Comparison of prophylactic antibiotics for endonasal transsphenoidal surgery using a national inpatient database in Japan.
The choice of prophylactic antibiotics for use in endonasal transsphenoidal surgery (ETSS) lacks universal standards. This study aimed to investigate the effectiveness of cefazolin, ampicillin and third-generation cephalosporins for preventing postoperative meningitis and secondary outcomes (in-hospital death and the combination of pneumonia and urinary tract infection) in patients who have undergone ETSS. The study used data from the Diagnosis Procedure Combination database in Japan. Data from 10 688 patients who underwent ETSS between April 2016 and March 2021 were included. Matching weight analysis based on propensity scores was conducted to compare the outcomes of patients receiving cefazolin, ampicillin or third-generation cephalosporins as prophylactic antibiotics. Of the 10 688 patients, 9013, 102 and 1573 received cefazolin, ampicillin and third-generation cephalosporins, respectively. The incidence of postoperative meningitis did not significantly differ between the cefazolin group and the ampicillin group (OR, 1.02; 95% CI, 0.14-7.43) or third-generation cephalosporins group (OR, 0.81; 95% CI, 0.10-6.44). Similarly, in-hospital death and the composite incidence of pneumonia and urinary tract infection did not differ between the cefazolin group and the ampicillin or third-generation cephalosporins group. Cefazolin, ampicillin and third-generation cephalosporins as perioperative prophylactic antibiotics for ETSS do not differ significantly in terms of preventing meningitis.


Vascular Loop of the Anterior Inferior Cerebellar Artery (AICA) as a Cause of Sensorineural Hearing Loss (SNHL): A Case Report.
Sensorineural hearing loss (SNHL) is one of the most common causes of hearing loss worldwide. Although highly prevalent, many patients often present with SNHL of unknown cause. Related to SNHL is tinnitus, which often presents with SNHL and can have debilitating effects on patients. The idiopathic nature of SNHL and tinnitus often makes treatment difficult, however, a relatively new etiology has been suggested as a cause of SNHL and tinnitus -- vascular loops within the internal auditory canal (IAC). This report presents the case of a 36-year-old male with bilateral SNHL and tinnitus treated with oral steroids. The patient reported subjective improvement of hearing loss and tinnitus, and the audiogram demonstrated hearing improvement, except in higher frequencies. After initial treatment, MRI revealed a vascular loop of the anterior inferior cerebral artery (AICA) in the right IAC, in contact with the vestibulocochlear nerve. Thus, this case report seeks to present a conservative strategy for SNHL and tinnitus in the presence of a vascular loop of the AICA. As a controversial cause of SNHL and tinnitus, there is no standard of treatment for AICA loops of the IAC which are often treated surgically. This case highlights the importance of an initial conservative prior to surgical intervention. Thus, we seek to contribute to the growing body of literature by further elucidating the relationship between SNHL, tinnitus, and vascular loops and discussing potential pathophysiological mechanisms to guide optimal management strategies.


Glutamine synthetase and alanine transaminase expression are decreased in livers of aged vs. young beef cows and GS can be upregulated by 17β-estradiol implants.
Aged beef cows (≥ 8 yr of age) produce calves with lower birth and weaning weights. In mammals, aging is associated with reduced hepatic expression of glutamine synthetase (GS) and alanine transaminase (ALT), thus impaired hepatic Gln-Glu cycle function. To determine if the relative protein content of GS, ALT, aspartate transaminase (AST), glutamate transporters (EAAC1, GLT-1), and their regulating protein (GTRAP3-18) differed in biopsied liver tissue of (a) aged vs. young (3 to 4 yr old) nonlactating, nongestating Angus cows (Exp. 1 and 2) and (b) aged mixed-breed cows with and without COMPUDOSE (17β-estradiol) ear implants (Exp. 3), Western blot analyses were performed. In Exp. 1, 12 young (3.62 ± 0.01 yr) and 13 aged (10.08 ± 0.42 yr) cows grazed the same mixed forage for 42 d (August-October). In Exp. 2, 12 young (3.36 ± 0.01 yr) and 12 aged (10.38 ± 0.47 yr) cows were individually fed (1.03% of BW) a corn-silage-based diet to maintain BW for 20 d. For both Exp. 1 and 2, the effect of cow age was assessed by ANOVA using the MIXED procedure of SAS. Cow BW did not change ( ≥ 0.17). Hepatic ALT (78% and 61%) and GS (52% and 71%) protein content (Exp. 1 and 2, respectively) was decreased ( ≤ 0.01), whereas GTRAP3-18 (an inhibitor of EAAC1 activity) increased ( ≤ 0.01; 170% and 136%) and AST, GLT-1, and EAAC1 contents did not differ ( ≥ 0.17) in aged vs. young cows. In Exp. 2, free concentrations (nmol/g) of Glu, Ala, Gln, Arg, and Orn in liver homogenates were determined. Aged cows tended to have less ( = 0.10) free Gln (15.0%) than young cows, whereas other AA concentrations did not differ ( 0.26). In Exp. 3, 14 aged (> 10 yr) cows were randomly allotted ( = 7) to sham or COMPUDOSE (25.7 mg of 17β-estradiol) implant treatment (TRT), and had ad libitum access to alfalfa hay for 28 d. Blood and liver biopsies were collected 14 and 28 d after implant treatment. Treatment, time after implant (DAY), and TRT × DAY effects were assessed by ANOVA using the MIXED procedure of SAS. Cow BW was not affected ( ≥ 0.96). Implant increased ( ≤ 0.02) total plasma estradiol by 220% (5.07 vs. 1.58 pg/mL) and GS protein by 300%, whereas the relative content of other proteins was not altered ( ≥ 0.16). We conclude that hepatic expression of ALT and GS are reduced in aged vs. young cows, and administration of 17β-estradiol to aged cows increases plasma estradiol and hepatic GS, but not that of other proteins that support hepatic Glu metabolism.


Biofilm formation by Haemophilus influenzae isolated from adeno-tonsil tissue samples, and its role in recurrent adenotonsillitis.
Aim of the present study was to identify bacterial biofilms in tissue samples obtained from paediatric patients undergoing surgical treatment, for chronic and recurrent adeno-tonsillitis, not responding to repeated cycles of selective medical antibiotic and anti-inflammatory treatment and to assay the ability of Haemophilus influenzae strains, most frequently identified in the culture examinations, to grow as biofilm in vitro. Overall, 25 surgical specimens (15 adenoids, 10 tonsils) were examined from the upper respiratory tract, from 15 paediatric patients (mean age 6 years). All patients were affected by recurrent and/or chronic adenoiditis and adenotonsillitis unresponsive to selective antibiotic and anti-inflammatory therapy. Tissues were cultured using conventional methods and subjected to scanning electron microscopy for detection of biofilm. Haemophilus influenzae strains, were cultured on 96-sterile well polystyrene microtitre plates (CELLSTAR-greiner bio-one) and stained with 1% crystal violet to quantify biofilm production. Bacterial cocci attached to the tissue surface and organized in colonies, with a morphology consistent with bacterial coccoid biofilms, were observed in all adenoid (15/15) and in 6/10 tonsil samples. Haemophilus influenzae isolates from 12/25 (48%) of our tissue samples scored a percent transmittance (%T(bloc)) > 50, displaying a high capacity to form biofilms (level 4). In conclusion identification of bacterial biofilms in chronic and/or recurrent paediatric upper airway inflammatory processes and the capacity to produce biofilm in vitro, demonstrated by Haemophilus influenzae (the most frequently identified bacteria in our samples), could be related to the aetiopathogenic role of biofilms in chronic inflammatory mucosal reactions and to the resistance of these infections to selective antibiotic therapy.


Pathological demography of native patients in a nephrology center in China.
To analysis the pathological demography in Chinese patients undergoing renal biopsy from our nephrology center. Between January 1979 and October 2000 in Jinling Hospital, Nanjing, China, 10,002 attempts of percutaneous renal were performed in patients with renal disease from 33 provinces of China. The pathological classifications were made according to the WHO criteria of 1982 for renal pathology or the modified WHO criteria of 1995 by a panel of pathologists and nephrologists during routine clinical-pathological rounds. The pathological demography between those specimens collected from 1979 - 1989 and those from 1990 - 1999 was compared. The mean age of the 10,002 subjects undergoing renal biopsy was 31.4 +/- 13.0 years (ranging from 1 to 78 years), with a male to female ratio of 1.3:1; for the 592 renal transplant recipients, the mean age was 37.5 +/- 9.1 years (ranging from 16 to 66 years), with a male to female ratio of 2.36:1. Primary glomerular diseases (PGD) accounted for 71% of the total patients undergoing renal biopsies, secondary glomerular nephritis (SGN) 23%, tubular-interstitial diseases 3.2%, unclassified renal diseases 1.3%, hereditary and congenital renal diseases 1.0%, end stage renal diseases 0.96%, and recently realized or rare renal diseases 0.15%. IgA nephropathy (IgAN) was the most frequent pathological pattern (40%) of PGD, followed by mesangial proliferative lesion (MsPL) (30%), membranous nephropathy (MN) (10%), and focal segmental glomerulosclerosis (FSGS) (6%). Lupus nephritis (LN) was the most pathology common seen (74%) in SGN. During the 22 years of the study period, there was a steady increase in patients with SGN discovered during pathological evaluation of renal disorders. A rise in prevalence was found in IgA nephropathy, MN (both P < 0.001), crescentic glomerulonephritis (P < 0.0001), anti-GBM disease, and hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura related renal damages (both P < 0.001). There was a decrease in endocapillary proliferative glomerulonephritis (P < 0.001) and IgM nephropathy (IgMN) (P < 0.01) from 1990 - 1999 as compared to 1979 - 1989. Infrequent renal pathological entities were also diagnosed in this group, including Niemann Pick disease, Fabry's disease, POEMS syndrome, and lipoprotein glomerulonephropathy. This is the largest series of renal biopsy data in China, and therefore may reflect the demographic picture of renal diseases in this country. Changes in prevalence of renal pathological entities were reflected in this group of patients over the last 22 years. In primary glomerular diseases, IgA nephropathy is still the most frequently observed pathological pattern. In SGN, LN appeared the most often. Increased prevalence was found in anti-GBM nephritis and HUS/TTP.


Use of intraoperative magnetic resonance imaging in tailored temporal lobe surgeries for epilepsy.
We investigated whether intraoperative magnetic resonance imaging (MRI) was able to assess immediately the extent of a tailored temporal lobe resection for epilepsy in comparison to delayed postoperative MRI. The recently proposed concept of an individually tailored procedure, preserving tissue not involved in seizures, leads to a variety of differently shaped resections. For intraoperative imaging we used a Magnetom Open 0.2 Tesla scanner. Fifty-eight patients undergoing temporal lobe resections for pharmacoresistant epilepsy were investigated. Half of these were nonlesional. All patients had delayed postoperative follow-up scans, which were compared with the intraoperative, postresection images. In 49 (84%) of 58 cases, intraoperative MRI depicted the resection cavity identical to delayed postoperative studies. Complete resection of the visible lesion was primarily proved in 23 of the 29 cases. In two patients with lesions and in one nonlesional case, the resection was extended after intraoperative imaging, thus increasing the rate of total resections in gliomas from 73 to 87%. In four patients, an extension into eloquent areas did not allow complete removal. In the nonlesional cases (n = 29), the extent of tailored temporal resections also could be exactly documented intraoperatively. Intraoperative MRI allowed a reliable evaluation of the localization and extent of resection in epilepsy surgery within the operative procedure. Furthermore, it provided the possibility of an image-based correction of an initially incomplete resection, particularly in lesional cases. In the majority of patients, the intraoperative images would have been able to replace delayed postoperative MRI. However, in 16%, there were postoperative changes in the resection volume.


Network Structure of Physical, Cognitive, and Emotional Symptoms at Preseason Baseline in Student Athletes with Attention-Deficit/ Hyperactivity Disorder.
Preexisting attention-deficit/hyperactivity disorder (ADHD) may be a risk factor for worse outcome following sport-related concussion. We used a statistical and psychometric approach known as network analysis to examine the architecture of physical, cognitive, and emotional symptoms at preseason baseline among student athletes with ADHD. A cohort of 44,527 adolescent student athletes completed baseline preseason testing with ImPACT® between 2009 and 2015. A subsample of athletes reporting a diagnosis of ADHD and at least one symptom were included in this study (N = 3,074; 14-18 years old, 32.7% girls). All participants completed the 22-item Post-Concussion Symptom Scale at preseason baseline. Student athletes reported high frequencies of difficulty concentrating (boys/girls = 50.7%/59.4%), emotional symptoms (nervousness: boys/girls = 30.2%/51.0%; irritability: boys/girls = 23.6%/34.8%; sadness: boys/girls = 21.4%/39.7%), sleep/arousal-related symptoms (trouble falling asleep: boys/girls = 39.5%/49.4%; sleeping less than usual: boys/girls = 36.2%/43.4%; and fatigue: boys/girls = 29.8%/36.4%), and headaches (boys/girls = 27.6%/39.0%) during preseason baseline testing. The most central symptoms included dizziness, which was related to multiple somatic symptoms, and increased emotionality, which was related to a cluster of emotional symptoms. Girls reported symptoms at a greater frequency than boys, and there was evidence for variance in the global strength of the symptom network across gender, but not specific intersymptom relationships. In the absence of injury, symptoms that commonly occur after concussion interact and potentially reinforce each other among student athletes with ADHD at preseason. Symptoms common in ADHD (i.e., difficulty concentrating) are not necessarily the most central within the symptom network. These findings may inform more precise interventions for athletes with ADHD and prolonged recovery following concussion.


Context matters: criticism and accommodation by close others associated with treatment attitudes in those with anxiety.
Many people with anxiety do not seek therapy due to negative views of treatment. Although close others (e.g. romantic partners, family members, close friends) are highly involved in treatment decisions, the role of specific relational behaviours in treatment ambivalence has yet to be studied. This study examines the relationship between social predictors (perceived criticism and accommodation of anxiety symptoms by close others) and treatment ambivalence. Community members who met diagnostic criteria for an anxiety-related disorder (N = 65) and students who showed high levels of anxiety (N = 307) completed an online study. They were asked to imagine they were considering starting cognitive behavioural therapy (CBT) for their anxiety and complete a measure of treatment ambivalence accordingly. They then completed measures of perceived criticism and accommodation by close others. Linear regression was used to examine the predictive value of these variables while controlling for sample type (clinical/analogue) and therapy experience. Greater reactivity to criticism from close others and greater accommodation of anxiety symptoms by close others were associated with greater treatment ambivalence in those with anxiety. These predictors remained significant even when controlling for therapy history and sample type. When it comes to treatment attitudes, relational context matters. Clients demonstrating ambivalence about starting therapy may benefit from discussion about the impact of their social environment on ambivalence.


Lifespan-increasing drug nordihydroguaiaretic acid inhibits p300 and activates autophagy.
Aging is characterized by the progressive loss of physiological function in all organisms. Remarkably, the aging process can be modulated by environmental modifications, including diet and small molecules. The natural compound nordihydroguaiaretic acid (NDGA) robustly increases lifespan in flies and mice, but its mechanism of action remains unclear. Here, we report that NDGA is an inhibitor of the epigenetic regulator p300. We find that NDGA inhibits p300 acetyltransferase activity in vitro and suppresses acetylation of a key p300 target in histones (i.e., H3K27) in cells. We use the cellular thermal shift assay to uniquely demonstrate NDGA binding to p300 in cells. Finally, in agreement with recent findings indicating that p300 is a potent blocker of autophagy, we show that NDGA treatment induces autophagy. These findings identify p300 as a target of NDGA and provide mechanistic insight into its role in longevity.


Construction of infectious cDNA clones for dengue 2 virus: strain 16681 and its attenuated vaccine derivative, strain PDK-53.
We identified nine nucleotide differences between the genomes of dengue-2 (DEN-2) 16681 virus and its vaccine derivative, strain PDK-53. These included a C-to-T (16681-to-PDK-53) mutation at nucleotide position 57 of the 5'-untranslated region, three silent mutations, and substitutions prM-29 Asp to Val, NS1-53 Gly to Asp, NS2A-181 Leu to Phe, NS3-250 Glu to Val, and NS4A-75 Gly to Ala. Unpassaged PDK-53 vaccine contained two genetic variants as a result of partial mutation at NS3-250. We constructed infectious cDNA clones for 16681 virus and each of the two PDK-53 variants. DEN-2 16681 clone-derived viruses were identical to the 16681 virus in plaque size and replication in LLC-MK2 cells, replication in C6/36 cells, E and prM epitopes, and neurovirulence for suckling mice. PDK-53 virus and both clone-derived PDK-53 variants were attenuated in mice. However, the variant containing NS3-250-Glu was less temperature sensitive and replicated better in C6/36 cells than did PDK-53 virus. The variant containing NS3-250-Val had smaller, more diffuse plaques, decreased replication, and increased temperature sensitivity in LLC-MK2 cells relative to PDK-53 virus. Both PDK-53 virus and the NS3-250-Val variant replicated poorly in C6/36 cells relative to 16681 virus. Unpassaged PDK-53 vaccine virus and the virus passaged once in LLC-MK2 cells had genomes of identical sequence, including the mixed NS3-250-Glu/Val locus. Although the NS3-250-Val mutation clearly affected virus replication in vitro, it was not a major determinant of attenuation for PDK-53 virus in suckling mice.


A Big Five-Based Multimethod Social and Emotional Skills Assessment: The Mosaic™ by ACT® Social Emotional Learning Assessment.
A focus on implementing social and emotional (SE) learning into curricula continues to gain popularity in K-12 educational contexts at the policy and practitioner levels. As it continues to be elevated in educational discourse, it becomes increasingly clear that it is important to have reliable, validated measures of students' SE skills. Here we argue that framework and design are additional important considerations for the development and selection of SE skill assessments. We report the reliability and validity evidence for The Mosaic™ by ACT® Social Emotional Learning Assessment, an assessment designed to measure SE skills in middle and high school students that makes use of a research-based framework (the Big Five) and a multi-method approach (three item types including Likert, forced choice, and situational judgment tests). Here, we provide the results from data collected from more than 33,000 students who completed the assessment and for whom we have data on various outcome measures. We examined the validity evidence for the individual item types and the aggregate scores based on those three. Our findings support the contribution of multi-method assessment and an aggregate score. We discuss the ways the field can benefit from this or similarly designed assessments and discuss how the assessment results can be used by practitioners to promote programs aimed at stimulating students' personal growth.


The stigma of public programs: does a separate S-CHIP program reduce it?
Previous studies suggest access to and satisfaction with care may be different for enrollees in S-CHIP and Medicaid, but it is unclear whether those differences are fully explained by socioeconomic characteristics of the enrollees. We analyze access and satisfaction of three groups of children: Medicaid enrolled, S-CHIP enrolled, and children who are income eligible for Medicaid but carry a card similar to the state's S-CHIP children's card. Both enrollees and providers may believe that these children are enrolled in S-CHIP despite the fact that reimbursement is through the state's Medicaid system. Results indicate that the same network of providers treat, or are perceived by families to treat, the three groups differently. They support the notion that some of the differences in satisfaction between S-CHIP and Medicaid enrollees are related to unmeasured characteristics (for example, income) of the families in the different programs, but that programmatic identity contributes substantially to differential care experience.


Green, fast and cheap paper-based method for estimating equivalence ratio of cationic carriers to DNA in gene delivery formulations.
To achieve efficient and safe cationic carrier-mediated gene delivery for gene therapy, the optimal ratio of carrier to DNA in formulations is a key factor and it is usually determined prior to transfection experiments. In this work, a simplified drop-and-read assay was developed for the first time using paper as a platform to estimate the equivalence ratio of cationic carriers to negatively charged DNA. By spotting a series of complexes containing varied ratios of carrier to DNA on filter paper, then allowing them to dry and finally dropping yellowish-green anionic 2',7'-dichlorofluorescein dye solution on top of the complexes, the equivalence point was detectable by the instant formation of stable pink spots as a result of the dye adsorption onto the positively charged complexes and free carriers. The method gave the same results as those determined by gel retardation assay and zeta potential measurement, however it allowed more rapid reporting of results in 5 min and required no tedious steps, harmful reagents or expensive instruments. By using paper instead of microcentrifuge tubes and omitting centrifugation, plasticware and electrical energy were no longer consumed and disposal of this degradable material was more environmentally friendly. With respect to analytical performance, filter paper inherently holding negative charge helped to trap and concentrate the complexes on the white background, enabling greater visibility of the colored spots and a lower required amount of DNA used for the assay. The method was successfully applied to estimate the equivalence ratios in a variety of gene delivery formulations containing different types of cationic carriers, i.e. polymers, dendrimers, liposomes and niosomes.


Thyroid-specific questions on work ability showed known-groups validity among Danes with thyroid diseases.
We aimed to identify the best approach to work ability assessment in patients with thyroid disease by evaluating the factor structure, measurement equivalence, known-groups validity, and predictive validity of a broad set of work ability items. Based on the literature and interviews with thyroid patients, 24 work ability items were selected from previous questionnaires, revised, or developed anew. Items were tested among 632 patients with thyroid disease (non-toxic goiter, toxic nodular goiter, Graves' disease (with or without orbitopathy), autoimmune hypothyroidism, and other thyroid diseases), 391 of which had participated in a study 5 years previously. Responses to select items were compared to general population data. We used confirmatory factor analyses for categorical data, logistic regression analyses and tests of differential item function, and head-to-head comparisons of relative validity in distinguishing known groups. Although all work ability items loaded on a common factor, the optimal factor solution included five factors: role physical, role emotional, thyroid-specific limitations, work limitations (without disease attribution), and work performance. The scale on thyroid-specific limitations showed the most power in distinguishing clinical groups and time since diagnosis. A global single item proved useful for comparisons with the general population, and a thyroid-specific item predicted labor market exclusion within the next 5 years (OR 5.0, 95 % CI 2.7-9.1). Items on work limitations with attribution to thyroid disease were most effective in detecting impact on work ability and showed good predictive validity. Generic work ability items remain useful for general population comparisons.


Peptide-nanowire hybrid materials for selective sensing of small molecules.
The development of a miniaturized sensing platform for the selective detection of chemical odorants could stimulate exciting scientific and technological opportunities. Oligopeptides are robust substrates for the selective recognition of a variety of chemical and biological species. Likewise, semiconducting nanowires are extremely sensitive gas sensors. Here we explore the possibilities and chemistries of linking peptides to silicon nanowire sensors for the selective detection of small molecules. The silica surface of the nanowires is passivated with peptides using amide coupling chemistry. The peptide/nanowire sensors can be designed, through the peptide sequence, to exhibit orthogonal responses to acetic acid and ammonia vapors, and can detect traces of these gases from "chemically camouflaged" mixtures. Through both theory and experiment, we find that this sensing selectivity arises from both acid/base reactivity and from molecular structure. These results provide a model platform for what can be achieved in terms of selective and sensitive "electronic noses."


Breast reconstruction following mastectomy.
The mutilating effect of surgery for cancer of the breast has left many women needful of reconstruction to restore the body contour and self-image. Reconstruction involves replacement of the three elements that have been lost: breast mass, skin, muscle and nipple-areolar complex. Methods for accomplishing this have been devised and are in common use. Because of the increased predisposition to malignancy in the remaining breast and the difficulty in achieving symmetry in both breasts, the remaining breast must be considered, with subcutaneous mastectomy being the most appropriate course in most cases. Patient acceptance has been excellent.


Strategies to Improve Quality of Life at the End of Life: Interdisciplinary Team Perspectives.
This ethnographic study draws on the experiences of members of interdisciplinary care teams working with end-of-life care patients to identify strategies to improve quality of life through care practices. We surveyed 133 staff and volunteers (physicians, physician assistants, nurse practitioners, registered nurses, social workers, chaplains, administrators, and volunteers) who provide end-of-life care to patients in both home and institutional settings for 4 organizations in 2 counties in Upstate New York. Survey responses were analyzed using qualitative content analysis. The results identified numerous strategies to enhance and safeguard quality of life for end-of-life care patients and their family members. These strategies can be categorized into 6 domains: organization philosophy and mission; organizational policies; caregivers' behaviors and practices; symptom management; facility design, operation and management; and patient, family member, and caregiver experience. The diverse list of identified strategies indicates that improving care to address the unique, complex, multilayered dimensions of quality of life at the end of life requires a multidisciplinary approach and consistency among care providers, including administration, clinical management, front-line caregivers, and support staff. When all of these strategies are used in harmony, care can truly be enhanced.


Investigation of the spin-lattice relaxation of 13CO and 13CO2 adsorbed in the metal-organic frameworks Cu3(btc)2 and Cu(3-x)Zn(x)(btc)2.
The (13)C nuclear spin-lattice relaxation time of (13)CO and (13)CO2 molecules adsorbed in the metal-organic frameworks (MOFs) Cu2.97Zn0.03(btc)2 and Cu3(btc)2 is investigated over a wide range of temperatures at resonance frequencies of 75.468 and 188.62 MHz. In all cases a mono-exponential relaxation is observed, and the (13)C spin-lattice relaxation times (T1) reveal minima within the temperature range of the measurements and both frequencies. This allows us to carry out a more detailed analysis of the (13)C spin relaxation data and to consider the influence due to the spectral functions of the thermal motion. In a model-free discussion of the temperature dependence of the ratios T1 (T)∕T1,min we observe a motional mechanism that can be described by a single correlation time. In relation to the discussion of the relaxation mechanisms this can be understood in terms of dominating translational motion with mean jump distance being larger than the minimum distances between neighboring adsorption sites in the MOFs. A more detailed discussion of the jump-like motion observed here might be carried out on the basis of self-diffusion coefficients. From the present spin relaxation measurements activation energies for the local motion of the adsorbed molecules in the MOFs can be estimated to be 3.3 kJ∕mol and 2.2 kJ∕mol, for CO and CO2 molecules, respectively. Finally, our findings are compared with our recent results derived from the (13)C line shape analysis.


Encysted cyathostomin larvae in foals - progression of stages and the effect of seasonality.
Cyathostomins (small strongyles) are ubiquitous in grazing horses and are known pathogens as cause of larval cyathostominosis. As part of their life cycle, cyathostomin larvae invade the mucosal walls of the large intestines and undergo encystment. Newly ingested third stage larvae are known to undergo arrested development and this can lead to an accumulation of encysted burdens over the course of a grazing season. It is believed that the host immune system plays a significant role in triggering this arrestment. Little is known about the development and progression of larval stages in foals that are not expected to mount a pronounced immune response to ingested cyathostomin larvae. This study evaluated counts of encysted larvae measured in 37 foals. The foals were born in 2013, 2014, and 2015 into a parasitology research herd kept without anthelmintic intervention and were humanely euthanatized between 50 and 293days of age as part of an ongoing parasite transmission study. A mucosal digestion technique was performed to enumerate encysted early third stage (EL3) and late third stage/fourth stage (LL3/L4) larvae in the cecum, ventral colon and dorsal colon. Counts were analyzed statistically to evaluate the influence of foal age, sex, and seasonality on the counts. Total counts as well as LL3/L4 counts were significantly higher during the grazing season (March-November). Three defined age groups (>100, 100-200, >200days) did not have statistically different counts. Male foals had significantly higher total counts compared to females, and this has not been reported before. The study found that 41% of the recovered larvae were EL3s, but no indication of arrested development of these was observed. This indicates that cyathostomin infection in foals progresses in a manner substantially different from mature horses.


Amplification of small analytes in polymer solution by capillary electrophoresis.
We report concentration methods for the analysis of small solutes by capillary electrophoresis in conjunction with laser-induced native fluorescence using a Nd:YAG laser. After injecting samples, poly(ethylene oxide) (PEO) in the anode reservoir entered a capillary filled with Tris-borate buffer. When migrating in PEO solution, the analytes slowed down and stacked at the interface between the sample zone and PEO solution. As a result, the limits of detection (LODs) down to 8 pM for 2-naphthalenesulfonic acid and 70 pM for L-tryptophan have been achieved when injecting at 30 cm height for 120 s and 230 s, respectively. Such low LODs are partially due to the effects of NaCl in the samples and PEO on the fluorescence characteristics of the analytes. In addition, the concentrations of NaCl and PEO have great impacts on the migration of the analytes and electroosmotic flow, thereby affecting resolution and speed. Without pretreatment, the determinations of five important markers in urine samples and two acids in a cerebrospinal fluid sample have been performed separately, with the relative standard deviations of the concentrations less than 3.6%. Furthermore, by applying a short plug of low-pH buffer after injection, the analysis of greater volumes of the urine sample has been carried out, resulting in detecting more peaks.


Increased conjugated dopamine in plasma after exercise training.
To evaluate the effect of endurance exercise on plasma catecholamines, we exercise trained eight dogs (group T) by treadmill running for 8 weeks. Six sedentary dogs constituted a nontrained control group (group NT). Heart rate response to a graded submaximal stress test was reduced in group T dogs (p less than 0.05), but mean resting aortic blood pressure (NT, 84 +/- 5 mm Hg; T, 82 +/- 4 mm Hg) and heart rate (NT, 87 +/- 1 bpm; T, 84 +/- 2 bpm) were unchanged by exercise, and no cardiac hypertrophy occurred after exercise. Plasma norepinephrine and epinephrine levels were reduced in group T at rest and during a fixed exercise workload. Plasma conjugated dopamine showed a marked increase in group T dogs (NT, 1398 +/- 130 pg/ml; T, 11346 +/- 1291 pg/ml; p less than 0.01) at rest, and no change in conjugated dopamine occurred in either group after short-term exercise stress. No intergroup differences were noted in resting coronary flow or coronary arteriovenous oxygen, or in myocardial oxygen consumption. The data verify previous findings of lower plasma levels of norepinephrine and epinephrine after training, and indicate that a marked rise in conjugated dopamine occurs after training. These findings suggest that norepinephrine and epinephrine metabolism is shifted toward conjugated dopamine by exercise training, thereby reducing active catecholamines in plasma, but retaining a large pool of usable metabolite.


Krüppel-like factor 4 contributes to the pathogenesis of mantle cell lymphoma.
Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL) with poor prognosis. Krüppel-like factor 4 (KLF4) has been reported as a bi-regulator in malignancies, but little is known about its role in MCL. Here, we showed that KLF4 was downregulated in three MCL cell lines and lymph nodes from MCL patients, which resulted in a negative prognosis. We also found that the regulation of KLF4 could inhibit the proliferation and induce apoptosis of Jeko-1 cells. The lentivirally over-expressed KLF4 protein was found bind to β-catenin and could inhibit downstream molecules such as cyclinD1 and c-Myc. Furthermore, 5-azacytidine could decrease the expression of methyltransferase-1 (DNMT-1) and restore the KLF4 expression in MCL cell lines, indicating that methylation might play an important role in the downregulation of KLF4. KLF4 may be a potential therapeutic target as a tumor suppressor in MCL.


In vivo high resolution human corneal imaging using full-field optical coherence tomography.
We present the first full-field optical coherence tomography (FFOCT) device capable of in vivo imaging of the human cornea. We obtained images of the epithelial structures, Bowman's layer, sub-basal nerve plexus (SNP), anterior and posterior stromal keratocytes, stromal nerves, Descemet's membrane and endothelial cells with visible nuclei. Images were acquired with a high lateral resolution of 1.7 µm and relatively large field-of-view of 1.26 mm x 1.26 mm - a combination, which, to the best of our knowledge, has not been possible with other in vivo human eye imaging methods. The latter together with a contactless operation, make FFOCT a promising candidate for becoming a new tool in ophthalmic diagnostics.


Association between chest CT features and clinical course of Coronavirus Disease 2019.
This retrospective study aims to illustrate the radiographic characteristics of Coronavirus Disease 2019 and the correlation with the clinical course. 195 hospitalized patients confirmed as Coronavirus Disease 2019 at First Hospital of Changsha, Hunan Province from December 31, 2019 to February 20, 2020 were enrolled. Chest computed tomography scan, clinical data and laboratory tests results were collected accordingly. Variable characteristics were recorded, radiographic evolution and outcome were analyzed along with the time course. Representative laboratory tests results were analyzed based on the image findings. Majority of the patients showed bilateral (73.8%), multiple lobes involvements (75.9%), peripheral distribution (83.1%), ground-glass opacification (41.0%), increased vascular margins (63.1%), long axis parallelism (55.9%), patchy ground-glass opacities beneath the pleura (51.3%) and consolidation (45.6%). According to the repeated radiology analysis, patients of improving/stable group tended to have younger age compared with worsening group (45.3 ± 15.0 VS. 59.3 ± 13.5, P = 0.001). Based on the laboratory test results, patients with positive image findings shared elder age, 46.0 (35.0-60.0)VS.31.0 (12.0-37.0) P < 0.001, and higher chance developing fever(P < 0.05); higher level of lymphocytes, C-reactive protein, erythrocyte sedimentation rate and lactate dehydrogenase; lower level of white blood cells, neutrophil and albumin(P < 0.001). There are several specific image changes along with the disease progression may be helpful in early recognition and differential diagnosis of Coronavirus Disease 2019. Comprehensive assessments of both imaging feature and laboratory test results may offer an intact knowledge of Coronavirus Disease 2019.


[A solitary neurofibroma in the parotid gland from nervus vagus].
A 37-year-old male, without stigmata of neurofibromatosis type 1, developed a firm mass below the right ear over several months without facial palsy. Clinical examination and ultra-sonography revealed a tumour in the parotid gland. Fine needle aspirationbiopsy was inconclusive. During complete resection, the tumour revealed an unusual anatomic location from the superficial lobe of the parotid to the deep and further into the parapharyngeal space. The pathological examination showed a solitary neurofibroma. In this case report, preoperative diagnosis, therapy and follow-up of this rare tumour in the parotid gland from n. vagus are discussed.


Historical review of carbamazepine for the treatment of bipolar disorder.
The management of bipolar disorder has seen significant evolution in terms of the number of treatment options now approved for both the acutely manic phase and the maintenance stages of the illness. In addition, new formulations of traditional agents are available for clinicians to use in their treatment approach. One such example is carbamazepine, which has approval by the United States Food and Drug Administration for the treatment of acute and mixed mania in an extended-release formulation that uses a three-bead delivery system. Although the parent compound has been available for decades, its approval for bipolar disorder is recent despite numerous clinical trials that have supported its use in both the acute and maintenance phases of bipolar disorder. Advantages of the new formulation include less fluctuation in plasma concentration and, in general, improved tolerability. However, issues remain with regard to cytochrome P450 drug-related interactions and the need for therapeutic drug monitoring (e.g., drug concentrations, epoxide metabolite concentrations, hematology, and liver function tests) as part of the treatment and monitoring process. We review the current body of literature describing the use of carbamazepine in bipolar disorder during both the acute and maintenance phases of the disorder, including trials of both monotherapy and combination therapy, as well as findings from trials that included patients with rapid cycling and mixed episodes.


[Short-term memory characteristics of vibration intensity tactile perception on human wrist].
In this study, a recall experiment and a recognition experiment were designed to assess the human wrist's short-term memory characteristics of tactile perception on vibration intensity, by using a novel homemade vibrotactile display device based on the spatiotemporal combination vibration of multiple micro vibration motors as a test device. Based on the obtained experimental data, the short-term memory span, recognition accuracy and reaction time of vibration intensity were analyzed. From the experimental results, some important conclusions can be made: (1) The average short-term memory span of tactile perception on vibration intensity is 3 ± 1 items; (2) The greater difference between two adjacent discrete intensities of vibrotactile stimulation is defined, the better average short-term memory span human wrist gets; (3) There is an obvious difference of the average short-term memory span on vibration intensity between the male and female; (4) The mechanism of information extraction in short-term memory of vibrotactile display is to traverse the scanning process by comparison; (5) The recognition accuracy and reaction time performance of vibrotactile display compares unfavourably with that of visual and auditory. The results from this study are important for designing vibrotactile display coding scheme.


Profiling Fast Healthcare Interoperability Resources (FHIR) of Family Health History based on the Clinical Element Models.
In this study we developed a Fast Healthcare Interoperability Resources (FHIR) profile to support exchanging a full pedigree based family health history (FHH) information across multiple systems and applications used by clinicians, patients, and researchers. We used previously developed clinical element models (CEMs) that are capable of representing the FHH information, and derived essential data elements including attributes, constraints, and value sets. We analyzed gaps between the FHH CEM elements and existing FHIR resources. Based on the analysis, we developed a profile that consists of 1) FHIR resources for essential FHH data elements, 2) extensions for additional elements that were not covered by the resources, and 3) a structured definition to integrate patient and family member information in a FHIR message. We implemented the profile using an open-source based FHIR framework and validated it using patient-entered FHH data that was captured through a locally developed FHH tool.


mRNAs that mature through trans-splicing in Caenorhabditis elegans have a trimethylguanosine cap at their 5' termini.
Approximately 10% of the mRNAs in the nematode Caenorhabditis elegans mature through a trans-splicing mechanism that involves the transfer of a 22-nucleotide spliced leader to the 5' end of the pre-mRNA. The spliced leader RNA exists as a small nuclear ribonucleoprotein particle and has the trimethylguanosine cap that is characteristic of eucaryotic small nuclear RNAs. We found that the trimethylguanosine cap present on the spliced leader RNA was transferred to the pre-mRNA during the trans-splicing reaction. Thereafter, the trimethylguanosine cap was maintained on the mature mRNA. This is the first example of eucaryotic cellular mRNAs possessing a trimethylguanosine cap structure.


Unilateral oval pupil with good outcome: Report of two cases.
Unilateral oval pupil has numerous causes, and several pathophysiologic mechanisms have been proposed. Prognosis is nearly universally poor. We present two patients, an 86-year-old woman and a 61-year-old woman, who developed coma and unilateral oval pupil due to ischemia and hypoglycemia, respectively. In the second case, a discrete area of ipsilateral brainstem ischemia was demonstrated by magnetic resonance imaging. Both patients recovered. The prognosis for comatose patients with unilateral oval pupil is not universally poor.


Sex and organ differences in oxidative DNA and RNA damage due to treatment of Sprague-Dawley rats with acetoxime or 2-nitropropane.
The hepatocarcinogens 2-nitropropane and acetoxime have previously been found to induce a specific and qualitatively identical pattern of base damage in rat liver DNA and RNA, including the induction of increased levels of 8-hydroxyguanine. Because both 2-nitropropane and acetoxime are weaker carcinogens in female rats than male rats, we examined the ability of these chemicals to induce this pattern of damage in liver and kidney nucleic acids of male and female Sprague-Dawley rats 6 and 18 h after administration. Significantly lower levels of 8-hydroxydeoxyguanosine, 8-hydroxyguanosine and other presumed modified nucleosides discernible by high-performance liquid chromatography with electrochemical detection were found in liver nucleic acids of female rats at both time points. In addition, minimal alteration of nucleic acids was observed in the kidney, which is not a target organ for the carcinogenicity of either 2-nitropropane (2-NP) or acetoxime (ACO). These results support the hypothesis that the specific DNA alterations observed are relevant to the hepatocarcinogenicity of 2-NP and ACO.


Lymphokines and thrombosis. I. Thrombocyte aggregating activity released by human lymphocytes stimulated with concanavalin-A.
Supernatants from Con-A stimulated human lymphocytes containing leucocyte migration inhibitory activity were measured for thrombocyte aggregation activity and for influence on thrombocyte rich plasma clot retraction and whole blood clot retraction. The lymphocyte released activity of the supernatants produced thrombocyte aggregation and an acceleration of clot retraction. The activity resisted heating at 56 degrees C for 30 min and was inactivated at 80 degrees C for 30 min. The active substance seems to have a molecular weight above 10,000 daltons. The findings suggest that thrombotic processes associated with cell-mediated (type IV) immune inflammation could be due, at least partially, to lymphokine effects on thrombocytes.


Next Generation House Call.
Just as online shopping is supplanting visits to the mall, and distance learning is part of the new wave in higher education, so is health care coming to a computer or mobile device near you. In the next few years, telehealth will increasingly become part of psychiatric and neurological care. Still to overcome is an unwieldy health care system that will need to adapt to practices that have the potential to lower costs and improve care.


[Prostate small cell carcinoma: report of two cases that differed in treatment responsiveness].
Case 1 : A 76-year-old man with a chief complaint of dysuria had an elevated prostate specific antigen (PSA) level of 24.9. He underwent a transperineal needle biopsy of the prostate, and the histopathological diagnosis was prostatic small cell carcinoma. The cancer was clinically diagnosed as T3bN1M1 with multiple lung metastases. He started receiving hormonal therapy. After three months of hormonal therapy, the multiple lung metastases disappeared. Thereafter, the serum PSA level and the tumor volume increased and he died 12 months from the start of therapy. Case 2: A 79-year-old man was referred to our hospital with a chief complaint of dysuria. The serum level of PSA was elevated to 10.4. Transperineal prostate biopsy revealed prostatic small cell carcinoma. The cancer was clinically diagnosed as T3bN1M1, and hormonal therapy was started. Subsequently, although his serum PSA level declined, his condition worsened rapidly and he died five months after the start of therapy.


Pentavalent Antimonials Combined with Other Therapeutic Alternatives for the Treatment of Cutaneous and Mucocutaneous Leishmaniasis: A Systematic Review.
The first choice drugs for the treatment of cutaneous and mucocutaneous leishmaniasis are pentavalent antimonials, sodium stibogluconate, or meglumine antimoniate. However, the treatment with these drugs is expensive, can cause serious adverse effects, and is not always effective. The combination of two drugs by different routes or the combination of an alternative therapy with systemic therapy can increase the efficacy and decrease the collateral effects caused by the reference drugs. In this systematic review we investigated publications that described a combination of nonconventional treatment for cutaneous and mucocutaneous with pentavalent antimonials. A literature review was performed in the databases Web of Knowledge and PubMed in the period from 01st of December 2004 to 01st of June 2017, according to Prisma statement. Only clinical trials involving the treatment for cutaneous or mucocutaneous leishmaniasis, in English, and with available abstract were added. Other types of publications, such as reviews, case reports, comments to the editor, letters, interviews, guidelines, and errata, were excluded. Sixteen articles were selected and the pentavalent antimonials were administered in combination with pentoxifylline, granulocyte macrophage colony-stimulating factor, imiquimod, intralesional sodium stibogluconate, ketoconazole, silver-containing polyester dressing, lyophilized LEISH-F1 protein, cryotherapy, topical honey, and omeprazole. In general, the combined therapy resulted in high rates of clinical cure and when relapse or recurrence was reported, it was higher in the groups treated with pentavalent antimonials alone. The majority of the articles included in this review showed that cure rate ranged from 70 to 100% in patients treated with the combinations. Serious adverse effects were not observed in patients treated with drugs combination. The combination of other drugs or treatment modalities with pentavalent antimonials has proved to be effective for cutaneous and mucocutaneous leishmaniasis and for most seemed to be safe. However, new randomized, controlled, and multicentric clinical trials with more robust samples should be performed, especially the combination with immunomodulators.


Parameters affecting fusion between Sendai virus and liposomes. Role of viral proteins, liposome composition, and pH.
A kinetic and quantitative characterization of the fusion process between Sendai virus and phospholipid vesicles is presented. Membrane fusion was monitored in a direct and continuous manner by employing an assay which relies on the relief of fluorescence self-quenching of the probe octadecylrhodamine B chloride which was located in the viral membrane. Viral fusion activity was strongly dependent on the vesicle lipid composition and was most efficient with vesicles solely consisting of acidic phospholipids, particularly cardiolipin (CL). This result implies that the fusion of viruses with liposomes does not display an absolute requirement for specific membrane receptors. Incorporation of phosphatidylcholine (PC), rather than phosphatidylethanolamine (PE), into CL bilayers strongly inhibited fusion, suggesting that repulsive hydration forces interfere with the close approach of viral and target membrane. Virus-liposome fusion products were capable of fusing with liposomes, but not with virus. In contrast to fusion with erythrocyte membranes, fusion between virus and acidic phospholipid vesicles was triggered immediately, did not strictly depend on viral protein conformation, and did not display a pH optimum around pH 7.5. On the other hand, with vesicles consisting of PC, PE, cholesterol, and the ganglioside GD1a, the virus resembled more closely the fusogenic properties that were seen with erythrocyte target membranes. Upon decreasing the pH below 5.0, the viral fusion activity increased dramatically. With acidic phospholipid vesicles, maximal activity was observed around pH 4.0, while with GD1a-containing zwitterionic vesicles the fusion activity continued to increase with decreasing pH down to values as low as 3.0.(ABSTRACT TRUNCATED AT 250 WORDS)


Antiaging Effects of Vicatia thibetica de Boiss Root Extract on Caenorhabditis elegans and Doxorubicin-Induced Premature Aging in Adult Mice.
The roots of Vicatia thibetica de Boiss are a kind of Chinese herb with homology of medicine and food. This is the first report showing the property of the extract of Vicatia thibetica de Boiss roots (HLB01) to extend the lifespan as well as promote the healthy parameters in Caenorhabditis elegans (C. elegans). For doxorubicin- (Doxo-) induced premature aging in adult mice, HLB01 counteracted the senescence-associated biomarkers, including P21 and γH2AX. Interestingly, HLB01 promoted the expression of collagen in C. elegans and mammalian cell systemically, which might be one of the essential factors to exert the antiaging effects. In addition, HLB01 was also found as a scavenger of free radicals, thereby performing the antioxidant ability. Lifespan extension by HLB01 was also dependent on DAF-16 and HSF-1 via oxidative stress resistance and heat stress resistance. Taken together, overall data suggested that HLB01 could extend the lifespan and healthspan of C. elegans and resist Doxo-induced senescence in mice via promoting the expression of collagen, antioxidant potential, and stress resistance.


Continuous degradation of phenanthrene in cloud point system by reuse of Sphingomonas polyaromaticivorans cells.
Extractive biodegradation of phenanthrene by Sphingomonas polyaromaticivorans was previously carried out in cloud point system (CPS). In this study, we explored the possibility of further increasing the efficiency of the culture by repeatedly reusing cells and the system for biodegradation. Three different recycling strategies were adopted. In reuse of cells plus CPS, cells were reused for 3 times while maintaining high degradation rates (> 90%). Thereafter, the accumulation of metabolites in the dilute phase resulted in a decrease in cell viability. This inhibition was avoided in recycling the cells plus coacervate phase by replacing the dilute phase with fresh Medium. However, due to the slow adaptation of the cells to the new degradation environment and the reduction in the volume of the coacervate phase, the cells were only reused twice and their activity decreased. However, the same long degradation cycle (5 days) as the reuse of cells plus coacervate phase reduced the overall degradation efficiency of phenanthrene. Finally, a combined strategy of 3 times of cells plus CPS reuse and individual cells reuse once was employed and run for two cycles. 3 rounds of reuse of cells plus CPS improved cells utilization and phenanthrene degradation efficiency. Then, the subsequent round of reuse of cells alone relieved the effect of increasing metabolites on cell viability. This study provides a potential application for reusing cells to continuously degrade phenanthrene in soil and water in CPS.


Marginal Ascorbate Status (Hypovitaminosis C) Results in an Attenuated Response to Vitamin C Supplementation.
Inadequate dietary intake of vitamin C results in hypovitaminosis C, defined as a plasma ascorbate concentration ≤23 μmol/L. Our objective was to carry out a retrospective analysis of two vitamin C supplementation studies to determine whether supplementation with 50 mg/day vitamin C is sufficient to restore adequate ascorbate status (≥50 μmol/L) in individuals with hypovitaminosis C. Plasma ascorbate data from 70 young adult males, supplemented with 50 or 200 mg/day vitamin C for up to six weeks, was analyzed. Hypovitaminosis C status was identified based on plasma ascorbate being ≤23 μmol/L and the response of these individuals to vitamin C supplementation was examined. Of the participants consuming 50 mg/day vitamin C for up to six weeks, those with hypovitaminosis C at baseline achieved plasma concentrations of only ~30 μmol/L, whereas the remainder reached ~50 μmol/L. Participants who consumed 200 mg/day vitamin C typically reached saturating concentrations (>65 μmol/L) within one week, while those with hypovitaminosis C required two weeks to reach saturation. Regression modelling indicated that the participants' initial ascorbate status and body weight explained ~30% of the variability in the final ascorbate concentration. Overall, our analysis revealed that supplementation with 50 mg/day vitamin C, which resulted in a total dietary vitamin C intake of 75 mg/day, was insufficient to achieve adequate plasma ascorbate concentrations in individuals with hypovitaminosis C. Furthermore, increased body weight had a negative impact on ascorbate status.


Developmental trajectories of personal and collective self-concept among American Indian adolescents.
Developmental trajectories of personal and collective self-concept were examined among American Indian adolescents. Personal self-concept (self-esteem) and collective self-concept (American Indian identity, Euro-American identity, community-mindedness) were assessed 6 times over 3 years in 4 cohorts of adolescents from 3 American Indian cultural groups (N=1,252). An accelerated longitudinal design was used to estimate developmental trajectories from 14 to 19 years; parallel-process and covariate models were used to examine variation in trajectories. Both personal and collective self-concepts were generally positive and showed small gains; they were moderately related to one another and differentially related to cultural group, gender, and perceived social support. The findings highlight the complexity of self-concept for American Indian youth and the significance of both personal and collective identity.


Outcomes of Renal Trauma in Indian Urban Tertiary Healthcare Centres: A Multicentre Cohort Study.
Renal trauma is present in 0.5-5% of patients admitted for trauma. Advancements in radiologic imaging and minimal-invasive techniques have led to decreased need for surgical intervention. We used a large trauma cohort to characterise renal trauma patients, their management and outcomes. We analysed "Towards Improved Trauma Care Outcomes in India" cohort from four urban tertiary public hospitals in India between 1st September 2013 and 31st December 2015. The data of patients with renal trauma were extracted using International Classification of Diseases 10 codes and analysed for demographic and clinical details. A total of 16,047 trauma patients were included in this cohort. Abdominal trauma comprised 1119 (7%) cases, of which 144 (13%) had renal trauma. Renal trauma was present in 1% of all the patients admitted for trauma. The mean age was 28 years (SD-14.7). A total of 119 (83%) patients were male. Majority (93%) were due to blunt injuries. Road traffic injuries were the most common mechanism (53%) followed by falls (29%). Most renal injuries (89%) were associated with other organ injuries. Seven of the 144 (5%) patients required nephrectomy. Three patients had grade V trauma; all underwent nephrectomy. The 30-day in-hospital mortality, in patients with renal trauma, was 17% (24/144). Most renal trauma patients were managed nonoperatively. 89% of patients with renal trauma had concomitant injuries. The renal trauma profile from this large cohort may be generalisable to urban contexts in India and other low- and middle-income countries.


The transmembrane domain of the acetylcholine receptor: insights from simulations on synthetic peptide models.
We have studied the structure and properties of a bundle of alpha-helical peptides embedded in a 1,2-dimyristoyl-3-phosphatidylcholine phospholipid bilayer by molecular dynamics simulations. The bundle of five transmembrane deltaM2 segments constitutes the model for the pore region of the nicotinic acetylcholine receptor, which is the neurotransmitter-gated ion-channel responsible for the fast propagation of electrical signals between cells at the nerve-muscle synapse. The deltaM2 segments were shown to oligomerize in biomembranes resulting in ion-channel activity with characteristics similar to the native protein, and the structure of the isolated peptides was studied in 1,2-dimyristoyl-3-phosphatidylcholine bilayers and micelles by NMR experiments (Opella, S. J., et al. 1999. Nat. Struct. Biol. 6:374-379). Our analyses indicate that the structure, helix tilt, and the overall shape of the channel are in good agreement with the NMR experiments and the proposed model for the channel, which we show is formed by rings of functional residues. The studied geometry resulted in a closed pore state, where the channel is partially dehydrated at the hydrophobic extracellular half and the extracellular mouth of the channel blocked by the hydrocarbon chains of Arg+ residues. The arginine amino acids form intermolecular salt-bridges with the C-terminus, which contribute as well to the bundle stabilization.


[Energy balance, water use efficiency and surface resistance in a maize field].
The characteristics of land surface/air energy translation was analysed on the basis of the observation data collected over a maize field in the North China Plain. The results indicated that the energy balance processes of land surface were greatly affected by the features of underlying face. Latent heat fluxes were the main component of land surface/air energy exchanges. Daily sensible heat fluxes were turned to be negative in the late growth period of maize. Among factors regulating surface energy translation, bulk canopy resistance was seasonally changed with high values in the early and late stage and with low value in the mid stage, and the lowest value of 25 s.m-1. This trend was closely related to soil cover fraction and leaf senescence condition. Water use efficiency (WUE) was not changed with evapotranspiration. The low WUE in the early stage means that the energy resources were not fully utilised, and the high WUE in the late stage means that enough soil water content was the key for high and stable yield.


Ganoderma microsporum immunomodulatory protein as an extracellular epidermal growth factor receptor (EGFR) degrader for suppressing EGFR-positive lung cancer cells.
Epidermal growth factor receptor (EGFR) abnormalities relevant to tumor progression. A newly developed strategy for cancer therapy is induction of EGFR degradation. GMI, an immunomodulatory protein from the medicinal mushroom Ganoderma microsporum, exhibits anticancer activity. However, its role in the intracellular trafficking and degradation of EGFR remains unclear. In this study, we discovered that GMI inhibits the phosphorylation of multiple tyrosine kinases. Specifically, GMI was discovered to suppress lung cancer cells harboring both wild-type and mutant EGFR by inhibiting EGFR dimerization and eliminating EGFR-mediated signaling. Functional studies revealed that GMI binds to the extracellular segment of EGFR. GMI interacts with EGFR to induce phosphorylation of EGFR at tyrosine1045, which triggers clathrin-dependent endocytosis and degradation of EGFR. Furthermore, in the mouse models, GMI was discovered to suppress tumor growth. Knockdown of EGFR in lung cancer cells abolishes GMI's anticancer activity in vivo and in vitro. Our results reveal the interaction mechanisms through which GMI induces EGFR degradation and abolishes EGFR-mediated intracellular pathway. Our study indicates that GMI is an EGFR degrader for inhibiting EGFR-expressing tumor growth.


The modulatory role of the lateral septum on neuroendocrine and behavioral stress responses.
The lateral septum (LS) has been shown to have a key role in emotional processes and stress responses. However, the exact role of the LS on stress modulation is not clear, as previous lesion studies mostly used electrolytic lesions, thereby destroying the whole septal area, including medial components and/or fibers of passage. The aim of the present study was therefore, to investigate the effects of selective excitotoxic ablation of the LS on neuroendocrine and behavioral stress responses in rats. Bilateral ibotenic acid lesions of the LS increased hypothalamo-pituitary-adrenocortical (HPA) axis responses to forced swim stress indicated by enhanced plasma ACTH and corticosterone responses and higher stress-induced c-Fos-like immunoreactivity in the paraventricular hypothalamic nucleus. Moreover, LS-lesioned animals showed a more passive coping style in the forced swim test indicated by increased floating and reduced struggling/swimming behavior compared with sham-lesioned controls. Interestingly, intraseptal corticosteroid receptor blockade modulated behavioral stress coping but failed to change HPA axis stress responses. Further experiments aimed at elucidating underlying neurochemical mechanisms revealed that intraseptal administration of the selective 5-HT(1A) receptor antagonist WAY-100635 increased and prolonged stress-induced ACTH and corticosterone levels mimicking lesion effects, while the agonist 8-OH-DPAT suppressed HPA axis activity facilitating the inhibitory role of the LS. In addition, 8-OH-DPAT-injected animals showed increased active and decreased passive coping strategies during forced swimming suggesting antidepressant efficacy. Taken together, our data suggest that the LS promotes active stress coping behavior and is involved in a HPA-inhibitory mechanism that is at least in part mediated by septal 5-HT(1A) receptors and does not involve a glucocorticoid mediated feedback mechanism.


Perinatal psychiatric practitioner consultation program delivers rapid response to OB/GYN practitioners.
Screening and treatment initiation for perinatal psychiatric conditions is a recommended competency in OB/GYN practitioners, yet perinatal psychiatry is rapidly evolving. Practitioner-to-psychiatrist consultation programs have the potential to improve the management of psychiatric conditions in perinatal women. This study describes utilization of a statewide perinatal psychiatric consultation service by OB/GYN practitioners through examination of the volume, responsivity, content and outcomes of clinical inquiries, and satisfaction. This quality improvement study describes the 460 telephone or e-mail consultations requested by OB/GYN practitioners over 2 years and housed within a REDCap database. Data include the characteristics of consult users, month-over-month and total utilization, the patient's perinatal status, the reason for contact, current symptoms and medications, and the consulting psychiatrist recommendations. Practitioner satisfaction with consultation is also described. After completion of triage, the psychiatrist returned the practitioner's call ≤5 min in 59% of consultations. The most common inquiries were for pregnant (64%) women for depressive (51%) or anxiety (46%) symptoms with 47% of inquiries reporting the patient was currently taking a psychiatric medication. Had consultation not been available, referral to mental health (41%) or starting a medication (15%) were most often reported. This perinatal psychiatric consultation service rapidly and effectively met the needs of practitioners practicing in OB/GYN settings across a state having a critical psychiatry shortage and varying urban and rural geography. Future recommendations include the assessment of direct patient outcomes, practitioner skill attainment, and long-term cost savings of this perinatal psychiatric consultation model.


Skeletal dosimetry based on µCT images of trabecular bone: update and comparisons.
Two skeletal dosimetry methods using µCT images of human bone have recently been developed: the paired-image radiation transport (PIRT) model introduced by researchers at the University of Florida (UF) in the US and the systematic–periodic cluster (SPC) method developed by researchers at the Federal University of Pernambuco in Brazil. Both methods use µCT images of trabecular bone (TB) to model spongiosa regions of human bones containing marrow cavities segmented into soft tissue volumes of active marrow (AM), trabecular inactive marrow and the bone endosteum (BE), which is a 50 µm thick layer of marrow on all TB surfaces and on cortical bone surfaces next to TB as well as inside the medullary cavities. With respect to the radiation absorbed dose, the AM and the BE are sensitive soft tissues for the induction of leukaemia and bone cancer, respectively. The two methods differ mainly with respect to the number of bone sites and the size of the µCT images used in Monte Carlo calculations and they apply different methods to simulate exposure from radiation sources located outside the skeleton. The PIRT method calculates dosimetric quantities in isolated human bones while the SPC method uses human bones embedded in the body of a phantom which contains all relevant organs and soft tissues. Consequently, the SPC method calculates absorbed dose to the AM and to the BE from particles emitted by radionuclides concentrated in organs or from radiation sources located outside the human body in one calculation step. In order to allow for similar calculations of AM and BE absorbed doses using the PIRT method, the so-called dose response functions (DRFs) have been developed based on absorbed fractions (AFs) of energy for electrons isotropically emitted in skeletal tissues. The DRFs can be used to transform the photon fluence in homogeneous spongiosa regions into absorbed dose to AM and BE. This paper will compare AM and BE AFs of energy from electrons emitted in skeletal tissues calculated with the SPC and the PIRT method and AM and BE absorbed doses and AFs calculated with PIRT-based DRFs and with the SPC method. The results calculated with the two skeletal dosimetry methods agree well if one takes the differences between the two models properly into account. Additionally, the SPC method will be updated with larger µCT images of TB.


Automating Quality Oncology Practice Initiative Quality Measure NHL78a.
Quality measurement and improvement is a focus of ASCO. In the era of electronic health records (EHRs), computerized order entry, and medication administration records, quality monitoring can be an automated process. The EHR data are usually stored within tables in a relational database management system. ASCO Quality Oncology Practice Initiative measure NHL78a (hepatitis B virus antigen test and hepatitis B core antibody test within 3 months before initiation of obinutuzumab, ofatumumab, or rituximab for patients with non-Hodgkin lymphoma) presents an opportunity for automation of a quality measure using existing data in the EHR. We used a locally developed Structured Query Language (SQL) language procedure in the Microsoft SQL Query Manager to access the EPIC CLARITY database. Access to the relational database management system of the EHR permits rapid case identification (the denominator set) of the unique ID of all of the patients who have received one of the target medications (ie, obinutuzumab, ofatumumab, or rituximab). Then, we went through a six-step process to find the number of patients who passed or failed the quality measure. When the final SQL procedure executes, it takes < 5 seconds to see the result set for a 12-month period. The procedure can be changed to incorporate a desired date range. Once the SQL procedure is created, there is essentially no labor and low costs to run the procedure at specific time intervals. Our method of quality measurement using EHRs is cost effective, fast, and precise, and can be reproduced at other centers.


Composite Assessment Using Intestinal Ultrasound and Calprotectin Is Accurate in Predicting Histological Activity in Ulcerative Colitis: A Cohort Study.
Beyond endoscopic remission, histological remission in ulcerative colitis (UC) is predictive of clinical outcomes. Intestinal ultrasound (IUS) may offer a noninvasive surrogate marker for histological activity; however, there are limited data correlating validated ultrasound and histological indices. Our aim was to determine the correlation of IUS activity in UC with a validated histological activity index. Twenty-nine prospective, paired, same-day IUS/endoscopy/histology/fecal calprotectin (FC) cases were included. Intestinal ultrasound activity was determined using the Milan Ultrasound Criteria, histological activity using the Nancy Histological Index, endoscopic activity using Mayo endoscopic subscore and Ulcerative Colitis Endoscopic Index of Severity, and clinical activity using the Simple Clinical Colitis Activity Score. Histological activity demonstrated a significant linear association with overall IUS activity (coefficient 0.14; 95% CI, 0.03-0.25; P = .011). Intestinal ultrasound activity was also significantly associated with endoscopic activity (0.32; 95% CI, 0.14-0.49; P < 0.001), total Mayo score (0.31; 95% CI, 0.02-0.60; P = .036) but not FC (0.10; 95% CI, -0.01 to 0.21; P = .064) or clinical disease activity (0.04; 95% CI, -0.21 to 0.28; P = .768). A composite of IUS and FC showed the greatest association (1.31; 95% CI, 0.43-2.18; P = .003) and accurately predicted histological activity in 88% of cases (P = .007), with sensitivity of 88%, specificity 80%, positive predictive value 95%, and negative predictive value 57%. Intestinal ultrasound is an accurate noninvasive marker of histological disease activity in UC, the accuracy of which is further enhanced when used in composite with FC. This can reduce the need for colonoscopy in routine care by supporting accurate point-of-care decision-making in patients with UC.


Women having abortion in urban Nepal: 2005 and 2010 compared.
The use of abortion services at the Maternity Hospital clinic, the largest public sector abortion clinic in Nepal, has risen over the years. Whether the profile of the clients, reasons for abortion, and contraceptive use have changed are not known and need to be investigated. This paper evaluates changes between 2005 and 2010 in the socio-demographic profile of abortion users, reasons for seeking abortion, and contraceptive use of two cohorts of women who had first-trimester abortion at the Maternity Hospital. We used data from two similar surveys conducted in 2005 and 2010 among 672 and 392 women, respectively, who obtained first-trimester surgical abortion in a large public sector clinic. We analyzed trend data in service utilization and carried out a cost analysis. The number of women having abortions has steadily increased over the years, and cumulatively about 19,800 women have received services. The profile of the clients at this clinic remained essentially the same between 2005 and 2010. The typical users of abortion services at the clinic has were 27 years old with two living children, mostly married, with the majority not wanting to have more children. About half of them used a contraceptive method-mostly condoms, withdrawal, the pill and rhythm-in the month of unintended pregnancy, suggesting failures with these methods. Health concerns, dislike of available methods, and perceived low risk of pregnancy were common reasons for not using a contraceptive method. Despite increases in the number of clients, the socio-demographic profile of the abortion clients has remained similar over the years. The linkage between the abortion and family planning clinics needs to be strengthened.


[Helicobacter pylori 2006: how to test, when to treat].
The role of Helicobacter pylori in peptic-disease, gastric adeno-carcinoma and the MALT- lymphoma is established. The H. pylori diagnostics and the eradication therapy are highly disputed in patients with dyspepsia. An endoscopy is recommended to patients older than 45 who have dyspeptic disorders. Non-invasive testing and treatment is an adequate option to those patients younger than 45, if no alarm symptoms exist. The H.pylori serology, the 13C- breath test and the stool-antigen test have proven to be the best in laboratory testing. The therapeutic regimen of H. pylori eradication consists of a proton pump inhibitor (PPI) and two antibiotics, though it isn't always successful. After a second treatment failure, a H. pylori culture is indicated to asses the antibiotic resistances.


Polarized structured illumination microscopy using polarization gratings for optical sectioning.
In this investigation, we describe polarized structured illumination microscopy based on polarization gratings to generate a stable polarized illumination pattern in an extensive area. The visibility of the illumination pattern is immediately calculated by using a polarizing pixelated camera, and the 3D surface profile of the specimen can be successfully reconstructed. Moreover, a polarization grating pair was used to reasonably eliminate the unexpected pattern caused by the polarization grating itself. To experimentally characterize the system performance, a step height standard specimen was measured. Moreover, the axial response for the visibility of the illumination pattern was discussed with the consideration of the spectral bandwidth of the source and the spatial coherence of incident light.


Possible links between immune system and stress response: the role of gamma delta T lymphocytes.
Heterologous heat shock proteins (hsps) are antigens in many infectious diseases involving bacteria, parasites and perhaps even fungi. T and B lymphocytes recognize multiple epitopes on these proteins. Recently, lymphocytes expressing gamma delta T cell receptors (gamma delta cells) were also found to react with hsps that are members of the 60 kiloDalton (kDa) family. The response of gamma delta cells to hsp 60 differs from that of alpha beta T cells and B cells in several ways: the frequency of reactive gamma delta clones is high. Many clones recognize the same portion of this protein instead of scattered antigenic epitopes; and most gamma delta cells that react with the mycobacterial hsp-60 homolog are also stimulated by the autologous homolog. Perhaps, such (self) hsp-reactive gamma delta populations function by distinguishing stressed from not stressed states in autologous cells and tissues, rather than by discriminating 'self' and 'non-self'.


Mesenchymal Stem Cells and Exosomes: A Novel Therapeutic Approach for Corneal Diseases.
The cornea, with its delicate structure, is vulnerable to damage from physical, chemical, and genetic factors. Corneal transplantation, including penetrating and lamellar keratoplasties, can restore the functions of the cornea in cases of severe damage. However, the process of corneal transplantation presents considerable obstacles, including a shortage of available donors, the risk of severe graft rejection, and potentially life-threatening complications. Over the past few decades, mesenchymal stem cell (MSC) therapy has become a novel alternative approach to corneal regeneration. Numerous studies have demonstrated the potential of MSCs to differentiate into different corneal cell types, such as keratocytes, epithelial cells, and endothelial cells. MSCs are considered a suitable candidate for corneal regeneration because of their promising therapeutic perspective and beneficial properties. MSCs compromise unique immunomodulation, anti-angiogenesis, and anti-inflammatory properties and secrete various growth factors, thus promoting corneal reconstruction. These effects in corneal engineering are mediated by MSCs differentiating into different lineages and paracrine action via exosomes. Early studies have proven the roles of MSC-derived exosomes in corneal regeneration by reducing inflammation, inhibiting neovascularization, and angiogenesis, and by promoting cell proliferation. This review highlights the contribution of MSCs and MSC-derived exosomes, their current usage status to overcome corneal disease, and their potential to restore different corneal layers as novel therapeutic agents. It also discusses feasible future possibilities, applications, challenges, and opportunities for future research in this field.


Fc Receptor-mediated Effector Function Contributes to the Therapeutic Response of Anti-TNF Monoclonal Antibodies in a Mouse Model of Inflammatory Bowel Disease.
Anti-tumour necrosis factor [TNF] monoclonal antibodies [infliximab, adalimumab] induce complete mucosal healing in a proportion of patients with Crohn's disease whereas a TNF receptor fusion protein [etanercept] is not effective and the anti-TNF F[ab']2 fragment [certolizumab] shows a very low rate of complete mucosal healing. In contrast, all four TNF-neutralising drugs have demonstrated efficacy in the treatment of rheumatoid arthritis. These observations suggest that factors other than neutralisation of TNF may contribute to clinical outcomes in Crohn's disease. Here we tested the hypothesis that Fc receptor [FcR]-mediated effects may contribute to the therapeutic response of anti-TNF antibodies in inflammatory bowel disease. We modified an IgG2c mouse anti-TNF antibody that binds the high-affinity FcRs to generate an IgG1 isotype with strongly diminished binding. We examined the therapeutic effects of both antibodies in the T cell transfer model of inflammatory bowel disease and the collagen-induced arthritis model. The IgG2c anti-TNF antibody prevented colonic inflammation in the T cell transfer model of colitis, whereas the IgG1 anti-TNF did not. Conversely, both the IgG2c and IgG1 anti-TNFs were similarly effective in reducing the severity of articular inflammation in mouse collagen-induced arthritis. These data support the concept that the mechanism of action for TNF-neutralising drugs may differ across immune-mediated diseases and, potentially, between therapeutics within a particular disease. Our data suggest a specific role of Fc-mediated immune regulation in the resolution of intestinal inflammation by anti-TNF monoclonal antibodies.


Trauma Exposure and Trauma Symptoms as Predictors of Police Perceptions in Latinx Youths.
The Latinx immigrant youth population composes nearly a quarter of all children in the U.S. and are a high-risk group for police encounters. Based on perceptions of Latinxs as criminals, increased enforcement actions against Latinxs in the U.S., and failures of policing and police brutality in immigrants' home countries, we expected that immigrants who reported increased trauma exposure and symptoms would have more negative perceptions of police. This study utilized data from 107 recently immigrated Latinx youth to examine how trauma exposure (Child Trauma Screen) and symptoms (Child PTSD Symptoms Scale) related to perceptions of police (Criminal Sentiments Scale-Modified). Consistent with the proposed hypotheses, trauma symptoms evidenced a significant main effect in relation to perceptions of police, B = .115, t = 2.35; p = .021, such that greater trauma symptoms were associated with more negative perceptions of law enforcement. Though trauma exposure did not evidence a significant main effect in relation to perceptions of police, B = .254, t = 1.46; p = .146, moderation analyses indicated that trauma exposure was associated with more negative perceptions of police, B = -.019, t = -2.08; p = .040. However, this interaction effect indicated that when both trauma symptoms and trauma exposure were high, less negative perceptions of police were observed. The present study provides novel data on police perceptions in young Latinx immigrants. Findings highlight the need for improved community relations and culturally responsive strategies between law enforcement and communities of color.


A consanguineous Turkish family with early-onset Parkinson's disease and an exon 4 parkin deletion.
The importance of parkin in early-onset Parkinson's disease in Japan, Europe, and the United States is well established. The contribution of this gene to the risk of Parkinson's disease in other populations is less well known. To explore the importance of parkin in those of Turkish ancestry, we studied familial cases from that country, and identified a consanguineous family with early-onset Parkinson's disease due to a homozygous mutation in parkin.


Controlling energy flow in multimetallic nanostructures for plasmonic catalysis.
It has been shown that photoexcitation of plasmonic metal nanoparticles (Ag, Au and Cu) can induce direct photochemical reactions. However, the widespread application of this technology in catalysis has been limited by the relatively poor chemical reactivity of noble metal surfaces. Despite efforts to combine plasmonic and catalytic metals, the physical mechanisms that govern energy transfer from plasmonic metals to catalytic metals remain unclear. Here we show that hybrid core-shell nanostructures in which a core plasmonic metal harvests visible-light photons can selectively channel that energy into catalytically active centres on the nanostructure shell. To accomplish this, we developed a synthetic protocol to deposit a few monolayers of Pt onto Ag nanocubes. This model system allows us to conclusively separate the optical and catalytic functions of the hybrid nanomaterial and determine that the flow of energy is strongly biased towards the excitation of energetic charge carriers in the Pt shell. We demonstrate the utility of these nanostructures for photocatalytic chemical reactions in the preferential oxidation of CO in excess H2. Our data demonstrate that the reaction occurs exclusively on the Pt surface.


The Role of Gay-Related Stigma in HIV-Risk Behavior Among Sexual Minority Men in Europe.
Sexual orientation stigma stems from discriminatory social contexts and may ultimately impact the behavioral health of stigmatized individuals through stress-related pathways. Sexual minority stigma is of particular concern in Europe given the diversity of social contexts on the continent and sexual minority men's rapidly increasing risk of HIV infection, especially in Central and Eastern Europe, potentially rooted in stigma. This study assesses whether stigma in the ubiquitous social contexts surrounding sexual minority men (e.g., family, workplace, government) may place them at higher risk for HIV contraction across six countries. We utilized a large cross-sectional survey sample of HIV-negative sexual minority men (N = 2087; mean age = 31.6, SD = 9.7) from six European countries to test whether those who reported sexual orientation stigma also engaged in more HIV risk-related behaviors, including condomless sex with casual partners (in the absence of PrEP) and substance use before and during sex. Regression analyses were performed in Mplus. We found that a one standard deviation increase in reported sexual orientation stigma was significantly associated with the following during the last sexual encounter: a 19% increase in odds of sex under the influence of alcohol, 27% increase in odds of sex under the influence of cannabis, 49% increase in odds of sex under the influence of illicit drugs, an 11% increase in odds of condomless sex with casual partners in the past 6 months, and a 26% increase in odds of knowing where to receive an HIV test. Sexual minority men who reported perceiving greater sexual orientation-related stigma within their ubiquitous social contexts were significantly more likely to report sexual risk and alcohol and drug use during their last sexual encounter, yet reported more knowledge of preventive services. Contextual stigma might serve as a precursor to behavioral risks of HIV infection, generating maladaptive stress responses capable of being modified through individually-focused interventions. Structural interventions are also needed to ultimately reduce stigma at its source.


Regional characterization of brain neurotensin receptor subtypes in LS and SS mice.
Neurotensin (NT) receptor subtypes were investigated in nine brain regions from long sleep (LS) and short sleep (SS) mice that were selectively bred for differences in sensitivity to ethanol. Differences in NT receptor densities may mediate, in part, genetically selected differences in ethanol sensitivity between the two lines of mice. The use of [3H] NT at concentrations from 0.02 to 20 nM yielded biphasic binding isotherms as revealed by Scatchard analysis. Membranes from LS ventral midbrain yielded dissociation constants (KD values) of 0.34 and 3.85 nM for the high (NTH) and low (NTL) affinity components, respectively. SS membranes displayed similar KD values, however the maximum number of binding sites (Bmax) for both receptor subtypes were significantly greater in SS than in LS membranes (46.7 vs. 71.5 fmol/mg protein for NTH and 170.2 vs. 208.2 fmol/mg protein for NTL). Using levocabastine, and H1 antagonist with selectivity for NTL, characterization of NTH and NTL binding in nine brain regions was performed. In general, membranes from each brain region of SS mice had higher densities than LS for both receptor subtypes. Significant differences for the total density of receptors and NTL were found in entorhinal cortex, nucleus accumbens, hippocampus, and ventral midbrain. The only region to differ in NTH was the ventral midbrain. Competition experiments using various NT fragments to compete for NTH binding showed the C-terminal amino acids to be essential for binding. The order of potency was NT1-13 = NT8-13 greater than Neuromedin N greater than NT1-8 = NT1-11.


Critical phenomenon of granular flow on a conveyor belt.
The relationship between the granular wafer movement on a two-dimensional conveyor belt and the size of the exit together with the velocity of the conveyor belt has been studied in the experiment. The result shows that there is a critical speed v(c) for the granular flow when the exit width d is fixed (where d=R/D, D being the diameter of a granular wafers). When v<v(c), the outflow rate Q increases linearly with the speed v and the flow rate Q=rho(v)R. The turning point of the Q-v curve occurs at the speed v(c). The critical speed v(c) is dependent on the exit width d. When v>v(c), the flow rate Q is described as Q=Crho(v)(beta)(d-k)(3/2). These are the effects of the interaction among the granular wafers and the change of the states of the granular flow due to the changing of the speed or the exit width d.


Neurological manifestations in lysosomal storage disorders - from pathology to first therapeutic possibilities.
Lysosomal storage disorders (LSDs) represent a large and heterogeneous group of inborn errors of metabolism with a rare incidence for the single disease but a respectable overall incidence of 1 in 7700 live births. Neurological involvement in LSDs is quite common and in the last years knowledge about the pathology and clinical course of LSDs has been rapidly increased. Enormous progress has been made in the treatment of LSDs by enzyme replacement, substrate reduction and research on gene therapy. This review aims to describe the progress made as well as the present limitations in this particular field of metabolic medicine. It focuses on those storage disorders with major neurological symptoms or complications where treatment is already available (Gaucher disease, Fabry disease, mucopolysaccharidosis type I) or predictable (Pompe disease, MPS II, MPS IV, MPS VI).


Practical and functional consequences of aging.
In the gerontologic and geriatric study of 70-year-old people in Göteborg, Sweden, the first cohort (born 1901/1902) has been followed for 15 years, the second (born 1906/1907) for 9 years, and an intervention study has been added to the third cohort (born 1911/1912). The results have allowed a comparison between age-related changes in joint function and manifestations of aging in other organs and organ systems, e.g. striated muscles, density of the skeleton, certain cardiovascular parameters, as well as changes in body mass and body composition. At age 79, a considerable proportion of the elderly had some restriction of their range of motion in one or several joints (one fifth in knee joints, two thirds in hip joints) compared with younger individuals. In the vast majority of probands, this restriction was rather limited and could be described as a stiffness of the locomotor system that could be due either to the aging process with a decrease in elastic tissue components or to age-related changes in behavior and physical activities. Joint complaints of the lower extremities were more frequent than complaints of the upper extremities. Previous sedentary workers were more disabled in activities of daily living than those whose work had previously been physically strenuous.(ABSTRACT TRUNCATED AT 250 WORDS)


Treatment with the nitric oxide synthase inhibitor L-NAME provides a survival advantage in a mouse model of Kras mutation-positive, non-small cell lung cancer.
Oncogenic mutations in the gene KRAS are commonly detected in non-small cell lung cancer (NSCLC). This disease is inherently difficult to treat, and combinations involving platinum-based drugs remain the therapeutic mainstay. In terms of novel, pharmacologically actionable targets, nitric oxide synthases (NOS) have been implicated in the etiology of KRAS-driven cancers, including lung cancer, and small molecular weight NOS inhibitors have been developed for the treatment of other diseases. Thus, we evaluated the anti-neoplastic activity of the oral NOS inhibitor L-NAME in a randomized preclinical trial using a genetically engineered mouse model of Kras and p53 mutation-positive NSCLC. We report here that L-NAME decreased lung tumor growth in vivo, as assessed by sequential radiological imaging, and provided a survival advantage, perhaps the most difficult clinical parameter to improve upon. Moreover, L-NAME enhanced the therapeutic benefit afforded by carboplatin chemotherapy, provided it was administered as maintenance therapy after carboplatin. Collectively, these results support the clinical evaluation of L-NAME for the treatment of KRAS mutation-positive NSCLC.


Catechol polymers for pH-responsive, targeted drug delivery to cancer cells.
A novel cell-targeting, pH-sensitive polymeric carrier was employed in this study for delivery of the anticancer drug bortezomib (BTZ) to cancer cells. Our strategy is based on facile conjugation of BTZ to catechol-containing polymeric carriers that are designed to be taken up selectively by cancer cells through cell surface receptor-mediated mechanisms. The polymer used as a building block in this study was poly(ethylene glycol), which was chosen for its ability to reduce nonspecific interactions with proteins and cells. The catechol moiety was exploited for its ability to bind and release borate-containing therapeutics such as BTZ in a pH-dependent manner. In acidic environments, such as in cancer tissue or the subcellular endosome, BTZ dissociates from the polymer-bound catechol groups to liberate the free drug, which inhibits proteasome function. A cancer-cell-targeting ligand, biotin, was presented on the polymer carriers to facilitate targeted entry of drug-loaded polymer carriers into cancer cells. Our study demonstrated that the cancer-targeting drug-polymer conjugates dramatically enhanced cellular uptake, proteasome inhibition, and cytotoxicity toward breast carcinoma cells in comparison with nontargeting drug-polymer conjugates. The pH-sensitive catechol-boronate binding mechanism provides a chemoselective approach for controlling the release of BTZ in targeted cancer cells, establishing a concept that may be applied in the future toward other boronic acid-containing therapeutics to treat a broad range of diseases.


Screening and partial immunochemical characterization of sulfite oxidase from plant source.
Sulfite oxidase [SO; EC 18.104.22.168] catalyses the physiologically vital oxidation of sulfite to sulfate, the terminal reaction in degradation of sulfur containing amino acids, cysteine and methionine. Sulfite oxidase from vertebrate sources is among the best studied molybdenum enzymes. Existence of SO in plants has been established recently by identification of a cDNA from Arabidopsis thaliana encoding a functional SO. The present study was undertaken to identify herbaceous and woody plants (viz., Azardirachta indica L., Cassia fistula L., Saraca indica L., Spinacea oleracea L., and Syzyzium cumini L.), a relatively less explored source, having significant SO activity and to characterize some of its immuno-biochemical properties. The Syzyzium cumini was chosen to characterize SO as it showed maximum enzyme activity in the crude extract as compared to other plants. Absorption spectra of SO revealed two peaks at 235 and 277 nm, but no distinct peak in the visible region could be observed. Crude extract of all the plants were taken into considerations for immuno-biochemical studies. Despite of significant protein structure-functional similarities between plant and animal SO, no cross-reactivity could be established between the two sources of SO. These data suggested that plants SO, however, differed with regards to their immunobiochemical properties.


Focal nodular hyperplasia and hepatic adenoma: epidemiology and pathology.
Focal nodular hyperplasia (FNH) and hepatic adenoma (HA) represent the most frequent non-vascular benign liver tumors. They are often asymptomatic. The widespread use of high-resolution imaging modalities leads to an increase of incidental detection of FNH and HA. Physicians are thus increasingly confronted with these formerly rarely recognized conditions, stressing the need for concise but adequate information on the optimal clinical strategies for these patients. FNH is the most common non-vascular benign tumor of the liver. It probably arises as a polyclonal, hyperplastic response to a locally disturbed blood flow. It is typically found in asymptomatic women. Histologically, FNH can be described as a focal form of cirrhosis. Complications of FNH are extremely rare and surgical resection is generally not advised. HA is a rare monoclonal, but benign liver tumor primarily found in young females using estrogen-containing contraceptives. Although its exact etiology is unknown, a direct link between sex steroid exposure and the uncontrolled hepatocellular growth is suspected. Complications of HA are spontaneous bleeding and malignant transformation. Withdrawal of estrogen treatment and excision of large tumors (>5 cm) are established therapeutic strategies. In conclusion, although FNH and HA are reasonably well-described clinical and histopathological entities, their epidemiology and pathophysiology need to be further unraveled.