to viruses, air pollutants, or bacterial pathogens can lead to pulmonary diseases. The molecular mechanism of mucous overproduction increased by these pathogens provides the knowledge for developing new therapeutic strategies. There is established in vitro data demonstrating that the overexpression of MUC5AC is induced by peptidoglycan (PGN) derived from Staphylococcus aureus. However, the mechanisms by which PGN activates MUC5AC gene expression in the airway remain unclear. The aim of this study was to identify the mechanism of PGN-induced MUC5AC gene expression. We found that PGN could induce MUC5AC gene expressions in a time- and dose-dependent manner. Moreover, activations of ERK1/2 and JNK increased after treatment of cells with PGN, whereas phosporylation of p38 was undetected. Of these MAPKs, pharmacologic inhibition of ERK1/2 decreased PGN-induced MUC5AC gene expression. In addition, we checked the activation of p90 ribosomal S6 kinase 1 (RSK1) as a downstream signaling target of ERK1/2 in PGN signaling. The activation of RSK1 was prevented by pretreatment with PD98059. We also found that RSK1 mediated the PGN-induced phosphorylation of cAMP response element-binding protein (CREB) and the transcription of MUC5AC. Furthermore, the cAMP-response element (CRE) in the MUC5AC promoter appears to be important for PGN-induced MUC5AC gene expression in NCI-H292 cells.


Alteration of gene expression in MDA-MB-453 breast cancer cell line in response to continuous exposure to Trastuzumab.
Development of resistance against cancer therapeutic agents is a common problem in cancer management. Trastuzumab resistance is one of the challenges in management of HER-2-positive breast cancer patients resulting in breast cancer progression, metastasis, and patient poor outcome. The aim of this study is to determine the alteration in gene expression in response to Trastuzumab resistance after long-term exposure to Trastuzumab. The Trastuzumab-resistant MDA-MB-453 (MDA-MB-453/TR) cell line was developed by exposing cells to 10 μM Trastuzumab continuously for 6 months. Sensitivity toward Trastuzumab was tested using cell viability assays. The acquisition of an epithelial-to mesenchymal transition (EMT) phenotype was also observed in parallel with the development of resistance. Based on the real-time-based PCR array technology, several genes were altered affecting multiple networks. The most up-regulated genes were TGF-β1 and EGF, and IGFBP-3. These genes are known to have a critical role in Trastuzumab resistance in breast cancer cell lines and/or in the acquisition of EMT. They are also recognized for their role in cancer progression and metastasis. These alterations indicate that the development of Trastuzumab resistance is multifactorial and involves a development of a mesenchymal like phenotype.


Oral Minoxidil for Chemotherapy-Induced Alopecia.
Chemotherapy-induced alopecia (CIA), one of the most dramatic side effects of chemotherapy, occurs in approximately 65% of patients receiving cytotoxic drugs. We report the case of a patient, 64 years old, affected by chemotherapy-induced alopecia treated with oral minoxidil with good results. Our case may be useful in the literature to propose a new therapy for this pathology that is fundamentally very difficult to treat.


Feasibility of Creation of an Endovascular Arteriovenous Fistula in Patients Undergoing Preoperative Vascular Mapping.
The first endovascular arteriovenous fistula (endoAVF) device (WavelinQ), a novel percutaneous technique of AVF creation, was approved by the Food and Drug Administration in 2018 and has been placed in a small number of United States patients on hemodialysis. It is unknown how often patients with advanced CKD have vascular anatomy suitable for WavelinQ creation. The goal of this study was to determine the proportion of patients with vascular anatomy suitable for WavelinQ creation and to assess patient characteristics associated with such suitability. All patients referred for vascular access placement at a large academic medical center underwent standardized preoperative sonographic vascular mapping to assess suitability for an AVF. During a 2-year period (March 2019 to March 2021), we assessed the suitability of the vessels for creation of WavelinQ. We then compared the demographic characteristics, comorbidities, and vascular mapping measurements between patients who were or were not suitable for WavelinQ. During the study period, 437 patients underwent vessel mapping. Of these, 51% of patients were eligible for a surgical AVF, and 32% were eligible for a WavelinQ AVF; 63% of those suitable for a surgical AVF were also suitable for a WavelinQ AVF. Patients with a vascular anatomy suitable for WavelinQ were younger (age 55±15 versus 60±14 years, P=0.01) but similar in sex, race, diabetes, hypertension, coronary artery disease, and peripheral artery disease. Among patients with CKD with vascular anatomy suitable for a surgical AVF, 63% are also suitable for a WavelinQ endoAVF. Older patients are less frequently suitable for WavelinQ.


Reduction of Salmonella Infantis on skin-on, bone-in chicken thighs by cetylpyridinium chloride application and the impact on the skin microbiota.
Salmonella Infantis has been the etiological agent of numerous foodborne outbreaks of nontyphoidal Salmonella. Consequently, there is an emergent need to mitigate Salmonella Infantis among poultry. Thus, this study evaluated the efficacy of cetylpyridinium chloride (CPC) versus peroxyacetic acid (PAA), on bone-in, skin-on chicken thighs for the reduction of Salmonella and changes in the microbiota. Exactly 100 skin-on, bone-in chicken thighs (2 trials, 0 and 24 h, k = 5, n = 5, N = 50) were inoculated with 108 CFU/mL of a nalidixic acid resistant strain of S. Infantis for an attachment of 106 CFU/g. Thighs were treated with 20 s part dips (350 mL): a no inoculum, no treatment control (NINTC); no treatment control (NTC); tap water (TW); TW+CPC; TW+PAA. Following treatment, thighs were rinsed in 150 mL of nBPW, and rinsates were collected. Rinsates were spot plated for Salmonella and aerobic bacteria (APC). Log10 transformed counts were analyzed using a mixed-effects model (random effect = trial) with means separated using Tukey's HSD (P ≤ 0.05). The genomic DNA of rinsates was extracted, and the 16S rDNA was sequenced on an Illumina MiSeq. Microbiota data were analyzed using QIIME2, with data considered significant at P ≤ 0.05 (main effects) and Q≤0.05 (pairwise differences). Treatment × time interactions were observed for both Salmonella and APC (P < 0.05). The treatment of thighs with PAA and CPC reduced Salmonella and APC in respect to the controls. Numerically, thighs treated with CPC had less Salmonella (4.29 log10CFU/g) and less APC (4.56 log10CFU/g) at 24 h than all other treatments (P > 0.05). Differences in diversity metrics were not consistently observed between treatments; however, in trial 2, the NTC treated thighs were different than those treated with CPC (P < 0.05; Q < 0.05). In both trials, ANCOM, the analysis of microbiome compositional profiles, revealed shifts at both the phylum and order levels with thighs being different in the relative abundances of Proteobacteria (P < 0.05). In conclusion, treatment of skin-on poultry parts with CPC may reduce the risk of foodborne outbreaks caused by Salmonella Infantis.


Effect of genetically modified Schwann cells with increased motility in end-to-side nerve grafting.
Taking into account that Schwann-cell (SC) motility is a prerequisite for myelination during peripheral nerve regeneration, the present study was designed with the intention to increase SC motility in vitro and to evaluate the effect of transduced SC on nerve regeneration in vivo, through silicone tubes after end-to-side nerve repair. Our in vitro study demonstrated that SC transduction with the pREV-HW3 retrovirus, encoding for sialyl-transferase-X (STX), significantly increased their motility compared to the control. In the in vivo study, 45 Wistar rats were randomized into three groups of 15 each. In all animals, the left peroneal nerve was severed, and a 10-mm segment was removed. The distal stump of the peroneal nerve was connected end-to-side to a perineurial window in the ipsilateral tibial nerve with either a silicone tube lined with SC (group A) or a silicone tube lined with STX-transduced SC (groups B and C). Fluorescence and light microscopy in group C showed that SCs were viable the first critical 15 postoperative days. After 90 days, light microscopy in group B demonstrated that STX-transduced SCs with increased motility ensured nerve regeneration, through silicone tubes, in all cases. Furthermore, STX-transduced SCs increased significantly fiber diameter and myelin thickness, and most importantly enhanced significantly the functional outcome compared to non-transduced SCs.


Comparison of peri-procedural anticoagulation with rivaroxaban and apixaban during radiofrequency ablation of atrial fibrillation.
Prospective studies on rivaroxaban and apixaban have shown the safety and efficacy of direct anticoagulation agents (DOAC)s used peri-procedurally during radiofrequency ablation (RFA) of atrial fibrillation (AF). Studies comparing the two agents have not been performed. Consecutive patients from a prospective registry who underwent RFA of AF between April 2012 and March 2015 and were on apixaban or rivaroxaban were studied. Clinical variables and outcomes were noted. There were a total of 358 patients (n = 56 on apixaban and n = 302 on rivaroxaban). There were no differences in baseline characteristics between both groups. The last dose of rivaroxaban was administered the night before the procedure in 96% of patients. In patients on apixaban, 48% of patients whose procedure was in the afternoon took the medication on the morning of the procedure. TIA/CVA occurred in 2 patients (0.6%) in rivaroxaban group with none in apixaban group (p = 0.4). There was no difference in the rate of pericardial effusion between apixaban and rivaroxaban groups [1.7% vs 0.6% (p = 0.4)]. Five percent of patients in both groups had groin complications (p = 0.9). In apixaban group, all groin complications were small hematomas except one patient who had a pseudoaneurysm (1.6%). One pseudo-aneurysm, 1 fistula and 3 large hematomas were noted in patients on rivaroxaban (1.7%) with the rest being small hematomas. DOACs were restarted post procedure typically 4 h post hemostasis. Peri-procedural uninterrupted use of apixaban and rivaroxaban during AF RFA is safe and there are no major differences between both groups.


Non-attendance in primary care: the views of patients and practices on its causes, impact and solutions.
More than 12 million appointments in primary care are not attended each year: this is about 6.5% of the appointments made. Missing appointments is widely perceived as a waste of resources and a potential barrier to the achievement of the 48-hour access target. To explore and compare the views of primary care team members and patients in relation to the causes, impacts and potential solutions to the issue of non-attendance. A qualitative study using semi-structured interviews with a purposive sample of 24 patients over the age of 18 years, 7 GPs, a GP Registrar, a Nurse Practitioner and 5 receptionists carried out in one health centre in urban South Essex with additional interviews in a practice in rural Essex and a practice in inner city London. The major themes were: competing priorities for patients; the efficiency of appointment booking systems; the significance of relationships on non-attendance; differing attitudes towards non-attendance between different groups; and interventions. Poor patient-staff relationships was given as a reason for non-attendance, while missing appointments was seen as making relationships worse. Inefficiencies in the appointment booking systems were perceived as key in this 'relationship' context. Some non-attendance is inevitable with pre-booked appointments, as GP appointments must compete with patients' other priorities and the complexities of their day. Utilising modern communication technologies, such as SMS text messaging, may make cancellation simpler. A structured approach to matching supply and demand of appointments might reduce problems arising from non-attendance.


Pathology of Free-Ranging and Captive Brazilian Anteaters.
There is little information on the anatomical pathology of Brazilian anteaters. Considering the relevance of knowledge of diseases of these species for their conservation, the aim of this study was to describe pathological changes in 99 captive and free-ranging anteaters from the Brazilian states of São Paulo, Minas Gerais, Bahia, Mato Grosso do Sul and Amazonas. Forty-two animals were killed on roads and 10 died from burns injuries. Other significant conditions included the metabolic diseases of iron storage disease, tissue mineralization and taurine deficiency, protozoan and metazoan infections, candidiasis, sporotrichosis, clostridiosis and proliferative disorders including squamous cell carcinoma.


Death to the Coral Reefs and More Money for Everybody Else.
It was a bad week for the residents of the world's rapidly disappearing coral reefs, says Science in its lead story. But it was a good week to be a mathematician. NSF director Rita Colwell proposed tripling their research budget, reports Nature's lead story.


Anti-DNA antibody subpopulations and lupus nephritis.
As a consequence of increased insight into the cellular and molecular mechanisms responsible for induction of B cell and T cell autoimmunity to DNA and nucleosomes, there is an obvious need to reconsider the dogma stating that anti-dsDNA antibodies serve as marker antibodies for SLE and also that anti-dsDNA antibodies per se are responsible for the initiation of lupus nephritis. Given that the potential to produce anti-dsDNA antibodies is an inherent property of the normal immune system and that few anti-DNA antibodies have nephritogenic potential, we must try to solve the problem whether it is avidity for DNA, specificity for unique DNA structures or cross-reactivity with non-DNA molecules, that make such antibodies pathogenic and thus potential markers for SLE and lupus nephritis. In this review, we will summarize contemporary problems related to these questions; (1) try to focus on phenotypic differences with respect to the ability to produce anti-dsDNA antibodies between individuals suffering from SLE and those not belonging to this diagnostic group, and (2) to describe differences between pathogenic and non-pathogenic anti-dsDNA antibodies.


Molecular cloning and characterization of leucine aminopeptidase from Fasciola gigantica.
M17 leucine aminopeptidase (LAP) is one of a family of metalloexopeptidases, of which short peptide fragments are cleaved from the N-terminals. In this study, the full length of cDNA encoding Fasciola gigantica LAP (FgLAP) was cloned from adult parasites. The amino acid sequences of FgLAP showed a high degree of identity (98%) with that from Fasciola hepatica and a low degree of identities (11% and 9%) with those from cattle and human. Phylogenetic analysis revealed that the FgLAP was closely related and grouped with F. hepatica LAP (FhLAP). Northern analysis showed that FgLAP transcriptional products have 1800 base pairs. Analysis by RNA in situ hybridization indicated that LAP gene was expressed in the cecal epithelial cells of adult parasites. A polyclonal antibody to a recombinant FgLAP (rFgLAP) detected the native LAP protein in various developmental stages of the parasite. In a functional test, this rFgLAP displayed aminolytic activity using a fluorogenic Leu-MCA substrate, and was significantly inhibited by bestatin. Its maximum activity was at pH 8.0 and enhanced by Mn(2+) ions. Localization of LAP proteins by immunohistochemistry and immunofluorescence techniques indicated that the enzyme was distributed in the apical cytoplasm of cecal epithelial cells. Because of its important metabolic role and fairly exposed position, FgLAP is a potential drug target and a possible vaccine candidate against fasciolosis.


Vertical and Horizontal Augmentation of Deficient Maxilla and Mandible for Implant Placement.
Ridge augmentation for implant procedures has been shown to be highly successful. There are several techniques available to the dentist, but they require some degree of surgical expertise and experience. No particular technique has been shown to be superior. This article presents the indications, techniques, and complications of the various procedures for alveolar ridge augmentation. This information will educate the general dental practitioner of the techniques available and provide information on the surgical procedures that could be used to discuss with patients when they are being referred to a specialist.


Identification of new acyl-CoA binding protein transcripts in human and mouse.
The ubiquitously expressed acyl-CoA binding protein (ACBP) is involved in lipid metabolism and is regulated by hormones and feeding status via transcription factors such as sterol regulatory element-binding protein 1 and peroxisome proliferator-activated receptor-gamma (PPARgamma). In humans, two transcripts encoding proteins of 86 and 104 amino acids are known, whereas in mouse only one protein of 86 amino acids is described. We identified new transcripts in human and mouse tissues, that had been generated by alternative first exon usage. Quantitative RT-PCR analyses showed a high expression of the new human transcript, ACBP-1c, in adipose tissue. By promoter reporter gene assays, specific regulation of this transcript by PPARgamma2 was revealed, implicating the usage of an alternative promoter that contains a PPARgamma responsive element. Subcellular localizations of the known human proteins and the new variant showed an occurrence in cytoplasma and nucleus. Reported studies concerning ACBP gene regulation should be re-evaluated with respect to a new ACBP gene model. Given the fact that the new variant is highly expressed in adipose tissue and a PPARgamma target, it might be relevant for diseases like diabetes and obesity.


Developing a culturally competent peer support intervention for Spanish-speaking Latinas with breast cancer.
Little research exists on the need for, barriers to, and acceptability and effectiveness of psychosocial support services among Latinas with breast cancer, despite their increased risks of psychosocial distress. This formative research study identifies barriers to and benefits and components of an effective peer support counselor intervention for Spanish-speaking Latinas recently diagnosed with breast cancer. Analysis was based on interviews of 89 Latino cancer patients referred to psychosocial services; 29 Spanish-speaking survivors of breast cancer; and 17 culturally competent advocates for Latinos with cancer. Results indicate that interventions should begin close to diagnosis; build self-care skills; be culturally competent and emotionally supportive; provide language appropriate cancer information; encourage self-expression; and address lack of access to and knowledge of services. Creating such psychosocial programs with input from survivors and advocates who have similar self-identities to patients would improve quality of life in diverse and underserved populations.


The effect on single and combined stresses for biomass and lipid production from Nannochloris atomus using two phase culture system.
The optimal conditions for high biomass and lipid production from Nannochloris atomus were evaluated. The parameters used in this study were light emitting diode (LED) wavelength mixing ratio, the photoperiod, salinity tolerance, and single and combined stresses. Biomass production was monitored in the first phase using red LED (625 nm), followed by lipid production by green LED (520 nm) in the second phase. The optimal conditions were obtained using a single red LED with light:dark durations of 20:4 h and two days of exposure in combined stresses of 1.06 M NaCl and green LED. Under these conditions, 68.6 % (w/w) lipid content were obtained. Compared to the non-stress control, the lipid content was increased by 31.9 %. Linolenic acid (C18:3) the omega-3 fatty acid was produced up to 52.4 % in 1.06 M NaCl as a single stress.


[Morphogenesis of the lung bud from albino Swiss mice embryos, in organ culture in the presence of anti-lung serum].
The study of morphological figures and morphometrical data observed in lung buds from ETAS, cultured in Agar and OPEP medium, with or without SCAPEP, at different concentrations, in order to detect its influence on the morphogenesis, has shown that: OPEP (5:0) supports gradual morphogenesis for a limited time; OPEP + SCAPEP (5:2) supports gradual morphogenesis for a prolonged time; OPEP+SCAPEP (5:5) supports fast and deep morphogenesis for a short time; OPEP+SCAPEP (5:7,5) causes early inhibition of morphogenesis and survival; SCAPEP (5:0) stops instantly morphogenesis and survival.


Effect of probiotic (Saccharomyces cerevisiae) supplementation on immune response in Trypanosoma brucei brucei infected rats.
The immunomodulatory effect of the probiotic (Saccharomyces cerevisiae) on Trypanosoma brucei brucei infected rats was studied. Thirty (30) rats divided into five groups (A-E) of 6 rats each were used for the study. Groups A, B and C rats received feed supplemented with S. cerevisiae (at 0.08, 0.12 and 0.16/kg of feed, respectively) for the duration of the study. Groups D and E diets were not supplemented. All the rats in the 5 groups were immunized with 0.3 ml of 10% sheep red blood cells (SRBC) at day 7 pre-supplementation, and booster doses given every 14 days thereafter. On day 28 post supplementation (PS), rats of groups A-D were infected with 1 × 10(6) of T. brucei brucei intraperitoneally. Supplementation resulted in increases in antibody titres to SRBC which later declined following T. brucei brucei infection, but remained higher than the pre supplementation titres. At termination of the study (i.e. day 49 PS) supplemented groups had significantly (p<0.05) higher antibody titres than either the infected or the non infected controls. The total and differential leucocyte counts followed a similar pattern with initial increases in counts following supplementation followed by reductions after T. brucei brucei infection. Supplementation also resulted in decline in parasitaemia with significant difference between the supplemented groups and the un-supplemented controls on day 42 post infection. The results are indication that probiotics can be used to ameliorate the immunosuppressive effect of T. brucei brucei infections.


Complementation of a defect in the asparagine-linked glycosylation of a mouse FM3A mutant G258 cell line by spheroplast fusion of a human mega YAC clone 923f5.
Mouse G258 mutant stopped both cell growth and the synthesis of lipid-linked oligosaccharide at the Man(3)GlcNAc(2)-P-P-Dolichol at a restricted temperature with a single gene mutation. To clarify the lesion in the G258 mutant, we isolated human genomic DNA transformants of the G258 mutant, which recovered from both defects by way of cell hybridization with X-ray irradiated HeLa cells. We detected a common 1.3-kb product by inter-human specific sequence in the L1 (L1Hs) PCR in the transformants (Kataoka et al., Somat. Cell Mol. Genet., 24, 235-243 (1998)). In the present study, we screened a human mega yeast artificial chromosome (YAC) library by PCR with primers designed according to the 1.3-kb DNA, and selected YAC clone 923f5. Moreover, we found by spheroplast fusion that YAC clone 923f5 complemented both defects of the G258 mutant. Since the human counterpart of the yeast ALG11 gene is localized in the region, the G258 mutant might have a defect in the mouse ALG11 gene.


Tellurium-induced neuropathy: correlative physiological, morphological and electron microprobe studies.
Elemental tellurium (TE) was included in the normal diet of 15-day-old rats and every day thereafter for 35 days. Within 24 hours a segmental demyelination was seen in the sciatic nerve. On the 2nd day, Te was localized in the cytoplasm of the Schwann cells. On the 3rd day paralysis of the hind legs appeared which lasted 7--10 days. The papralysis then disappeared and demyelination ceased, although the rats were still ingesting Te. After one week there was also slight demyelination in the brachial plexus. Motor nerve conduction velocities were reduced below the normal control range, but only after the rats had taken Te for a least 7 days. This peripheral neuropathy can only be induced in the rat by Te ingestion between the 15th and 35th days of post-natal life, not before or after this period of time.


Blood kallikrein. Kinin system in acute pancreatitis.
Three chief components of the kallikrein-kinin system (kallikrein, kininogen, kininase) were studied in the blood of 42 patients with acute pancreatitis. Significant increase in content of kallikrein, decrease in level of kininogen, and increase of kininase activity were observed. The highest values for kallikrein, kininogen and kininase activity were found in patients in whom acute pancreatitis was accompanied by hemodynamic changes.


Study on clinical outcomes between non-transecting urethroplasty and lingual mucosal urethroplasty for iatrogenic bulbar urethral stricture treatment.
This study aimed to compare the clinical outcomes of non-transecting urethroplasty and lingual mucosal urethroplasty in the treatment of iatrogenic bulbar urethral stricture. A total of 25 patients with iatrogenic bulbar urethral stricture were enrolled, 12 of whom underwent lingual mucosal urethroplasty, 13 patients who underwent non-transecting urethroplasty. All patients were followed-up and evaluated at 3 postoperative months. Evaluations included urethrography, maximum urine flow rate (Qmax), nocturnal erectile function testing, International Index of Erectile Function (IIEF-5) assessment, and Anxiety Related Scale (SAS) assessment. In terms of operation time, there was a significant difference between non-transecting urethroplasty and lingual mucosal urethroplasty. However, there was no significant intergroup difference in intraoperative blood loss. Both techniques were associated with significantly improved Qmax relative to preoperative rates, but there was no significant difference between the groups in this regard over 3 months of postoperative follow-up. Nocturnal penile tumescence and rigidity results showed that there was no significant change in tip hardness after surgery in the non-transecting urethroplasty group. Moreover, IIEF-5 scores indicated that there was no significant intergroup difference in terms of subjective postoperative erectile function. According to the preliminary psychological evaluations during postoperative follow-up, the anxiety scores of patients undergoing non-transecting urethroplasty significantly improved, but there was no significant change in the mean SAS score among patients who underwent lingual mucosal urethroplasty. Both surgical methods can achieve the clinical goal of treating iatrogenic bulbar urethral stricture. Non-transecting urethroplasty has the characteristics of short operation time, relative technical simplicity, and retention of the original erectile function of most patients, and the surgical outcomes of non-transecting urethroplasty are not inferior to those of lingual mucosal urethroplasty, and it is a promising technique for widespread use to treat bulbar urethral strictures.


Binding of the cytoplasmic domain of intercellular adhesion molecule-2 (ICAM-2) to alpha-actinin.
Intercellular adhesion molecule-2 (ICAM-2) functions as a ligand for lymphocyte function-associated antigen-1 (LFA-1) and is involved in leukocyte adhesion. We studied intracellular associations of ICAM-2 using a peptide encompassing the cytoplasmic amino acids 231-254 as an affinity matrix. Among the proteins from placental lysates that bound to the peptide was alpha-actinin as demonstrated by immunoblotting. Purified, 125I-labeled alpha-actinin also bound to the peptide. Confocal microscopic analysis of Eahy926 cells demonstrated a colocalization of ICAM-2 and alpha-actinin. Of overlapping octapeptides covering the entire ICAM-2 cytoplasmic amino acids, ICAM-2241-248 bound alpha-actinin most avidly and effectively competed with the longer cytoplasmic peptide for binding. The site of interaction in alpha-actinin was studied using bacterially expressed alpha-actinin fusion proteins. Several constructs covering nonoverlapping regions of alpha-actinin bound to the ICAM-2 cytoplasmic peptide suggesting that multiple regions in alpha-actinin can mediate the interaction. These results, together with previously demonstrated interactions between alpha-actinin and the adhesion proteins ICAM-1, L-selectin, beta1- and beta2-integrins emphasize the role of alpha-actinin as a linker between cell surface adhesion molecules and the actin-containing cytoskeleton.


Ultrasound diagnosis of hematotrachelos: a case report.
Hematotrachelos, the engorgement of the cervix uteri with retained blood, is discussed with reference to clinical presentation, ultrasonographic findings, and etiologies. Other disease processes related to hematotrachelos such as hematometra, hematocolpos, and hydrocolpos are also reviewed.


Synthesis and biological activities of some new fluorinated coumarins and 1-aza coumarins.
A series of new fluorinated coumarins and 1-aza coumarins have been synthesized and the presence of fluorine in these molecules and its effect on their anti-microbial, anti-inflammatory and analgesic activities are discussed. The results of bioassay showed that these newly synthesized compounds containing fluorine exhibit moderate analgesic and excellent anti-inflammatory and potential anti-bacterial and anti-fungal activities, compared to the other halogenated compounds. All the newly synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, 19F NMR, EI-MS, and FAB-MS. The ORTEP diagram of one of the compounds is reported herein.


Operated descending thoracic and thoracoabdominal atherosclerotic aortic aneurysm prognosis.
The long-term survival of patients treated from descending thoracic aneurysm (DTA) is well known, more than those treated from a thoracoabdominal aortic aneurysm (TAAA). Moreover, studies are rarely focused on the aneurysmal etiology and include both degenerative and post dissecting aneurysms. The aim of this study is to compare the long-term survival of patients operated from DTA or TAAA due to degenerative atherosclerosis. Thirty-nine atherosclerotic aneurysm patients were operated between January 2007 and July 2015 at Rouen University Hospital. Eighteen DTA patients were operated by TEVAR and 21 TAAA patients (8 type I and 13 type III) by open approach. The main endpoint was remote survival patients. Overall, the initial population was similar in the two groups. However, one third of DTA were treated in context of emergency for painful aneurysm versus 9.5% of patients with TAAA (P=0.066). Survival median of 18 DTA was 18 months (1-68). Survival median of 21 TAAA followed was 66 months (1-91). Survival in both groups was statistically different with the log-rank test (P=0.044). Long-term prognosis of atherosclerotic DTA may be worse than that of TAAA's. This retrospective study reflects experience in the management of DTA and TAAA in a single-center. Prospective data in patients treated with endovascular procedures for DTA or TAAA, with fenesterated or branched endoprosthesis, are warranted to confirm these results.


Analysis of the usefulness of magnetic resonance imaging and clinical parameters in the detection of prostate cancer in the first systematic biopsy combined with targeted cognitive biopsy.
The study aimed to assess the suitability of multiparametric magnetic resonance prostate imaging (mpMRI) in combination with clinical parameters [prostate-specific antigen (PSA), digital rectal examination (DRE)] in the identification of men at risk of the presence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa, Gleason Score ≥3+4) in the cognitive fusion with systematic prostate biopsy. We retrospectively evaluated a population of 215 biopsy - naive patients with a clinical suspicion of prostate cancer. The results of mpMRI, DRE, PSA and biopsy were analyzed. MpMRI of the prostate according to the Prostate Imaging Reporting and Data System (PI-RADS) v.2.0 scheme preceded cognitive fusion and systematic transrectal prostate biopsy. Uni- and multivariable logistic regression analysis (MVA) was used to identify the variables determining the risk of detecting PCa overall and csPCa. In MVA, it was established that the combination of variables such as PSA level [odds ratio (OR) 1.195; p = 0.002], PI-RADS ≥3 (OR 7.7; p = 0.002), prostate volume (OR 0.98; p = 0.017) significantly determines the probability of PCa detection in biopsy, while for csPCa it is PSA level (OR 1.14; p = 0.004), DRE (+) (OR 5.75; p <0.001), PI-RADS ≥4 (OR 6.5; p <0.001). Analysis of mpMRI diagnostic value for PI-RADS ≥4 revealed better sensitivity (88.9% vs 82.6%) and better negative predictive value (NPV) (94.5% vs 82.4%) for detection of csPCa than for PCa overall. MpMRI results combining with DRE and PSA parameters help to identify men at high - or low risk of csPCa detection in the first - time biopsy.


Brood translocation and circadian variation of temperature preference in the ant Camponotus mus.
1) When a thermal gradient (20-40° C) was established along a laboratory nest, Camponotus mus nurse workers showed a photoperiodic circadian rhythm of temperature preferences for brood rearing. Two different temperatures were daily selected to translocate the brood, i.e. 30.8° C selected at the middle of the photophase, and 27.5° C selected during the scotophase, 8 h later. 2) The daily temperature response of nurse workers consisted of paired high and low-temperature translocations, with a 8 hs-interval in between: high-temperature translocation was shown to be entrained by the photophase length, whereas low-temperature translocation was shown to be dependent on the precedent one. 3) Prey deprivation to the colony modified the brood transport behaviors resulting in translocations of only cocoons and large (ripe) larvae, stages in which the pupation processes are triggered. Small larvae and eggs remained located at 27.5° C. 4) Evaluation of pupa developmental time as well as percentage of pupa mortality at different temperature regimes allowed to construct an efficiency index relating pupa survival and cocoon developmental time. In the range of temperatures selected by nurses, the index reached its maximal values. 5) The ecological significance of these results is discussed.


Malondialdehyde inhibits cardiac contractile function in ventricular myocytes via a p38 mitogen-activated protein kinase-dependent mechanism.
(1) Increased oxidative stress plays a significant role in the etiology of cardiovascular disease. Lipid peroxidation, initiated in the presence of hydroxy radicals resulting in the production of malondialdehyde, directly produces oxidative stress. This study was designed to examine the direct impact of malondialdehyde on ventricular contractile function at the single cardiac myocyte level. Ventricular myocytes from adult rat hearts were stimulated to contract at 0.5 Hz, and mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix Myocam system. Contractile properties analyzed included peak shortening amplitude (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)), maximal velocity of shortening/relengthening (+/-dLdt), and Ca(2+)-induced intracellular Ca(2+) fluorescence release (CICR) and intracellular Ca(2+) decay (tau). p38 mitogen-activated protein (MAP) kinase phosphorylation was assessed with Western blot. (2) Our results indicated that malondialdehyde directly depressed PS, +/-dLdt and CICR in a concentration-dependent manner and shortened TPS without affecting TR(90) and tau. Interestingly, the malondialdehyde-induced cardiac mechanical effect was abolished by both the p38 MAP kinase inhibitor SB203580 (1 and 10 micro M) and the antioxidant vitamin C (100 micro M). Western blot analysis confirmed direct phosphorylation of p38 MAP kinase by malondialdehyde. (3) These findings revealed a novel role of malondialdehyde and p38 MAP kinase in lipid peroxidation and oxidative stress-associated cardiac dysfunction.


Bioresponsive drug delivery systems for the treatment of inflammatory diseases.
Inflammation is intimately related to the pathogenesis of numerous acute and chronic diseases like cardiovascular disease, inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative diseases. Therefore anti-inflammatory therapy is a very promising strategy for the prevention and treatment of these inflammatory diseases. To overcome the shortcomings of existing anti-inflammatory agents and their traditional formulations, such as nonspecific tissue distribution and uncontrolled drug release, bioresponsive drug delivery systems have received much attention in recent years. In this review, we first provide a brief introduction of the pathogenesis of inflammation, with an emphasis on representative inflammatory cells and mediators in inflammatory microenvironments that serve as pathological fundamentals for rational design of bioresponsive carriers. Then we discuss different materials and delivery systems responsive to inflammation-associated biochemical signals, such as pH, reactive oxygen species, and specific enzymes. Also, applications of various bioresponsive drug delivery systems in the treatment of typical acute and chronic inflammatory diseases are described. Finally, crucial challenges in the future development and clinical translation of bioresponsive anti-inflammatory drug delivery systems are highlighted.


[New approaches to treatment of occupational bronchial asthma].
Clinical and biochemical studies considering pathogenetic mechanisms of bronchial asthma supported efficiency of "Singular" preparation and its promising quality for complex therapy of bronchial asthma.


A DM9-containing protein from oyster Crassostrea gigas (CgDM9CP-3) mediating immune recognition and encapsulation.
DM9 domain containing protein (DM9CP) is a recently identified pattern recognition molecules exiting in most organisms except plants. In the present study, a novel DM9-containing protein (CgDM9CP-3) was identified from Pacific oyster Crassostrea gigas with an open reading frame of 438 bp, encoding a polypeptide of 145 amino acids containing two tandem DM9 repeats. The deduced amino acid sequence of CgDM9CP-3 shared 52.4% and 58.6% identity with CgDM9CP-1 and CgDM9CP-2, respectively. The mRNA transcripts of CgDM9CP-3 were highest expressed in oyster gills and its protein was mainly distributed in cytomembrane of haemocytes. After the stimulations with Vibrio splendidus and mannose, the mRNA expression of CgDM9CP-3 in oyster gills was significantly up-regulated and reached the peak level at 12 h and 24 h (p < 0.05), which was 7.80-fold (p < 0.05) and 42.82-fold (p < 0.05) of that in the control group, respectively. The recombinant CgDM9CP-3 protein (rCgDM9CP-3) was able to bind LPS, PGN and d-Mannose, fungi Pichia pastoris and Yarrowia lipolytica, as well as gram-negative bacteria Escherichia coli, Vibrio anguillarum and V. splendidus in a Ca2+-dependent manner. Moreover, it could enhance the encapsulation of haemocytes and exhibited agglutination activity towards fungi P. pastoris and Y. lipolytica in vitro with Ca2+. These results suggested that CgDM9CP-3 not only acted as a PRR involved in the pathogen recognition, but also enhanced cellular encapsulation in oyster C. gigas.


Increased sympathetic tone is associated with illness burden in bipolar disorder.
We recently described an association between reduced heart rate variability (HRV) and illness burden in bipolar disorder (BD) using a novel Illness Burden Index (IBI). We aimed to further characterize this association by using spectral analyses to assess whether the IBI is also associated with autonomic imbalance in BD patients. In this cross-sectional study, 53 participants with BD wore a device for 24 h to assess association between HRV spectral measures and the IBI or each of its components (age of onset, number and type of previous episode(s), duration of the most severe episode, history of suicide attempts or psychotic symptoms during episodes, co-morbid psychiatric disorders, and family history). We ran both unadjusted models and models controlling for age, sex, years of education, marital status, BMI, pharmacotherapy, and baseline functional cardiovascular capacity. HRV low-frequency (LF) normalized values were almost twice as high as published in healthy controls. Higher IBI was associated with higher LF and lower High Frequency (HF) values, resulting in a higher LF/HF ratio, indicating an increased sympathetic tone. Four individual components of the IBI were similarly associated with measures of increased sympathetic tone: earlier age of onset, number of depressive episodes, co-morbid anxiety disorders, and family history of suicide. Adjusted and unadjusted models had similar results. Our models used mean LF and HF and do not consider their dynamic variations over 24 h or phase of the illness. Burden of illness is associated with increased sympathetic tone in patients with BD, putting them at risk for arrythmias and sudden death.


[Hematuria due to foreign bodies in a woman-patient with the Munchhausen syndrome].
It is reported on a female patient with Münchhausen syndrome who was referred by the family doctor for the clarification of a haematuria. As cause of the haematuria two stones of about 1 cm in diameter each were found which were artificially brought into the bladder.


Estimating the age-specific duration of herpes zoster vaccine protection: a matter of model choice?
The estimation of herpes zoster (HZ) vaccine efficacy by time since vaccination and age at vaccination is crucial to assess the effectiveness and cost-effectiveness of HZ vaccination. Published estimates for the duration of protection from the vaccine diverge substantially, although based on data from the same trial for a follow-up period of 5 years. Different models were used to obtain these estimates, but it is unclear which of these models is most appropriate (if any). Only one study estimated vaccine efficacy by age at vaccination and time since vaccination combined. Recently, data became available from the same trial for a follow-up period of 7 years. We aim to elaborate on estimating HZ vaccine efficacy (1) by estimating it as a function of time since vaccination and age at vaccination, (2) by comparing the fits of a range of models, and (3) by fitting these models on data for a follow-up period of 5 and 7 years. Although the models' fit to data are very comparable, they differ substantially in how they estimate vaccine efficacy to change as a function of time since vaccination and age at vaccination. An accurate estimation of HZ vaccine efficacy by time since vaccination and age at vaccination is hampered by the lack of insight in the biological processes underlying HZ vaccine protection, and by the fact that such data are currently not available in sufficient detail. Uncertainty about the choice of model to estimate this important parameter should be acknowledged in cost-effectiveness analyses.


Variation in use of procurement biopsies and its implications for discard of deceased donor kidneys recovered for transplantation.
The use of procurement biopsies in deceased donor kidney acceptance is controversial. We analyzed Scientific Registry of Transplant Recipients data (n = 59 328 allografts, 2014-2018) to describe biopsy practices across US organ procurement organizations (OPOs) and examine relationships with discards, using hierarchical modeling to account for OPO and donor factors. Median odds ratios (MORs) provide the median of the odds that allografts with identical reported traits would be biopsied or discarded from 2 randomly drawn OPOs. Biopsies were obtained for 52.7% of kidneys. Biopsy use rose in a graded manner with kidney donor profile index (KDPI). Biopsy rates differed significantly among OPOs (22.8% to 77.5%), even after adjustment for KDPI and other donor factors. Discard rates also varied from 6.6% to 32.1% across OPOs. After adjustment for donor factors and OPO, biopsy was associated with more than 3 times the likelihood of discard (adjusted odds ratio [95%LCL aOR95%UCL ], 3.29 3.513.76 ). This association was most pronounced for low-risk (KDPI <20) kidneys (aOR, 5.45 6.477.69 ), with minimal impact at KDPI >85 (aOR, 0.88 1.151.51 ). Adjusted MORs for kidney discard and biopsy were greatest for low-risk kidneys. Reducing the rate of unnecessary biopsy and improving the accuracy of histologic assessments in higher KDPI organs may help reduce graft discard rates.


A randomized, double-blind, placebo-controlled trial of heparin and aspirin for women with in vitro fertilization implantation failure and antiphospholipid or antinuclear antibodies.
To investigate whether heparin and low-dose aspirin increase the pregnancy rate in antiphospholipid antibody or antinuclear antibody-seropositive women with IVF implantation failure. A double-blind, randomized, transfer-by-transfer of fresh or cryopreserved embryos, crossover trial.A hospital infertility clinic and associated IVF service. Women seropositive for at least one antiphospholipid (APA), antinuclear (ANA), or beta(2) glycoprotein I autoantibody and >or=10 embryos transferred without achieving pregnancy (n = 143). Subcutaneous unfractionated heparin (5000 IU b.i.d.) and aspirin (100 mg daily) (158 transfers of 296 embryos) or placebo (142 transfers of 259 embryos) from the day of embryo transfer. Fetal heart per embryo transferred (implantation rate). There was no significant difference in pregnancy rates or implantation rates between treated and placebo cycles; for example, fetal hearts per embryo transferred implantation rates were 6.8% (20/296) and 8.5% (22/259), respectively, and the generalized estimating equation covariate adjusted relative pregnancy rate was 0.65 (95% confidence interval, 0.33-1.28). The implantation rate for seropositive trial participants (42/555, 7.6%) compared favorably with that for IVF implantation-failure patients continuing treatment outside the trial (147/3237, 4.5%). Heparin and aspirin did not improve pregnancy or implantation rates for APA-positive or ANA-positive patients with IVF implantation failure.


Investigation of anaerobic biodegradation of phenanthrene by a sulfate-dependent Geobacter sulfurreducens strain PheS2.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous and harmful contaminants, which can be degraded aerobically. However, the persistence of PAHs in anoxic environments indicates that anaerobic biodegradation of PAHs should also be investigated. Pure-culture and biotransformation processes for anaerobic phenanthrene biodegradation with sulfate as a terminal electron acceptor remains in its infancy. In this study, we investigated anaerobic biodegradation of PAHs by PheS2, an isolated phenanthrene-utilizing sulfate-reducer, using phenanthrene as a model compound. PheS2 was phylogenetically closely related to Geobacter sulfurreducens and reduced sulfate to sulfide during anaerobic phenanthrene biodegradation. Phenanthrene biodegradation processes were detected using gas chromatography-mass spectrometry, genome, and reverse transcription quantitative PCR analyses. Carboxylation was the initial step of anaerobic phenanthrene biodegradation based upon detection of 2- and 4-phenanthroic acid, its isotopically labeled analogs when using 13C-labeled bicarbonate and fully deuterated-phenanthrene (C14D10), and genes encoding enzymes putatively involved in the biodegradation. Further, ring-system reducing and cleavage occurred, and substituted benzene series and cyclohexane derivatives were detected in downstream biotransformation metabolites. Additionally, PheS2 can degrade benzene, naphthalene, anthracene, and benz[a]anthracene, but not pyrene and benz[a]pyrene. This study describes the isolation of an anaerobic phenanthrene-degrading sulfate-reducer, the first pure-culture evidence of phenanthrene biotransformation processes with sulfate as an electron acceptor.


Mycobacterium tuberculosis Rv2324 is a multifunctional feast/famine regulatory protein involved in growth, DNA replication and damage control.
Feast/famine regulatory proteins (FFRPs) are multifunctional regulators. We show that Mtb Rv2324 is important for growth, survival, and countering DNA damage in Mycobacterium tuberculosis (Mtb). DNA-relaxation activity against linear and supercoiled substrates suggest its involvement in transcription activation, while its high affinity for recombination, replication and repair substrates suggest a role there too. Small-Angle-X-ray scattering supports the adoption of an 'open' quaternary association in response to amino-acid binding. Size-exclusion-chromatography and glutaraldehyde cross-linking identify the adoption of diverse oligomers modulated by amino-acid binding, and DNA interactions. We tested G52A, G101T and D104A mutants which correspond to highly conserved residues, distal to the DNA-binding site, and are important for amino acids binding. G101T exhibits increased DNA affinity, while G52A and D104A exhibit weak DNA-binding thereby suggesting that they mediate effector-binding, and DNA binding activities. Gain and loss-of-function studies show that Rv2324 overexpression promotes growth-rate, while its knock-down leads to retarded growth. Rv2324 down-regulation lowers Mtb survival inside resting and IFN-ϒ-activated macrophages. Rv2324 protects the pathogen from DNA damage, as evidenced by the reduction in the knockdown strain's survival following treatment with H2O2 and UV light. Overall, we show that Rv2324 plays a crucial role in regulating survival and growth of Mtb.


Role of intrapulmonary lymph nodes in patients with NSCLC and visceral pleural invasion. The VPI 1314 multicenter registry study protocol.
In the lung cancer classification (TNM), the involvement of thoracic lymph nodes is relevant from a diagnostic and prognostic point of view. Even if imaging modality could help in selecting patients who should undergo surgery, a systematic lymph node dissection during lung surgery is mandatory to identify the subgroup of patients who can benefit from an adjuvant treatment. Patients undergoing elective lobectomy/bilobectomy/segmentectomy) for non-small cell lung cancer and lymphadenectomy with lymph nodes station 10-11-12-13-14 sampling that meet the inclusion and exclusion criteria will be recorded in a multicenter prospective database. The overall incidence of N1 patients (subclassified in: Hilar Lymph nodes, Lobar Lymph nodes and Sublobar Lymph nodes) will be examined as well as the incidence of visceral pleural invasion. The aim of this multicenter prospective study is to evaluate the incidence of intrapulmonary lymph nodes metastases and the possible relation with visceral pleural invasion. Identifying patients with lymph node station 13 and 14 metastases and/or a link between visceral pleural invasion and presence of micro/macro metastases in intrapulmonary lymph nodes may have an impact on decision-making process. ClinicalTrials.gov ID: NCT05596578.


Extracellular glucose-producing exodextranase of the yeast Lipomyces lipofer.
A dextran-hydrolysing enzyme from Lipomyces lipofer IGC 4042 was purified from the supernatant of cultures grown on a mineral medium with dextran, by ultrafiltration and gel filtration on Bio Gel A-0.5 m. This preparation gave only one band by disc gel electrophoresis. Glucose was the only product of dextran hydrolysis. Optimum pH and temperature for the activity of the enzyme were pH 4.5-5.0 and 45 degrees C, respectively. The enzyme was most stable over a pH range of 4.5-6.0, and after 2 hours at 50 degrees C maintained over 60% of its original activity. The molecular weight was 29,000 daltons and the isoelectric point was at pH 7. Km (45 degrees C, pH 5) for dextran T-40 was 1.2 X 10(-5) M. Glucose inhibited the enzyme competitively with a Ki (45 degrees C, pH 5) of 0.5 mM.


[Effect of the Pechenezhskiy reservoir on species distribution and number of blood-sucking Diptera].
Studies of the fauna, density and specificity of formation of the blood-sucking Diptera habitats have demonstrated rapid reduction of biotopes and the density of insects in the first years after the construction of the reservoir. In the following years aggravation of the entomological situation was observed, relative stability being attained only by the 20th year of the reservoir' functioning. Further increase in anthropogenic impact may lead to entomologic changes in the area.


Why Do People Believe What They Do? A Functionalist Perspective.
Why do people believe what they do? Scholars and laypeople alike tend to answer this question by focusing on the representational functions of beliefs (i.e., representing the world accurately). However, a growing body of theory and research indicates that beliefs also can serve important hedonic functions (i.e., decreasing/increasing negative or positive emotional states). In this manuscript, we describe: (1) the features of belief, (2) the functions served by beliefs, with a focus on the hedonic function, (3) an integrative framework highlighting the hedonic function and contrasting it with the representational function, (4) the implications of our framework, and related future research directions for individual differences in belief, belief change, and the ways in which beliefs contribute to adaptive versus maladaptive psychological functioning.


The pH dependence of the hydrolysis of benzoyl-L-arginine ethyl ester in cooled mixed solvents.
Tables of protonic activity (paH) of a number of buffers, determined in mixed solvents and at subzero temperatures, are reported for the following media: water-1,2-propanediol, water-glycerol, and water-dimethylsulfoxide (50:50, in volume). These data with those previously reported allowed us to study enzymic reactions under these conditions. The paH dependence of the tryptic hydrolysis of benzoyl-L-arginine ethyl ester has been studied in the presence of organic solvents (methanol, ethylene glycol, 1,2-propanediol, glycerol, and dimethylsulfoxide, all 50% by volume) between 20 and -20 degrees. The results have allowed us to show the validity of our paH scales in mixed solvents. The paH profiles obtained under these conditions are similar to those observed in pure water at 20 degrees. They are shifted nevertheless by both solvent and temperature. Such shifts are interpreted in terms of the effects of solvents and temperature on pKES on the basis of the conclusions drawn from a study of the effect of these variables on small dissociable molecules. The results obtained under these conditions of solvents and temperature are consistent with the presence at the active site of the enzyme of a histidine residue, and thus provide, concerning the solvent effect, a direct verification of the method of Findlay et al. (Findlay, D., Mathias, A. P., and Rabin, B. R. (1962) Biochem. J. 85, 139-144). On the other hand, the large temperature interval provided by the low temperature procedure, allows us to vary significantly the pK of ionizable groups of the enzymes and thus makes possible their identification, on the basis of their enthalpy of ionization.


Novel experimental model of enlarging abdominal aortic aneurysm in rabbits.
This study tested the hypothesis that an experimental model of abdominal aortic aneurysm in rabbits results in progressive enlargement when induced by a combination of periaortic elastase administration and aortic coarctation. Male New Zealand white rabbits were randomly divided into four groups: (A) stenosis (n = 12), (B) elastase (n = 12), (C) aneurysm (n = 15), and (D) control (n = 12). The stenosis group received an extrinsic coarctation below the right renal artery, the elastase group received a 10-minute administration of 60 μL elastase (1 U/μL) in a 1.5-cm aortic segment, the aneurysm group received stenosis and elastase, and a sham operation was performed in the control group. The aortic diameter was measured after 1, 2, 4, 8, and 16 weeks, and animals were subsequently euthanized for histopathologic and immunohistochemical studies. All animals in the aneurysm group developed aneurysm by 2 weeks after treatment, with average diameters of 5.21 ± 0.74 mm by 2 weeks, 6.23 ± 1.10 mm by 4 weeks, 7.87 ± 0.50 mm by 8 weeks, and 9.40 ± 0.36 mm by 16 weeks. Aortic diameter dilated progressively, and all aneurysms developed by 4 weeks in the stenosis group (4.17 ± 0.22 mm). Only one aneurysm was seen in the elastase group by week 1 (3.60 ± 0.64 mm), and no aneurysm formed in the control group by week 8 (2.47 ± 0.38 mm). The aneurysm group exhibited less media thickness, elastin content, and endothelial recovery, but stronger expression of matrix metalloproteinase 2 and 9 and rabbit macrophage compared with the control group. This novel rabbit abdominal aortic aneurysm model with a gradually enlarging diameter is simply and reliably induced, appropriately mimicking human aortic aneurysm disease.


Cancer Stem Cells, CD44, and Outcomes Following Chemoradiation in Locally Advanced Cervical Cancer: Results From a Prospective Study.
Although cancer stem cells (CSCs) have been reported across solid tumors, there is a dearth of data regarding CSC and its impact on outcomes of cervical cancer. From October 2013 to December 2015, patients with squamous cancer of the cervix (stage IB2-IVA) were included. Pretreatment and posttreatment biopsy was obtained and immunohistochemistry was performed for SOX-2, OCT-4, Nanog, CD44, and Podoplanin. All patients received concurrent radiation and brachytherapy to an equivalent dose of 80 to 84 Gy to point A with concurrent weekly cisplatin. Correlation of CSC expression was performed with known prognostic factors. The effect of stem cell expression on disease outcomes was tested within multivariate analysis. One hundred fifty patients were included. The median dose to point A was 83 Gy (46-89 Gy) and a median of 4 cycles (range, 0-6 cycles) of chemotherapy was administered. At baseline, moderate to strong immunohistochemical expression of SOX-2, OCT-4, Nanog, CD44, and Podoplanin was observed in 12.8%, 4.8%, 24.4%, 15.5%, and 1.3% of patients, respectively. At median follow-up of 30 months (range, 3-51 months), locoregional and distant relapse was observed in 12.2% and 23.1% of patients, of whom 4.7% had both local and distant relapse. The 3-year disease-free survival rate was 87%. On multivariate analysis, moderate to high CSC expression and CD44 low status (hazard ratio [HR] = 8.8; 95% confidence interval [CI], 1.0-77.2; P < .04) independently predicted for locoregional relapse-free survival. International Federation of Gynecology and Obstetrics stage (HR = 2.6; 95% CI, 1.3-5.4; P = .004) and presence of residual tumor after external radiation (HR = 3.5; 95% CI, 1.8-6.5; P = .0001) predicted for a detriment in disease-free survival. The presence of stem cell proteins and loss of CD44 independently predicts for reduced locoregional control in locally advanced cervical cancer. Further investigation into the interaction of stem cell and CD44 biology is warranted.


Mapping the energetic and allosteric landscapes of protein binding domains.
Allosteric communication between distant sites in proteins is central to biological regulation but still poorly characterized, limiting understanding, engineering and drug development1-6. An important reason for this is the lack of methods to comprehensively quantify allostery in diverse proteins. Here we address this shortcoming and present a method that uses deep mutational scanning to globally map allostery. The approach uses an efficient experimental design to infer en masse the causal biophysical effects of mutations by quantifying multiple molecular phenotypes-here we examine binding and protein abundance-in multiple genetic backgrounds and fitting thermodynamic models using neural networks. We apply the approach to two of the most common protein interaction domains found in humans, an SH3 domain and a PDZ domain, to produce comprehensive atlases of allosteric communication. Allosteric mutations are abundant, with a large mutational target space of network-altering 'edgetic' variants. Mutations are more likely to be allosteric closer to binding interfaces, at glycine residues and at specific residues connecting to an opposite surface within the PDZ domain. This general approach of quantifying mutational effects for multiple molecular phenotypes and in multiple genetic backgrounds should enable the energetic and allosteric landscapes of many proteins to be rapidly and comprehensively mapped.


Raf-1 is involved in the regulation of the interaction between guanine nucleotide exchange factor and Ha-ras. Evidences for a function of Raf-1 and phosphatidylinositol 3-kinase upstream to Ras.
The observation that activated c-Ha-Ras p21 interacts with diverse protein ligands suggests the existence of mechanisms that regulate multiple interactions with Ras. This work studies the influence of the Ras effector c-Raf-1 on the action of guanine nucleotide exchange factors (GEFs) on Ha-Ras in vitro. Purified GEFs (the catalytic domain of yeast Sdc25p and the full-length and catalytic domain of mouse CDC25Mm) and the Ras binding domains (RBDs) of Raf-1 (Raf (1-149) and Raf (51-131)) were used. Our results show that not only the intrinsic GTP/GTP exchange on Ha-Ras but also the GEF-stimulated exchange is inhibited in a concentration-dependent manner by the RBDs of Raf. Conversely, the scintillation proximity assay, which monitors the effect of GEF on the Ras.Raf complex, showed that the binding of Raf and GEF to Ha-Ras.GTP is mutually exclusive. The various GEFs used yielded comparable results. It is noteworthy that under more physiological conditions mimicking the cellular GDP/GTP ratio, Raf enhances the GEF-stimulated GDP/GTP exchange on Ha-Ras, in agreement with the sequestration of Ras.GTP by Raf. Consistent with our results, the GEF-stimulated exchange of Ha-Ras.GTP was also inhibited by another effector of Ras, the RBD (amino acid residues 133-314) of phosphatidylinositol 3-kinase p110alpha. Our data show that Raf-1 and phosphatidylinositol 3-kinase can influence the upstream activation of Ha-Ras. The interference between Ras effectors and GEF could be a regulatory mechanism to promote the activity of Ha-Ras in the cell.