Treatment and prognosis of patients with late rectal bleeding after intensity-modulated radiation therapy for prostate cancer.
Radiation proctitis after intensity-modulated radiation therapy (IMRT) differs from that seen after pelvic irradiation in that this adverse event is a result of high-dose radiation to a very small area in the rectum. We evaluated the results of treatment for hemorrhagic proctitis after IMRT for prostate cancer. Between November 2004 and February 2010, 403 patients with prostate cancer were treated with IMRT at 2 institutions. Among these patients, 64 patients who developed late rectal bleeding were evaluated. Forty patients had received IMRT using a linear accelerator and 24 by tomotherapy. Their median age was 72 years. Each patient was assessed clinically and/or endoscopically. Depending on the severity, steroid suppositories or enemas were administered up to twice daily and Argon plasma coagulation (APC) was performed up to 3 times. Response to treatment was evaluated using the Rectal Bleeding Score (RBS), which is the sum of Frequency Score (graded from 1 to 3 by frequency of bleeding) and Amount Score (graded from 1 to 3 by amount of bleeding). Stoppage of bleeding over 3 months was scored as RBS 1. The median follow-up period for treatment of rectal bleeding was 35 months (range, 12-69 months). Grade of bleeding was 1 in 31 patients, 2 in 26, and 3 in 7. Nineteen of 45 patients (42%) observed without treatment showed improvement and bleeding stopped in 17 (38%), although mean RBS did not change significantly. Eighteen of 29 patients (62%) treated with steroid suppositories or enemas showed improvement (mean RBS, from 4.1 ± 1.0 to 3.0 ± 1.8, p = 0.003) and bleeding stopped in 9 (31%). One patient treated with steroid enema 0.5-2 times a day for 12 months developed septic shock and died of multiple organ failure. All 12 patients treated with APC showed improvement (mean RBS, 4.7 ± 1.2 to 2.3 ± 1.4, p < 0.001) and bleeding stopped in 5 (42%). After adequate periods of observation, steroid suppositories/enemas are expected to be effective. However, short duration of administration with appropriate dosage should be appropriate. Even when patients have no response to pharmacotherapy, APC is effective.


Interferon regulatory factor-1 suppresses DNA damage response and reverses chemotherapy resistance by downregulating the expression of RAD51 in gastric cancer.
Recent studies have shown that IRF-1 plays a significant role in various tumour-induced chemoresistance, but its role and mechanism in gastric cancer-associated chemoresistance are not clear. Our study showed that IRF-1 expression could reverse gastric cancer-related chemoresistance. Dysregulated DNA repair is an important cause of chemoresistance. We established a chemoresistant gastric cancer cell line and found that drug-resistant gastric cancer cells had increased DNA repair ability and that IRF-1 regulated DNA damage repair. Further studies showed that IRF-1 inhibited the expression of RAD51 directly by binding to the RAD51 promoter to affect DNA damage repair; this binding reversed resistance. However, restoring the expression of RAD51 halted the inhibitory effect of IRF-1 partially. Also, we revealed that the overexpression of IRF-1 in a mouse model synergized with chemotherapeutic drugs to inhibit tumour growth. Finally, IRF-1 expression correlated with RAD51 expression in gastric cancer specimens. The expression of IRF-1 and RAD51 are both related to the survival duration of patients with gastric cancer. These results suggest that targeting IRF-1-RAD51 could be an effective approach to reversing multidrug resistance in gastric cancer.


[Circadian CLOCK Gene Variants, Parameters of Arterial Stiffness and Blood Pressure Levels in Subjects Without Arterial Hypertension].
CLOCK gene polymorphic variants, parameters of arterial stiffness and blood pressure (BP) variability were studied in 115 normotensive Russian patients without cardiovascular diseases (62 men, 53 women; mean age 36.4+/-1.01 years). Examination included ECG, 24h BP monitoring, duplex scan of carotid arteries, registration of vascular stiffness parameters, and genotyping of the following polymorphic markers of CLOCK: 3111T>C (3-untranslated region), 862T>C (exon 9) and 257T>G (promoter region) by PCR-RFLP method. Pulse wave velocity was not significantly different among carriers of various 257T>G, 862T>C, 3111T>C genotypes. Augmentation index (Aix night, Aix max) values were lower in individuals with genotypes allegedly associated with essential hypertension and ischemic heart disease (257GG, 862CC, 3111CC). Arterial stiffness index (ASI) was significantly higher in men having CC genotype of 862T>C. Polymorphic variants 257T>G and 862T>C SNPs of CLOCK gene were found to be associated with parameters reflecting BP variability (morning rise of diastolic BP and rate of BP rise). These results provide a basis for suggestion that the CLOCK gene polymorphism is one of factors determining elastic properties of vascular wall. The suggestion is supported by discussion of possible molecular mechanisms of circadian genes impact on elasticity and rigidity of vessel.


The influence of sex on efficacy, adverse events, quality of life, and delivery of treatment in National Cancer Institute of Canada Clinical Trials Group non-small cell lung cancer chemotherapy trials.
Female sex is a favorable prognostic factor in lung cancer. In small-cell lung cancer, women have been shown to experience greater toxicity from chemotherapy, but there are few studies of sex-related toxicity in non-small cell lung cancer (NSCLC). This retrospective analysis evaluated the effect of sex on efficacy, adverse events (AEs), dose intensity (DI), and quality of life (QoL) in three phase III NSCLC trials conducted by the National Cancer Institute of Canada Clinical Trials Group; BR.10 (adjuvant chemotherapy), BR.14, and BR.18 (first-line advanced disease). Only patients with National Cancer Institute of Canada Clinical Trials Group data were included, and patients in the BR.10 observation arm were excluded. Of 1,108 patients analyzed, 29% were female. On study entry, women were less likely to be overweight or obese (40% versus 51%, p < 0.0001), more likely to have adenocarcinoma (70% versus 44%, p < 0.0001), and less likely to be anemic at baseline (29% versus 55%, p < 0.0001) or have medical comorbidities. There were no significant differences in response rate to chemotherapy (27% versus 31%, p = 0.44 [excluding BR.10]), grade 3 or 4 AEs, DI, or QoL between sexes, although women reported more nausea and vomiting of any grade (77% versus 66%, p = 0.0004). In multivariate analysis, women had longer progression-free survival than men (hazard ratio 0.83, 95% confidence interval 0.71-0.97, p = 0.02) but not overall survival (hazard ratio 0.89, 95% confidence interval 0.75-1.05, p = 0.17). Women demonstrate modestly longer progression-free survival than men in chemotherapy-treated NSCLC, with no differences observed in response rates, serious AEs, or QoL.


Intergenerational Transmission of Relationship Quality in Later-Life Families.
This article examines the transmission of older women's relationship quality with their mothers and fathers to their relationship quality with their own adult children in midlife. We also investigate how the transmission is moderated by the dimension of relationship quality (closeness vs. strain) and the gender of both the older women's parents and their adult children. Prior research has primarily examined parents' transmission of relationship quality to young children with little attention to whether and when this pattern occurs in later-life families. We conducted multilevel analyses using data collected from 249 older women and 643 of their adult children as part of the Within-Family Differences Study-I. We found evidence for transmission of older women's reported closeness and tension with their mothers and fathers to their reported closeness and tension with their adult children. Adult children's reports also revealed that older women's closeness with their own mothers was transmitted to their adult children's reported closeness with the older women themselves. Mother-child closeness was transmitted more strongly than mother-child tension, and mother-child closeness was transmitted more strongly to daughters than sons, based on adult children's reports. This study demonstrates the continuity of intergenerational influence in later-life families and highlights the essential roles that selective social learning and social structural position (i.e., gender) play in conditioning the socialization process.


Catalytic Effect of Photoluminescent Zinc Oxide Nanoparticles Formed in the Presence of Quaternary Ammonium Salts.
The comparative effect of two quaternary ammonium salts from 1,2-bis(4-pyridyl)ethane (PyQAs), namely N,N'-diphenacyl-1,2-bis(4-pyridinium)ethane dibromide (PyQAs1) and N,N'-di(p-methoxyphenacyl)-1,2-bis(4-pyridinium)ethane dibromide (PyQAs2), upon the size and photoluminescence of zinc oxide nanoparticles (ZnO NPs) was investigated. The formation of ZnO NPs took place in the presence of variable amounts of the two PyQAs species (1, 2.5, and 5%), according to the chemical precipitation of zinc(II) acetate with potassium hydroxide in ethanol under reflux. The obtained ZnO NPs were structurally characterized by means of X-ray powder diffraction, infrared, and Raman spectroscopy. The fluorescence of all supernatant solutions, observed under ultraviolet light, determined us to make an investigation of the solutions by means of liquid chromatography coupled with electrospray ionization mass spectrometry (LC-MS-ESI) in order to elucidate the identity of the newly formed fluorescent species. Such an occurrence thus allowed the invocation of the catalytic effect of zinc(II) ions towards the organic transformation of both nonfluorescent PyQAs surfactants into new fluorescent organic species.


Disease-Causing Variants in the ATL1 Gene Are a Rare Cause of Hereditary Spastic Paraplegia among Czech Patients.
Variants in the ATL1 gene have been repeatedly described as the second most frequent cause of hereditary spastic paraplegia (HSP), a motor neuron disease manifested by progressive lower limb spasticity and weakness. Variants in ATL1 have been described mainly in patients with early onset HSP. We performed Sanger sequencing of all coding exons and adjacent intron regions of the ALT1 gene in 111 Czech patients with pure form of HSP and additional Multiplex-Ligation Probe Analysis (MLPA) testing targeting the ATL1 gene in 56 of them. All patients except seven were previously tested by Sanger sequencing of the SPAST gene with negative results. ATL1 diagnostic testing revealed only five missense variants in the ATL1 gene. Four of them are novel, but we suppose only two of them to be pathogenic and causal. The remaining variants are assumed to be benign. MLPA testing in 56 of sequence variant negative patients revealed no gross deletion in the ATL1 gene. Variants in the ATL1 gene are more frequent in patients with early onset HSP, but in general the occurrence of pathogenic variants in the ATL1 gene is low in our cohort, less than 4.5% and less than 11.1% in patients with onset before the age of ten. Variants in the ATL1 gene are a less frequent cause of HSP among Czech patients than has been previously reported among other populations.


Determinants of voltage attenuation in neocortical pyramidal neuron dendrites.
How effectively synaptic and regenerative potentials propagate within neurons depends critically on the membrane properties and intracellular resistivity of the dendritic tree. These properties therefore are important determinants of neuronal function. Here we use simultaneous whole-cell patch-pipette recordings from the soma and apical dendrite of neocortical layer 5 pyramidal neurons to directly measure voltage attenuation in cortical neurons. When combined with morphologically realistic compartmental models of the same cells, the data suggest that the intracellular resistivity of neocortical pyramidal neurons is relatively low ( approximately 70 to 100 Omegacm), but that voltage attenuation is substantial because of nonuniformly distributed resting conductances present at a higher density in the distal apical dendrites. These conductances, which were largely blocked by bath application of CsCl (5 mM), significantly increased steady-state voltage attenuation and decreased EPSP integral and peak in a manner that depended on the location of the synapse. Together these findings suggest that nonuniformly distributed Cs-sensitive and -insensitive resting conductances generate a "leaky" apical dendrite, which differentially influences the integration of spatially segregated synaptic inputs.


[Value of computerized tomography of the thorax in germinal testicular tumors].
Sporadic informations in the literature that by means of CT of the thorax by far smaller intrapulmonary foci can be recognized in comparison to the conventional x-ray examination are just to be confirmed. With the help of instances the indication for thorax CT in germinal testicular tumours is presented. The evidence and exclusion, respectively, of pulmonary metastases are of decisive importance actually for the therapy and prognosis in patients with germinal testicular tumours. In this respect our observations confirm the indications for a CT-examination of the thorax in these groups of patients.


Community-Level Awareness of Proper Immediate Steps for Ocular Chemical Injury in Saudi Arabia.
The human eyes are the most vital sensory organ. Eye injury is the main factor leading to monocular blindness. There is a lack of understanding in the Saudi community regarding the appropriate response to a chemical injury to the eyes. To provide accurate and clear medical information about ocular chemical damage, it is crucial to identify areas where healthcare professionals fall short. To address the gaps in critical knowledge, this study aimed to focus on the Saudi Arabian community to determine if healthcare professionals have fulfilled their responsibility as health promoters in providing education on eye emergencies. We examined the immediate reaction of the study participants to evaluate the community's awareness of chemical eye injuries and immediate management strategies. This study aimed to assess and evaluate the general population's knowledge and awareness of immediate management steps following an ocular chemical injury in Saudi Arabia. A cross-sectional design was employed. A random sampling method was used to select 2,295 individuals from the Saudi community. Participants completed an electronic closed-ended, pre-validated, anonymous, and self-administered questionnaire. The majority of the respondents were females (71.6%) and Saudis (94.5%) aged 18 to 30 years (46.6%). The majority of the respondents correctly stated that eye injuries could cause complications (89.6%) and that common substances that could result in eye injuries are chloride and detergents (93.3%) and battery materials (73.1%). Furthermore, complications after eye injuries could include blindness (80.6%), perforation (44.5%), and scar formation (38.1%). A substantial proportion of the respondents indicated that water should be used to treat chemical injuries due to acidic and alkaline substances (68.1%). However, only a small proportion of the respondents correctly answered that the eyes should be washed for 30 minutes or more after an ocular injury (7.9%). The overall knowledge levels on injury mechanisms and complications were generally high with a lack of knowledge regarding immediate management for injuries. Therefore, there is a need for targeted educational interventions and training programs to enhance the general public's understanding of immediate management strategies for chemical eye injuries.


Human Milk Oligosaccharides: A Critical Review on Structure, Preparation, Their Potential as a Food Bioactive Component, and Future Perspectives.
Human milk is the gold standard for infant feeding. Human milk oligosaccharides (HMOs) are a unique group of oligosaccharides in human milk. Great interest in HMOs has grown in recent years due to their positive effects on various aspects of infant health. HMOs provide various physiologic functions, including establishing a balanced infant's gut microbiota, strengthening the gastrointestinal barrier, preventing infections, and potential support to the immune system. However, the clinical application of HMOs is challenging due to their specificity to human milk and the difficulties and high costs associated with their isolation and synthesis. Here, the differences in oligosaccharides in human and other mammalian milk are compared, and the synthetic strategies to access HMOs are summarized. Additionally, the potential use and molecular mechanisms of HMOs as a new food bioactive component in different diseases, such as infection, necrotizing enterocolitis, diabetes, and allergy, are critically reviewed. Finally, the current challenges and prospects of HMOs in basic research and application are discussed.


Broadly tunable continuous wave 2.3-µm Tm3+:tellurite bulk glass laser.
We report, for the first time to the best of our knowledge, a continuous wave trivalent thulium ion (Tm3+)-doped bulk glass near 2.3 µm. In the experiments, a bulk Tm3+-doped tellurite glass with the stoichiometric composition of 74TeO2-12ZnO-4La2O3-10Na2O (Tm3+:TZLN) was used. Lasing operation was achieved by using an x-fold cavity at the free-running wavelength of 2303 nm. The maximum slope efficiency of 6.2% was obtained with respect to the absorbed pump power with a 1% transmitting output coupler. In this case, as high as 100-mW output power was generated with 2.2 W of absorbed pump power. Continuous, broad tuning was achieved from 2233 nm to 2400 nm. The excitation spectrum of the laser was also investigated and 2.3-µm lasing was obtained by varying the pump wavelength over the 773-809-nm range. The absorption cross section was determined to be 4.4 × 10-21 cm2, based on open-aperture z-scan measurement. By using the laser efficiency data, the emission cross section of the Tm3+:TZLN glass was further determined to be 1.3 × 10-20 cm2 at 2.3 µm.


Involvement of Scn1b and Kcna1 ion channels in audiogenic seizures and PTZ-induced epilepsy.
We have undertaken chemical genetic approach using Qingyangshenylycosides (QYS), a natural product compound, to explore the molecular mechanisms underlying different types of epilepsy models. Two animal models were used for these studies, i.e., audiogenic seizure (AGS) and pentylenetetrazol (PTZ)-induced generalized epilepsy in DBA/2J mice. We show that the latency of AGS is prolonged and the severity of seizures (the percentages of the tonus, Tonus_%) is reduced in the QYS-treated animals. These results indicate that QYS has anticonvulsant effect on the AGS model. However, we find that administration of QYS has an opposite effects on PTZ-induced generalized epilepsy. Both the latency of the generalized epilepsy and the latency of death are decreased after QYS treatment in PTZ-induced epilepsy. We examine the molecular basis of the distinct roles of QYS in these two epilepsy models by using gene expression data. Our results show that a voltage-gated sodium channel (Scn1b) and a voltage-gated potassium channel (Kcna1) are differentially expressed in AGS and PTZ-induced epilepsy models as well as in QYS-treated animals. Our results demonstrate that a chemical genetic approach may help to reveal both the molecular mechanisms of different epilepsies and the mechanism of action of the antiepileptic drugs.


[Anesthesia for dental care management in children with dystrophic epidermolysis bullosa].
Was to summarize our experience in dental treatment of children with dystrophic epidermolysis bullosa (DEB) under deep intravenous sedation. The study comprised 11 DEB patients aged 2-17 years who received full oral rehabilitation under deep sedation in Hospital Pediatric Dentistry department of the Central Research Institute of Dentistry and Maxillofacial Surgery in 2021-2022. Intravenous induction was used if a child already had venous access installed or it was feasible before sedation. If not the case inhalation induction with sevoflurane was performed for vein catheterization. Sedation was sustained by propofol infusion up to aimed concentration. Both dental treatment and extractions were carried out. In 11 children 37 teeth were treated and 14 extracted. Mean duration of the procedure under deep sedation was 53 min (30-190 min). In two children multiple dental extractions resulted in extensive oral mucosa injury with bullae and erosions formation in vermillion, cheeks, and hard palate areas. No skin injuries, airway obstruction or long-term complications of both anesthesiologic an dental procedure were observed. The paper describes main preventive measures minimizing risks of skin and mucosa adverse events. Intravenous sedation with spontaneous respiration allows full oral rehabilitation in DEB children with minimal risks of skin and mucosal injury associated with intubation techniques when performing described preventive measures. Use of cofferdam is crucial for success and safety of the procedure as it prevents water, dust and dental fragments contamination of oropharynx which is especially important in case of sedation with spontaneous respiration.


Dynamics and biological relevance of DNA demethylation in Arabidopsis antibacterial defense.
DNA methylation is an epigenetic mark that silences transposable elements (TEs) and repeats. Whereas the establishment and maintenance of DNA methylation are relatively well understood, little is known about their dynamics and biological relevance in plant and animal innate immunity. Here, we show that some TEs are demethylated and transcriptionally reactivated during antibacterial defense in Arabidopsis. This effect is correlated with the down-regulation of key transcriptional gene silencing factors and is partly dependent on an active demethylation process. DNA demethylation restricts multiplication and vascular propagation of the bacterial pathogen Pseudomonas syringae in leaves and, accordingly, some immune-response genes, containing repeats in their promoter regions, are negatively regulated by DNA methylation. This study provides evidence that DNA demethylation is part of a plant-induced immune response, potentially acting to prime transcriptional activation of some defense genes linked to TEs/repeats.


Dental wear among cercopithecid monkeys of the Taï forest, Côte d'Ivoire.
Studies of dental macrowear can be useful for understanding masticatory and ingestive behavior, life history, and for inferring dietary information from the skeletal material of extinct and extant primates. Such studies to date have tended to focus on one or two teeth, potentially missing information that can be garnered through examination of wear patterns across the tooth row. Our study measured macrowear in the postcanine teeth of three sympatric cercopithecid species from the Taï Forest, Côte d'Ivoire (Cercocebus atys, Procolobus badius, and Colobus polykomos), whose diets have been well-described. Inter-specific analyses suggest that different diets and ingestive behaviors are characterized by different patterns of wear across the molar row, with Cercocebus atys emphasizing tooth use near P4 -M1 , P. badius emphasizing a large amount of tooth use near M2 -M3 , and Colobus polykomos exhibiting wear more evenly across the postcanine teeth. Information regarding differential tooth use across the molar row may be more informative than macrowear analysis of isolated teeth for making inferences about primate feeding behavior.


Optimal induction of T-cell responses against hepatitis C virus E2 by antigen engineering in DNA immunization.
Although DNA immunization is a safe and efficient method for inducing cellular immune responses, it generates relatively weak and slow immune responses. Here, we investigated the effect of hepatitis C virus (HCV) antigen modifications on the induction of T-cell responses in DNA immunization. It is likely that the strength of T-cell responses has an inverse relationship with the length of the insert DNA. Interestingly, a mixture of several plasmids carrying each gene induced a higher level of T-cell responses than a single plasmid expressing a long polyprotein. Moreover, the presence of a transmembrane domain in HCV E2 resulted in stronger T-cell responses against E2 protein than its absence. Taken together, our results indicate that the tailored modifications of DNA-encoded antigens are capable of optimizing the induction of T-cell responses which is required for eliminating the cells chronically infected with highly variable viruses such as HCV and human immunodeficiency virus.


Maternal stress, HPA activity, and fetal/infant outcome.
Preliminary conclusions from our research include the possibility that each of the HPA products evaluated, even though correlated (e.g., ACTH and beta E), may be linked to unique and specific outcomes. Maternal stress during the 28-30 weeks of gestation is associated with birth outcome. Increased levels of psychosocial stress were significantly related to gestational age at birth and infant birth weight. Maternal stress during the third trimester was associated with increased maternal plasma levels of ACTH and cortisol. This finding is consistent with possible mechanisms whereby psychosocial stress influences birth outcome. CRH controls the timing of labor and delivery. Precocious elevation of CRH is related to the risk of preterm delivery. This system may be "stress-sensitive." Even though pregnant women may be immunized from stress, the stress signal that is transmitted (release of ACTH and cortisol) is amplified by the placental release of CRH. This possibility has at least two consequences: (1) influencing the timing of delivery and (2) desensitization of hypophyseal corticotrophs and further "protection" of the pregnant women from the results of stress (i.e., release of ACTH and beta E). Beta E appears to influence fetal learning and perhaps the developing nervous system.


Influence of restraint stress on ligature-induced periodontitis in rats.
The influence of stress on periodontal breakdown in Wistar rats was analyzed during experimental periodontitis, induced by placing silk ligatures around the maxillary right second molar teeth. The rats were divided into three groups with 10 animals in each; the first group was exposed to restraint stress for 12 h d(-1) for a period of 4 wk; the second group was exposed to restraint stress for 2.5 h d(-1) for a period of 4 wk; the third group served as a control group. Ligation for 4 wk resulted in an accelerated periodontal degradation, whereas the restraint stress by itself had no significant effect. Combined stress and ligation resulted in a significantly higher attachment loss and alveolar bone resorption than either treatment alone, while no differences were seen between the two stress regimens. After 4 wk, a reduced body weight was found in both restrained groups of rats and a reduced weight of the thymus in the rats restrained for 12 h d(-1), while no changes were observed in the weight or composition of the suprarenal glands. We conclude that stress alone does not result in periodontal disease but may modulate the pathophysiological processes of already present periodontal inflammation, resulting in accelerated degradation of periodontal tissues.


[Methodological approaches to the evaluation of the effectiveness of anti-anginal preparations in patients with stenocardia by 24-hour ECG monitoring].
Scientific rationale are given for methodological approaches promoting improved reproducibility of 24-hour ECG monitoring data, for the method to be used repeatedly in assessing patient's condition. Repeated 24-hour-ECG monitoring in identical motor conditions (a standard mobility regimen) has been shown to improve considerably the reproducibility of its results. Criteria for the efficiency of antianginal therapy in patients with angina of the 2nd and 3d functional classes, as evidenced by 24-hour ECG monitoring, have been developed and substantiated. They are a drop in the number of ST depression episodes (by 3 and more) and in the total depth of depression (by 50% and more). The sensitivity of the assessment of each of the two indicators of myocardial ischemia or their combination was 70%, and the specificity was 77.8% and 88.9%, respectively.


Long-term oxygen therapy in the home.
Medicare introduced new policies and guidelines for oxygen therapy in 1998 including the HCFA 484.2, Certificate of Medical Necessity: Oxygen. This article outlines how nurses can collaborate with prescribers and oxygen suppliers to ensure that patients receive the appropriate oxygen delivery system that best meets their lifestyle, needs, and oxygen prescription.


Nosocomial infections in left ventricular assist device recipients.
Infection remains a serious complication of left ventricular assist device (LVAD) implantation. We performed a cohort study to assess infections among patients who underwent LVAD implantation from October 1996 through May 1999. Thirty-six LVADs were implanted in 35 patients; the mean duration (+/- standard deviation) of LVAD use was 73+/-60 days (total for all patients, 2565 days). Sixteen patients developed surgical site infections (SSIs; rate, 6.2 infections per 1000 LVAD days); 9 were deep-tissue or organ/space infections and 7 were superficial. Other infections included 7 cases of pneumonia (rate, 2.7 cases per 1000 LVAD days), 6 venous infections (rate, 2.3 per 1000 LVAD days), 2 bloodstream infections (rate, cases 0.8 per 1000 LVAD days), 3 urinary tract infections, and 2 skin and soft-tissue infections. Deep SSIs were associated with the requirement for postoperative hemodialysis (P=.02). Overall use of antibiotics was extensive, and a trend toward infection with antibiotic-resistant organisms was noted. Infections were a frequent complication of LVAD implantation. Further studies of interventions for preventing infection in LVAD recipients are warranted.


Loss of DMBT1 expression in human prostate cancer and its correlation with clinical progressive features.
To investigate alterations of DMBT1 in prostate cancer and determine the correlation of its alterations to the clinicopathologic features of prostate cancer. DMBT1 has been proposed as a candidate tumor suppressor gene for epithelial cancer. The alterations of DMBT1 expression after treatment with DNA methyltransferase inhibitor in 2 prostate cancer cell lines (LNCaP and PC-3) were analyzed by genome microarray and real-time polymerase chain reaction (PCR). A total of 36 prostate cancer tissues and 16 benign prostatic tissues were evaluated with reverse transcription-PCR, Western blot, and immunohistochemistry for DMBT1 expression. Treatment with 5-aza-2'-deoxycytidine reactivated expression of DMBT1 in PC3 cells, but not in LNCaP cells. Downregulation or loss of DMBT1 mRNA and protein expression was observed in prostate cancer, but not in benign tissues. Immunostaining analysis showed DMBT1 protein was absent in 14 cancer samples with Gleason score of 8-10 and weakly stained in 16 cancer samples with Gleason score of 4-7, compared with strong immunostaining in all 15 benign prostatic tissues. Loss of DMBT1 expression was correlated with local invasion (P = .048) and bone metastasis (P = .039) but was not correlated with patient age, prostate-specific antigen level, or tumor grade at diagnosis. Our study provides evidence that loss of DMBT1 expression is associated with prostate cancer, suggesting that DMBT1 may function as a tumor suppressor gene in prostate carcinogenesis.


[Spondylolysis and spondylolisthesis in the young].
Authors think the early recognition of the spondylolysis and spondylolisthesis in young age important, as for the further life of the patients (sport, military service) adequate councels have to be given. In mild or more serious lumbago in adolescents, appearing mainly on load, other developmental anomalies, easy to be recognized, call attention to the presence of spondylolysis and spondylolisthesis. Considering the factors of risk the development of the disease and its tendency may be followed on Roentgenogram of exact projections.


The anti-apoptotic property of NS-398 at high dose can be mediated in part through NF-kappaB activation, hsp70 induction and a decrease in caspase-3 activity in human osteosarcoma cells.
Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to produce an anti-proliferative and pro-apoptotic effect on different types of cancer cell lines. Previously, we demonstrated that high dose of NS-398 (100 microM), a selective cyclooxygenase-2 inhibitor, induced a cell cycle slowing or arrest and, in contrast to low dose (10 microM), a marked decrease in apoptosis in human 1547 osteosarcoma cells. In this study, we investigated particularly the effect of 100 microM NS-398 on p53 and p21 expression, caspase activities and nuclear factor-kappaB (NF-kappaB). We found a correlation between p53, p21 mRNA expression and NF-kappaB activation and, we observed an induction of heat shock protein 70 expression with a large decrease in caspase-3 activity after 100 microM NS-398 treatment. Moreover, the inhibition of apoptosis was correlated with an increase in bcl-2/bax ratio. Our new findings confirm the novel anti-apoptotic property of NS-398 at 100 microM, as we previously found, which contrasts to the described NS-398 pro-apoptotic effect on other cancer cell lines.


Comparison of individuals with low versus high consumption of home-prepared food in a group with universally high dietary quality: a cross-sectional analysis of the UK National Diet & Nutrition Survey (2008-2016).
Despite inconclusive evidence, the idea that a lack of home food preparation and skills is a limiting factor in achieving a healthy diet is widespread. Cooking skills interventions proliferate, and several countries now mention cooking in their dietary guidelines. The aim of this study was to determine whether substantial consumption of home-prepared food is necessary for high dietary quality by exploring whether individuals can eat healthily while eating little home-prepared food. The diets of these individuals were characterised, and socio-demographic characteristics and prevalence of obesity were also explored. Cross-sectional analysis of UK dietary survey data with objectively measured height and weight and a 4-day food diary for each participant was conducted. A subsample (N = 1063, aged ≥19 years) with a high dietary quality (determined using a score derived from the Dietary Approaches to Stopping Hypertension (DASH) diet) was analysed. Within this, participants were grouped as either high or low home preparation based on the proportion of energy derived from home-prepared food. Regression models were used to determine whether and how those in the high and low home preparation groups differed in terms of socio-demographic characteristics, DASH score, energy intake, prevalence of obesity, and dietary composition. The low home preparation group included 442 participants, while 621 participants were in the high home preparation group. The low home preparation group were more likely to be older and white, and less likely to have a degree level education. After adjustment for socio-demographic characteristics, there were no differences in DASH score, energy intake or obesity prevalence between the groups. After adjustment, the low home preparation group consumed more fruit (30.8 additional g/day, 95% CI 5.5-56.1), more low-fat dairy foods (24.6 additional g/day, 95% CI 1.7-47.5) and less red meat (10.4 fewer g/day, 95% CI 4.3-16.6), but also more sugar (11.6 additional g/day, 95% CI 7.5-15.6) and sodium (107.8 additional mg/day, 95% CI 13.8-201.8). Home food preparation should not be presented as a prerequisite to a high quality diet. The public health community should recognise the existence of a set of food practices which allows individuals to achieve a healthy diet with little contribution from home-prepared food, and make space for it in the design of their policies and interventions.


Beware the empty curette!
Chalazions are a common occurrence in the eyelids due to chronic inflammation in the tarsal plate. Treatment of non-resolving cases may involve incision and curettage. Chalazions that are recurrent should arouse suspicion. We present a case of a pleomorphic adenoma of the palpebral portion of the lacrimal gland, which was misdiagnosed as a chalazion. A 41-year-old Caucasian lady initially presented with a swelling in the outer part of her right upper eyelid. A diagnosis of chalazion was made and two attempts at incision and curettage failed to resolve the lesion. She was then referred to the oculoplastics/adnexal unit. A more detailed examination revealed involvement of the palpebral part of her lacrimal gland. A CT-scan confirmed this and she proceeded to have a lateral orbitotomy to remove the tumour. Histological confirmation of a pleomorphic adenoma of the palpebral portion of the lacrimal gland was obtained. The lacrimal gland had been completely excised. Persistent or recurrent meibomian cyst should be treated with suspicion. A careful orbital examination including lid eversion should always be performed to outrule a more sinister pathology.


Immediate loading of Brånemark implants in edentulous mandibles: a preliminary report.
A study involving the immediate loading of Brånemark implants in the edentulous mandibles of 10 patients is reported. The design involved the immediate loading of four widely distributed implants with a transitional fixed implant-supported prosthesis at first-stage surgery, avoiding the need for a removable prosthesis. A sufficient number of additional implants are allowed to heal in the conventional manner to provide sufficient support for a definitive fixed prosthesis even if all of the immediately loaded implants fail. Preliminary results have been favorable, with all patients functioning with a fixed implant prosthesis from the day of first-stage surgery.


Magnetic resonance imaging of normal and abnormal brain development.
Magnetic resonance imaging (MRI) improves our ability to assess brain development and to detect anomalies of brain formation. MRI allows the assessment of brain development by analysis of the effects of myelination on the T1 and T2 relaxation times of the pediatric brain. This article discusses specific imaging strategies and the normal progression of signal intensity changes. Familiarity with this evolution of signal changes allows an estimation of the approximate stage of brain development. High-resolution multiplanar MRI provides good anatomic detail, with excellent distinction between gray and white matter. This technique allows improved detection of many classes of abnormalities of brain formation, some of which were previously detectable only at autopsy. These malformations and their imaging characteristics are discussed under the headings of: corpus callosal dysgenesis, intracranial lipomas, holoprosencephalies, septooptic dysplasia, the cephaloceles, the Chiari malformations, the Dandy-Walker complex, the cerebellar anomalies including Joubert's syndrome, and rhombencephalosynapsis, and the spectrum of neuronal migration anomalies.


Transtympanic iontophoresis: personal experience.
After having described the method of application used for iontophoresis and the results of previous studies carried out by other authors in the hope of finding a definite use for its clinical application, the authors present their personal experience carried out with the use of various chemical substances applied to both the guinea pig and to man. The chemicals taken into consideration were those used in the treatment of otitis media: anti-inflammatory, antibiotic, and mucolytic products. Iontophoresis proved to be a simple and effective method for the treatment of certain middle ear diseases, and offered a more rapid recovery in comparison with subjects treated uniquely by traditional methods.


MPS: An artificially intelligent software system for the analysis and synthesis of metabolic pathways.
The concepts of artificial intelligence have been applied for the development of a software system for metabolic pathway synthesis (MPS). An easily expandable data base system for storing enzyme and substance descriptions is used by a search algorithm for the identification of possible ways to interconvert carbon-carrying metabolites. A versatile screening capability permits the user to identify all pathways which contain or exclude any combination of enzymes, substrates, and/or products. Information provided by MPS can be used to predict on a qualitative basis the effects of adding or deleting enzymatic activities to or from the cellular environment, to classify pathways with respect to cellular objectives, and to extract information about metabolic regulation. MPS can be used subsequently to aid the identification of appropriate genotypes or genetic modifications that will redirect metabolism towards amplified production of desirable bioproducts. Two examples illustrating the capabilities of MPS are presented. In the first example, which considers the conversion of glucose 6-phosphate to pyruvate, MPS synthesized the classical catabolic pathways (EMP, pentose phosphate and ED) along with possible variations. A route for the biosynthesis of L-alanine that does not incorporate the enzyme alanine aminotransferase was revealed by MPS during synthesis of alternative pathways which produce L-alanine from pyruvate.


Changes in central opioid receptor binding in relation to inflammation and pain in patients with rheumatoid arthritis.
A group of four patients with RA were examined to test the hypothesis that there is a change in the endogenous opioid system in the brain during inflammatory pain. Regional cerebral opioid receptor binding was quantified using the opioid receptor antagonist [11C] diprenorphine and positron emission tomography (PET). In the four patients studied in and out of pain, significant increases in [11C]diprenorphine binding were seen in association with a reduction in pain. Increases were seen in most of the areas of the brain that were sampled apart from the occipital cortex. Significant region-specific increases over and above the more generalized changes were also seen in the frontal, cingulate and temporal cortices in addition to the straight gyrus. These findings are consistent with the hypothesis that there are substantial increases in occupancy by endogenous opioid peptides during inflammatory pain.


Acetylcholine in the corneal epithelium of diurnal and nocturnal mammals.
To analyze the concentration of acetylcholine (ACh) in the corneal epithelium and aqueous humor of various diurnal and nocturnal mammals. The following species were examined: roe deer, cattle, horse, human, moose, sheep, reindeer, wild boar, polecat, lynx, cat, and rat. ACh was determined by liquid chromatography-tandem mass spectrometry. ACh was present in significant amounts in the corneal epithelium of all diurnal mammals, the concentrations varying from one species to the next. By contrast, it was not detected in any of the nocturnal tissue samples. None of the species showed detectable amounts of ACh in the aqueous humor. The amount of ACh in the corneal epithelium varies from one species to the next, with diurnal species showing significant concentrations and nocturnal species no detectable concentrations.


Beyond hospital walls: educating pediatric nurses for the next millennium.
As pediatric units in acute care hospitals close, as lengths of stay shorten, and as increasing numbers of procedures are completed on an outpatient basis, faculty must find different learning experiences for their prelicensure students. Some programs have discontinued pediatric rotations, others are seeking clinical experiences in community settings. These community experiences hopefully produce a more well-rounded, globally thinking nurse to practice in the 21st century, yet they also raise a number of concerns.


Youngism: The content, causes, and consequences of prejudices toward younger adults.
Research on ageism has focused largely on perceptions of and biases targeting older adults, implicitly assuming that age-based stigma increases throughout the life span and that young adults benefit from favorable views relative to their older counterparts. In a series of eight studies (N = 2,323), we provide evidence to the contrary. We theorize that, in sharp contrast with ageism toward older adults, which revolves around fear and discomfort with the target's later life stage, youngism (i.e., ageism toward young adults) is primarily generationally focused, aiming at contemporaneous generations of young adults rather than young adults in general. Consistent with this theorizing, we find that today's young adults are ascribed a mixed stereotype content (Study 1a-1c), subject to harsher social judgments than both older age groups (Study 2) and recollections of former generations at the same age (Study 3a and 3b), and victim of discriminatory behaviors (Study 4 and 5). By comprehensively documenting cognitive, emotional, and behavioral evidence of youngism, the present work challenges the idea that ageism only reflects a plight of later-life aging. Instead, we show not only that ageism can target other age groups but also that the nature and content of ageism vary across the life span. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Extended state observer based dynamic iterative learning for trajectory tracking control of a six-degrees-of-freedom manipulator.
With the development of industrial automation comes an ever, broadening number of application scenarios for manipulators along with increasing demands for their precise control. However, manipulator trajectory tracking control schemes often exhibit problems such as those related to high levels of coupling, complex calculations, and in various difficulties in application for industrial environments. For the problems of low accuracy in control and poor robustness of multiple-jointed robotic trajectory tracking, iterative learning control (ILC) with model compensation (MC) based on extended state observer (ESO) has been proposed for the trajectory tracking control of six-degrees-of-freedom (six-DOF) manipulators. The scheme has excellent features to overcome uncertainties in repetitive tasks, including unknown bounded perturbations that are external to the model or dynamic perturbations that are internal to the model. The proposed control strategy combines ESO, iterative learning, and MC, for precise control of trajectory tracking. Here, ESO is used to estimate disturbances, iterative learning allows fast and accurate control in repeated tasks, and the model-compensated control algorithm alleviates the necessary for many inverse operations. The convergence of our proposed control scheme is proved through Lyapunov function and time-varying approximation theory. Simulation and experimental results verify the validity of the proposed scheme.


Is task-irrelevant learning really task-irrelevant?
In the present study we address the question of whether the learning of task-irrelevant stimuli found in the paradigm of task-irrelevant learning (TIPL) [1]-[9] is truly task irrelevant. To test the hypothesis that associations that are beneficial to task-performance may develop between the task-relevant and task-irrelevant stimuli, or the task-responses and the task-irrelevant stimuli, we designed a new procedure in which correlations between the presentation of task-irrelevant motion stimuli and the identity of task-targets or task-responses were manipulated. We found no evidence for associations developing between the learned (task-irrelevant) motion stimuli and the targets or responses to the letter identification task used during training. Furthermore, the conditions that had the greatest correlations between stimulus and response showed the least amount of TIPL. On the other hand, TIPL was found in conditions of greatest response uncertainty and with the greatest processing requirements for the task-relevant stimuli. This is in line with our previously published model that suggests that task-irrelevant stimuli benefit from the spill-over of learning signals that are released due to processing of task-relevant stimuli.


A Lightweight, Elastic, and Thermally Insulating Stealth Foam With High Infrared-Radar Compatibility.
The development of infrared-radar compatible materials/devices is challenging because the requirements of material properties between infrared and radar stealth are contradictory. Herein, a composite of poly(3, 4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) coated melamine foam is designed to integrate the advantages of the dual materials and the created heterogeneous interface between them. The as-designed PEDOT:PSS@melamine composite shows excellent mechanical properties, outstanding thermal insulation, and improved thermal infrared stealth performance. The relevant superb radar stealth performance including the minimum reflection loss value of -57.57 dB, the optimum ultra-wide bandwidth of 10.52 GHz, and the simulation of radar cross section reduction value of 17.68 dB m2 , can be achieved. The optimal specific electromagnetic wave absorption performance can reach up as high as 3263.02 dB·cm3 g-1 . The average electromagnetic interference shielding effectiveness value can be 30.80 dB. This study provides an approach for the design of high-performance stealth materials with infrared-radar compatibility.


Are "normal hips" being labeled as femoroacetabular impingement due to EE angle?
Gluteal muscle contracture (GMC) is a clinical syndrome characterized by gait abnormality and limb dysfunction, as well as secondary deformities of pelvis and femur. Femoroacetabular impingement (FAI) typically could be diagnosed on the basis of computed tomography (CT) such as the equatorial-edge angle (EE angle), but it did not work well in GMC patients. In this study, we retrospected all image data and found small EE angles in GMCs, which meant retroverted acetabulum; however, none of them showed no symptoms and signs of FAI. Therefore, we had reasons to think that, some normal hips with unbalanced hip myodynamia as same as GMCs, may be incorrectly diagnosed as FAI through measuring EE angle only.In consequence, the paper was designed to assess the use of the EE angle in the assessment of FAI in the diagnosis, as described by Werner.Twenty-three patients (46 hips) were collected and calculated with the "equatorial-edge angle" (EE angle) by CT scans. All of them were excluded from FAI.Review of the hips showed a mean EE angle was 12.93°, with a minimum of -3.42° and a maximum of 24.08°. The mean value for males and females were 13.52° and 12.40°, respectively, without statistical significance, although the mean value of left hips and right sides reached 13.32° and 12.54° individually, not having statistical differences neither. There were not any symptoms or signs of FAI in all patients. Thus, the reduced EE angle could suggest the local excessive coverage of the femoral head by the anterior acetabular edge, but might not be a reasonably good predictor of FAI.GMC patient's acetabular deformity mainly manifests as increased retroversion, which may be the anatomical basis for FAI and lead to high risks of the acetabular impingement. However, all patients in this study showed no symptoms and signs of FAI, suggesting that the measurement of EE angle can only be applied to assessing those people with normal hip myodynamia, and the bone deformity and the muscular disorder should be both considered in the diagnosis of FAI.


Benchmarking and evidence-based practice: complementary approaches to achieving quality process improvement.
The terms benchmarking and evidence-based practice have gained a great deal of attention of late. Although these 2 processes are not identical, they are complementary and can be applied concurrently in an improvement strategy. This article aims to illustrate the strengths and potential weaknesses of the 2 processes and to explain how they may be used together to improve operational performance.


Effects of visual illusion and transcutaneous electrical nerve stimulation on neuropathic pain in patients with spinal cord injury: A randomised controlled cross-over trial.
Chronic pain is a common consequence of spinal cord injury (SCI). No therapeutic drugs or drug groups are proven to be superior for neuropathic pain and treatments only aim to convert pain from dull to tolerable levels and not to remove it. This study was planned to compare the effect of visual illusion (VI) and transcutaneous electrical nerve stimulation (TENS) on pain intensity, pain quality and functional capacity in SCI patients with neuropathic pain. Twenty-four patients were included and randomly categorized into two groups. In the first group (n= 12), visual illusion was applied for first two weeks, 1 week wash out period and then TENS was applied for 2 weeks. In second group (n= 12), TENS was applied firstly, 1 week wash out and then %visual illusion VI were applied. Pain severity, pain quality, and functional capacity were assessed with the visual analog scale (VAS), the neuropathic pain scale (NPS), and the brief pain inventory (BPI), respectively. A pre-post-treatment and cross over design was used. Wilcoxon signed-rank tests were used for within group analyses. Mann-Whitney U tests were used for analyses that compared different groups. It was observed that pain intensity decrease immediately after both applications (VI: p= 0.07, TENS: p= 0.08). After TENS application for 2 weeks, it was observed that significant decrease in most (p= 0.04) and less (p= 0.02) pain intensity; while there was no significant decrease in pain intensity after 2 weeks for VI (p> 0.05). When findings of NPS were analyzed, hot (p= 0.047), sharp (p= 0.02), unpleasant (p= 0.03) and deep items (p= 0.047) decreased after VI application. When the results of BPI were detected, they were observed that the negative effect of pain on moving ability (p= 0.04) after visual illusion application and the negative effect of pain on mood (p= 0.03), relationships with others (p= 0.04) and sleep (p= 0.04) after TENS application decreased significantly. TENS and VI therapies can be successfully used in clinical practice as an alternative treatment or as a supportive method separetely or together.


Infrared light elicits endothelium-dependent vasodilation in isolated occipital arteries of the rat via soluble guanylyl cyclase-dependent mechanisms.
The left and right occipital arteries provide blood supply to afferent cell bodies in the ipsilateral nodose and petrosal ganglia. This supply is free of an effective blood-ganglion barrier, so changes in occipital artery blood flow directly affect the access of circulating factors to the afferent cell bodies. The application of infrared (IR) light to modulate neural and other cell processes has yielded information about basic biological processes within tissues and is gaining traction as a potential therapy for a variety of disease processes. To address whether IR can directly modulate vascular function, we performed wire myography studies to determine the actions of IR on occipital arteries isolated from male Sprague-Dawley rats. Based on our previous research that functionally-important differences exist between occipital artery segments close to their origin at the external carotid artery (ECA) and those closer to the nodose ganglion, the occipital arteries were dissected into two segments, one closer to the ECA and the other closer to the nodose ganglion. Segments were constricted with 5-hydroxytryptamine to a level equal to 50% of the maximal response generated by the application of a high (80 mM) concentration of K+ ions. The direct application of pulsed IR (1,460 nm) for 5 s produced a rapid vasodilation in occipital arteries that was significantly more pronounced in segments closest to the ECA, although the ECA itself was minimally responsive. The vasodilation remained for a substantial time (at least 120 s) after cessation of IR application. The vasodilation during and following cessation of the IR application was markedly diminished in occipital arteries denuded of the endothelium. In addition, the vasodilation elicited by IR in endothelium-intact occipital arteries was substantially reduced in the presence of a selective inhibitor of the nitric oxide-sensitive guanylate cyclase, 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ). It appears that IR causes endothelium-dependent, nitric-oxide-mediated vasodilation in the occipital arteries of the rat. The ability of IR to generate rapid and sustained vasodilation may provide new therapeutic approaches for restoring or improving blood flow to targeted tissues.


Passenger Flow Forecasting in Metro Transfer Station Based on the Combination of Singular Spectrum Analysis and AdaBoost-Weighted Extreme Learning Machine.
The metro system plays an important role in urban public transit, and the passenger flow forecasting is fundamental to assisting operators establishing an intelligent transport system (ITS). The forecasting results can provide necessary information for travelling decision of travelers and metro operations of managers. In order to investigate the inner characteristics of passenger flow and make a more accurate prediction with less training time, a novel model (i.e., SSA-AWELM), a combination of singular spectrum analysis (SSA) and AdaBoost-weighted extreme learning machine (AWELM), is proposed in this paper. SSA is developed to decompose the original data into three components of trend, periodicity, and residue. AWELM is developed to forecast each component desperately. The three predicted results are summed as the final outcomes. In the experiments, the dataset is collected from the automatic fare collection (AFC) system of Hangzhou metro in China. We extracted three weeks of passenger flow to carry out multistep prediction tests and a comparison analysis. The results indicate that the proposed SSA-AWELM model can reduce both predicted errors and training time. In particular, compared with the prevalent deep-learning model long short-term memory (LSTM) neural network, SSA-AWELM has reduced the testing errors by 22% and saved time by 84%, on average. It demonstrates that SSA-AWELM is a promising approach for passenger flow forecasting.


Phosphotyrosine phosphatase R3 receptors: Origin, evolution and structural diversification.
Subtype R3 phosphotyrosine phosphatase receptors (R3 RPTPs) are single-spanning membrane proteins characterized by a unique modular composition of extracellular fibronectin repeats and a single cytoplasmatic protein tyrosine phosphatase (PTP) domain. Vertebrate R3 RPTPs consist of five members: PTPRB, PTPRJ, PTPRH and PTPRO, which dephosphorylate tyrosine residues, and PTPRQ, which dephosphorylates phophoinositides. R3 RPTPs are considered novel therapeutic targets in several pathologies such as ear diseases, nephrotic syndromes and cancer. R3 RPTP vertebrate receptors, as well as their known invertebrate counterparts from animal models: PTP52F, PTP10D and PTP4e from the fruitfly Drosophila melanogaster and F44G4.8/DEP-1 from the nematode Caenorhabditis elegans, participate in the regulation of cellular activities including cell growth and differentiation. Despite sharing structural and functional properties, the evolutionary relationships between vertebrate and invertebrate R3 RPTPs are not fully understood. Here we gathered R3 RPTPs from organisms covering a broad evolutionary distance, annotated their structure and analyzed their phylogenetic relationships. We show that R3 RPTPs (i) have probably originated in the common ancestor of animals (metazoans), (ii) are variants of a single ancestral gene in protostomes (arthropods, annelids and nematodes); (iii) a likely duplication of this ancestral gene in invertebrate deuterostomes (echinodermes, hemichordates and tunicates) generated the precursors of PTPRQ and PTPRB genes, and (iv) R3 RPTP groups are monophyletic in vertebrates and have specific conserved structural characteristics. These findings could have implications for the interpretation of past studies and provide a framework for future studies and functional analysis of this important family of proteins.


Simian immunodeficiency virus infects follicular helper CD4 T cells in lymphoid tissues during pathogenic infection of pigtail macaques.
T follicular helper (Tfh) cells are a specialized subset of memory CD4(+) T cells that are found exclusively within the germinal centers of secondary lymphoid tissues and are important for adaptive antibody responses and B cell memory. Tfh cells do not express CCR5, the primary entry coreceptor for both human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), and therefore, we hypothesized that these cells would avoid infection. We studied lymph nodes and spleens from pigtail macaques infected with pathogenic strain SIVmac239 or SIVmac251, to investigate the susceptibility of Tfh cells to SIV infection. Pigtail macaque PD-1(high) CD127(low) memory CD4(+) T cells have a phenotype comparable to that of human Tfh cells, expressing high levels of CXCR5, interleukin-21 (IL-21), Bcl-6, and inducible T cell costimulator (ICOS). As judged by either proviral DNA or cell-associated viral RNA measurements, macaque Tfh cells were infected with SIV at levels comparable to those in other CD4(+) memory T cells. Infection of macaque Tfh cells was evident within weeks of inoculation, yet we confirmed that Tfh cells do not express CCR5 or either of the well-known alternative SIV coreceptors, CXCR6 and GPR15. Mutations in the SIV envelope gp120 region occurred in chronically infected macaques but were uniform across each T cell subset investigated, indicating that the viruses used the same coreceptors to enter different cell subsets. Early infection of Tfh cells represents an unexpected focus of viral infection. Infection of Tfh cells does not interrupt antibody production but may be a factor that limits the quality of antibody responses and has implications for assessing the size of the viral reservoir.


Two-team simultaneous total radical vulvectomy and inguino-femoral lymphadenectomy via separate incisions for locally advanced (FIGO stages IB ≥ 4 cm-III) squamous vulvar cancer.
To describe the feasibility, safety, and oncological outcomes of a modified triple-incision total radical vulvectomy and inguino-femoral lymphadenectomy in patients with locally advanced squamous vulvar cancer. A modified triple-incision technique performed by two surgical teams operating simultaneously under regional anesthesia was performed on a consecutive series of 57 patients with Fédération Internationale de Gynécologie Ostétrique (FIGO) stages IB ≥ 4 cm to III squamous vulvar cancer. Adjuvant radiation therapy was delivered according to margin status and groin involvement. Surgical outcomes and follow-up data were retrospectively analyzed. The mean age of patients was 75.5 ± 10.7 years and 54 (94.7%) had at least one comorbidity. Fifteen (26.3%) had disease of clinical FIGO stage I ≥ 4 cm, 7 (12.3%) had stage II, and 35 (61.4%) had a stage III. All surgical procedures were completed as planned. The mean surgical duration was 108 ± 37 min. Major intraoperative complications were observed in two cases (3.5%). Twenty-one (36.8%) patients received adjuvant radiation therapy. During a mean follow-up of 51.6 ± 50.5 months, 29 (50.9%) patients developed local, regional or distant recurrence. The disease-free survival was 39.5 ± 20.9 months. Nineteen (33.3%) patients died of primary disease. Overall survival for the entire cohort was 65.4%, with 3-year and 5-year overall survival of 60.5% and 48.6%, respectively. Our results seem to reveal that the procedure is safe, with surgical and oncological outcomes comparable to classic sequential triple-incision technique. The shortening of surgical duration along with the use of regional anesthesia can have significant advantages for perioperative care, reducing the global burden of treatment and increasing the number of patients eligible for therapeutic surgery.


Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways.
The stress response molecule nuclear protein‑1 (NUPR1) is essential for the growth of multiple types of human malignant tumor cells. However, the significance of NUPR1 in lung cancer is still not entirely elucidated. Therefore, this study is aimed to explore the function and underlying mechanisms of NUPR1 in lung cancer. NUPR1 mRNA and protein levels in lung cancer cell lines (A549 or H1299 cells) were silenced through siRNA transfection and western blot observed its successful infection efficiency. Then, using tube formation and wound healing experiments, the effects of si-NUPR1 on angiogenesis and migration of human umbilical vein endothelial cells (HUVEC) were examined, respectively, which indicated inhibitory effects on the angiogenesis and migration of HUVEC. Vascular endothelial growth factor A (VEGFA), a vital molecule in angiogenesis, was detected by PCR and western blot assays, manifesting NUPR1 knockdown represses VEGFA expression. Furthermore, the knockdown of NUPR1 may reduce angiogenesis by lowering VEGFA expression through inositol-requiring enzyme 1 (IRE1)/X box binding protein 1 (XBP1) and protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2 A (eIF2α)/recombinant activating transcription factor 4 (ATF4) signaling pathways in A549 or H1299 cells. In conclusion, these findings demonstrated that NUPR1 knockdown inhibits angiogenesis in A549 and H1299 cells through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways, indicating that NUPR1 could represent a novel lung cancer therapeutic target.


Transcriptional activity in lysates of cultured mesenchymal cells from embryonic tooth germs.
Mesenchymal cells isolated from the papilla of embryonic tooth germs of the mouse were cultured in a complex medium for five to six days. Liquid nitrogen lysates, prepared from these cells, incorporated nucleoside monophosphates into a cold acid-insoluble product. The product was sensitive to RNase and no product was formed if the lysate was pretreated with DNase. The reaction was sensitive to EDTA and, in its presence, optimum activity was obtained with 2 mM MgCl2. On sucrose gradients, the reaction product was distributed between two broad peaks; one centered about 18S and the other above 28S. The RNA polymerase inhibitor alpha-amanitin inhibited approximately 50% of the activity at a concentration of 10 microgram/ml.


Synthesis and Characterization of Contorted Pentabenzo-Fused Coronenes as Semiconducting Materials.
Here, we report the synthesis and characterization of a series of contorted, yet noncentrosymmetrical, polycyclic aromatic hydrocarbons with a pentabenzo-fused coronene as the core framework. The parent pentabenzo[a,d,g,j,m]coronene (PBC) compound is shown to exhibit a shifted and rotated type of π-π stacking interactions, which render this series a semiconducting material. Single-crystal-based field-effect transistor devices of PBC exhibited efficient charge transport behavior, giving a p-channel field-effect mobility of 0.42 cm2 V-1 s-1 and an on/off ratio of 105.


Effects of Paternal Obesity on Fetal Development and Pregnancy Complications: A Prospective Clinical Cohort Study.
To evaluate the association between paternal obesity and fetal development and pregnancy complications. This prospective cohort clinical trial analyzed data from 7683 women with singleton pregnancies. All study subjects were sequentially divided into four groups based on paternal BMI. We compared the differences in fetal growth and pregnancy complications between different paternal BMI groups by univariate logistic regression and independent t-test. Finally, the independent predictors of SGA and macrosomia were determined. The incidences of preeclampsia, cesarean section, SGA, macrosomia, and postpartum hemorrhage in the paternal obesity group were significantly higher than the normal BMI group. With the increase of paternal BMI, fetal ultrasound measurement parameter, neonatal and placental weight showed an increasing trend (trend P < 0.05). However, these differences disappeared in the obese group. The test for interaction showed the effect of paternal obesity on SGA and macrosomia was significantly affected by maternal obesity. We also found paternal obesity was an independent predictor of both SGA and macrosomia. Based on the above results, we plotted the Nomograms for clinical prediction. Paternal obesity can affect fetal growth parameters and placental development, which has an adverse impact on pregnancy outcomes. Optimizing the paternal BMI will help improve the health of the next generation.


Carcinogenic activity of Symphytum officinale.
The carcinogenicity of Symphytum officinale L., Russian comfrey, used as a green vegetable or tonic, was studied in inbred ACI rats. Three groups of 19--28 rats each were fed comfrey leaves for 480--600 days; four additional groups of 15--24 rats were fed comfrey roots for varying lengths of time. A control group was given a normal diet. Hepatocellular adenomas were induced in all experimental groups that received the diets containing comfrey roots and leaves. Hemangioendothelial sarcoma of the liver was infrequently induced.


Imprinted segments in the human genome: different DNA methylation patterns in the Prader-Willi/Angelman syndrome region as determined by the genomic sequencing method.
A deletion of 15q11-q13 and uniparental disomy 15 lead to Prader-Labhart-Willi syndrome (PWS) or Angelman syndrome (AS) because this region contains genes expressed exclusively from the paternal (PWS) or maternal (AS) chromosome, respectively. DNA methylation plays a role in the control of imprinted gene expression, but so far only a few 5'-CG-3' dinucleotides within the recognition sites of the methylation sensitive enzymes have been studied. As part of a study on DNA methylation patterns in the human genome, we have applied the bisulfite protocol of genomic sequencing to study all 5'-CG-3' dinucleotides around exon 1 of SNRPN and at the D15S63 locus, which contains a start site for alternative SNRPN transcripts possibly involved in imprint switching during gametogenesis. At least 17 PCR products derived from single chromosomes of normal individuals as well as PWS and AS patients have been sequenced. We have found that cytosine residues outside 5'-CG-3' dinucleotides are always unmethylated. However, > 96% of all of the 23 5'-CG-3' dinucleotides around SNRPN exon 1 are methylated on the maternal chromosome and completely devoid of methylation on the paternal chromosome. This finding is in contrast to the D15S63 locus, where only the two Cfol/Hhal sites are methylated on the maternal chromosome at the same frequency as seen for the SNRPN segment. At the other five 5'-CG-3' dinucleotides, differential methylation is less pronounced, i.e. 45-70% on the maternal chromosome and 5-14% on the paternal chromosome. The differences between SNRPN and D15S63 methylation may reflect different biological functions of the alternative SNRPN transcripts. The systematic investigation of 5'-CG-3' methylation patterns as reported here will provide the basis for a PCR-based methylation test to diagnose PWS and AS.


Patisiran for the Treatment of Transthyretin-mediated Amyloidosis with Cardiomyopathy.
Transthyretin (TTR) is a tetrameric protein, synthesized primarily by the liver, that acts as a physiological transport protein for retinol and thyroxine. TTR can misfold into pathogenic amyloid fibrils that deposit in the heart and nerves, causing a life-threatening transthyretin amyloidosis cardiomyopathy (ATTR-CM), and a progressive and debilitating polyneuropathy (ATTR-PN). Recent therapeutic advances have resulted in the development of drugs that reduce TTR production. Patisiran is a small interfering RNA that disrupts the complimentary mRNA and inhibits TTR synthesis, and is the first gene-silencing medication licensed for the treatment of ATTR amyloidosis. After encouraging results following the use of patisiran for the treatment of patients with ATTR-PN, there has been increasing interest in the use of patisiran for the treatment of ATTR-CM. Various studies have demonstrated improvements across a wide range of cardiac biomarkers following treatment with patisiran, and have changed the perception of ATTR-CM from being thought of as a terminal disease process, to now being regarded as a treatable disease. These successes represent a huge milestone and have the potential to revolutionize the landscape of treatment for ATTR-CM. However, the long-term safety of patisiran and how best to monitor cardiac response to treatment remain to be determined.


Communication About End of Life for Patients Living With Amyotrophic Lateral Sclerosis: A Scoping Review of the Empirical Evidence.
Background: Communication about end of life, including advance care planning, life-sustaining therapies, palliative care, and end-of-life options, is critical for the clinical management of amyotrophic lateral sclerosis patients. The empirical evidence base for this communication has not been systematically examined. Objective: To support evidence-based communication guidance by (1) analyzing the scope and nature of research on health communication about end of life for amyotrophic lateral sclerosis; and (2) summarizing resultant recommendations. Methods: A scoping review of empirical literature was conducted following recommended practices. Fifteen health-related and three legal databases were searched; 296 articles were screened for inclusion/exclusion criteria; and quantitative data extraction and analysis was conducted on 211 articles with qualitative analysis on a subset of 110 articles that focused primarily on health communication. Analyses summarized article characteristics, themes, and recommendations. Results: Analysis indicated a multidisciplinary but limited evidence base. Most reviewed articles addressed end-of-life communication as a peripheral focus of investigation. Generic communication skills are important; however, substantive and sufficient disease-related information, including symptom management and assistive devices, is critical to discussions about end of life. Few articles discussed communication about specific end-of-life options. Communication recommendations in analyzed articles draw attention to communication processes, style and content but lack the systematized guidance needed for clinical practice. Conclusions: This review of primary research articles highlights the limited evidence-base and consequent need for systematic, empirical investigation to inform effective communication about end of life for those with amyotrophic lateral sclerosis. This will provide a foundation for actionable, evidence-based communication guidelines about end of life. Implications for research, policy, and practice are discussed.


Antitumor activity of benzaldehyde.
Ninety patients with inoperable carcinoma in the terminal stages and 12 patients in serious condition with other tumor types were given benzaldehyde in the form of beta-cyclodextrin benzaldehyde inclusion compound (CDBA) orally or rectally at a daily dose of 10 mg/kg divided in four doses. Toxic effects, including hematologic or biochemical disturbances, were not seen during long-term successive administration of CDBA. Fifty-seven of the patients treated were evaluable; 19 patients responded completely and ten patients responded partially (greater than 50% regression). For all responding patients longer response durations were associated with longer CDBA treatment periods. Treatment of squamous cell carcinoma induced the cancer cells to change into a conglomeration of pearls (the well-known product of differentiation) which consisted of keratinized normal squamous cells.


Can administrative data be used to measure chemotherapy side effects?
Many of the issues with using data from clinical trials and observational studies for economic evaluations are highlighted in the case of chemotherapy side effects. We present the results of an observational cohort study using linked administrative data. The chemotherapy side effects identified in the administrative data are compared with patient self-reports of such events. The results of these comparisons are then used to guide a discussion of the issues surrounding the use of administrative data to identify clinical events for the population of economic models. Although the advantages of easy access and generalizability of the results make administrative data an attractive option for populating economic models, this is not always possible because of the limitations of these data.


Improving Psychological Wellbeing and Healthcare Outcomes Through Decentralization of Healthcare Expenditures in Pakistan.
This article contributes to the limited empirical literature on the impact of decentralization on psychological wellbeing by investigating the hypothesis which signifies that shifts toward more fiscal decentralization in health services would be accompanied by improvements in health outcomes. Formulating a conventional public finance model applied to health care, this hypothesis is tested on a panel data of the Pakistan's provinces during the period 1990 to 2015. The empirical underpinning of the article suggested that the economic reforms of 2001 in Pakistan's healthcare sector, through fiscal decentralization, have imposed a substantial and positive influence on the effectiveness of the public policy in improving the healthcare outcomes over the examined period.


Gene manipulation and genetic toxicology.
Transgenic mice with recoverable target genes, with genes modified in expression or with ablated gene function provide important tools for defining the biological effects of chemicals. In many cases studies can be conducted with fewer animals and in a shorter timeframe. They also provide important tools for studies of carcinogenesis mechanisms and processes, for early detection of carcinogens and for identification of potential cancer therapies.


Quality control in mammography: practical implications.
The programme "Europe against cancer" stimulated, among other activities, breast screening activities in the member states. From the beginning, it was clear that a rigorous and efficient approach required the highest possible quality of the three major components of a breast screening programme: the medical performance (correct positioning, training of the medical staff, double reading of the mammograms and feedback from the pathologist and the epidemiologist), the organisation (attendance rate, data base) and the quality of the imaging process (compliance of the image quality and the breast dose with the CEC document of 1990). The first part of this paper will be limited to the latter component and the second part to the subject of correct positioning of the breast.


Exact weight cancellation in Monte Carlo eigenvalue transport problems.
Random walks are frequently used as a model for very diverse physical phenomena. The Monte Carlo method is a versatile tool for the study of the properties of systems modeled as random walks. Often, each walker is associated with a statistical weight, used in the estimation of observable quantities. Weights are typically assumed to be positive; nonetheless, some applications require the use of positive and negative weights or complex weights and often pose particular challenges with convergence. In this paper we examine such a case from the field of nuclear reactor physics, where the negative particle weights prevent the power iteration algorithm from converging on the sought fundamental eigenstate of the Boltzmann transport equation. We demonstrate how the use of weight cancellation allows convergence on the physical eigenstate. To this end, we develop a method to perform weight cancellation in an exact manner, in three spatial dimensions. The viability of this algorithm is then demonstrated on a reactor physics problem.


Serum prostate-specific antigen is better correlated to body surface area than body mass index in a population of healthy Korean men.
It has been suggested that the larger vascular volume among obese men causes a dilution effect, decreasing the concentration of serum prostate-specific antigen (PSA). However, plasma volume is proportional to body surface area (BSA) rather than to body mass index (BMI). We determined whether serum PSA level is better correlated to BSA than BMI in a population of ostensibly healthy Korean men. Data from 2604 men who visited our health promotion center were evaluated. All men underwent anthropometric measurements, digital rectal examination, serum PSA determination, and transrectal ultrasound examination. The correlation between serum PSA and other parameters was statistically analyzed. The mean age was 49.9 years and the mean serum PSA level was 1.14 ng/mL. The multivariate analysis revealed that the serum PSA was positively correlated with age, prostate volume, and negatively correlated with BSA only and not with BMI. In addition, BSA, rather than BMI, was the significant factor in predicting the prostate volume. Our results suggest that men with larger BSA (rather than BMI), have larger prostate volumes, and lower serum PSA.


Graph Decoupling Attention Markov Networks for Semisupervised Graph Node Classification.
Graph neural networks (GNNs) have been ubiquitous in graph node classification tasks. Most GNN methods update the node embedding iteratively by aggregating its neighbors' information. However, they often suffer from negative disturbances, due to edges connecting nodes with different labels. One approach to alleviate this negative disturbance is to use attention to learn the weights of aggregation, but current attention-based GNNs only consider feature similarity and suffer from the lack of supervision. In this article, we consider label dependency of graph nodes and propose a decoupling attention mechanism to learn both hard and soft attention. The hard attention is learned on labels for a refined graph structure with fewer interclass edges so that the aggregation's negative disturbance can be reduced. The soft attention aims to learn the aggregation weights based on features over the refined graph structure to enhance information gains during message passing. Particularly, we formulate our model under the expectation-maximization (EM) framework, and the learned attention is used to guide label propagation in the M-step and feature propagation in the E-step, respectively. Extensive experiments are performed on six well-known benchmark graph datasets to verify the effectiveness of the proposed method.


HyperCard: teaching technology for successful learning.
A brief review of the effectiveness of instructional media is presented, with reference to mastery learning and the effects of illustrations. This is related to the need for instructional media to incorporate both of these essential elements if they are to succeed in enhancing the level of student performance. The role of computer technology, and in particular the authoring system HyperCard, in achieving this is discussed. An experimental program, HyperHeart, is used to illustrate the potential of such a system in biology.


Morphological changes in mouse embryos cryopreserved by different techniques.
Cryopreservation of mammalian embryos is an important tool for the application of reproductive biotechnologies. Subjective evaluation to determine embryo viability is often used. The determination of the best cryopreservation protocol depends on morphological and molecular analysis of cellular injuries. The main objective of this study was to compare two methods of cryopreservation by assessing morphological alterations of frozen embryos using light, fluorescence, and transmission electron microscope. Fresh (control), slow frozen, and vitrified mouse embryos were composed. To evaluate the viability of the embryos, the cell membrane integrity was assessed using Hoechst33342 and propidium iodide (H/PI) staining. Morphological analyses using hematoxylin and eosin (HE) staining were performed to test different techniques (in situ, paraffin, and historesin) by both light and fluorescence microscopy. Transmission electron microscope was used to detect ultrastructural alterations in Spurr- and Araldite-embedded samples. H/PI staining detected more membrane permeability in the vitrification (69.8%) than in the slow freezing (48.4%) or control (13.8%) groups (P < 0.001). Historesin-embedded samples showed to be more suitable for morphological analyses because cellular structures were better identified. Nuclear evaluation in historesin sections showed the induction of pycnosis in slow freezing and vitrification groups. Cytoplasm evaluation revealed a condensation and an increase in eosinophilic intensity (indicating apoptosis) in the slow freezing group, and weakly eosinophilic structures and degenerated cells (indicating oncosis) in the vitrification group (P < 0.05). Ultrastructural analyses confirmed HE morphological findings. It was concluded that both cryopreservation techniques resulted in oncosis and apoptosis injuries. However, vitrification caused more severe cellular alterations and reduced embryonic viability compared to slow freezing.


[Video laparoscopic cholecystectomy in situ viscerum inversus totalis].
Situs viscerum inversus totalis is a rare condition with a genetic predisposition that is autosomal recessive. We present a case in an elderly patient with transposition of the viscera and cholelithiasis, who was successfully treated with laparoscopic cholecystectomy. This paper further expands the application of this technique and shows that they can be safely and effectively applied in the setting of situs viscerum inversus totalis, although attention must be paid to the details of left-right reversal.


Quercetin enhances TRAIL-mediated apoptosis in colon cancer cells by inducing the accumulation of death receptors in lipid rafts.
Cytokines such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in colon cancer cells through engagement of death receptors. Nevertheless, evading apoptosis induced by anticancer drugs characterizes many types of cancers. This results in the need for combination therapy. In this study, we have investigated whether the flavonoid quercetin could sensitize human colon adenocarcinoma cell lines to TRAIL-induced apoptosis. We report that quercetin enhanced TRAIL-induced apoptosis by causing the redistribution of DR4 and DR5 into lipid rafts. Nystatin, a cholesterol-sequestering agent, prevented quercetin-induced clustering of death receptors and sensitization to TRAIL-induced apoptosis in colon adenocarcinoma cells. In addition, our experiments show that quercetin, in combination with TRAIL, triggered the mitochondrial-dependent death pathway, as shown by Bid cleavage and the release of cytochrome c to the cytosol. Together, our findings propose that quercetin, through its ability to redistribute death receptors at the cell surface, facilitates death-inducing signaling complex formation and activation of caspases in response to death receptor stimulation. Based on these results, this study provides a challenging approach to enhance the efficiency of TRAIL-based therapies.


Statistics for Evaluating Pre-post Change: Relation Between Change in the Distribution Center and Change in the Individual Scores.
In a number of scientific fields, researchers need to assess whether a variable has changed between two time points. Average-based change statistics (ABC) such as Cohen's d or Hays' ω2 evaluate the change in the distributions' center, whereas Individual-based change statistics (IBC) such as the Standardized Individual Difference or the Reliable Change Index evaluate whether each case in the sample experienced a reliable change. Through an extensive simulation study we show that, contrary to what previous studies have speculated, ABC and IBC statistics are closely related. The relation can be assumed to be linear, and was found regardless of sample size, pre-post correlation, and shape of the scores' distribution, both in single group designs and in experimental designs with a control group. We encourage other researchers to use IBC statistics to evaluate their effect sizes because: (a) they allow the identification of cases that changed reliably; (b) they facilitate the interpretation and communication of results; and (c) they provide a straightforward evaluation of the magnitude of empirical effects while avoiding the problems of arbitrary general cutoffs.


Unusual electron charge density in carboxylic acid. 17O quadrupole coupling in cis-cyclobutane-1,2-dicarboxylic acid.
The (17)O NQR frequencies have been measured in cis-cyclobutane-1,2-dicarboxylic acid and the quadrupole coupling tensors have been determined at various temperatures. Two O···H oxygen positions and two O-H oxygen positions are observed, showing the presence of two different types of O-H···O hydrogen bonds in the unit cell. The quadrupole coupling constants at the O-H oxygen positions are approximately 30% lower than the lowest quadrupole coupling constants experimentally observed at the C-O-H positions in other carboxylic acids with either ordered or disordered hydrogen bonds. The O-H distances have been calculated from the (17)O-(1)H dipole-dipole interaction at the O-H oxygen positions. The obtained values are longer than the O-H distances usually found in O-H···O hydrogen bonds with comparable O···O distance, in agreement with the proposed proton exchange O-H···O ↔ O···H-O, which partially averages the dipole-dipole interaction. The energy difference of the two proton configurations, O-H···O and O···H-O, is calculated from the O-H distances determined by NQR. The temperature dependence of the (17)O quadrupole coupling tensors at the (17)O···H-O oxygen positions is analyzed in the model of proton exchange and the energy differences of the two proton configurations obtained by this analysis agree with the values obtained from the O-H distances. The quadrupole coupling tensors are analyzed in a model based on the Townes and Dailey model. The model shows that the population of an oxygen lone pair orbital is at this oxygen position reduced from 2 to approximately 1.3. The electron electric charge is most probably transferred to the oxygen σ and π electron orbitals. This may be associated with the structure of the cyclobutane ring, where the X-ray data show the presence of two unusually short C-C bonds.


Inhibition of human lysosomal elastase by the cartilage bone marrow extract Rumalon.
Human lysosomal elastase from polymorphonuclear leucocytes is inhibited by the cartilage bone marrow extract Rumalon. Separately, both the cartilage and the bone marrow extracts are able to inhibit the enzymatic activity by 73%, under saturating conditions. The mixture of the two extracts inhibits elastase by 93%. It is suggested that the two partners act as a cumulative inhibition mechanism and this phenomenon is emphasized in a general theoretical model for synergy of proteinase-directed inhibitors.


Overexpression of HvHGGT Enhances Tocotrienol Levels and Antioxidant Activity in Barley.
Vitamin E is a potent lipid-soluble antioxidant and essential nutrient for human health. Tocotrienols are the major form of vitamin E in seeds of most monocots. It has been known that homogentisate geranylgeranyl transferase (HGGT) catalyzes the committed step of tocotrienol biosynthesis. In the present study, we generated transgenic barley overexpressing HvHGGT under endogenous D-Hordein promoter (proHor). Overexpression of HvHGGT increased seed size and seed weight in transgenic barley. Notably, total tocotrienol content increased by 10-15% in seeds of transgenic lines, due to the increased levels of δ-, β-, and γ-tocotrienol, but not α-tocotrienol. Total tocopherol content decreased by 14-18% in transgenic lines, compared to wild type. The antioxidant activity of seeds was determined by using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), and lipid peroxidation assays. Compared to wild type, radical scavenging activity of seed extracts was enhanced by 17-18% in transgenic lines. Meanwhile, the lipid peroxidation level was decreased by about 20% in transgenic barley seeds. Taken together, overexpression of HvHGGT enhanced the tocotrienol levels and antioxidant capacity in barley seeds.


It Could Have Been True: How Counterfactual Thoughts Reduce Condemnation of Falsehoods and Increase Political Polarization.
This research demonstrates how counterfactual thoughts can lead people to excuse others for telling falsehoods. When a falsehood aligned with participants' political preferences, reflecting on how it could have been true led them to judge it as less unethical to tell, which in turn led them to judge a politician who told it as having a more moral character and deserving less punishment. When a falsehood did not align with political preferences, this effect was significantly smaller and less reliable, in part because people doubted the plausibility of the relevant counterfactual thoughts. These results emerged independently in three studies (two preregistered; total N = 2,783) and in meta- and Bayesian analyses, regardless of whether participants considered the same counterfactuals or generated their own. The results reveal how counterfactual thoughts can amplify partisan differences in judgments of alleged dishonesty. I discuss implications for theories of counterfactual thinking and motivated moral reasoning.


Nucleolar activity in differentiated cells after stimulation.
Initiation of nucleolar organizer region (NOR) activity was observed by using the silver staining method at various times after activation or stimulation of differentiated cells. Two methods were used: (1) activation of human lymphocytes by treatment with phytohemagglutinin (PHA), and (2) cell-cell fusion of chick erythrocytes with squirrel monkey cells. An increase in NOR activity in lymphocytes was seen as early as 4 h after PHA treatment and between 10 and 22 h in the chick erythrocytes after fusion. In both systems, as the size of the dormant cell nucleus increased, the amount of silver staining increased until the silver-stained area approached that of cycling cells.


Identification of genotoxic compounds in the airborne particulate matter endowed by small aerodynamic diameter in the city of Catania (Italy).
Airborne particulate matter (PM) is one of the most important polluting factors in the atmosphere containing solid particles generated during the combustion processes. PM, due to the particle size, is easily inhaled and constitutes a potential hazard for the human health. We previously documented, using in vitro cell culture systems, cytogenetic damages caused by exposure to a non-fractionated PM in two different areas from the city of Catania (Sicily, Italy). In the present work, the PM was fractionated in six different sub-fractions, and the relative extractable organic matters (EOM) were analyzed in order to quantify the presence of Polycyclic Aromatic Hydrocarbons (PHAs), a well known class of genotoxic agents. More than 70% of the total EOM was found in the PM with aerodynamic diameters less than 3.5 microm (PM35), and about 60% of the total EOM was detected between PM0.14 and PM1.2. Also the large amount of all the analyzed PAHs were found between the PM0.14 and PM1.2. The obtained data indicates that the genotoxic effect previously shown on mammalian cells (Chinese hamster epithelial liver cells) should be due, in the large part, to the PM with smaller particle size, namely less than PM1.2.


Role of placental tissues in the intrauterine transmission of hepatitis B virus.
The purpose of this study was to determine the mechanism of intrauterine transmission of hepatitis B virus. Placental tissues from 158 pregnant women who tested positive for hepatitis B surface antigen were examined for hepatitis B virus markers, Fc gamma receptors, and hepatitis B surface antigen-anti-hepatitis B surface antigen in different layers of cells. It was shown that the hepatitis B virus infection rate among different layers of placental cells gradually decreased from the maternal side to the fetal side. Furthermore, the closer the infected cell layer was to the fetal side, the higher the risk of intrauterine hepatitis B virus infection. Fc gamma receptors were found on cells of both hepatitis B surface antigen positive and negative placentas; Fc gamma receptors III were found on trophoblastic cells and villous mesenchymal cells, and Fc gamma receptors II were found on only villous mesenchymal cells. Hepatitis B surface antigen-antibodies to hepatitis B surface antigen was detected in the cytoplasm and on the membrane of trophoblastic cells and villous mesenchymal cells in 2 hepatitis B surface antigen-positive placentas. The results support the hypothesis that intrauterine hepatitis B virus transmission could be caused through "cellular transfer" in the placenta. One of the means of cellular transfer could be through Fc gamma receptor III-mediated entry of hepatitis B surface antigen-antibodies to hepatitis B surface antigen into cells.