Examining the consequences of dehumanization and adultification in justification of police use of force against Black girls and boys.
Given the greater contact that Black youth have with the legal system compared with White youth, it is important to consider the differential ways that police use of force against these youth is perceived. Black youth may be at greater risk than White youth for animalistic (being seen as animal-like) and mechanistic (being seen as object-like) dehumanization, which, along with a tendency for Black youth to be perceived as older (adultification), may impact observers' perceptions of police use of force toward Black youth. This study examined whether dehumanization and adultification were associated with the perceptions of force used and harm caused by police. We made five hypotheses. First, participants would dehumanize Black individuals more than White individuals, more mechanistically dehumanize Black women than Black men, and more animalistically dehumanize Black men than Black women. Second, dehumanization would be positively associated with adultification. Third, force would be rated as less appropriate and more excessive for White than for Black targets, particularly for males. Fourth, dehumanization, particularly animalistic dehumanization, would be associated with higher participant ratings of force justification and lower participant ratings of force severity and excessiveness. Fifth, participants would perceive girls as more harmed than boys and White individuals as more harmed than Black individuals. After completing an implicit dehumanization measure, participants viewed an image (varied on age and gender) of a juvenile, estimated the juvenile's age, and read a vignette in which the juvenile had an altercation with police. Participants rated the amount, severity, and justification of the force used by the officer as well as the physical and emotional harm caused to the juvenile. We found that Black targets were dehumanized more than White targets. Adultification, unrelated to implicit dehumanization, predicted perceiving police use of force against juveniles as more justified and less severe. Black girls were most likely to experience adultification; participants generally perceived them as less victimized than Black boys and White girls. Adultification is associated with fewer protections for youth. Those with particular intersectional identities, such as Black girls, may be uniquely vulnerable to harm caused by police victimization. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Optimal exit choice during highway tunnel evacuations based on the fire locations.
In the case of a fire, the choice of exit in the highway tunnel is strictly limited by fire location, which seriously affects the evacuation time. A spontaneous or disorderly exit choice might result in a decreased evacuation efficiency and utilization rate of exits. In this paper, we propose a strategy to obtain the optimal exit choice based on fire location during highway tunnel evacuations. In our strategy, first, the vehicle distributions and locations of evacuating occupants are determined in the traffic simulation program VISSIM. The evacuation simulation software BuildingEXODUS is employed to obtain the corresponding parameters of the evacuation process and analyze the impacts of different fire locations on the evacuation time. During the analysis, the optimal productivity statistics (OPS) is selected as the evaluation index. Then, the feature points of the crowding occupants are captured by the fuzzy c-means (FCM) cluster algorithm. Next, based on the feature points, the relationship between the location of the fire and boundary of the optimal exit choice under the optimal OPS is obtained through the polynomial regression model. It is found that the R-squared(R2) and sum of squares for error (SSE) of the polynomial regression model, reflecting the accuracy estimation, are 98.02% and 2.79×10-4, respectively. Moreover, different fire locations impact the evacuation time of tunnel entrance and evacuation passageway. This paper shows that the location of the fire and boundary of optimal exit choice have a negative linear correlation. Taking the fire 110 m away from the evacuation passageway as an example, the OPS of our strategy can be decreased by 35.6% when compared with no strategies. Our proposed strategy could be applied to determine the location of variable evacuation signs to help evacuating occupants make optimal exit choices.


Effect of Enhancers on in vitro and in vivo Skin Permeation and Deposition of S-Methyl-L-Methionine.
S-methyl-L-methionine (SMM), also known as vitamin U, is commercially available as skin care cosmetic products for its wound healing and photoprotective effects. However, the low skin permeation expected of SMM due to its hydrophilic nature with a log P value of -3.3, has not been thoroughly addressed. The purpose of this study thus was to evaluate the effect of skin permeation enhancers on the skin permeation/deposition of SMM. Among the enhancers tested for the in vitro skin permeation and deposition of SMM, oleic acid showed the most significant enhancing effect. Moreover, the combination of oleic acid and ethanol further enhanced in vitro permeation and deposition of SMM through hairless mouse skin. Furthermore, the combination of oleic acid and ethanol significantly increased the in vivo deposition of SMM in the epidermis/dermis for 12 hr, which was high enough to exert a therapeutic effect. Therefore, based on the in vitro and in vivo studies, the combination of oleic acid and ethanol was shown to be effective in improving the topical skin delivery of SMM, which may be applied in the cosmetic production process for SMM.


Activation of the enhancer of zeste homologue 2 gene by the human papillomavirus E7 oncoprotein.
The malignant phenotype of human papillomavirus (HPV)-positive cancer cells is maintained by the activity of the viral E6 and E7 genes. Here, we identified the polycomb group gene enhancer of zeste homologue 2 (EZH2) as a novel downstream target for the viral oncogenes in HPV-transformed cells. EZH2 expression was activated by HPV16 E7 at the transcriptional level via E7-mediated release of E2F from pocket proteins. RNA interference analyses showed that continuous EZH2 expression is required for the proliferation of HPV-positive tumor cells by stimulating cell cycle progression at the G1-S boundary. In addition to its growth-promoting activity, EZH2 also contributed to the apoptotic resistance of cervical cancer cells. Furthermore, we found that HPV-positive dysplastic and tumorigenic cervical lesions were characterized by high levels of EZH2 protein in vivo. We conclude that the E7 target gene EZH2 is a major determinant for the proliferation of HPV-positive cancer cells and contributes to their apoptotic resistance. Moreover, EZH2 may serve as a novel therapeutic target for the treatment of cervical cancer.


Amplification of DNA at a prophage attachment site in Haemophilus influenzae.
The Escherichia coli plasmids pBR322 and pBR327 can be taken up by Haemophilus influenzae but do not replicate in this organism; however, integration of pBR into the H. influenzae chromosome was achieved by ligation to a fragment of the Haemophilus phage S2 that carried a phage attachment site (attP). Once these sequences were integrated, they could serve as sites of recombination and amplification for homologous (pBR or phage) DNA. Amplification appeared to occur in one of two prophage sites (attB) present in the H. influenzae chromosome. The extent of amplification was different in different cells and reflected the ability of these sequences to undergo rearrangement leading to the formation of a DNA ladder. The ladder was obtained by treatment of DNA with restriction enzymes that cut outside of the inserted DNA, i.e., did not cut in the repeat sequence, and represented different numbers of repeat elements. Reversed-field gel electrophoresis was instrumental in resolving amplified structures. Inasmuch as single-cell isolates gave rise to the same ladder structure, it was assumed that amplification was under regulatory control and that it reproduced the same equilibrium of repeat structures. Transformation of E. coli with the amplified H. influenzae DNA resulted in precise excision and replication of the original monomeric plasmids. This excision was independent of the recA and recBC genes.


Health-related quality of life in children and adolescents with cerebral palsy.
In a cross-sectional cohort study, health-related quality of life of Slovenian children and adolescents with cerebral palsy was examined, and factors associated with it have been identified. Caregivers of 122 children and adolescents with cerebral palsy were addressed to fill out proxy versions of HRQoL questionnaires (DISABKIDS generic and cerebral palsy module). Children and adolescents without cognitive deficit were asked to fill out the self-report versions. Ninety-one families of 43 children (the mean age is 10 years, 6 months, SD 1.2; 26 males and 17 females) and 48 adolescents (the mean age is 14 years, SD 0.9; 23 males and 25 females) completed proxyreports. Forty-eight individuals were able to self-report (26 children and 22 adolescents). Health-related quality of life was perceived as good. Self-reporting participants scored higher than their caregivers (mean score 75.6, SD 15.9 versus mean 72.3, SD 17.9; p=0.048). Adolescents scored lower than children in all domains (mean score 69.4, SD 19.4 versus mean 80.8, SD 10.0; p=0.01). Higher age (p<0.001), pain (p<0.001) and disturbed sleep (p=0.002) were strong predictors of worse health-related quality of life. Social Inclusion and Independence domains received the lowest scores. Slovenian children and adolescents with cerebral palsy have a good health-related quality of life, with Social Inclusion and Independence being the weakest domains. Children reported higher scores than adolescents or their caretakers. Pain was the strongest predictor of poor health-related quality of life.


[Islet flaps from the forearm in plastic surgery of the hand].
An analysis of islet flaps of the forearm used in the performing of complex reconstructive operations on the hand in 37 patients is presented. A substantial shortcoming of transplantation of the radial and elbow flaps is a possible development of disturbance of blood circulation in the hand tissues which can require emergent plasty of the transected artery. In transplantation of the posterior flap of the forearm the blood circulation in the hand tissues was not disturbed.


Triple negative breast cancer: the role of metabolic pathways.
The incidence of breast cancer in Malaysia and other Asian countries is on the increase, reflecting lifestyle changes some of which are known risk factors for the development of breast cancer. Most breast cancers are amenable to adjuvant therapies that target hormone receptors or HER2 receptors on the surface of the cancer cells and bring about significant improvement in survival. However, approximately 17% of Malaysian women with breast cancer, present with tumours that are devoid of these receptors and are consequently termed 'triple negative' breast cancers. These triple negative breast cancers typically occur in women of a younger age than receptor positive cancers, are predominantly of high grade tumours and the prognosis is usually poor. There is therefore a pressing need to understand the biological pathways that drive these tumours, in order that effective strategies are developed to treat these aggressive tumours. With the increasing affluence of developing countries, obesity and Type II Diabetes are also on the rise. These diseases are associated with an increased risk of developing a range of cancers including those of the breast. In particular, the metabolic syndrome has been shown to be associated with triple negative breast cancer. This article reviews some of the metabolic pathways and biomarkers which have been shown to be aberrantly expressed in triple negative breast cancer and highlights some of the ongoing work in this area.


Role of JAK2 V617F mutation and aberrant expression of microRNA-143 in myeloproliferative neoplasms.
Myeloproliferative neoplasms (MPNs) are clonal myeloid disorders characterized by the overproduction of mature blood cells. The pathogenetic hallmark of MPNs is the dysregulation of JAK-STAT signaling, usually associated with the JAK2 V617F mutation. Multiple additional genetic and epigenetic alterations that constitutively activate the JAK-STAT signaling pathway have been described, including the modulation of the microRNAs (miRs) expression levels. The aims of our study were to investigate JAK2 V617F mutation allele burden and miR-143 expression levels in MPNs patients and to investigate the correlation between these genetic signatures and hematological parameters. In total 78 patients with a clinical diagnosis of polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IM), made according to the WHO 2008 criteria, were included in the study. Twenty healthy subjects were checked as controls. Quantification of JAK2 V617F mutation and miR-143 expression levels were determined by real-time quantitative polymerase chain reaction. The miR-143 expression in MPNs patients was 2.97-fold higher than in controls. JAK2 V617F mutation allele burden and miR-143 expression level resulted higher in PV and IM respect to ET patients. Patients who had V617F allele burden >50% displayed a higher miRNA-143 expression level than patients with allele burden <50%. In MPNs patients, a statistically significant positive correlation was observed between JAK2 V617F mutation allele burden and hemoglobin and hematocrit values and between miR-143 expression levels and platelet count. Our findings of aberrant miR-143 expression support the concept that factors other than JAK2 V617F mutation may contribute to the pathogenesis and some clinical signs of MPNs.


[Cone-beam CT imaging features of common cystic lesions associated with the impacted mandibular third molar].
Objective: To analyze the imaging features of cone-beam CT (CBCT) of ameloblastoma (AB), odontogenic keratocyst (OKC) and dentigerous cysts (DC) associated with the mandibular impacted third molars,so as to provide useful information for differential diagnosis of these lesions. Methods: The patients who were with complete clinical data, pathological diagnosis and CBCT images from AB, OKC and DC around the mandibular impacted third molars were collected in Peking University Hospital of Stomatology from August 2016 to December 2021. A total of 109 patients (14 were diagnosed as AB, 23 were diagnosed as OKC and the others were diagnosed as dental cysts) were collected, including 73 males and 36 females. The age ranged from 11 to 70. The analyzed imaging features included location and internal density of the lesions, bone expansion, root resorption of adjacent teeth and types of the impacted teeth. The Chi square test was used to compare the gender of different lesions, and the Fisher's exact test was used to compare imaging features of lesions. When P<0.05, there was a significant difference among the three. Logistic regression analysis was performed to determine the imaging features that significantly contribute to correct imaging diagnosis. Corresponding P-values were calculated for all factors from multivariate models. Results: In the 23 cases of OKC, no special location was observed for the center of the lesion, heterogeneous high-density were seen in 21.7% of the cases, 56.5% of the cases had no significant bone expansion and the impacted teeth were not specially oriented. Among the 14 AB, 7 cases (7/14) were mainly located in the ramus of the mandible, and all cases (14/14) had buccal/lingual expansion of the jaw, 8 cases (8/14) presented root resorption of the adjacent teeth, and mesial impacted mandibular third molar were seen in 6 cases (6/14). Among the 72 DC, 88.9% (64/72) of the cases were mainly limited to the crown of the impacted third molar, 72.2% (52/72) of the cases had no obvious bone expansion, inverted impacted teeth were shown in 56.9% (41/72) of the cases. There was a significant difference among the three groups (χ2=7.30, P=0.026) in gender. AB and odontogenic cyst were more common in men than in women, while the incidence of OKC was roughly equal between men and women.There were significant differences in the location (P<0.001), internal density (P=0.001) of the lesions, bone expansion (P<0.001) and types of the impacted teeth (P<0.001), while no statistical difference was found for root resorption of adjacent teeth (P=0.153). Logistics regression analysis showed that the location of the lesion, internal density, bone expansion, root resorption of adjacent teeth and the types of impacted teeth had significant effects on the accurate diagnosis of the three kinds of lesions. Conclusions: Location, internal density, bone expansion and types of the impacted teeth played an important role in the correct imaging diagnosis. Further analysis indicates that when the classification of impacted teeth and the location of lesions are considered synchronously, DC can be differentiated from AB and OKC.


Goals of Treatment for Improved Survival in Primary Biliary Cholangitis: Treatment Target Should Be Bilirubin Within the Normal Range and Normalization of Alkaline Phosphatase.
In primary biliary cholangitis (PBC), bilirubin and alkaline phosphatase (ALP) are widely established as independent predictors of prognosis. Current treatment goals do not aim for normalization of surrogate markers because their association with survival has not been defined. The patient cohort from the GLOBAL PBC Study Group was used, comprising of long-term follow-up data from European and North American centers. Ursodeoxycholic acid-treated and untreated patients with bilirubin levels ≤1 × upper limit of normal (ULN) at baseline or 1 year were included. The association of normal ALP with transplant-free survival was assessed in a subgroup with ALP ≤1.67 × ULN at 1 year. Optimal thresholds of bilirubin and ALP to predict liver transplantation (LT) or death were evaluated. There were 2,281 patients included in the time zero cohort and 2,555 patients in the 1-year cohort. The bilirubin threshold with the highest ability to predict LT or death at 1 year was 0.6 × ULN (hazard ratio 2.12, 95% CI 1.69-2.66, P < 0.001). The 10-year survival rates of patients with bilirubin ≤0.6 × ULN and >0.6 × ULN were 91.3% and 79.2%, respectively (P < 0.001). The risk for LT or death was stable below the bilirubin levels of 0.6 × ULN, yet increased beyond this threshold. Ursodeoxycholic acid-induced reduction in bilirubin below this threshold was associated with an 11% improvement in 10-year survival. Furthermore, ALP normalization was optimal, with 10-year survival rates of 93.2% in patients with ALP ≤ 1 × ULN and 86.1% in those with ALP 1.0-1.67 × ULN. Attaining bilirubin levels ≤0.6 × ULN or normal ALP are associated with the lowest risk for LT or death in patients with PBC. This has important implications for treatment targets.


Indications of intrinsic chemical and structural inhomogeneity in lightly doped La1-xSrxMnO3.
X-ray absorption fine structure measurements of the Sr and La K edges of the solid solution La(1-x)SrxMnO3 reveal a consistent deviation from a random distribution of Sr at the La/Sr sites for x less than or similar to 0.3. Local structural disorder on the cation sublattice in the low-x samples is also observed to differ in the vicinity of the La-rich and Sr-rich clusters. The local clustering and structural disorder establish an intrinsic chemical as well as structural inhomogeneity on the nanometer scale, which may provide a mechanism for the nucleation of magnetoelectronic phase separation.


A web-based comprehensive head and neck cancer patient education and support needs program: Usability testing.
Background: With increasing accessibility of the World Wide Web, patients are using it to obtain patient education materials (PEM). With this in mind, our group (surgeons, radiation oncologists, medical oncologists, nursing, allied health professionals and academic researchers) developed a comprehensive information resource for patients with head and neck cancer (HNC), the Head and Neck Cancer Australia, formerly Beyond Five website. The aim of this study was to determine patient usability of the Head and Neck Cancer Australia website. Methods: Usability testing (Cognitive walkthrough & Think-Aloud) in 18 patients treated for HNC was undertaken at a Cancer centre (anonymous for reviewers). Results: The tasks rated easiest by patients were finding information on psychological well-being (mean time spent: 66 s, range: 10-565), health and well-being effecting quality of life (mean time spent: 36 s, range 9-117) and carer information (mean time spent: 10 s, range 3-35). Patients indicated the website contained a lot of information, covers most topics, was a trusted source of information and a springboard to other information. Conclusions: The Head and Neck Cancer Australia website provides a wide range of information and support in multiple formats available to HNC patients. Further refinements in design, navigation and website instructions are needed to allow effective patient interaction.


Predictors of neurocognitive outcomes on antiretroviral therapy after cryptococcal meningitis: a prospective cohort study.
Cryptococcal meningitis is the most common cause of adult meningitis in Africa, yet neurocognitive outcomes are unknown. We investigated the incidence and predictors of neurologic impairment among cryptococcal survivors. HIV-infected, antiretroviral-naive Ugandans with cryptococcal meningitis underwent standardized neuropsychological testing at 1, 3, 6, and 12 months. A quantitative neurocognitive performance z-score (QNPZ) was calculated based on population z-scores from HIV-negative Ugandans (n = 100). Comparison was made with an HIV-infected, non-meningitis cohort (n = 110). Among 78 cryptococcal meningitis survivors with median CD4 count of 13 cells/μL (interquartile range: 6-44), decreased global cognitive function occurred through 12 months compared with the HIV-infected, non-cryptococcosis cohort (QNPZ-6 at 12 months, P = 0.036). Tests of performance in eight cognitive domains was impaired 1 month after cryptococcal diagnosis; however, cryptococcal meningitis survivors improved their global neurocognitive function over 12 months with residual impairment (mean z-scores < -1), only in domains of motor speed, gross motor and executive function at 12 months. There was no evidence that neurocognitive outcome was associated with initial demographics, HIV parameters, or meningitis severity. Paradoxically, persons with sterile CSF cultures after 14 days of induction amphotericin therapy had worse neurocognitive outcomes than those still culture-positive at 14 days (P = 0.002). Cryptococcal meningitis survivors have significant short-term neurocognitive impairment with marked improvement over the first 12 months. Few characteristics related to severity of cryptococcosis, including Cryptococcus burden, were associated with neurocognitive outcome.


Logistics of large scale commercial IVF embryo production.
The use of IVF in agriculture is growing worldwide. This can be explained by the development of better IVF media and techniques, development of sexed semen and the recent introduction of bovine genomics on farms. Being able to perform IVF on a large scale, with multiple on-farm experts to perform ovum pick-up and IVF laboratories capable of handling large volumes in a consistent and sustainable way, remains a huge challenge. To be successful, there has to be a partnership between veterinarians on farms, embryologists in the laboratory and animal owners. Farmers must understand the limits of what IVF can or cannot do under different conditions; veterinarians must manage expectations of farmers once strategies have been developed regarding potential donors; and embryologists must maintain fluent communication with both groups to make sure that objectives are met within predetermined budgets. The logistics of such operations can be very overwhelming, but the return can be considerable if done right. The present mini review describes how such operations can become a reality, with an emphasis on the different aspects that must be considered by all parties.


Effect of growing CNTs onto bamboo charcoals on adsorption of copper ions in aqueous solution.
One kind of novel hierarchical carbon nanotubes/bamboo charcoal (CNTs/BC) was prepared by CVD growth of CNTs on low-cost bamboo charcoal (BC). The obtained CNTs/BC composites were characterized by SEM and TEM observations. Adsorption of copper ions by CNTs/BC in aqueous solution was investigated. The adsorbed copper species were analyzed by X-ray photoelectron spectroscopy (XPS). The results showed that the CNTs/BC composites exhibited higher adsorption capacities toward aqueous copper ions than the pristine BCs and commercial activated bamboo charcoals (ABCs) with a specific surface area of over 1000 m(2) g(-1). The adsorption capacity increases with nanotube growth time. Moreover, nitric acid treatment was used for the oxidation of the carbon surface. The surface functional groups of carbon samples were analyzed by Fourier transform infrared spectroscopy (FT-IR), Boehm's titration method, and zeta potential analysis. It was found that nitric acid treatment for CNTs/BC produced more oxygen-containing functional groups, leading to a higher copper ion adsorption capability than conventional carbon adsorbents under the same treatment condition.


Antibacterial Composite Film-Based Triboelectric Nanogenerator for Harvesting Walking Energy.
As a green and eco-friendly technology, triboelectric nanogenerator (TENG) can harvest energy from human motion to generate electricity, so TENGs have been widely applied in wearable electronic devices to replace traditional batteries. However, the surface of these TENGs is easily contaminated and breeds bacteria, which is a threat to human health. Here, we report an antibacterial composite film-based triboelectric nanogenerator (ACF-TENG) that uses Ag-exchanged zeolite (Ag-zeolite) and polypropylene (PP) composite film as the triboelectric layer. Adding a small amount of Ag-zeolite with excellent antibacterial properties can increase the dielectric permittivity and improve the surface charge density of composite films, which enhances the output performance of the ACF-TENG. The open-circuit voltage (VOC), short-circuit current (ISC), and transferred charge (QTr) of the ACF-TENG are about 193.3, 225.4, and 233.3% of those of a pure PP film-based TENG, respectively. Because of the silver in the Ag-zeolite, the ACF-TENG can effectively kill Escherichia coli and fungi. When used in insoles, the ACF-TENG can resist the athlete's foot fungus effectively and work as a power source to light up light-emitting diodes and charge capacitors. The ACF-TENG has wide application prospects in self-powered medical and healthcare electronics.


Targeted designed variants of alpha-2-macroglobulin (A2M) attenuate cartilage degeneration in a rat model of osteoarthritis induced by anterior cruciate ligament transection.
The study was performed to evaluate whether targeted alpha-2-macroglobulin (A2M) variants have a similar or enhanced function at wild-type (wt)-A2M to attenuate cartilage degeneration in vivo. In and ex-vivo experiment, bovine cartilage explants (BCE) were incubated with TNF-α and IL-1β with or without wt-A2M or A2M variants. Cartilage catabolism was measured in culture supernatant by sulfated glycosaminoglycan (sGAG). In an in-vivo experiment, 2-month-old male Wistar rats (n = 77) were randomly divided into seven groups and treated with different doses of A2M or its variants by intra-articular injection at 24 hours and day 14 after anterior cruciate ligament transection (ACLT), receiving (1) ACLT/PBS; (2) ACLT/wt-A2M (0.153 mg); (3) ACLT/CYT-108 A2M (0.153 mg); (4) ACLT/CYT-108 A2M (0.077 mg); (5) ACLT/CYT-98 A2M (0.153 mg); (6) ACLT/CYT-98 A2M (0.077 mg); or (7) sham/PBS. The joints and synovial lavage were collected 8 weeks after surgery. Fluorescence molecular tomography was used to monitor inflammation in vivo using probes ProSense and MMPSense at 24 hours, and weeks 2, 4, and 6 after surgery. The cartilage damage was quantified using Osteoarthritis Research Society International score and matrix metalloproteinase (MMP)-3, -13, collagen (Col) X, Col 2, Runx2, and aggrecan (Acan) were detected by immunohistochemical analysis (IHC), ELISA, and RT-PCR. A2M variants inhibited catabolism in the BCE model by up to 200% compared with wt-A2M. ProSense and MMPSense were dramatically increased in all groups after surgery. Supplemental A2M or its variants reduced ProSense and MMPSense compared with the PBS treatment. Less cartilage damage, lower MMP-13 and Col 2 degraded product, and stronger Col 2 synthesis were detected in animals treated with A2M or its variants compared with PBS-treated animals. A2M and its variants enhanced Col 2 and Acan synthesis, and suppressed MMP-3, MMP-13, Runx2, and Col X production. A2M-108 variant demonstrated less cartilage damage compared with wt-A2M and A2M-98 variant. The targeted variants of A2M have a chondroprotective effect similar to wt-A2M. However, A2M-108 variant has enhanced function to attenuate cartilage degeneration compared with wt-A2M.


Physical and psychosocial correlates of severe fatigue in rheumatoid arthritis.
Fatigue is a frequently experienced and patient-relevant complaint in RA. Disease activity, anaemia and pain are regarded as disease-related factors that may lead to fatigue in RA. However, psychosocial factors may also play a role in maintaining severe fatigue. The objectives of this study were to determine the prevalence of severe fatigue in RA patients, to study patient perceptions of fatigue and to determine which disease-related factors and psychosocial factors are independently associated with fatigue severity. For this study consecutive RA outpatients were enrolled (n = 228). The patients filled out questionnaires regarding fatigue using the Checklist Individual Strength (CIS), including psychosocial factors, pain and disability. The clinical data that were collected included ESR, CRP, haemoglobin level and 28-joint disease activity score (DAS-28). Chunk-wise backward linear regression was used for analysis. Severe fatigue (CIS > or = 35) was experienced by 42% of the RA patients, and they perceived their fatigue as frustrating or exhausting. The severely fatigued RA patients scored worse on all measured psychosocial items, compared with patients without severe fatigue. Pain severity, role functioning, depressive mood, self-efficacy on fatigue, worrying, helplessness and non-restorative sleep were the factors most strongly associated with fatigue level. A considerable proportion of RA patients had severe fatigue, with fatigue levels similar to chronic fatigue syndrome. Fatigue in RA was related to pain and functioning, not inflammation, as disease-related factors and to several psychosocial factors including coping and cognitions concerning fatigue.


Evaluation of GeneXpert MTB/RIF for detecting Mycobacterium tuberculosis in a hospital in China.
Objective To evaluate the performance of GeneXpert MTB/RIF in diagnosing pulmonary tuberculosis (TB) in China. Methods This cross-sectional study included sputum specimens of 240 suspected TB cases. Specimens were examined by light microscopy for the presence of acid-fast bacilli, which were cultured by the BACTEC MGIT 960 (M960) system and detected by the GeneXpert MTB/RIF assay. The positive rate, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and average turnaround time of methods were evaluated. Results The positive rate was 36.6% (87/238) for the GeneXpert MTB/RIF assay and 34.0% (81/238) by M960 culture, with no significant difference between methods (χ2 = 0.33, p > 0.05). According to culture results, sensitivity of the GeneXpert MTB/RIF assay was 84.0% (68/81), specificity was 87.8% (129/147), the PPV was 78.2% (68/87), and the NPV was 87.2% (129/148). The agreement for results between Gene Xpert MTB/RIF and the M960 system was 82.8% and the Kappa value was 0.73. Conclusion The GeneXpert MTB/RIF assay is a simple, rapid, and accurate test for detecting Mycobacterium tuberculosis in sputum specimens.


[Association and interaction of peroxisome proliferator-activated receptor α with low high-density lipoprotein hyperlipidemia and with peroxisome proliferator-activated receptor γ].
To investigate the association of ten single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors (α, δ, γ) with low high-density lipoprotein-cholesterol (HDL-C) hyperlipidemia and the additional role of a gene-gene interactions among the 10 SNPs. Participants were recruited under the framework of the PMMJS (Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province) cohort populations survey, in the urban community of Jiangsu province, China. 820 subjects (579 normal HDL-C, 241 low HDL-C) were randomly selected, with one of them related to each other. Ten SNPs (rs135539, rs4253778, rs1800206, rs2016520, rs9794, rs10865710, rs1805192, rs709158, rs3856806, rs4684847) were selected from the HapMap database, which covered PPARα, PPARδ and PPARγ. Logistic regression model was used to examine the association between ten SNPs in the PPARs and low HDL-C. Odds ratios (OR) and 95% confident interval (95%CI) were calculated. Interactions were explored by using the method of Generalized Multifactor Dimensionality Reduction (GMDR). After adjusting the factors as age, sex, smoking status, occupational physical activity, high-fat diet as well as low-fiber diet, both rs135539 and rs1800206 were significantly associated with the incidence of low HDL-C, with the OR (95% CI) values as 1.46 (1.07 - 1.99) and 0.62 (0.42 - 0.90). No statistically significant difference was found between other SNPs and the occurrence of low HDL-C. Data from GMDR analysis showed significant gene-gene interaction among rs135539, rs4253778 of PPARα and rs10865710, rs3856806, rs709158 and rs4684847 of PPAR γ (P = 0.0107). PPARα rs135539 was associated with the occurrence of low HDL-C, and had interacted with rs4253778, rs10865710, rs3856806, rs709158 and rs4684847.


Longitudinal study of microbial diversity and seasonality in the Mexico City metropolitan area water supply system.
In the Mexico City metropolitan area (MCMA), 70% of the water for 18 million inhabitants is derived from the Basin of Mexico regional aquifer. To provide an overview of the quality of the groundwater, a longitudinal study was conducted, in which 30 sites were randomly selected from 1,575 registered extraction wells. Samples were taken before and after chlorine disinfection during both the rainy and dry seasons (2000-2001). Microbiological parameters (total coliforms, fecal coliforms, streptococci, and Vibrio spp.), the presence of Helicobacter pylori, and physicochemical parameters, including the amount of trihalomethanes (THMs), were determined. Although microorganisms and inorganic and organic compounds were evident, they did not exceed current permissible limits. Chlorine levels were low, and the bacterial counts were not affected by chlorine disinfection. Eighty-four bacterial species from nine genera normally associated with fecal contamination were identified in water samples. H. pylori was detected in at least 10% of the studied samples. About 40% of the samples surpassed the THM concentration allowed by Mexican and U.S. regulations, with levels of chloroform being high. The quality of the water distributed to the MCMA varied between the rainy and dry seasons, with higher levels of pH, nitrates, chloroform, bromodichloromethane, total organic carbon, and fecal streptococci during the dry season. This study showed that the groundwater distribution system is susceptible to contamination and that there is a need for a strict, year-round disinfection strategy to ensure adequate drinking-water quality. This situation in one of the world's megacities may reflect what is happening in large urban centers in developing countries which rely on a groundwater supply.


Characterization and localization of drug resistance determinants in multidrug-resistant, integron-carrying Salmonella enterica serotype Typhimurium strains.
The genetic background of the antimicrobial resistance of 10 selected multiresistant Salmonella serotype Typhimurium (S. Typhimurium) strains (including the emerging monophasic variant [4,5,12:i:- ]) was investigated. All strains shared class 1 integrons (with seven types of variable regions) and belonged to different lineages (L1-L6) according to their phage types, DNA polymorphisms by XbaI-pulsed-field gel electrophoresis (PFGE), integrons, and/or resistance patterns. The strains were screened for the presence and localization (chromosomal or plasmid) of 32 DNA sequences representing integron-, Tn21-like transposon-, resistance-, and virulence-plasmid genes. Strains belonging to lineage L1 (definitive phage type DT104) carried the 90-kb Salmonella virulence plasmid together with the complete or partial chromosomally located Salmonella Genomic Island 1 (SGI1). All strains belonging to the other five lineages carried their resistance determinants on various resistance plasmids. Two of these strains showed complex plasmid profiles, which included a 95 kb virulence plasmid together with two or four resistance plasmids. Two strains carried a resistance plasmid that lacked the virulence-plasmid-encoding sequences. The remaining two strains carried two different hybrid virulence-resistance plasmids. Twenty-three of the DNA sequences could be assigned to distinct XbaI genomic restriction patterns (PFGE profiles). In this way, the influence of the resistance and virulence plasmids on the PFGE profiles was determined, and several groups of resistance genes could be identified. The data obtained represent a useful epidemiological tool for tracing the emergence and distribution of multiresistant S. Typhimurium worldwide.


A new animal model for human colon cancer metastasis.
An animal model for human colon cancer metastasis is described in which spontaneously metastasizing colonic tumors are formed after injection of human colon cancer cells into the cecal wall of young athymic nude mice. Lymphatic and vascular invasion were demonstrated histologically after injection of both well- and poorly-differentiated cell lines, and metastases were found in a pattern similar to that of naturally occurring human colonic cancer. In contrast, little or no visceral organ involvement could be demonstrated after s.c. injection. Cells with increased liver-metastasizing potential were obtained by serial selection in this system. These cells had an enhanced ability to penetrate a reconstituted basement membrane in the presence of partially purified liver extract when compared to lung or brain extracts in a modified Boyden chamber assay. These results demonstrate the ability of human epithelial tumor cells to metastasize reproducibly in an animal model system, which may be useful for studying many aspects of the pathogenesis of cancer metastasis. In addition, it is suggested that local invasion by colon cancer cells may be influenced in part by tissue-specific factors.


Hierarchical organization and catalytic activity of high-surface-area mesoporous ceria microspheres prepared via hydrothermal routes.
Mesoporous Ce(OH)CO(3) microspheres with flowerlike three-dimensional (3D) hierarchical structure were successfully synthesized via different hydrothermal systems, including glucose/acrylic acid, fructose/acrylic acid, glucose/propanoic acid, and glucose/n-butylamine systems. After Ce(OH)CO(3) microspheres were calcined, mesoporous CeO(2) microspheres with the same flowerlike morphology as Ce(OH)CO(3) microspheres were obtained. Especially, flowerlike CeO(2) microspheres prepared via the glucose/acrylic acid system are composed of many interconnected mesoporous petal-like nanosheets with thicknesses of 40-60 nm and have high surface area (211 m(2) g(-1)), large pore volume (0.32 cm(3) g(-1)), and narrow pore size distribution ( approximately 3.8 nm in diameter). A possible formation mechanism of Ce(OH)CO(3) microspheres is proposed: the large N-containing organic compounds in situ produced in the above reaction systems played a crucial role in controlling the assembly of Ce(OH)CO(3) building blocks into the flowerlike Ce(OH)CO(3) microspheres. For trichloroethylene combustion, flowerlike CeO(2) microspheres were found to exhibit much higher catalytic activity than general CeO(2) prepared with the conventional methods and the T(10%) and T(90%) were as low as 100 and 204 degrees C, respectively.


Acquired aplastic anemia associated with trisomy eight converting into acute myeloid leukemia.
Aplastic anemia (AA) is nowadays considered to be a clonal disorder arising from a defective hematopoietic stem cell developing after a generalized insult to bone marrow. Immunosuppressive treatment (IST) of AA causes suppression of the target dominant population of haematopoietic cells allowing the defective non targeted clones to expand. This may give rise to acute leukemia. Cytogenetic studies for chromosomal aberrations such as trisomy and monosomy may help in detecting such conversions. We present a case of acquired AA in a 60-year-old male presenting with pancytopenia and hypoplastic marrow treated with antithymocyte globulin, converting into myelodysplastic syndrome and later on acute promyelocytic leukemia after being in remission for 4 years. The patient was found to have trisomy 8 on fluorescence in situ hybridization and karyotyping.


Preparation and topotactical oxidation of ScVO3 with bixbyte structure: a low-temperature route to stabilize the new defect fluorite ScVO(3.5) metastable phase.
ScVO3 has been prepared by controlled reduction of a ScVO4 precursor under an H2/N2 flow at 1250 degrees C. The crystal structure of this material has been studied at room temperature by Rietveld refinement of high-resolution neutron powder diffraction (NPD) data. Sc3+ and V3+ are distributed at random over the metal sites of a C-M2O3 bixbyite-type structure, space group Ia3, a = 9.6182(1) Angstroms. The thermal analysis of ScVO3 in an air flow shows two subsequent oxidation processes, with a final reversal to ScVO4 above 600 degrees C. An intermediate phase of composition ScVO(3.5), containing V4+ cations, can be isolated by isothermal annealing at 350 degrees C in air. This metastable phase has been identified by X-ray diffraction (XRD) as a fluorite-type oxide (space group Fm3m, a = 4.947(2) Angstroms), also showing a random distribution of Sc and V cations over the metal positions. The Rietveld refinement of the ScVO(3.5) structure from powder XRD data in a fluorite structural model yields abnormally high thermal factors for the oxygen atoms, suggesting oxygen mobility in this metastable material.


Low-carbohydrate diet and oxidative stress in diabetic and nondiabetic rats.
Hyperglycemia of diabetes has been implicated in increased tissue oxidative stress, with consequent development of secondary complications. Thus, stabilizing glucose levels near normal levels is of utmost importance. Because diet influences glycemic control, this study investigated whether a low-carbohydrate (5.5%) diet confers beneficial effects on the oxidative status of the heart, kidney, and liver in diabetes. Male and female normal and diabetic rats were fed standard chow (63% carbohydrates) or low-carbohydrate diet for 30 days. Elevated glucose, HbA(1c), and alanine and aspartate aminotransferases in diabetic animals were reduced or normalized by the low-carbohydrate diet. While diabetes increased cardiac activities of glutathione peroxidase and catalase, low-carbohydrate diet normalized cardiac glutathione peroxidase activity in diabetic animals, and reduced catalase activity in females. Diabetic rats fed low-carbohydrate diet had altered activities of renal glutathione reductase and superoxide dismutase, but increased renal glutathione peroxidase activity in diabetic animals was not corrected by the test diet. In the liver, diabetes was associated with a decrease in catalase activity and glutathione levels and an increase in glutathione peroxidase and gamma-glutamyltranspeptidase activities. Decreased hepatic glutathione peroxidase activity and lipid peroxidation were noted in diet-treated diabetic rats. Overall, the low-carbohydrate diet helped stabilize hyperglycemia and did not produce overtly negative effects in tissues of normal or diabetic rats.


[Epidemiological aspects of cytomegalovirus infection in babies aged under one].
Sreening data obtained on babies aged under one and selected by random (1,910 children) or target (2,658 children) choice for cytomegalovirus (CMV) infection during the period of 10 years (1992-2001) were compared with mortality rate. The methods used were enzyme immunoassay, immunofluorescence and polymerase chain reaction. The babies were divided as follows: newborn infants (group I), babies aged 1-3 months (group II), 4-6 months (group III) and 7-12 months (group IV). Specific clinical features of CMV infection in newborn infants were studied on 69 cases (37--with CMV monoinfection and 32--with mixed infection). The serological screening revealed a 2.1-fold growth of the infection rate among randomly selected newborn infants during the 10 year period. Positive correlation between the infection rate among children of this age group and the neonatal mortality rate was established. High risk factors of CMV infection were revealed as well as increased infection rate and frequency of clinical cases with the prevailing neurological pathology in group III. Early diagnosis, the exclusion of mixed infections and early adequate therapy were shown to play a decisive role in the outcome of the disease. The algorithm of epidemiological surveillance and the regional program of prophylaxis were worked out.


Group versus Individual Acupuncture (AP) for Cancer Pain: A Randomized Noninferiority Trial.
A service delivery model using group acupuncture (AP) may be more cost-effective than individual AP in general, but there is little evidence to assess whether group AP is a comparable treatment in terms of efficacy to standard individual AP. The study aimed to compare the group to individual delivery of 6-week AP among cancer patients with pain. The study design was a randomized noninferiority trial of the individual (gold standard treatment) vs. group AP for cancer pain. The primary outcome was pain interference and severity, measured through the Brief Pain Inventory (BPI). Secondary outcomes included measures of mood, sleep, fatigue, and social support. Changes in outcomes from pre- to postintervention were examined using linear mixed effects modeling and noninferiority was inferred using a noninferiority margin, a difference of change between the two arms and 95% CIs. Pain interference was tested with a noninferiority margin of 1 on the BPI, while pain severity and secondary outcomes were compared using conventional statistical methods. The trial included 74 participants randomly allocated to group (35) or individual (39) AP. The noninferiority hypothesis was supported for pain interference [Ө - 1, Δ 1.03, 95% CI: 0.15-2.20] and severity [Ө - 0.81, Δ 0.52, 95% CI:.33-1.38] as well as for mood [Ө - 7.52, Δ 9.86, 95% CI: 0.85-18.86], sleep [Ө - 1.65, Δ 2.60, 95% CI: 0.33-4.88], fatigue [Ө 8.54, Δ - 15.57, 95% CI: 25.60-5.54], and social support [Ө.26, Δ - 0.15, 95% CI: - 0.42-0.13], meaning that group AP was not inferior to individual AP treatment. Both arms evidenced statistically significant improvements across all symptoms before and after the intervention. Effect sizes for the group vs. individual AP on outcomes of pain, sleep, mood, and social support ranged from small to very large and were consistently larger in the group condition. The total average cost-per-person for group AP ($221.25) was almost half that of individual AP ($420). This is the first study to examine the noninferiority of group AP with the gold standard individual AP. Group AP was noninferior to individual AP for treating cancer pain and was superior in many health outcomes. Group AP is more cost-effective for alleviating cancer pain and should be considered for implementation trials.


Cardiotrophin-1 administration prevents the renal toxicity of iodinated contrast media in rats.
Although generally reversible, contrast media toxicity often induces contrast-induced nephropathy (CIN), which is associated with longer hospitalization time, the need for dialysis, and higher incidence of later cardiovascular events and higher mortality. Preventive cotreatments have been assayed at the preclinical and clinical levels, but recent meta-analysis has not demonstrated a beneficial effect, which supports the search for new nephroprotective strategies. We have assessed if the administration of cardiotrophin-1 (CT-1), an endogenous cytokine with protective properties on the heart and liver, might mitigate CIN in rats. We have developed a model of CIN induced by the administration of the contrast medium gastrographin iv (3.7mg/kg) in rats sensitized by previous administration of subnephrotoxic doses of gentamicin (50mg/kg/day, ip) for 6 days. The severity of CIN was assessed by the measurement of renal function; renal histological damage; urinary excretion of markers of tubular damage, including N-acetyl beta glucosaminidase (NAG), kidney injury molecule 1 (KIM-1), and plasminogen activator inhibitor 1; lipid peroxidation; and renal apoptosis. Treatment with CT-1 almost completely prevented the renal tissue damage, as evidenced by almost total prevention of tubular desepithelization and tubular obstruction, reduced caspase activation, and cell proliferation. Besides, CT-1 also prevented the increment in renal tissue levels of renal tissue injury markers NAG, KIM-1, and neutrophil gelatinase-associated lipocalin. Oxidative stress, a hallmark of CIN, was also prevented by CT-1. Administration of CT-1 also prevented the derangement in kidney function induced by CIN. Renal hemodynamics, also impaired by the contrast medium, was normal in rats cotreated with CT-1. CT-1 administration significantly prevents the alterations in renal function and structure observed in a rat model of CIN.


Social and Contextual Constraints on Embodied Perception.
A number of papers have challenged research on physiological and psychological influences on perception by claiming to show that such findings can be explained by nonperceptual factors such as demand characteristics. Relatedly, calls for separating perception from judgment have been issued. However, such efforts fail to consider key processes known to shape judgment processes: people's inability to report accurately on their judgments, conversational dynamics of experimental research contexts, and misattribution and discounting processes. Indeed, the fact that initially observed effects of embodied influences disappear is predicted by an extensive amount of literature on judgments studied within social psychology. Thus, findings from such studies suggest that the initially presumed underlying processes are at work-namely, functional considerations that are informative in the context of preparing the body for action. In this article, I provide suggestions on how to conduct research on perception within the social constraints of experimental contexts.


Impact of parity on obesity: a cross-sectional study in Iranian women.
The aim of the present study was to analyze whether or not parity influenced the prevalence of obesity in both pre- and postmenopausal women. A cross-sectional study was conducted on characteristics of urban women regarding parity. A total of 1,620 women aged 45-63 years were selected using cluster sampling. A face-to-face household interview was conducted by trained, skillful personnel. A risk factor questionnaire was used to obtain information on reproductive history and sociodemographic factors. Statistical associations between parity and obesity using logistic regression were then investigated. The mean BMI was 29.1 ± 5.1, and 96.8% of the sample population were parous, with a median of 4 births. Of the total women enrolled, 216 (13.3%) had <3 parities, while 1,404 (86.7%) had ≥3 parities. The prevalence of obesity (BMI ≥30) was 38.3%, diagnosed at a mean age of 51.4 ± 5.2 years. After adjustment for a range of potential confounders (age, marital status, employment, education, smoking status, abortion history, savings situation and menopausal status), women with ≥3 parities were at higher risk of being obese (OR 1.74, 95% CI 1.24-2.45; p = 0.001). A positive association was observed between the number of parities and obesity. The findings of this study suggest that the BMI is associated with high parity in Babolian women. Health policymakers should work with health providers to develop appropriate postpartum weight loss interventions.


An update on long intergenic noncoding RNA p21: a regulatory molecule with various significant functions in cancer.
Long intergenic noncoding RNA p21 was mapped on the human chromosome 6p21.2. Accordingly, it was firstly described by promoting the p53-dependent apoptosis in the mouse. Also, it is a new lncRNA playing some vital roles in the cell cycle, apoptosis, cell proliferation, tumorigenesis, invasion, metastasis, and angiogenesis. In this regard, it was shown that, lincRNA-p21 regulates these biological processes involved in carcinogenesis through various signaling pathways including Notch signaling, JAK2/STAT3, and AKT/mTOR pathways. Another mechanism by that lincRNA-p21 can affect these processes is a cross-talk with different miRNAs. In vitro and in vivo studies revealed dysregulation of lincRNA-p21 in various human cancers. In addition, emerging evidence demonstrated that, lincRNA-p21 can be considered as a potential prognostic and therapeutic biomarker in cancers. Also, lincRNA-p21 enhances the response to radiotherapy for colorectal cancer. However, the molecular mechanisms of lincRNA-p21 in carcinogenesis have not been fully elucidated so far. So, this review summarizes the function of lincRNA-p21, as a tumor suppressor factor in different biological processes implicated in cancers.


[Recent Trends of Trace Element Studies in Clinical Medicine in Japan].
The deficiency or excess intake of trace elements, including zinc, copper, selenium and iodine, has often been reported. Zinc deficiency is often observed in infants fed breast milk with low zinc concentration, individuals administered chelating medicines, athletes and patients with diabetes mellitus, hepatic cirrhosis or nephrosis syndrome. Menkes disease is associated with severe copper deficiency, and there is no effective treatment. Deficiencies of selenium and iodine are observed in patients who receive special formulas of milk and enteral formula with low selenium and iodine concentrations, respectively. In contrast, neonatal transient hypothyroidism due to excess intake of iodine in pregnant women has also reported in Japan. It is expected that collaborative studies by researchers and clinicians will contribute to clarify the detail mechanism, diagnosis and treatment of these abnormalities.


Acute Ischemic Stroke in Children - Should We Thrombolyze?
Ischemic stroke is a major cause of acute neurological symptoms in children with significant long-term neurological sequelae. Unlike in the adult population, the clinical presentation of strokes in children may not be stereotyped. Hence, many other differential diagnostic possibilities might have to be considered in the emergency setting. Due to this heterogeneous presentation and the resultant clinical dilemma in the early detection, acute thrombolysis even now remains as a very rarely tried therapeutic option in children. Many case reports over these years have shown consistently good results of acute intravenous thrombolysis in children with tissue plasminogen activator (tPA) administered within the time frame. There are also some recent reports of endovascular interventions. However, unlike in the adult population, class 1 clinical studies and good Randomized controlled trials (RCT) are yet to emerge in children. The absence of age-appropriate safety and outcome data for the commonly used thrombolytic agents in children is another major roadblock for developing clinical guidelines and recommendations for this age group. The ambitious Thrombolysis in Pediatric Stroke (TIPS) trial had to be terminated prematurely due to poor patient enrolment. This review critically looks at the current status of the acute management of ischemic strokes in children with a specific emphasis on thrombolytic therapy. Until we have better evidence-based guidelines for this age group, it will be prudent to develop robust institutional pathways to provide this important intervention for all eligible children with acute strokes.


Epstein-Barr virus-induced haemophagocytic syndrome.
Haemophagocytic syndrome or haemophagocytic lymphohistiocytosis is a disorder of histiocytes that has sepsis-like features, combined with haemophagocytosis, cytopenias, hyperferritinaemia, hypercytokinaemia and splenomegaly. Diagnostic, therapeutic and prognostic guidelines are available for childhood (familial) haemophagocytic syndrome. The disorder is diagnosed less frequently among adults than children. We report a case of Epstein-Barr virus-induced haemophagocytic syndrome in a 23-year-old man, who responded to treatment with steroids and chemotherapy.


Mechanistic Basis for Epitope Proofreading in the Peptide-Loading Complex.
The peptide-loading complex plays a pivotal role in Ag processing and is thus central to the efficient immune recognition of virally and malignantly transformed cells. The underlying mechanism by which MHC class I (MHC I) molecules sample immunodominant peptide epitopes, however, remains poorly understood. In this article, we delineate the interaction between tapasin (Tsn) and MHC I molecules. We followed the process of peptide editing in real time after ultra-fast photoconversion to pseudoempty MHC I molecules. Tsn discriminates between MHC I loaded with optimal and MHC I bound to suboptimal cargo. This differential interaction is key to understanding the kinetics of epitope proofreading. To elucidate the underlying mechanism at the atomic level, we modeled the Tsn/MHC I complex using all-atom molecular dynamics simulations. We present a catalytic working cycle, in which Tsn binds to MHC I with suboptimal cargo and thereby adjusts the energy landscape in favor of MHC I complexes with immunodominant epitopes.


Testing a formal theory of perception is not easy: Comments on Yu, Todd & Petrov (2021) and Yu, Petrov & Todd (2021).
Yu, Todd, and Petrov (2021, Journal of Vision) and their follow-up study (Yu, Petrov, & Todd, 2021, i-Perception) aimed at evaluating the role of three-dimensional (3D) symmetry in binocular shape perception by comparing their experimental data to predictions they derived from our computational models. We point out in this note that their predictions were incorrect, so their studies can neither reject nor support our models of 3D shape perception. We explain (1) the role of the data and the constraints in solving ill-posed inverse problems, (2) the role of binocular depth-order, as opposed to binocular depth-intervals in shape perception, (3) the nature and the effect of 3D compactness as an a priori constraint, and (4) the implications of the separation of binocular disparity and stereoacuity in the two functional streams in the visual cortex.


An interesting case of an antihypertensive causing post-prostatectomy incontinence.
A 70-year-old man underwent a laparoscopic radical prostatectomy with preservation of bladder neck for T3aN0R0 prostate cancer in December 2009, (Gleason 4+3, negative surgical margin). His postoperative prostate-specific antigen rose from 0.01 to 0.05 ng/mL over 19 months. He had salvage radiotherapy in May 2012. Following radiotherapy, his urinary control worsened and he needed to wear up to four pads per day. He was being considered for an artificial urinary sphincter placement. He was also taking doxazosin for hypertension, which was discontinued. After stopping the doxazosin, his urinary control improved and he did not require any further intervention. Doctors should be aware of the effect of α-blockers on the internal sphincter and the risk of incontinence in patients post-prostate cancer treatment.


Dynamics of large-scale brain activity in normal arousal states and epileptic seizures.
Links between electroencephalograms (EEGs) and underlying aspects of neurophysiology and anatomy are poorly understood. Here a nonlinear continuum model of large-scale brain electrical activity is used to analyze arousal states and their stability and nonlinear dynamics for physiologically realistic parameters. A simple ordered arousal sequence in a reduced parameter space is inferred and found to be consistent with experimentally determined parameters of waking states. Instabilities arise at spectral peaks of the major clinically observed EEG rhythms-mainly slow wave, delta, theta, alpha, and sleep spindle-with each instability zone lying near its most common experimental precursor arousal states in the reduced space. Theta, alpha, and spindle instabilities evolve toward low-dimensional nonlinear limit cycles that correspond closely to EEGs of petit mal seizures for theta instability, and grand mal seizures for the other types. Nonlinear stimulus-induced entrainment and seizures are also seen, EEG spectra and potentials evoked by stimuli are reproduced, and numerous other points of experimental agreement are found. Inverse modeling enables physiological parameters underlying observed EEGs to be determined by a new, noninvasive route. This model thus provides a single, powerful framework for quantitative understanding of a wide variety of brain phenomena.


Nanofabricated adjustable multicontact devices on membranes.
Adjustable atomic size contacts realized by break junctions have become a standard tool during the last decade. Although nanofabricated break junctions may in principle be incorporated onto complex electronic circuits, a fundamental drawback of the standard break junction technique is its limitation to a single adjustable junction per device. We have fabricated single break junctions as well as devices containing two break junctions on a silicon membrane. The junctions are adjusted by positioning a fine tip via piezocontrol on the rear side of the membrane. We describe the fabrication process of the membranes and the devices and present results obtained on circuits made of gold and platinum. We show that the junctions can be addressed independently by a suitable choice of the tip position. Single-atom contacts, vacuum tunneling contacts as well as larger contacts can be stabilized.


Notes on Sigmund Freud's 'Analysis Terminable and Interminable'.
The author suggests that 'Analysis terminable and interminable' should be considered in the context of its particular background of political and scientific history as well as of Freud's personal biographical circumstances. It should not be considered only as a technical discussion. The author looks at Freud's own statements about the paper, together with those of contemporary (Fenichel) and later commentators.


Short-wavelength radiation pulses with time-varying orbital angular momentum from tailored relativistic electron beams.
In this Letter, we propose a novel, to the best of our knowledge, technique to generate short-wavelength radiation carrying time-varying orbital angular momentum (OAM) by tailoring relativistic beams in free-electron lasers. To manipulate the temporal properties of OAM beams, two time-delayed seed lasers with different OAM values are used to interact with the electron beam in the undulator. With this method, high-harmonic electron beam microbunching with a time-varying helical distribution can be tailored to match the time-varying instantaneous helical phase structure of the x ray beams. Theoretical and simulation results demonstrate that high-power x ray beams with time-varying OAM can be produced by the proposed technique, which opens new routes to scientific research in x ray science.


[The value of ultrasound diagnosis in blunt abdominal and thoracic injuries].
In a prospective study, real-time ultrasonography was applied as the initial imaging procedure in 103 consecutive patients with blunt abdominal or thoracic trauma. Additional peritoneal lavage was not performed. Pathological findings were present in 22 patients (21%). Sensitivity of the examination was 95.5%, with two false positive results, specificity was 97.5% with one false negative result. Lesions of intraabdominal or thoracic organs were demonstrated directly by ultrasonography in 14 patients. In the remaining patients free fluid was discovered in the abdominal cavity. Splenic and hepatic lesions occurred most frequently followed by hematothorax. Ultrasonography can be recommended as the initial imaging procedure, giving a high amount of information in the primary diagnosis of blunt abdominal thoracic trauma.


Strategies for engaging with future radiation protection professionals: a public outreach case study.
It is evident that there is a nuclear skills shortage within the UK, and logically it can be assumed that the shortfall extends to the radiation protection arena. Plans for nuclear new-build and the decommissioning of existing nuclear sites will require many more people with radiological knowledge and practical competencies. This converts to a nuclear industry requirement in the order of 1000 new recruits per year over at least the next ten years, mainly as new apprentices and graduates. At the same time, the strong demand for persons with radiation protection know-how in the non-nuclear and health care sectors is unlikely to diminish. The task of filling this skills gap is a significant one and it will require a determined effort from many UK stakeholders. The Society for Radiological Protection (SRP) has adopted a strategy in recent years to help address this skills gap. The aim is to engage the interest of secondary school students in the science of radiation and inspire them to follow a career in radiation protection. This paper presents the reasoning behind this strategy and, in an 'outreach case study', describes the establishment of the annual SRP Schools Event. This event is becoming an important addition to the national efforts aimed at increasing the numbers of skilled UK radiation protection professionals over the forthcoming decades.


Living markers for actin block myosin-dependent motility of plant organelles and auxin.
Expression-based techniques using recombinant actin-binding proteins (ABPs) have been developed as advantageous means of visualising actin filaments. As actin function is linked to the movement of cellular cargoes, and overexpression of ABPs may compete with endogenous cytoskeletal proteins, such as myosins, secondary effects on cellular motility might be observed during actin visualisation. Cytoplasmic streaming and auxin transport were chosen as examples of cargo movement and investigated in two Arabidopsis thaliana lines stably transformed with fluorescently labelled talin (GFP-mTn) or fimbrin (GFP-FABD2). In both lines, the maximal streaming velocity of organelles was reduced to 80% in hypocotyl epidermal cells, where actin was broadly equally labelled by both ABPs. In contrast, observations of streaming and actin organisation during treatments with cytochalasin D (CD) suggested GFP-mTn-labelled actin to remain more stable. Furthermore, basipetal auxin transport was undisturbed in the GFP-FABD2 line but reduced by GFP-mTn. Remarkably, treatments with CD and 2,3-butanedione monoxime, which immobilizes myosin by impairing its ATPase, produced not only failures in organelle movement but also in basipetal auxin transport in the wild-type. These observations suggest that myosin is involved in processes of auxin translocation. In parallel, reduced motility in transgenic plants may be explained by a disturbed acto-myosin interplay, if overexpressed ABPs block the processive movement of myosin along actin filaments. This report shows that the use of live markers for actin visualisation may affect motility of cellular compounds and underlines the general need for critical investigation of actin-related processes in wild-type as well as transgenic plants prior to further interpretation.


Proteomic and metallomic strategies for understanding the mode of action of anticancer metallodrugs.
Since the discovery of cisplatin and its introduction in the clinics, metal compounds have been intensely investigated in view of their possible application in cancer therapy. In this frame, a deeper understanding of their mode of action, still rather obscure, might turn crucial for the design and the obtainment of new and better anticancer agents. Due to the extreme complexity of the biological systems, it is now widely accepted that innovative and information-rich methods are absolutely needed to afford such a goal. Recently, both proteomic and metallomic strategies were successfully implemented for the elucidation of specific mechanistic features of anticancer metallodrugs within an innovative "Systems Biology" perspective. Particular attention was paid to the following issues: i) proteomic studies of the molecular basis of platinum resistance; ii) proteomic analysis of cellular responses to cytotoxic metallodrugs; iii) metallomic studies of the transformation and fate of metallodrugs in cellular systems. Notably, those pioneering studies, that are reviewed here, allowed a significant progress in the understanding of the molecular mechanisms of metal based drugs at the cellular level. A further extension of those studies and a closer integration of proteomic and metallomic strategies and technologies might realistically lead to rapid and significant advancements in the mechanistic knowledge of anticancer metallodrugs.


Experience with titanium devices for rib fixation and coverage of chest wall defects.
To describe our experience with two new titanium-based devices for chest wall reconstruction and stabilization. A retrospective analysis of 18 consecutive patients (multiple rib fractures n = 9, iatrogenic rib fracture n = 2, lung herniation n = 2, chest wall tumour n = 5) who underwent surgery for rib fractures or chest wall tumours requiring chest wall resection and reconstruction between October 2010 and March 2012 was conducted. Chest wall defects and rib fractures were fixed with titanium clips and bars or titanium plates and screws through a posterolateral thoracotomy. There were 12 males, and the median age was 61 years. There were no postoperative deaths. The only postoperative complication observed was a pleural effusion requiring drainage in one patient who had titanium clips for the fixation of multiple traumatic rib fractures. Median length of stay of the drain and median length of hospital stay were 3 days (range 1-6) and 4 days (range 2-42 days), respectively. The average follow-up period of operatively managed patients was 6 months, (range 2-14 months). Two cases of hardware failure occurred in two patients treated for a lung hernia with large chest wall defects involving the anterior costal margin with either devices. Titanium devices (clips and bars; screws and plates) are effective and safe for repair of rib fractures and large chest wall defect reconstruction with minimal complications and good long-term results.


Congestive heart failure. Current and future strategies to decrease mortality.
The prevalence of and mortality from congestive heart failure increase with advancing age. The most important prognostic indicators are exercise tolerance and left ventricular function. Currently, drug treatment consists of digitalis, diuretics, and ACe inhibitors. Future management may include medications to modulate the extracardiac mechanisms of decompensation and newer surgical techniques to assist or replace the failing heart.


Therapies in Parkinson's disease.
This review examines currently available therapeutic strategies for Parkinson's disease, emphasizing evidence-based data as well as a patient-centered approach to the treatment of motor and nonmotor symptoms. Although clinical trials of disease-modifying approaches have been thus far disappointing, steady advances are being made in the symptomatic treatment of Parkinson's disease. In this review, we focus on recent studies with monoamine oxidase type B inhibitors (selegiline and rasagiline), coenzyme Q10, creatine, and exercise in early Parkinson's disease. We also discuss the relative merits and disadvantages of delaying the initiation of levodopa therapy, the role of dopamine agonists, particularly ropinirole and pramipexole, and management of motor and behavioral complications, such as fluctuations, dyskinesias and impulse-control disorders. Novel formulations and delivery approaches for conventional and new drugs are also discussed. Finally, we review recent studies of surgical treatments of Parkinson's disease, such as deep brain stimulation. Numerous clinical trials have provided evidence that health-related quality of life can be substantially improved with early diagnosis and institution of exercise and other physical measures, appropriate timing of dopaminergic therapy, and strategies to delay and treat levodopa-related motor complications and nonmotor Parkinson's disease-related symptoms.


Comparison of fracture loads of CAD/CAM and conventionally fabricated temporary fixed dental prostheses after different aging regimens.
This study evaluated the fracture loads of different threeunit fixed dental prostheses (FDPs) for temporary restorations. In total, three CAD/CAM materials (VITA CADTemp [CT], Telio CAD [TC], and ZENO ProFix [ZP]) and two chairside materials (Protemp 4 [PT], and Dentalon Plus [DP]) were used for the fabrication of the FDPs. Sixteen FDPs were fabricated from each material in an anatomical shape and stored in 0.9% NaCl solution at 37°C for 14 days. Thereafter, one half of the specimens from each group (n = 8) were additionally mechanically and thermally loaded (240,000 chewing cycles, 50 N, 5°/55°C, 2,100 thermal cycles). Fracture loads were measured and data analyzed using two- and one-way ANOVA, followed by Scheffé's post hoc test. ZP showed the highest mean fracture loads, regardless of the aging regime. Significantly lowest values were identified for DP and TC within the non-thermal loaded group, and for PT and CT within the thermal loaded group. No negative impact of aging regimes could be observed.


Computerized colour vision testing.
There are many advantages to the computerization of colour vision tests. However, previous computerized colour vision tests have involved equipment and methods not commonly used in clinical practice. We created computer emulations of the City University Colour Vision Test (CUT), Ishihara plates and American Optical Hardy-Rand-Rittler (AO-HRR) plates using a commonly available 24-bit colour Macintosh computer. Our colour monitor was calibrated to standard display white (D65), and colour plates were imaged with a colour scanner. The computerized colour images were compared with the standard test plates in a sample of 21 subjects with normal colour vision, 10 patients with congenital red-green defect and 1 patient with an acquired mixed colour defect. The computer images of the three tests correlated well with their conventional counterparts on kappa statistic analysis (p < 0.001), for both the colour normal and colour defective groups. We conclude that our computer emulations of the CUT, Ishihara and AO-HRR tests screen subjects with normal colour vision with high specificity and delineate congenital colour defects with a sensitivity comparable to that of their conventional counterparts.


An established routine method for differential staining of epoxy-embedded tissue sections.
A method is described for staining semithin sections of epoxy-embedded cells and tissues. PAS-positive structures are specifically demonstrated by a red staining providing a vivid contrast to the other tissue components differentially stained in shades of blue, using methylene blue/azure II. Typical staining conditions for 1 to 2 micron thick Epon sections include 30 min oxidation with 5% periodic acid at 50 degrees C, 30 min incubation with Shiff's reagent at 50 degrees C, 20 min counter-staining with 0.5% methylene blue/0.5% azure II in 0.5% aqueous borax solution at room temperature. For 10 years, this method has provided excellent differential staining with a variety of tissues. Stained sections showed no signs of fading during this period of time. Therefore, this procedure is recommended as a simple method of staining semithin sections both for tissue orientation in electron microscopy and for brillant representation of cells and tissues, required for microphotography in color or black-and-white.


Lesions to the medial preoptic nucleus differentially affect singing and nest box-directed behaviors within and outside of the breeding season in European starlings (Sturnus vulgaris).
Little is known about how the brain regulates context-appropriate communication. European starlings produce song in various social contexts. During the breeding season, males with nest sites sing high levels of sexually motivated song in response to a female. Outside of this context, song rates are not affected by female presence. The medial preoptic nucleus (POM) regulates male sexual behavior, and studies in songbirds implicate the POM in sexually motivated song. Recent data suggest that the role of the POM might extend to song produced in other contexts as well. To examine this possibility, effects of bilateral electrolytic lesions of the POM on singing and other behaviors in adult male starlings within sexually relevant and nonsexual contexts were studied. Lesions to the POM exclusively reduced song and nest box-directed behaviors within highly sexually relevant contexts. Unexpectedly, POM lesions increased song in a nonsexual context, suggesting an inhibitory role for the POM in this context. These data suggest that the POM interacts with the song control system so that song occurs in an appropriate social context in response to appropriate stimuli.


Multianalytical Method Validation for Qualitative and Quantitative Analysis of Solvents of Abuse in Oral Fluid by HS-GC/MS.
The use of oral fluid as a biological matrix to monitor the use of drugs of abuse is a global trend because it presents several advantages and good correlation to the blood level. Thus, the present work aimed to develop and validate an analytical method for quantification and detection of solvents used as inhalants of abuse in oral fluid (OF), using Quantisal™ as collector device by headspace and gas chromatography coupled with a mass detector (HS-GC/MS). Chromatographic separation was performed with a ZB-BAC1 column and the total time of analysis was 11.8 min. The method showed good linearity (correlation coefficient higher than 0.99 for all solvents). The limits of detection ranged from 0.05 to 5 mg/L, while the lower limits of quantification ranged from 2.5 to 12.5 mg/L. Accuracy, precision, matrix effect, and residual effect presented satisfactory results, meeting the criteria accepted for the validation of bioanalytical methods. The method showed good selectivity considering that, for solvents coeluting at the same retention time, resolution was performed by the mass detector. The method developed proved to be adequate when applied in OF samples from users of drugs and may be used to monitor the abuse of inhalants in routine forensic analyses.


Ionic Liquid-Based Polymer Electrolytes via Surfactant-Assisted Polymerization at the Plasma-Liquid Interface.
We first report an innovative method, which we refer to as interfacial liquid plasma polymerization, to chemically cross-link ionic liquids (ILs). By this method, a series of all-solid state, free-standing polymer electrolytes is successfully fabricated where ILs are used as building blocks and ethylene oxide-based surfactants are employed as an assisted-cross-linking agent. The thickness of the films is controlled by the plasma exposure time or the ratio of surfactant to ILs. The chemical structure and properties of the polymer electrolyte are characterized by scanning electron microscopy (SEM), Fourier transformation infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) spectroscopy, X-ray photoelectron spectroscopy (XPS), differential scanning calorimetry (DSC), and electrochemical impedance spectroscopy (EIS). Importantly, the underlying polymerization mechanism of the cross-linked IL-based polymer electrolyte is studied to show that fluoroborate or halide anions of ILs together with the aid of a small amount of surfactants having ethylene oxide groups are necessary to form cross-linked network structures of the polymer electrolyte. The ionic conductivity of the obtained polymer electrolyte is 2.28 × 10(-3) S·cm(-1), which is a relatively high value for solid polymer electrolytes synthesized at room temperature. This study can serve as a cornerstone for developing all-solid state polymer electrolytes with promising properties for next-generation electrochemical devices.


Chemical synthesis of proanthocyanidins in vitro and their reactions in aging wines.
Proanthocyanidins are present in many fruits and plant products like grapes and wine, and contribute to their taste and health benefits. In the past decades of years, substantial progresses has been achieved in the identification of composition and structure of proanthocyanidins, but the debate concerning the existence of an enzymatic or nonenzymatic mechanism for proanthocyanidin condensation still goes on. Substantial attention has been paid to elucidating the potential mechanism of formation by means of biomimetic and chemical synthesis in vitro. The present paper aims at summarizing the research status on chemical synthesis of proanthocyanidins, including non-enzymatic synthesis of proanthocyanidin precursors, chemical synthesis of proanthocyanidins with direct condensation of flavanols and stereoselective synthesis of proanthocyanidins. Proanthocyanidin-involved reactions in aging wines are also reviewed such as direct and indirect reactions among proanthocyanidins, flavanols and anthocyanins. Topics for future research in this field are also put forward in this paper.


Effects of massage therapy and occlusal splint therapy on electromyographic activity and the intensity of signs and symptoms in individuals with temporomandibular disorder and sleep bruxism: a randomized clinical trial.
Temporomandibular disorder (TDM) is the most common source of orofacial pain of a non-dental origin. Sleep bruxism is characterized by clenching and/or grinding the teeth during sleep and is involved in the perpetuation of TMD. The aim of the present study was to investigate the effects of massage therapy, conventional occlusal splint therapy and silicone occlusal splint therapy on electromyographic activity in the masseter and anterior temporal muscles and the intensity of signs and symptoms in individuals with severe TMD and sleep bruxism. Sixty individuals with severe TMD and sleep bruxism were randomly distributed into four treatment groups: 1) massage group, 2) conventional occlusal splint group, 3) massage + conventional occlusal splint group and 4) silicone occlusal splint group. Block randomization was employed and sealed opaque envelopes were used to conceal the allocation. Groups 2, 3 and 4 wore an occlusal splint for four weeks. Groups 1 and 3 received three weekly massage sessions for four weeks. All groups were evaluated before and after treatment through electromyographic analysis of the masseter and anterior temporal muscles and the Fonseca Patient History Index. The Wilcoxon test was used to compare the effects of the different treatments and repeated-measures ANOVA was used to determine the intensity of TMD. The inter-group analysis of variance revealed no statistically significant differences in median frequency among the groups prior to treatment. In the intra-group analysis, no statistically significant differences were found between pre-treatment and post-treatment evaluations in any of the groups. Group 3 demonstrated a greater improvement in the intensity of TMD in comparison to the other groups. Massage therapy and the use of an occlusal splint had no significant influence on electromyographic activity of the masseter or anterior temporal muscles. However, the combination of therapies led to a reduction in the intensity of signs and symptoms among individuals with severe TMD and sleep bruxism. This study is registered in August, 2014 in the ClinicalTrials.gov (NCT01874041).


Paeoniflorin regulates GALNT2-ANGPTL3-LPL pathway to attenuate dyslipidemia in mice.
N-acetylgalactosaminyltransferase 2-Angiopoietin-like protein 3-lipoprotein lipase (GALNT2-ANGPTL3-LPL) pathway may be a useful pharmacologic objective for dyslipidemia. The present study was conducted to test the effect of paeoniflorin, a monoterpene Glycoside, on dyslipidemia in mice. Fifty mice were randomly divided into five groups (n = 10): three groups of apolipoprotein E-null (ApoE-/-) mice treated with paeoniflorin (10 or 20 or 30 mg/kg/day), untreated ApoE-/- mice group, and C57BL/6J control group. Six weeks after treatment, expression of hepatic ANGPTL3, hepatic GALNT2 and adipose tissue LPL, lipid levels in the liver and blood were quantified. Treatment with paeoniflorin (10 or 20 or 30 mg/kg) obviously down-regulated expression of ANGPTL3 and up-regulated expressions of GALNT2 and LPL concomitantly with elevated plasma high-density lipoprotein cholesterol level, reduced plasma concentrations of low-density lipoprotein cholesterol, total cholesterol, triglyceride, malonaldehyde, and 8-isoprostane. The present results suggest that paeoniflorin regulates GALNT2-ANGPTL3-LPL pathway to attenuate dyslipidemia in mice.


Hypogastric artery ligation for intractable pelvic hemorrhage.
To assess the outcomes of bilateral hypogastric (internal iliac) ligation performed to control intractable pelvic hemorrhage and avoid hysterectomy. A review of indications and outcomes for 117 cases of bilateral hypogastric artery ligation over 15 years (1990-2004). Apart from a slight lesion to the hypogastric vein, no complications were observed. Hemorrhage was effectively controlled in all 37 obstetric cases. In 13 of these cases, the uterus was preserved even when there was cervical pregnancy, placenta previa, placental abruption, uterine atony, and uterine rupture, and 4 women were delivered of mature infants. Hemorrhage was effectively controlled in 41 of 80 gynecologic cases. Prophylactic reduction of pelvic blood flow was the indication for the procedure in 39 cases, 5 of whom involving Jehovah's Witnesses adverse to blood transfusion. The uterus was preserved in only a few of the 41 controlled cases, but one woman (so far) was delivered of a mature infant. Hypogastric artery ligation was found to be indicated if (1) life-threatening pelvic hemorrhage could not be controlled by conservative methods; (2) prophylactic reduction of pelvic blood flow was needed to prevent anticipated hemorrhage; and (3) preservation of reproductive function was desired. The procedure was found to be safe and usually effective and should be taught during obstetric and gynecologic training.


Maternal Adverse Childhood Experiences and Child Behavior Problems: A Systematic Review.
A growing body of research has examined the role of maternal adverse childhood experiences (ACEs) on child behavior problems. To summarize the literature examining the association between maternal ACEs and child behavior problems via a systematic review. Electronic searches were conducted in Medline, PsycINFO, and Embase (1998-June 2020). Reference lists were reviewed. In total, 3048 records were screened. Studies were included if an association between maternal ACEs and child externalizing (eg, aggression) and/or internalizing (eg, anxiety) problems was reported. In total, 139 full-text articles were reviewed for inclusion. Data from 16 studies met full inclusion criteria. Studies were synthesized by child externalizing and internalizing outcomes. Maternal ACEs were significantly associated with child externalizing problems across all studies (number of studies synthesized per outcome [k] = 11). Significant associations were also found for inattention, hyperactivity, and impulsivity (k = 4), and aggression (k = 2). For internalizing problems (k = 11), significant associations were identified across 8 studies and nonsignificant associations were reported for 3 studies. Maternal ACEs were consistently associated with child anxiety and depression (k = 5). However, inconsistent findings were reported for somatization (k = 2). Results are limited to mother-child dyads and questionnaire measures of behavior problems in primarily North American countries. Mothers' ACEs demonstrated largely consistent associations with children's behavior problems. Future research is needed to determine if specific types of maternal ACEs (eg, household dysfunction) are more strongly associated with child behavior problems.


The Bt gene cry2Aa2 driven by a tissue specific ST-LS1 promoter from potato effectively controls Heliothis virescens.
Expression of the Cry2Aa2 protein was targeted specifically to the green tissues of transgenic tobacco Nicotiana tabacum cv. Xanthi plants. This deployment was achieved by using the promoter region of the gene encoding the Solanum tuberosum leaf and stem specific (ST-LS1) protein. The accumulated levels of toxin in the leaves were found to be effective in achieving 100% mortality of Heliothis virescens larvae. The levels of Cry2Aa2 expression in the leaves of these transgenic plants were up to 0.21% of the total soluble proteins. Bioassays with R1 transgenic plants indicated the inheritance of cry2Aa2 in the progeny plants. Tissue-specific expression of the Bt toxin in transgenic plants may help in controlling the potential occurrence of insect resistance by limiting the amount of toxin to only predated tissues. The results reported here validate the use of the ST-LS1 gene promoter for a targeted expression of Bt toxins in green tissues of plants.


Genetic counseling for hereditary cancer: A primer for NPs.
Many patients have concerns regarding their family's cancer history and may be appropriate for referral to genetic counseling. This article examines indications for referral for genetic counseling for hereditary cancer, the process of genetic counseling and testing, and ways for NPs to collaborate with genetics providers.


Translational Aspects of the Multidisciplinary Study of Metacognition.
Metacognition, self-awareness, self-knowledge, and insight each refer to the process by which individuals reflect upon and appraise their own abilities. Self-awareness is a complex, dynamic, and multifactorial construct that spans various domains such as motor, sensory, functional and cognitive abilities. Various disciplines including cognitive psychology, neuropsychology, psychiatry and neurology have attempted to understand healthy and pathologic self-awareness of cognition in particular. Although intrinsically connected, the study of healthy and pathologic states of self-awareness have remained relatively discrete from one another. Indeed, different disciplines examining self-awareness of cognition have operationalized and measured awareness through distinct theoretical frameworks. More recently, however, various authors have attempted to bridge constructs across disciplines in an effort to develop a unitary theoretical model for self-awareness of cognitive abilities. In this commentary, we summarize the study of self-awareness of cognitive abilities across various disciplines, highlighting translational aspects between them.


Prediction of calving date in beef cows by real-time ultrasonic scanning.
Three hundred pregnant beef cows between 35 and 125 days of gestation were scanned ultrasonically and their calving dates were predicted from measurements of fetal parts. The mean difference between the actual and predicted calving dates was 0.9 day with a standard deviation of 9.0 days. The accuracy and precision of the prediction of calving date were sufficient to be of benefit in the management of cows in late pregnancy and at calving.


Fatal toxic epidermal necrolysis related to lamotrigine administration.
Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are severe life-threatening dermatologic conditions. To date, eight cases of TEN and one of SJS related to lamotrigine administration have been reported in the literature. Most patients were also taking concomitant valproic acid. It was hypothesized that valproic acid may interfere with glucuronidation of lamotrigine, leading to increased serum lamotrigine levels, or perhaps alter the drug's metabolism, resulting in accumulation of a toxic intermediate metabolite. Ultimately, this may possibly predispose a patient to increased dermatologic reactions, including TEN. A 54-year-old man developed TEN 4 weeks after beginning lamotrigine for complex partial seizures related to a glioblastoma multiforme brain tumor. The patient had also been taking concomitant allopurinol and captopril for more than 4 years with no complications, and valproic acid 3 months before the cutaneous event. Despite aggressive intensive care management, the patient died 17 days from the onset of symptoms due to multiple organ failure. Administration of lamotrigine, especially in combination with valproic acid, may lead to the development of TEN.


Feasibility of salvage robotic partial nephrectomy after ablative treatment failure (UroCCR-62 study).
Ablative therapies (AT) are increasingly being offered to patients with kidney tumors. In cases of failure or local relapse, salvage surgery may be required. Such procedures often require an open approach, are difficult and have received little attention in the literature. We aim to evaluate the feasibility of salvage robot-assisted partial nephrectomy (sRAPN) after AT. We conducted a monocentric retrospective study of all patients who benefited from sRAPN. Clinical data were collected prospectively after written consent in the French UroCCR database. Between 2013 and 2020, 724 RAPN were performed in our center; of these, 11 patients underwent salvage RAPN and four (36.4%) had an imperative indication for a solitary kidney. The median patient age was 54 (49-72) years, median preoperative glomerular filtration rate (GFR) was 65.5 (42.9-88.4) mL/min/1.73 m2, and median tumor diameter was 34 (16-38) mm. Extensive perinephric fibrosis was present in 90.9% of cases. Postoperative complications occurred in 36.4% of patients, including major complications in 18.2%. The median GFR at three months (56.8 [45.9-63.9] mL/min/1.73 m2) and at last follow-up (52.1 [45.85-68.3] mL/min/1.73 m2) were not significantly different to the preoperative GFR (P=0.51 and P=0.65, respectively). During follow-up (median 12 months), three patients (all with Von Hippel Lindau disease) developed a recurrence, but none were on the sRAPN site. Our series of sRAPN following AT failure confirms that such surgery is feasible with good functional and oncological results. However, these surgeries remain difficult, are associated with significant complication rate and should be performed in expert centers.


Quench dynamics of edge states in a finite extended Su-Schrieffer-Heeger system.
We examine the quench dynamics of an extended Su-Schrieffer-Heeger (SSH) model involving long-range hopping that can hold multiple topological phases. Using winding number diagrams to characterize the system's topological phases geometrically, it is shown that there can be multiple winding number transition paths for a quench between two topological phases. The dependence of the quench dynamics is studied in terms of the survival probability of the fermionic edge modes and postquench transport. For two quench paths between two topological regimes with the same initial and final topological phase, the survival probability of edge states is shown to be strongly dependent on the winding number transition path. This dependence is explained using energy band diagrams corresponding to the paths. Following this, the effect of the winding number transition path on transport is investigated. We find that the velocities of maximum transport channels varied along the winding number transition path. This variation depends on the path we choose, i.e., it increases or decreases depending upon the path. An analysis of the coefficient maps, energy spectrum, and spatial structure of the edge states of the final quench Hamiltonian provides an understanding of the path-dependent velocity variation phenomenon.


The responses in renal nerves to stimulation of atrial receptors, carotid sinus baroreceptors and carotid chemoreceptors.
The reflex reduction in activity in renal sympathetic nerves in response to distension of small balloons in the pulmonary vein-atrial junctions was studied in dogs anaesthetized with chloralose; the carotid sinuses were isolated and perfused with blood. In the first group of dogs, the response to distension of the balloons was studied at different levels of carotid sinus pressure. In thirteen preparations of renal nerves in eight dogs the response was not significantly influenced when the mean carotid sinus pressure was changed from 9.5 kPa to 17.5 kPa, despite marked changes in control frequencies of activity in the nerves. In the second group of dogs, the response to distension of the balloons was studied when the carotid sinuses were perfused alternately with arterial and venous blood. In six preparations of renal nerves in five dogs the response was not significantly influenced when the blood perfusing the carotid sinuses was changed, despite marked changes in control frequencies of activity in the nerves. In a third group of dogs, the reflex reduction in activity in renal nerves in response to a step increase in pressure in one carotid sinus was examined at different levels of pressure in the contralateral carotid sinus. In six preparations of renal nerves in five dogs the response to an increase in pressure in one carotid sinus was significantly reduced when the mean pressure in the contralateral sinus was changed from 8.7 kPa to 17.1 kPa. It is concluded that there is no interaction between the projections of atrial receptors and carotid sinus baroreceptors or carotid chemoreceptors in their convergence on the same efferent renal neurones.