Influence of maternal diet during early pregnancy on the fatty acid profile in the fetus at late pregnancy in rats.
The aim of the study was to determine the effects of different dietary fatty acids during the first half of pregnancy on the fatty acid composition of maternal adipose tissue and of maternal and fetal plasma at mid- and late-pregnancy. Pregnant rats received soybean-, olive-, fish-, linseed- or palm-oil diets from conception to day 12 of gestation. Virgin rats receiving the same treatments were studied in parallel. At day 12, some rats were sacrificed and others were returned to the standard diet and studied at day 20. At day 12, the concentrations of most fatty acids in plasma reflected the dietary composition and individual fatty acids in lumbar adipose tissue of pregnant rats correlated with those in the diet. At day 20, the plasma concentration of each fatty acid was higher in pregnant than in both virgin rats and day-12 pregnant rats. The composition in 20-day pregnant (but not in virgin) rats resembled the diet consumed during the first 12 days. Fatty acid concentration in fetal plasma was also influenced by the maternal diet during the first 12 days of pregnancy, and long-chain polyunsaturated fatty acid (LC-PUFA) concentrations correlated with those in the mothers. In conclusion, during the first half of pregnancy maternal adipose tissue stores dietary-derived fatty acids, which are released into blood during late pregnancy enabling LC-PUFA to become available to the fetus.


Survival in a patient with severe paraneoplastic hyponatremia: a case report.
Hyponatremia is a common and potentially life threatening problem in patients with neuroendocrine tumors. A 54-year-old female with a history of smoking and narcotic dependency presented to her primary care physician with nausea, vomiting, fatigue, malaise, ataxia and a serum sodium of 100 mEq/L. A chest computerized tomography (CT) revealed a 4.1 x 4.9 cm precarinal/pretracheal mass encircling the right brachiocephalic vein. A mediastinal biopsy found a malignant, intermediate-size small cell (oat cell) carcinoma. Saline infusion along with intravenous furosemide successfully corrected her hyponatremia. Unfortunately, the patient later died of complications related to her cancer and cancer therapy. Paraneoplastic hyponatremia can be severe, but even severe cases may be successfully treated.


Fractal genomics of SOD1 evolution.
To understand the fundamental processes of gene evolution such as the impact of point mutations and segmental duplications on statistical topography, superoxide dismutase-1 (SOD1) orthologous sequences (n = 50) are studied. These demonstrate scale invariant self-similarity patterns and long-range correlations (LRCs) indicating fractal organization. Phylogenetic hierarchies change when SOD1 orthologs are grouped according to fractal measures, indicating that statistical topographies can be used to study gene evolution. Sliding window k-mer analysis show that majority of k-mers across all SOD1 orthologs are unique, with very few duplications. Orthologs from simpler species contribute minimally (< 1% of k-mers) to more complex species. Both simple and complex random processes fail to produce significant matching k-mer sequences for SOD1 orthologs. Point mutations causing amyotrophic lateral sclerosis do not impact the fractal organization of human SOD1. Hence, SOD1 did not evolve by a patchwork of repetitive sequences modified by point mutations. Moreover, fractal and other methods described here can be used to study the origin and evolution of genomes.


Long-term results of low power, long duration laser trabeculoplasty.
We performed argon laser trabeculoplasty using 0.2-second duration on 15 patients with primary open-angle glaucoma. We then retrospectively compared the results to a similar group of 14 patients on whom a duration of 0.1 second was used. Power was titrated to achieve blanching or small bubble formation. All the other treatment variables were kept constant. Before treatment, the two groups did not differ in mean age, visual acuity, intraocular pressure, or number of drugs. After treatment, there was a 7 to 8 mm Hg decrease in intraocular pressure for both groups over a two-year follow-up period. No statistically significant difference between the two groups was observed for intraocular pressure, visual acuity, or drug score at the various follow-up periods. No patient required subsequent filtering surgery.


High cell density perfusion cultures of anchorage-dependent Vero cells in a depth filter perfusion system.
A depth filter perfusion system (DFPS) with polypropylene fibers had been demonstrated to support high density cultures of anchorage-independent hybridoma cells. The DFPS provides advantages of high surface-to-volume ratio of 450-600 cm(2)/cm(3), low cost set-up, easy operation and scale-up. To test the feasibility of using DFPS for high density cultures of anchorage-dependent cells, Vero cells were cultivated in the DFPS. Gelatin coating on polypropylene fibers in the DFPS was necessary to promote cell attachment and growth. Dissolved oxygen (DO) concentrations could be controlled by sparging air into the reservoir vessel through a filter sparger. When DO concentration was controlled above 40% of air saturation in the DFPS with 40 μm pore size, the maximum cell concentration as estimated on specific lactate production rate, was 3.81×10(7) cells/ml of the total reactor volume. This viable cell concentration is approximately 18 times higher than that obtained in a T-flask batch culture. Taken together, the results obtained here showed the potential of DFPS for high-density cultures of anchorage-dependent cells.


Risk factors of invasive fungal infections in liver transplant recipients: A systematic review and meta-analysis.
Invasive fungal infections (IFIs) remain one of the most common infectious complications after organ transplantation, and liver transplant recipients (LTRs) have the highest mortality rate. However, risk factors associated with IFIs have only been evaluated in small single-center studies. We performed a meta-analysis by conducting a comprehensive search using Ovid MEDLINE, Ovid Embase, Cochrane database of systematic reviews, and Cochrane central register of controlled trials. All case-control and cohort studies evaluating risk factors for IFIs in adult LTRs were screened. Utilizing a random-effects model, a multivariate analysis was completed, and 28 studies were eligible for meta-analysis. Rates of IFIs ranged from 1.4% to 32.7%. Previous antibiotic use (OR 9.3; 95% CI 3.2-27.0) and bacterial infection (OR 4.3; 95% CI 2.1-8.6) were risk factors of invasive candidiasis. Yet for invasive aspergillosis, posttransplant renal replacement therapy (OR 9.2; 95% CI 4.2-20.4), reoperation (OR 8.0; 95% CI 2.9-21.7), and cytomegalovirus infection (OR 6.2; 95% CI 2.0-19.3) were risk factors. The top independent risk factors for IFIs during studies from 2010 to 2019 were previous fungal colonization (OR 9.19; 95% CI 4.92-17.16), reoperation (OR 5.45; 95% CI 2.93-10.15), and previous bacterial infections (OR 3.81; 95% CI 2.13-6.83). These risk factors may be targeted by antifungal prophylaxis in LTRs.


Effectiveness of multiple bolus administration of tissue-type plasminogen activator in acute myocardial infarction.
The feasibility and possible advantages of intravenous bolus administration of recombinant tissue-type plasminogen activator (rt-PA) were investigated in 26 consecutive patients with early (less than 6 hours) evolving acute myocardial infarction. Either an intravenous infusion of 40 clot-lysis megaunits (cIMU) double-chain rt-PA over 1.5 hours followed by 20 cIMU over 5 hours (infusion group, n = 12) or 4 intravenous bolus injections of 10 cIMU at 20 minute intervals (bolus group, n = 14) were randomly administered. Coronary arteriography was performed before and at regular predefined intervals up to 90 minutes from the start of rt-PA administration, and at 24 hours. Acute recanalization of the infarct-related coronary artery was demonstrated in 7 of 12 patients (58%; 95% confidence interval 28 to 85%) in the infusion group and 11 of 14 patients (79%; 95% confidence interval 49 to 95%) in the bolus group (difference not significant). Two patients in the bolus group had reoccluded by 24 hours. Mean time from the start of rt-PA to patency of the infarct-related coronary artery was 39 +/- 6 (standard error of the mean) minutes in the infusion group and 28 +/- 6 minutes in the bolus group (p = 0.2). There were no significant differences in the minimum infarct-related coronary artery luminal diameter measured by computerized quantitative arteriography between the infusion group and the bolus group at 90 minutes or at 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)


The magnitude and distribution of open-loop accommodation using three different methods of opening the loop.
The present study examines the magnitude, distribution, and relationship of open-loop accommodation obtained using the three most common methods of opening the accommodation loop. Open-loop accommodation was measured in 93 young, emmetropic subjects using a Canon R1 objective infrared optometer, and the accommodation loop was opened using the following methods: (1) dark empty field (DA), (2) bright empty field (BA), and (3) viewing a target through a small artificial pupil (PA). PA was found to elicit significantly (p = 0.0001) higher values of open-loop accommodation than either DA or BA and demonstrated a much wider distribution of values than DA or BA. A further experiment demonstrated that the higher PA was attributable to the proximal effect of placing a small artificial pupil close to the eye. Our results suggest that using a small artificial pupil to open the accommodation loop may not produce a veridical measure of open-loop accommodation.


Chimeric GnRH-LH receptors and LH receptors lacking C-terminus palmitoylation sites do not localize to plasma membrane rafts.
Luteinizing hormone and gonadotropin releasing hormone receptors (LHR and GnRHR, respectively) are G protein-coupled receptors with important functions in reproduction. We have developed chimeric GnRHR-LHR that contain the full GnRHR coupled to various forms of the LH receptor C-terminus to explore the role of the LH receptor C-terminus in raft localization of the receptor and signaling. Addition of the full-length LHR C-terminus to GnRHR resulted in localization of the resting chimeric receptor in the bulk membrane rather than plasma membrane rafts as has been reported for the wild-type GnRHR [A. Navratil, S. Bliss, K. Berghorn, J. Haughian, T. Farmerie, J. Graham, C. Clay, M. Roberson, Constitutive localization of the gonadotropin-releasing hormone (GnRH) receptor to low density membrane microdomains is necessary for GnRH signaling to ERK, J. Biol. Chem. 278 (2003) 31593-31602]. With truncation of the LHR C-terminus, approximately 3% of chimeric receptors appeared in low density membrane fractions. Palmitoylation of sites on the LHR C-terminus appears important for raft localization. Mutations to C-terminus palmitoylation sites eliminated translocation of LH receptors from the bulk membrane to rafts upon binding of hCG although these mutant receptors retained the ability to signal via cAMP.


Condyloma latum mimicking keratoacanthoma in patient with secondary syphilis.
A 31 year old man with a condyloma latum simulating a keratoacanthoma at the umbilicus is reported. The umbilicus should be included in the list of known sites of predilection for condylomata lata.


Observer variability in assessment of angiographic vasospasm after aneurysmal subarachnoid haemorrhage.
In clinical practice and in many reported studies about incidences and time courses of vasospasm the angiographic spasms are judged by eye without clear definition of vessel narrowings. To evaluate the reliability of this diagnostic method two experienced neuroradiologists and two experienced neurosurgeons independently in two sessions, examined 30 carotid angiograms performed after an aneurysmal subarachnoid haemorrhage. The intra- and inter-observer agreements for the absent/present and localization diagnosis of vasospasm were calculated by means of Kappa statistics. Kappa values for both intra- and inter-observer agreement showed great variability and in general most of the agreements were not much better than chance expected agreement. The diagnostic method of judging angiographic vasospasm by eye without clear-cut definitions of vessels narrowings is unreliable and should not be used in the future, neither in clinical practice nor in research.


Nanopore-based long-read metagenomics uncover the resistome intrusion by antibiotic resistant bacteria from treated wastewater in receiving water body.
Wastewater treatment plant (WWTP) effluent discharge could induce the resistome enrichment in the receiving water environments. However, because of the general lack of a robust antibiotic-resistant bacteria (ARB) identification method, the driving mechanism for resistome accumulation in receiving environment is unclear. Here, we took advantage of the enhanced ARBs recognition by nanopore long reads to distinguish the indigenous ARBs and the accumulation of WWTP-borne ARBs in the receiving water body of a domestic WWTP. A bioinformatic framework (named ARGpore2: https://github.com/sustc-xylab/ARGpore2) was constructed and evaluate to facilitate antibiotic resistance genes (ARGs) and ARBs identification in nanopore reads. ARGs identification by ARGpore2 showed comparable precision and recall to that of the commonly adopt BLASTP-based method, whereas the spectrum of ARBs doubled that of the assembled Illumina dataset. Totally, we identified 33 ARBs genera carrying 65 ARG subtypes in the receiving seawater, whose concentration was in general 10 times higher than clean seawater's. Notably we report a primary resistome intrusion caused by the revival of residual microbes survived from disinfection treatment. These WWTP-borne ARBs, including several animal/human enteric pathogens, contributed up to 85% of the receiving water resistome. Plasmids and class 1 integrons were reckoned as major vehicles facilitating the persistence and dissemination of ARGs. Moreover, our work demonstrated the importance of extensive carrier identification in determining the driving force of multifactor coupled resistome booming in complicated environmental conditions, thereby paving the way for establishing priority for effective ARGs mitigation strategies.


[Observation on clinical efficacy of activating renal blood circulation and ovarian stimulation formula in treating ovulation failure infertility].
To discuss the clinical efficacy of the activating renal blood circulation and ovarian stimulation formula in treating ovulation failure infertility. Eighty-six cases were randomly divided into two groups: the treatment group and the control group. The treatment group is administered with the activating renal blood circulation and ovarian stimulation formula (composed of 15 g Cuscutae Semen, 15 g Dipsaci Asperoidis Radix, 15 g Lycii Fructus, 15 g Spatholobi Caulis, 10 g Ligustri Lucidi Fructus, 15 g Lycopi Herba, 10 g Typhae Polleu, 10 g Angelicae Sinensis Radix, 15 g Cyathulae Radix etc.), whereas the control group was given clomiphene. The treatment group showed a pregnancy rate of 58.14%, with an ovulation rate of 68.6%. While the control group showed a pregnancy rate of 36.67%, with an ovulation rate of 70%. The comparison between the two groups showed that the activating renal blood circulation and ovarian stimulation formula was significantly different from clomiphene in statistical analysis (P < 0.05), without notable difference in the ovulation rate. Before and after the treatment, there is no significant difference in diameter of dominant follicles between the two groups, with remarkable difference in endometrium (P < 0.05).


Caregiving for elder relatives: which caregivers experience personal benefits/gains?
The present study asks whether the positive, rewarding experiences of caregiving (benefits/gains) emerge merely as a function of caregiver personality, or whether, after personality traits (agreeableness, conscientiousness, extroversion, neuroticism) are taken into account, other interpersonal factors make a difference. Survey data were collected from 63 family caregivers. Bivariate analyses revealed that caregiving benefits/gains were significantly and positively associated with two personality traits (agreeableness, extroversion), family and spouse/partner socio-emotional support, and prior relationship quality. Hierarchical regressions indicated that whereas neither family socio-emotional support nor prior relationship quality significantly predicted variance in caregiving benefits/gains beyond that accounted for by agreeableness and extroversion, spouse/partner socio-emotional support did. Implications for research and practice are discussed.


Barium enemas are a headache.
The frequency of headache after Picolax (sodium picosulphate, Nordic Ltd) preparation for barium enema was investigated and its association with dehydration, as assessed by haemoconcentration, was determined. Eleven out of 41 patients (26.8%) complained specifically of headaches. Although patients with and without headaches developed significant increases in haemoglobin concentration after Picolax preparation, the rise in haemoglobin in those with headaches was significantly greater than in those without (P less than 0.05). In both groups the haemoglobin concentration returned to normal after a bowel washout. These results suggest an association between dehydration and headache developing after a Picolax regimen. It may be possible to prevent this symptom by advising on the intake of specific volumes of fluid during preparation for barium enema.


[Clinical characteristics and prognostic factors of patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis associated interstitial lung disease].
Objective: To analyze the clinical characteristics and prognostic factors of patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5)-positive dermatomyositis associated interstitial lung disease (DM-ILD). Methods: The patients with MDA5+DM-ILD who were admitted to Department of Respiratory Medicine, Nanjing Drum Tower Hospital from January 2017 to March 2021 were enrolled. The clinical data and survival information were analyzed retrospectively. Patients were divided into survival group or death group, and rapid progressive ILD (RP-ILD) group or non-rapid progressive ILD group, according to their survival status and clinical progression. Results: A total of 105 patients with anti-MDA5+DM-ILD (median age of onset 54 years) were enrolled, 58% being female (61 cases). The main sub-type of dermatomyositis was amyopathic dermatomyositis (n=74, 70%), followed by dermatomyositis (n=31, 30%). The main extrapulmonary manifestations were skin lesions (n=60, 57.1%), muscle manifestations(n=20, 19%) and arthralgia/arthritis (n=20, 19%). 15.4% of the patients had positive ANA (antibody titer≥1∶320), and 61.9% of the patients had anti-RO-52 kDa antibody. A total of 66 patients (62.8%) developed RP-ILD, and 58 patients (56.3%) died. Lower oxygenation index (OR=0.974, 95%CI:0.954-0.994, P=0.012) and no joint pain (OR=0.032, 95%CI: 0.002-0.663 P=0.026) were independent risk factors for RP-ILD. Cox regression analysis showed that RP-ILD (HR=3.194, 95%CI:1.025-9.954, P=0.045), older than 53 years (HR=3.450, 95%CI: 1.388-8.577, P=0.008), ferritin level more than 1 330.5 ng/ml (HR=3.032, 95%CI 1.208-7.610, P=0.018) and C-reactive protein (CRP) above 16.95 mg/L (HR=2.794, 95%CI:1.102-7.084, P=0.030) were independent predictors of mortality. Conclusions: The clinical manifestations of patients with anti-MDA5+DM-ILD presenting to the respiratory department were heterogeneous, with most being amyopathic dermatomyositis, and both the incidence of RP-ILD and the risk of death were high. Even in the absence of associated rash, joint, or muscle manifestations, anti-MDA5 antibody screening should be considered in patients with rapidly progressive ILD who were negative on baseline autoantibody screening but positive for anti-RO52kDa antibody.


Special Section on Multimodal Multilingual Development of DHH Learners.
This issue begins the inclusion of a series of articles on multimodal, multilingual communication development. This special section is intended to run for two or three issues, with two or three contributions in each issue.


Assessing a new hip index as a risk predictor for diabetes mellitus.
Recently, a new anthropometric parameter (a new hip index [HI]) was developed, and the HI shows a U-shaped relationship to mortality in the USA population. It is well known that there is an inverse relationship between hip circumference (HC) and the risk of diabetes mellitus. Accordingly, the study sought to investigate whether HI could predict future diabetes mellitus, as compared with HC and the waist-to-hip ratio (WHR), in a general Chinese population. In 2007, we carried out a health examination of 687 participants (mean age 48.1 ± 6.2 years, male 58.1%). Development of diabetes mellitus by the 2007 examination was studied in relation to data from a baseline health examination carried out in 1992. During the follow up, 74 participants were diagnosed with diabetes mellitus. Across the quintiles of baseline HI, the incidence rates of diabetes mellitus were 12.4, 12.4, 9.9, 7.8 and 11.3% in quintile (Q)1, Q2, Q3, Q4 and Q5, respectively (P = 0.698). With the lowest quintile (Q1) as reference, univariate and multivariate Cox regression analyses showed that HI was not associated with diabetes mellitus. In contrast, HC and WHR could predict future diabetes mellitus. Furthermore, WHR had the best discriminatory power for diabetes mellitus (area under the receiver operating characteristic curve 0.691, 95% confidence interval 0.621-0.761), followed by HC (area under the receiver operating characteristic curve 0.623, 95% confidence interval 0.558-0.689) and HI (area under the receiver operating characteristic curve 0.464, 95% confidence interval 0.396-0.531). Compared with HC and WHR, HI was not an independent risk factor for diabetes mellitus in the Chinese population. More studies are required to delineate the limits of the utility of HI.


TiO2 nanoparticles and multi-walled carbon nanotubes monitoring and bioremediation potential using ciliates Pseudocohnilembus persalinus.
In recent years, the release of nanomaterials pollutants to water bodies, to a great extent, attributed to anthropogenic activities. Their impacts on aquatic organisms as well as nanomaterial monitoring and bioremediation using organism have drawn much attentions. However, studies on relationship of nano-contaminants and aquatic organisms are very scarce. Our results showed that titanium dioxide nanoparticles (TiO2-NPs) and Multi-walled carbon nanotubes (MWCNTs) caused an obvious cell decreases on the whole, but a significant increase at 48 h TiO2-NPs exposure, indicating a resistant mechanism in ciliates for nano-toxic. Besides, MWCNTs was more toxic to Pseudocohnilembus persalinus than that of TiO2-NPs in terms of EC50 value. It is firstly found that P. persalinus ingested and released TiO2-NPs through cytostome and cytoproct, which might be the reason that TiO2-NPs less toxic than MWCNTs. The significantly increased superoxide dismutase (SOD) and glutathione S-transferase (GST) enzyme activities and expression levels were evaluated by reactive oxygen species ROS generation, which demonstrated that P. persalinus antioxidant defense enzyme played roles on nano-toxic resistant in ciliates. Moreover, the integrated biomarker response (IBR) was also determined, which demonstrated that MWCNTs had comparatively higher values than those of TiO2-NPs after higher concentration exposure to ciliates. In addition, it was confirmed by the present work that sod, gst and cat played different roles on immunity, and the sensitivity of cat gene expression to these two nanomaterials exposure was dissimilar. Damages of shrunk as well as losses of cilia on the cell surface caused by TiO2-NPs and MWCNTs exposure in P. persalinus using SEM revealed possible physical hazards of aggregated nanomaterials. Our findings will be helpful to understand the effect mechanisms of NPs on ciliates, and also demonstrated the possibility of P. persalinus as bio-indicator of nanomaterials in aquatic and potentials on bioremediation.


"I don't just say, Hi! I'm gay": Sexual Orientation Disclosures in Oncology Clinic Settings Among Sexual Minority Women Treated for Breast Cancer in the U.S. South.
Few studies examine sexual orientation disclosures (SODs) among women with breast cancer; fewer examine the impact of culture and geography on disclosure processes. This study explores how sexual minority women (SMW) in the Southern United States engage in SODs with oncology clinicians. We conducted in-depth interviews with SMW (eg, lesbian, bisexual) treated for early-stage (stages I-III), hormone receptor-positive breast cancer (N = 12), using a semistructured interview guide. Participants completed an online survey prior to the 60-minute interview. Data was analyzed using an adapted pile sorting approach and thematic analysis conventions. Average age of participants was 49.5 years (range: 30-69), all self-identified as cisgender; 83.3% as lesbian, 58.3% were married, 91.7% had completed a 4-year college degree or higher, 66.7% identified as non-Hispanic White, 16.7% as Black, and 16.7% as Hispanic/Latina. Half of the sample had not engaged in SODs with an oncology clinician. Key themes were: (1) religious and political conservatism in the South create SOD barriers; (2) oncologist-specific barriers to SODs; (3) "straight passing" as a discrimination mitigation strategy; and (4) SOD facilitators in oncology settings (ie, strategic disclosures, medical privilege, and lesbian, gay, bisexual, and transgender-friendly branding of oncology centers). SMW with breast cancer living in the U.S. South navigate unique interpersonal barriers to SODs in oncology settings. Clinicians could encourage SODs by fostering inclusive environments via nonheteronormative language, inclusive intake forms, and respect for SMW's SOD navigation processes. Oncology clinicians require culturally relevant, geographic-specific communication training to facilitate SODs among SMW.


Dorsal and Volar Surgical Approaches to the Metacarpophalangeal Joint: A Comparative Anatomic Study.
We compared 3 surgical approaches to the MP joint: a dorsal extensor tendon-splitting approach, a dorsal extensor tendon-reflecting parasagittal approach, and the volar A1 pulley approach. We quantitatively compared each of these approaches by measuring the amount of articular cartilage exposed on the base of the proximal phalanx. We hypothesize that visualization of the articular cartilage of the proximal phalangeal base is enhanced with the volar approach. The MP joints of the 32 available digits were randomly assigned to 1 of 3 surgical approaches: extensor tendon splitting (A), extensor tendon reflecting (B), or volar approach (C). After each approach, the visible articular surface of the base of the proximal phalanx was stained with methylene blue. The MP joints were then disarticulated, and the proximal phalanges were digitally mapped using a 3-dimensional digitizer. Three-dimensional computer software was used to analyze and calculate the dyed exposed surface area and total surface area of each specimen. The mean % exposed joint surface area for the dorsal extensor splitting, dorsal extensor reflecting and volar approaches were 62%, 67% (over the dorsal side of the proximal phalanx) and 54% (over the volar side of the proximal phalanx), respectively. Multiple linear regression showed statistical significance for a smaller percentage of articular surface area exposed with the volar approach. However, this was not clinically significant. A significant association was found between location in the small finger and greater % exposed joint surface, compared to approaches in the index finger. In all volar approach specimens, the collateral insertion site was visible, but not in the dorsal approach specimens. Knowledge of the limits of each exposure is essential for planning the most appropriate surgical approach. The A1 pulley approach provided greater access to the volar 50% of the joint and collateral ligament insertion without violating the extensor mechanism. The amount of joint surface visualized through all 3 approaches was not significantly different. However, based on the accessibility to the collateral ligament insertion site among three different approaches, we recommend the volar A1 pulley approach for treatment of avulsion fractures of the base of the proximal phalanx. For other injuries of the MP joint, including the intra-articular proximal phalanx base fractures, and metacarpal head fractures, the dorsal approaches are still indicated.


Inter- and intra-species crosses between Candida albicans and Candida guilliermondii.
Hybridization was shown to occur both between strains of the imperfect diploid yeast Candida albicans and between C. albicans and the distantly related haploid yeast Candida (Pichia) guilliermondii. Prototrophic hybrids were selected from crosses of multiply marked auxotrophic mutants of the two species. In most cases, mild ultraviolet irradiation of the C. albicans partner was required. Examination of auxotrophic markers in segregants from the hybrids indicated that recombination, rather than heterokaryon formation, had occurred in these crosses. The DNA content of the hybrids varied from diploid or aneuploid (for crosses between C. albicans and C. guilliermondii) to triploid (for C. albicans x C. albicans). It seems possible that genetic exchange analogous to this may occur in nature.


Enhancement of protein modeling by human intervention in applying the automatic programs 3D-JIGSAW and 3D-PSSM.
Fourteen models were constructed and analyzed for the comparative modeling section of Critical Assessment of Techniques for Protein Structure Prediction (CASP4). Sequence identity between each target and the best possible parent(s) ranged between 55 and 13%, and the root-mean-square deviation between model and target was from 0.8 to 17.9 A. In the fold recognition section, 10 of the 11 remote homologues were recognized. The modeling protocols are a combination of automated computer algorithms, 3D-JIGSAW (for comparative modeling) and 3D-PSSM (for fold recognition), with human intervention at certain critical stages. In particular, intervention is required to check superfamily assignment, best possible parents from which to model, sequence alignments to those parents and take-off regions for modeling variable regions. There now is a convergence of algorithms for comparative modeling and fold recognition, particularly in the region of remote homology.


Relationship between depressive symptoms and anemia among the middle-aged and elderly: a cohort study over 4-year period.
The association between anemia and depression has been demonstrated in previous studies, but it's still unclear whether depressive symptoms as a hazard factor for anemia. The findings of a large-scale cross-sectional and longitudinal examination of such an association of among the middle-aged and elderly individuals in China were presented in our study. The data from China Health and Retirement Longitudinal Study in 2011 and 2015 were evaluated. 10,179 and 5,887 participants were included in cross-sectional and longitudinal study, respectively. According to the World Health Organization, hemoglobin concentrations below 13 g/dL for males and 12 g/dL for females are considered anemia. The research population was separated into two groups based on scores of the 10-item short form of the Center for Epidemiologic Studies Depression Scale (CES-D-10): the group with depressed symptoms had a score of more than 10 points, and the group with depressive disorder had a score of more than 20 points. Multilevel logistic regression analyses were conducted to explore the relationship between anemia and varying degrees of depressive symptoms, utilizing three models based on adjusting for different types of covariates. In our cross-sectional investigation, depression disorders were more likely to link to the occurrence of anemia (OR, 1.34; 95% CI, 1.02-1.77; P = 0.035). Additionally, there seems a linear connection between depression questionnaire scores and hemoglobin concentrations (r = - 0.053, P < 0.001). Depressive symptom was significantly associated with anemia over 4 years of follow-up, and the more intense the depressive symptoms, the greater the danger of anemia (depressive symptoms group: OR, 1.27; 95% CI, 1.02-1.57, P = 0.032; depressive disorder group: OR, 1.59; 95% CI, 1.12-2.25, P = 0.010). Our findings suggest that depression symptoms seem related to anemia in the middle-aged and elderly in China cross-sectionally and longitudinally, and that the risk of anemia increases with the severity of depressive symptoms.


Two independent replicons can support replication of the anthrax toxin-encoding plasmid pXO1 of Bacillus anthracis.
The large pXO1 plasmid (181.6kb) of Bacillus anthracis encodes the anthrax toxin proteins. Previous studies have shown that two separate regions of pXO1 can support replication of pXO1 miniplasmids when introduced into plasmid-less strains of this organism. No information is currently available on the ability of the above two replicons, termed RepX and ORFs 14/16 replicons, to support replication of the full-length pXO1 plasmid. We generated mutants of the full-length pXO1 plasmid in which either the RepX or the ORFs 14/16 replicon was inactivated by TargeTron insertional mutagenesis. Plasmid pXO1 derivatives containing only the RepX or the ORFs 14/16 replicon were able to replicate when introduced into a plasmid-less B. anthracis strain. Plasmid copy number analysis showed that the ORFs 14/16 replicon is more efficient than the RepX replicon. Our studies demonstrate that both the RepX and ORFs 14/16 replicons can independently support the replication of the full-length pXO1 plasmid.


Short communication: Ascorbyl/ascorbate ratio as a marker of oxidative stress in larvae (Apis mellifera) exposed to Paenibacillus larvae.
Paenibacillus larvae, the causal agent of American foulbrood disease (AFB), affects Apis mellifera larvae and can induce oxidative stress by overproduction of radical oxygen species (ROS). This study aimed to assess the oxidative stress levels in larvae exposed to three different strains of P. larvae through their diet by examining the ascorbyl radical (A) to ascorbate anion (AH¯) ratio. The results revealed that larvae inoculated with P. larvae exhibited a lower value of this index compared to uninoculated ones. Interestingly, the level of A remained constant, while the concentration of AH¯ increased. Said increase correlated with the virulence of the specific P. larvae strain used in the inoculation. These findings suggest a potential link between AH¯ molecules and a defense response in A. mellifera larvae against infection, consistent with their resistance to P. larvae (LD50).


Backbone and side-chain resonance assignment of the A147T polymorph of mouse TSPO in complex with a high-affinity radioligand.
The integral polytopic membrane protein TSPO is the target for numerous endogenous and synthetic ligands. However, the affinity of many ligands is influenced by a common polymorphism in TSPO, in which an alanine at position 147 is replaced by threonine, thereby complicating the use of several radioligands for clinical diagnosis. In contrast, the best-characterized TSPO ligand (R)-PK11195 binds with similar affinity to both variants of mitochondrial TSPO (wild-type and A147T variant). Here we report the (1)H, (13)C, (15)N backbone and side-chain resonance assignment of the A147T polymorph of TSPO from Mus Musculus in complex with (R)-PK11195 in DPC detergent micelles. More than 90 % of all resonances were sequence-specifically assigned, demonstrating the ability to obtain high-quality spectral data for both the backbone and the side-chains of medically relevant integral membrane proteins.


"Waterpipe Is Like a Wife": Qualitative Assessment of Perspectives on Waterpipe Smoking Dependence.
Waterpipe (WP) smoking has become a global public health problem in recent decades and growing evidence indicates that it can cause nicotine dependence. Most evidence on WP dependence to date has been derived from survey- or laboratory-based studies. This study employed qualitative methods to explore WP users' perceptions of dependence in Aleppo, Syria. A total of 15 focus groups were conducted with 64 adult WP smokers (51 males and 13 females) using a semi-structured interview. All focus group discussions were audiotaped, transcribed, and coded using directed content analysis. Several WP dependence features were consistent with those commonly reported by cigarette smokers. These included positively reinforced features, such as smoking's association with social gatherings and cultural connectedness, and negatively reinforced features including relief of withdrawal symptoms, stress, and boredom. Although interest in quitting was low, many users perceived quitting WP to be difficult and an indicator of loss of control over smoking, a common marker of dependence. Several observed dependence features were specific to WP, including transitioning from social smoking to smoking alone, and adapting one's behavior to the considerable effort normally required to engage in WP smoking despite inconvenience or cost, and often at the expense of other reinforcers such as social interaction. The general and specific features of WP dependence need to be considered in developing instruments to measure WP dependence, in clinical assessment of WP dependence, and in developing cessation programs.


6,6'-Disubstituted benzothiazole trimethine cyanines--new fluorescent dyes for DNA detection.
The influence of methyl-, 2-hydroxyethyl-, dimethyl-, diethyl- and benzoyl-amino substituents in the 6,6'-positions of benzothiazole heterocycle of trimethine cyanines on their spectral-luminescent properties and behavior in presence of DNA, RNA and BSA was studied. It was shown that incorporation of 6,6'-substituents generally leads to the increase in dyes tendency to aggregation, resulting in the considerable decrease in the emission intensity of the disubstituted dyes as compared to the unsubstituted ones. Emission of the studied 6,6'-disubstited dyes in DNA presence is considerably more intensive than in presence of RNA, that points on the existing of DNA binding preference for the mentioned dyes. Insertion of benzoyl-amino groups into the 6,6'-positions permitted us to design the DNA-sensitive dyes on the basis of symmetric trimethine cyanines with unsubstituted polymethine chain, while typically such dyes slightly respond on the presence of biopolymers. 6,6'-Benzoyl-amino-disubstituted trimethine cyanines are proposed as efficient dyes for DNA detection.


Lateral diffusion of membrane proteins in protein-rich membranes. A simple hard particle model for concentration dependence of the two-dimensional diffusion coefficient.
A model for the effect of protein concentration on the rate of lateral diffusion of integral membrane proteins is presented, in which the proteins are represented by equivalent hard circular particles on a surface. As the density of particles increases, the probability of finding a vacancy immediately adjacent to a tracer particle into which it may diffuse decreases, resulting in a concomitant reduction of the tracer diffusion coefficient. Using scaled particle theory to calculate the concentration-dependent probabilities, a simple approximate result is obtained in closed form, that is compared with the results of previously published Monte Carlo lattice simulations and experimental observations.


[A primary care program in old age psychiatry: background, implementation and first experiences].
The specific characteristics of elderly people, who are likely to develop somatic and psychiatric co-morbidity, and cognitive deterioration, require tailored support in primary care. The first results of a support programme for the elderly in primary care are encouraging. Further research will show whether the EPO has sufficient added value for both the GP and the patient to justify large-scale introduction.


Changes in the prevalence of rotavirus G and P types in diarrheic calves from the Kagoshima prefecture in Japan.
G8 bovine group A rotavirus was the most predominant serotype in calf diarrheal fecal specimens examined between 1995 and 1996 in Japan [Vet. Microbiol. 66 (1999) 301]. To date, no evidence that G8 was the most predominant in the typeable specimens has been observed outside Japan. To investigate whether G8 continues to be as common as G6 and G10, the incidence of the main serotypes was determined in the same area (Kagoshima prefecture) between 1997 and 1998 by reverse transcription-polymerase chain reaction. From a total of 104 rotavirus-positive specimens, we successfully identified G type in 79 (76.0%) and P type in 71 (68.3%). The combination of G and P types varied periodically; in 1995, G10P[11] was most common. The most predominant types changed drastically in 1996, and G8 and mixed P types were the most predominant. A dramatic shift of the most predominant type occurred again in 1997 when G6P[5] was most common. This frequency of G6P[5] also continued in 1998. These results suggest that the serotypes prevailing in certain areas change periodically.


Speckle noise reduction in ultrasound biomedical B-scan images using discrete topological derivative.
Over three decades, several despeckling techniques have been developed by researchers to reduce the speckle noise inherently present in ultrasound B-scan images without losing the diagnostic information. The topological derivative (TD) is the recently adopted technique in the area of biomedical image processing. In this work, we computed the topological derivative for an appropriate function associated to the ultrasound B-scan image gradient by assigning a diffusion factor k, which indicates the cost endowed to that particular image. In this article, a novel image denoising approach, called discrete topological derivative (DTD) has been implemented. The algorithm has been developed in MATLAB7.1 and tested over 200 ultrasound B-scan images of several organs such as the liver, kidney, gall bladder and pancreas. Further, the performance of the DTD algorithm has been estimated by calculating important performance metrics. A comparative study was carried out between the DTD and the traditional despeckling techniques. The calculated peak signal-to-noise ratio (PSNR) (the ratio between the maximum possible power of a signal and the power of corrupting noise that affects the fidelity of its representation) value of the DTD despeckled liver image is found to be 28 which is comparable with the outperformed speckle reducing anisotropic diffusion (SRAD) filter. SRAD filter is an edge-sensitive diffusion method for speckled images of ultrasonic and radar imaging applications. Canny edge detection and visual inspection of DTD filtered images by the trained radiologist found that the DTD algorithm preserves the hypoechoic and hyperechoic regions resulting in improved diagnosis as well as tissue characterization.


Basic essential education program (BEEP): a brief introductory faculty development course for medical teachers.
Physicians have a unique role in teaching future physicians and allied health professionals. Yet, most medical doctors have limited instruction in this critical component of their daily activity. This study was a prospective cohort study of the effectiveness of a local teaching program at two teaching hospitals for junior faculty. Based on a needs analysis and literature review, the teaching program was developed in an accessible and compact format of six consecutive, one-hour "lunch and learn" sessions, held locally over a six week period. Pre-post questionnaires and focus groups were used to evaluate the program. Participants reported being satisfied with the course as whole, particularly in respect to the format and location. There was an improvement in their knowledge in all content areas covered. The greatest benefits were derived from fostering a community of practice and having the opportunity to role play and simulate teaching skills. An attitudinal change towards teaching was noted. A brief, local faculty development program was effective in enhancing physicians' knowledge, skills, and attitudes in teaching.


Euglycemic Diabetic Ketoacidosis Precipitated by SGLT-2 Inhibitor Use, Pericarditis, and Fasting: A Case Report.
Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes mellitus. Less prevalent is euglycemic DKA (eDKA)-DKA with serum glucose less than 200 mg/dL; however, it is increasing in frequency with the introduction of sodium glucose cotransporter 2 (SGLT-2) inhibitors for treatment of type 2 diabetes. We report a case of SGLT-2 inhibitor-associated eDKA presenting with concurrent acute pericarditis. Our case suggests that the cause of eDKA can be multifactorial when decreased oral intake occurs in the setting of an acute cause of physiologic stress. Prompt recognition of eDKA in the emergency department may allow earlier diagnosis and treatment directed at one or more of its underlying causes.


Teaching socially appropriate behavior to eliminate hoarding in a brain injured adult.
A brain injured male hoarded large quantities of unuseable items at every opportunity. The treatment consisted of two phases. First, he was taught to collect baseball cards. Second, after each meal, the client was provided with an apron and a glove and asked to pick up trash in the area and deposit the trash in an appropriate receptacle. If he hoarded, he was told not to pick up trash without his apron and glove and escorted to a quiet area for about 10 seconds. The procedure was successful in suppressing the behavior within 8 days.


Identification of acetylcholine and propionylcholine in bull spermatozoa by integrated pyrolysis, gas chromatography and mass spectrometry.
Acetylcholine was identified in fertile bull spermatozoa using combined pyrolysis gas-chromatography and mass spectrometry. Bull spermatozoa contain other minor choline esters in smaller quantities than acetylcholine. One of the minor choline esters is possibly propionylcholine. The spermatozoa from infertile bulls exhibited low motility and very low levels of acetylcholine.


Effect of pullet body weight and hen dietary amino acid treatments on their progeny fed high and low amino acid diets.
Four studies were conducted on Cobb 700 broilers to evaluate the dietary protein and any maternal effects on live production and processing parameters. Day-old Cobb 700 broiler breeder pullets were reared to conform to 2 different BW curves (control BW and increased BW) with 8 replicate pens per treatment. Birds were fed common diets from 1 d of age until first egg (24 wk). At 24 wk, 12 pens of each pullet treatment were given different amino acid (AA) diets (low = 14% CP, high = 15% CP). The performance of female and male progeny from 32 and 45 wk hens were evaluated on low AA and high AA density diets. The 4 progeny trial designs were identical factorial 2 × 2 × 2 designs, with 2 pullet BW curves (control BW and increased BW), 2 dam CP diet levels (low and high), and 2 progeny CP diets (low and high), with 6 replicates each containing 18 birds, for a total of 108 broiler progeny per treatment. Broiler chickens on the higher AA density feed exhibited consistent improvement in mid-growth BW and FCR and white meat yield percentage. Some maternal effects were noted, including increased carcass yield in female broilers from 32 wk old hens. There were 3-way interactions of pullet BW × hen dietary AA × progeny dietary AA treatments for female progeny carcass yield (from 32-week-old hens) and male tender yield (from 45-week-old hens). There were 2-way interactions of pullet BW x hen dietary AA treatments effect on female and male progeny drumstick yield from 32-week-old hens, pullet BW × progeny dietary AA treatments effect on male 27 d BW from 32-week-old hens, and hen dietary AA × progeny dietary AA treatments effect on male thigh yield from 45-week-old hen. The epigenetic effects of maternal pullet BW and dietary AA treatments were seen in processing yields suggesting, the need of dietary CP changes of the progeny.


Cross-sectional echocardiographic demonstration of biventricular thrombus.
Nine months following extensive myocardial infarction, a 60-year-old man presented with intermittent right heart failure. Cross-sectional echocardiography demonstrated biventricular thrombi, the right ventricular thrombus being very close to the tricuspid valve and possibly interfering with its function. Post-mortem examination confirmed the echocardiographic findings.


Carcinoid valve disease.
Carcinoid is a rare neuroendocrine tumor that typically originates in the gastrointestinal tract and can result in a constellation of symptoms, mediated by vasoactive substances, referred to as carcinoid syndrome. Carcinoid valve and heart disease is characterized by the plaque-like, endocardial fibrous tissue deposits, primarily affecting the right heart endocardium and valves, which result as a consequence of the disease process. Potential mechanisms for the carcinoid valve disease include the complex role of excess serotonin and its interaction with serotonin receptors and transporters. Carcinoid valve and heart disease is a frequent occurrence in patients with carcinoid syndrome and is accountable for substantial morbidity and mortality. Cardiac surgery remains the most effective treatment option for carcinoid valve disease and a multidisciplinary approach at an experienced center is recommended for patients with metastatic carcinoid and carcinoid heart disease.


Quadruple Semitendinosus Graft Construct and Suspensory Button Fixation for Anterior Cruciate Ligament Reconstruction.
Surgical techniques for anterior cruciate ligament reconstruction are evolving, becoming less invasive, with fewer and smaller incisions, preservation of knee bone stock and tendons at the donor site, and better graft positioning and fixation. We describe an anterior cruciate ligament reconstruction technique that aims to preserve bone stock and spares the gracilis. The semitendinosus graft construct is prepared in a quadruple way and fixed with a cortical button in both tunnels, with increased stiffness and resistance of the graft construct. The tibial tunnel is filled at the end of the operation with a bone dowel, keeping the bone stock intact. This technique is safe, with a short learning curve; preserves the gracilis; saves bone; and increases the stiffness and resistance of the tibial fixation.


Purification, crystallization and preliminary X-ray diffraction analysis of yeast regulatory particle non-ATPase subunit 6 (Nas6p).
The regulatory particle non-ATPase subunit, Nas6p, from Saccharomyces cerevisiae has been crystallized by the hanging-drop vapour-diffusion method using PEG 4000 as precipitant. The crystals belong to the space group P2(1)2(1)2(1), with unit-cell parameters a = 41.43 (2), b = 61.74 (1), c = 98.09 (2) A, and contain one molecule in the asymmetric unit. A complete diffraction data set using synchrotron radiation was collected to 2.6 A resolution.


Photothrombotic infarction triggers multiple episodes of cortical spreading depression in distant brain regions.
The purposes of this study were to determine whether cortical spreading depression occurs outside of the infarct produced by photothrombotic vascular occlusion, and also the direction of spreading. Focal cerebral thrombotic infarction was produced by irradiating the exposed skull of anesthetized rats with green light (560 nm) following systemic injection of rose bengal dye. At proximal sites (approximately 2 mm anterior to the infarct border), transient, severe hyperemic episodes (THEs) lasting 1-2 min were intermittently recorded. THE frequency was greatest in the first hour and declined over a 3-h period. THEs were accompanied (and usually preceded) by a precipitous rise in [K+]0 (from approximately 3 to > 40 mM) and were associated with increases in local tissue oxygen tension (tPO2). Following the rise in [K+]0, clearance of [K+]0 to its pre-THE baseline preceded baseline recovery of CBF. These data indicate that THEs were reactive to physiologic events resembling cortical spreading depression (CSD), which provoked increased demand for oxygen and blood flow, and which spread from proximal sites to areas more distal (approximately 4 mm) from the rim of the evolving infarct. MK-801 (1 mg/kg, i.v.) inhibited subsequent CSD-like episodes. We conclude that photothrombosis-induced ischemia provoked CSD which was triggered either within the infarct core or in the infarct rim and spread to more distal sites. Whether multiple episodes of CSD during infarct generation are responsible for the remote consequences of focal brain injury remains to be determined.


Resection of a thoracoabdominal ganglioneuroma via a retroperitoneal minimally invasive approach.
A 10-year-old girl presented to her pediatrician with a history of cough and fever. A chest radiograph revealed a paraspinal mass. On cross-sectional imaging, the mass traversed the diaphragm, extending from T9 to L1 spinal levels with involvement of the T10-12 neural foramen. Vanillylmandelic and homovanillic acid levels were normal. On review of historical radiographs, the mass had increased in size. Thus, surgical resection was recommended for diagnosis and treatment. The patient was placed in left lateral decubitus position. The retroperitoneal space was accessed inferior to the twelfth rib. One 12 mm and two 5 mm ports were used. Development of the retroperitoneal space was achieved with both blunt dissection and a vessel-sealing device. The diaphragm was incised to resect the thoracic component of the mass. The tumor was adherent at the neural foramen and was resected flush with the spine. The diaphragm repaired primarily. She was discharged home on post-operative day four without complication. Pathology demonstrated a ganglioneuroma. The patient was well at her follow-up, and imaging one year postoperatively was without recurrence. No additional treatment was required. A laparoscopic retroperitoneal approach allows for a safe, minimally invasive resection of a thoracoabdominal mass without violation of the abdominal cavity.


Affinity chromatography with monolithic capillary columns. II. Polymethacrylate monoliths with immobilized lectins for the separation of glycoconjugates by nano-liquid affinity chromatography.
Monolithic capillary columns with surface bound lectin affinity ligands were introduced for performing lectin affinity chromatography (LAC) by nano-liquid chromatography (nano-LC). Two kinds of polymethacrylate monoliths were prepared, namely poly(glycidyl methacrylateco-ethylene dimethacrylate) and poly(glycidyl methacrylate-co-ethylene dimethacrylate-co-[2-(methacryloyloxy)ethyl]trimethyl ammonium chloride) to yield neutral and cationic macroporous polymer, respectively. Two lectins including concanavalin (Con A) and wheat germ agglutinin (WGA) were immobilized onto the monolithic capillary columns. The neutral monoliths with immobilized lectins exhibited lower permeability under pressure driven flow than the cationic monoliths indicating that the latter had wider flow-through pores than the former. Both types of monoliths with immobilized lectins exhibited strong affinity toward particular glycoproteins and their oligosaccharide chains (i.e., glycans) having sugar sequences recognizable by the lectin. Due to the strong binding affinity, the monoliths with surface bound lectins allowed the injection of relatively large volume (i.e., several column volumes) of dilute samples of glycoproteins and glycans thus allowing the concentration of the glycoconjugates and their subsequent isolation and detection at low levels (approximately 10(-8) M). To further exploit the lectin monoliths in the isolation of glycoconjugates, two-dimensional separation schemes involving LAC in the first dimension and reversed-phase nano-LC in the second dimension were introduced. The various interrelated methods established in this investigation are expected to play a major role in advancing the sciences of "nano-glycomics".


Blood loss associated with uncemented total hip replacement: hypotension does not affect blood loss.
Twenty-seven patients who were moderately hypotensive during uncemented total hip replacement were compared with a group of normotensive patients. There was no statistical difference (P less than 0.05) in blood loss measured at time of operation, following operation or in the calculated loss. Hypotension, which is known to be dangerous in the elderly, conferred no benefit and should be avoided.


Feasibility of a 59Fe ferrokinetic study based on bone-marrow scans.
The purpose of this study was to evaluate the feasibility of a method that would use 59Fe quantitative sequential scintigrams together with a few blood samples in place of conventional ferrokinetic studies. To quantitate the efficiency of erythropoiesis or iron deposition sites, the radio-iron blood activity was subtracted by means of a whole body scanning with 99mTc-labelled erythrocytes. The study was performed on 31 patients (36 examinations) and regions of interest were drawn by three physicians on the sacral bone, the liver, the spleen and the femoral bone. To assess the physical feasibility of the scintigraphic method, correlation coefficients were computed between the number of counts of the 59Fe and 99mTc images and the corresponding 99mTc and 59Fe activities. To assess the clinical feasibility, the consistency of the data resulting from the drawing of the ROIs was verified and those of conventional ferrokinetics were introduced and their consistency verified. These assessments suggest that the scintigraphic method can be used in place of the conventional external counting method.


Diagnostic ability and sectoral structure-function relationship of circumpapillary and macular superficial vessel density in early glaucomatous eyes.
This study aimed to evaluate the diagnostic ability and sectoral structure function relationship of circumpapillary vessel density (cpVD) and macular vessel density (mVD) with optical coherence tomography angiography (OCTA) in early glaucomatous (EG) eyes. 224 EG eyes of 167 patients (mean deviation (MD) > - 6 dB) and 70 normal eyes of 70 subjects were enrolled in this retrospective cross-sectional study. All patients underwent OCT and OCTA scanning. Diagnostic abilities were evaluated with area under receiver operating characteristic curves (AUROC). Structure function relationships of superior, inferior and Garway-Heath sectoral values with its corresponding visual field (VF) sensitivity were determined using linear mixed models. AUROCs were 0.798, 0.621, 0.876 and 0.835 for cpVD, mVD, circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and ganglion cell-inner plexiform layer, respectively. AUROC of cpVD was significantly lower than cpRNFLT (P = 0.010) and higher than mVD (P < 0.001). All Garway-Heath sectors of cpVD significantly correlated with its corresponding VF sensitivity except for the nasal sector. MVD also showed significant structure function relationship and the correlations were stronger in the perifoveal region (6 mm annulus) than in the parafoveal region (3 mm annulus). CpVD demonstrated moderate diagnostic ability and both cpVD and mVD demonstrated significant association with VF sensitivity in EG eyes.


Afro-Caribbeans Have a Lower Prevalence of Advanced Colon Neoplasia than African-Americans.
The black population in the USA is a heterogeneous group composed of smaller subgroups from different origins. The definition of black in many colorectal cancer (CRC) risk studies is vague, and differences in CRC risk comparing black subpopulations have not been evaluated. The aim of the study is to compare advanced colorectal neoplasia (ACN) between two subgroups of black populations: African-American (AA) and Afro-Caribbean (AC). A secondary aim was to determine whether there are differences in prevalence of adenomas. This was a retrospective study of 3797 AA and AC patients undergoing first time screening colonoscopy in two different institutions in the USA. Overall adenoma prevalence was 29.3% for the entire population with 29.5% in AAs and 29.0% in AC with no statistically significant difference between the study groups (AOR: 1.02; 95% CI 0.88-1.18, P = 0.751). However, ACN was significantly higher in the AA group (11.8%) compared to AC (9.0%) (AOR: 1.30, 95% CI 1.02-1.66, P = 0.034). It was observed that AAs had ACN at a higher BMI than AC. After adjusting for BMI/ethnicity interactions, the difference in ACN between both groups became more significant (AOR: 1.93, 95% CI 1.16-3.23, P = 0.012). AAs have a higher risk of ACN than AC. Current recommendations to start screening in average-risk AAs at an earlier age may not apply to other black subgroups.


Do Contrast-Fill Patterns Immediately After Coil Embolization of Small Saccular Aneurysms Impact Long-Term Results?
It is generally accepted that filling of a saccular aneurysm with contrast immediately after coil embolization predisposes to later recanalization. However, not all such scenarios evolve similarly over time. We investigated outcomes of small (≤ 7 mm) aneurysms with contrast-filled sacs immediately after coil embolization, evaluating the impact of pattern and degree of filling on subsequent recanalization. Between January, 2008 and December, 2010, 186 small (≤ 7 mm) saccular aneurysms that retained contrast after coil embolization accrued for this study. Lesions were categorized by pattern (eccentric vs. concentric) and degree of filling on working projections. Clinical and morphologic factors were also analyzed to assess impact on subsequent recanalization. Morphologic outcomes at 6 months or more were assessed. In 93.5 % (174/186) of aneurysms with visible contrast retention, complete occlusion was evident on follow-up imaging studies at 6 months. Multiple logistic regression analysis indicated that eccentric (vs. concentric) contrast filling carried greater risk of subsequent recanalization (p = 0.020). Stent placement and progressive occlusion were also linked, falling short of statistical significance (p = 0.089). Of 166 progressively occluded aneurysms followed for more than 12 months (mean, 30.8 ± 7.3 months), 158 (95.2 %) exhibited stable occlusion. Small (≤ 7 mm) aneurysms that retain contrast immediately after coil embolization are more likely to become completely occluded over time through progressive thrombosis. However, an eccentric fill pattern may predispose to recanalization.


Effect of inhaled anaesthetics on cognitive and psychiatric outcomes in critically ill adults: a systematic review and meta-analysis.
Sedation of critically ill patients with inhaled anaesthetics may reduce lung inflammation, time to extubation, and ICU length of stay compared with intravenous (i.v.) sedatives. However, the impact of inhaled anaesthetics on cognitive and psychiatric outcomes in this population is unclear. In this systematic review, we aimed to summarise the effect of inhaled anaesthetics on cognitive and psychiatric outcomes in critically ill adults. We searched MEDLINE, EMBASE, and PsycINFO for case series, retrospective, and prospective studies in critically ill adults sedated with inhaled anaesthetics. Outcomes included delirium, psychomotor and neurological recovery, long-term cognitive dysfunction, ICU memories, anxiety, depression, post-traumatic stress disorder (PTSD), and instruments used for assessment. Thirteen studies were included in distinct populations of post-cardiac arrest survivors (n=4), postoperative noncardiac patients (n=3), postoperative cardiac patients (n=2), and mixed medical-surgical patients (n=4). Eight studies reported delirium incidence, two neurological recovery, and two ICU memories. One study reported on psychomotor recovery, long-term cognitive dysfunction, anxiety, depression, and PTSD. A meta-analysis of five trials found no difference in delirium incidence between inhaled and i.v. sedatives (relative risk 0.95 [95% confidence interval: 0.59-1.54]). Compared with i.v. sedatives, inhaled anaesthetics were associated with fewer hallucinations and faster psychomotor recovery but no differences in other outcomes. There was heterogeneity in the instruments used and timing of these assessments. Based on the limited evidence available, there is no difference in cognitive and psychiatric outcomes between adults exposed to volatile sedation or intravenous sedation in the ICU. Future studies should incorporate outcome assessment with validated tools during and after hospital stay. PROSPERO CRD42021236455.


The use of 18F-2-fluorodeoxyglucose (FDG) to label antibody fragments for immuno-PET of pancreatic cancer.
We generated 18F-labeled antibody fragments for PET imaging using a sortase-mediated reaction to install a transcyclooctene (TCO)-functionalized short peptide onto proteins of interest, followed by reaction with a tetrazine-labeled-18F-2-deoxyfluoroglucose (FDG). The method is rapid, robust, and site-specific (radiochemical yields >25%, not decay corrected). The availability of 18F-2-deoxyfluoroglucose avoids the need for more complicated chemistries used to generate carbon-fluorine bonds. We demonstrate the utility of the method by detecting heterotopic pancreatic tumors in mice by PET, using anti-Class II MHC single domain antibodies. We correlate macroscopic PET images with microscopic two-photon visualization of the tumor. Our approach provides easy access to 18F-labeled antibodies and their fragments at a level of molecular specificity that complements conventional18F-FDG imaging.


Transcriptional effects of actin-binding compounds: the cytoplasm sets the tone.
Actin has emerged as a versatile regulator of gene transcription. Cytoplasmatic actin regulates mechanosensitive-signaling pathways such as MRTF-SRF and Hippo-YAP/TAZ. In the nucleus, both polymerized and monomeric actin directly interfere with transcription-associated molecular machineries. Natural actin-binding compounds are frequently used tools to study actin-related processes in cell biology. However, their influence on transcriptional regulation and intranuclear actin polymerization is poorly understood to date. Here, we analyze the effects of two representative actin-binding compounds, Miuraenamide A (polymerizing properties) and Latrunculin B (depolymerizing properties), on transcriptional regulation in primary cells. We find that actin stabilizing and destabilizing compounds inversely shift nuclear actin levels without a direct influence on polymerization state and intranuclear aspects of transcriptional regulation. Furthermore, we identify Miuraenamide A as a potent inducer of G-actin-dependent SRF target gene expression. In contrast, the F-actin-regulated Hippo-YAP/TAZ axis remains largely unaffected by compound-induced actin aggregation. This is due to the inability of AMOTp130 to bind to the amorphous actin aggregates resulting from treatment with miuraenamide. We conclude that actin-binding compounds predominantly regulate transcription via their influence on cytoplasmatic G-actin levels, while transcriptional processes relying on intranuclear actin polymerization or functional F-actin networks are not targeted by these compounds at tolerable doses.


Corrigendum: Novel TTC37 Mutations in a Patient with Immunodeficiency without Diarrhea: Extending the Phenotype of Trichohepatoenteric Syndrome.
[This corrects the article on p. 2 in vol. 3, PMID: 25688341.].


[Predominant respiratory symptoms in indications for prolonged esophageal pH-monitoring in children].
An increasing prevalence of extraesophageal complications of gastroesophageal reflux (GER) has been seen. Evaluation of clinical profiles of patients submitted to prolonged esophageal pH monitoring could help to identify the patients who could benefit from the early diagnosis of GER. To evaluate the population, indications and results of esophageal pH-monitoring for the diagnosis of GER in a pediatric gastroenterology clinic. Data from 190 children and adolescents who had esophageal pH-monitoring were analyzed. A descriptive analysis of the population was performed and the children were categorized in five groups according to the age. The equipment used was a Digitrapper MKIII (Synetics) and all data were analyzed by using a software EsopHogram 5.7. Reflux index was established for analysis. The most frequent indications for the exam were: asthma (26.8%), apnea/cyanosis (20%), recurrent pulmonary infections (18.4%), wheezing infant syndrome (15.8%) and chronic cough/horseness (11%). The most frequent groups of age for the respiratory symptoms were: asthma--above 5 years (92.2%); apnea/cyanosis--under 3 months (55.3%); recurrent pulmonary infections and wheezing infant syndrome--3 to 12 months (31.4% and 83.3%). Reflux index of patients with positive exam for GER was significantly higher in patients under 2 years than above 2 years of age. Respiratory symptoms were predominant among the indications for esophageal pH-monitoring in children. The knowledge of the clinical profile of the patients who had esophageal pH monitoring could help to improve the technical quality of the exam.


Exposure to occupational air pollution and cardiac function in workers of the Esfahan Steel Industry, Iran.
Air pollution is recognized as an important risk factor for cardiovascular disease. We investigated association of exposure to occupational air pollution and cardiac function in the workers of the steel industry. Fifty male workers of the agglomeration and coke-making parts of the Esfahan Steel Company were randomly selected (n = 50). Workers in the administrative parts were studied as controls (n = 50). Those with known history of hypertension, dyslipidemia, or diabetes, and active smokers were not included. Data of age, body mass index, employment duration, blood pressure, fasting blood sugar, and lipid profile were gathered. Echocardiography was performed to evaluate cardiac function. Left ventricular ejection fraction was lower in workers of the agglomeration/coke-making parts than in controls (mean difference = 5 to 5.5 %, P < 0.001). Mild right ventricular dilatation and grade I pulmonary hypertension were present in three (12 %) workers of the coke-making part, but none of the controls (P = 0.010). According to these results, occupational air pollution exposure in workers of the steel industry is associated with left heart systolic dysfunction. Possible right heart insults due to air pollution exposure warrant further investigations.


Managing spastic hypertonia in children with cerebral palsy via repetitive passive knee movements.
Most children with cerebral palsy have increased muscle tension in the lower extremities, which inevitably leads to abnormal gait characteristics. Proper management of excessive muscle tension is therefore of great importance. The aim of this study was to explore the effects of continuous passive motion on children with cerebral palsy, regarding their lower extremity spastic hypertonia and ambulatory function. A repeated measures design. Sixteen children with cerebral palsy. Intervention was applied to the subject's knees with a continuous passive motion device (at velocities of 15 and 0º/s) for 20 min. Effects were evaluated via variables measuring range-of-motion, muscle tone, and ambulatory function before, immediately after, and 30 min after intervention. For the 15º/s intervention, significant differences were found in time, intervention, and interaction among variables, including active range-of-motion of the knee (increased), relaxation index (increased), Modified Ashworth Scale (decreased), Timed Up-and-Go (decreased), and 6-Minute Walk test (increased). No difference was found in passive range of motion measurements. For the 0º/s control condition, none of the dependent variables demonstrated statistically significant differences. Repetitive passive movement can reduce lower extremity spastic hypertonia in children with cerebral palsy, and improve ambulatory function in terms of walking speed.


GP-14 protects against severe hypoxia-induced neuronal injury through the AKT and ERK pathways and its induced transcriptome profiling alteration.
Gypenosides are major bioactive ingredients of G. pentaphyllum. In our previous study, we found that gypenosides had neuroprotective effects against hypoxia-induced injury. In the current study, we focused on the protective effects of gypenoside-14 (GP-14), which is one of the newly identified bioactive components, on neuronal injury caused by severe hypoxia (0.3% O2). The results showed that GP-14 pretreatment alleviated the cell viability damage and apoptosis induced by hypoxia in PC12 cells. Moreover, GP-14 pretreatment also attenuated primary neuron injuries under hypoxic conditions. Additionally, GP-14 pretreatment significantly ameliorated neuronal damage in the hippocampal region induced by high-altitude cerebral edema (HACE). At the molecular level, GP-14 pretreatment reversed the decreased activities of the AKT and ERK signaling pathways caused by hypoxia in PC12 cells and primary neurons. To comprehensively explore the possible mechanisms, transcriptome sequencing was conducted, and these results indicated that GP-14 could alter the transcriptional profiles of primary neuron. Taken together, our results suggest that GP-14 acts as a neuroprotective agent to protect against neuronal damage induced by severe hypoxia and it is a promising compound for the development of neuroprotective drugs.


A trinorsesterterpene glycoside from the North American fern Woodwardia virginica (L.) Smith.
A new trinorsesterterpene glycoside was isolated from the ethanol extract of the American fern Woodwardia virginica having a 3-[6-(4,8-dimethyl-nona-1,3,7-trienyl)-4-hydroxy-2,6-dimethyl-cyclohex-1-enyl]-3-hydroxypropionic acid, as the aglycone and a saccharide moiety linked at C-4 to glucoses, xylose or arabinofuranose. The structure was elucidated using extensive spectroscopic analysis (1D and 2D NMR, MS, IR and UV) including determination of absolute stereochemistry by means of the MTPA and PGME derivatives and also by chemical methods.


The effect of almond intake on cardiometabolic risk factors, inflammatory markers, and liver enzymes: A systematic review and meta-analysis.
Almond intake may be correlated with improvements in several cardiometabolic parameters, but its effects are controversial in the published literature, and it needs to be comprehensively summarized. We conducted a systematic search in several international electronic databases, including MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov until April 2021 to identify randomized controlled trials that examined the effects of almond consumption on cardiometabolic risk factors, inflammatory markers, and liver enzymes. Data were pooled using the random-effects model method and presented as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Twenty-six eligible trials were analyzed (n = 1750 participants). Almond intake significantly decreased diastolic blood pressure, total cholesterol, triglyceride, low-density lipoprotein (LDL), non-high-density lipoprotein (HDL), and very LDL (p < 0.05). The effects of almond intake on systolic blood pressure, fasting blood glucose, insulin, hemoglobin A1c, homeostatic model assessment of insulin resistance, C-peptide, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, C-reactive protein (CRP), hs-CRP (high sensitivity C-reactive protein), interleukin 6, tumor necrosis factor-α, ICAM (Intercellular Adhesion Molecule), VCAM (Vascular Cell Adhesion Molecule), homocysteine, HDL, ox-LDL, ApoA1, ApoB, and lipoprotien-a were not statistically significant (p > .05). The current body of evidence supports the ingestion of almonds for their beneficial lipid-lowering and antihypertensive effects. However, the effects of almonds on antiinflammatory markers, glycemic control, and hepatic enzymes should be further evaluated via performing more extensive randomized trials.


Midfacial growth in a consecutive series of preadolescent children with complete unilateral cleft lip and palate following a one-stage simultaneous repair.
To evaluate midfacial growth in prepubertal children with complete unilateral cleft lip and palate following one-stage simultaneous repair. A series of 28 consecutively treated subjects with complete unilateral cleft lip and palate were compared with age- and gender-matched controls with normal midfacial structure. On the lateral cephalograms taken at the age of approximately 10 years, size and position of the maxilla and upper dental arch were evaluated in vertical and horizontal planes. Statistical analysis included independent t tests and nonparametric Mann-Whitney tests. The maxilla was found to be retruded (sella-nasion-point A angle decreased by 4.5 degrees and nasion to point A distance increased by 4.2 mm) and rotated posteriorly (sella-nasion/palatal plane angle decreased by 4.5 degrees) in the cleft group. Maxillary length (pterygomaxillare-point A distance) was diminished by approximately 2 mm. Upper incisors were found retroclined in comparison to controls (both upper incisor axis/sella-nasion and upper incisor axis/palatal plane angles were decreased by 10.7 degrees and 6.1 degrees, respectively). Maxillary prominence, as measured with the sella-nasion-point A angle and the condylion-point A and articulare-point A distances, was decreased. Shortened length and posterior position of the maxillary body were responsible at a ratio of 60% to 40% for a decreased prominence of the maxillary complex. The palatal plane demonstrated a larger inclination to the sella-nasion plane by 4.5 degrees due to a decreased sella-posterior nasal spine distance.


Estimating propulsive forces--sink or swim?
The purpose of this study was to investigate the validity of hydrodynamic force estimation in swimming as calculated by the quasi-static approach. To achieve this a full-scale mechanical arm was developed, built and tested. The mechanical arm, covered with a prosthetic shell and driven at the shoulder was used to simulate a single plane underwater rotation at four elbow configurations. A computer program controlled the shoulder movement to achieve a replicable angular velocity profile for each arm movement. A strain gauge system was used to directly measure the generated arm torque. Repeated trials were conducted at fixed elbow angles of 110 degrees, 135 degrees, 160 degrees and 180 degrees. All trials were filmed using a three-dimensional underwater set-up. Each trial was digitised at 25 Hz and the hydrodynamic drag force profile of the hand calculated using the quasi-static procedure. From these data, the estimated shoulder torque was calculated and compared to the direct measurement of shoulder torque from the mechanical arm. The results showed that the arm produced a repeatable movement through the water. The shoulder torque profiles using the direct measure (the arm) and the indirect measures (quasi-static approach) differed considerably. The quasi-static approach appears not to accurately reflect the hydrodynamic force profile generated by the arm movement in swimming. Furthermore, it seems that the swimmer's hand contribution is overstated in up to date studies. It is essential that the propulsive mechanisms in swimming be further investigated if factors underpinning an optimal technique are to be established.


Skinfold thickness versus isotope dilution for body fat assessment during simulated microgravity: results from three bed-rest campaigns in men and women with and without countermeasures.
Because body composition is altered during head-down bed rest (HDBR), body mass can not be used as an index of energy balance. Consequently diet allowances should not be based on body mass evolution but on fat mass changes. Though criticized, skinfold thickness (ST) is the costless, easiest and fastest method to use for such an objective. The aim of this study was to compare the percentage of body fat (%BF) estimated by ST with the isotope dilution of H2 18O. We compiled data from three HDBR campaigns, one on women (n=8) in November 1998 and two on the same men (n=8) in December 1997 (without countermeasure) and January 1998 (with thigh-cuffs countermeasure), according to a crossover design. Body composition was assessed before and after 6 days of HDBR. %BF was derived from the biceps, triceps, sub-scapular and sup-iliac ST according to Durnin and Wormersly (1974). Fat-free mass was measured on the same day by H2 18O dilution and fat mass was calculated by the difference with body mass and expressed as a percentage. Based on precision tests, the minimum measurable change by ST was 1.1%BF for single measurement point. Both intercepts (F (4,30)=0.89, P=0.45) and slopes (F (4,30)=0.74; P=0.57) of the ST versus dilution relationships were not affected by the periods (December vs January), experimental conditions (control vs HDBR vs HDBR + thigh cuffs) or sex allowing the derivation of a common relationship %BF(st)=0.94 x %BF(dil) (F (1,47)=97.9, P<0.0001; non-significant intercept excluded) with a bias between methods of -1.7+/-2.0 %BF (95% CI: -5.8, 2.4 %BF). ST can be used to measure %BF during HDBR provided great care is placed on training and changes are higher than 1.1 %BF. If the method can be applied for in-flight energy balance monitoring given the high observed energy deficit, a tight monitoring of the individual nutritional status as needed during simulation appears, however, dubious based on this solely method.


The molecular mechanism by which insulin stimulates glycogen synthesis in mammalian skeletal muscle.
The ability of insulin to promote the phosphorylation of some proteins and the dephosphorylation of others is paradoxical. An insulin-stimulated protein kinase is shown to activate the type-1 protein phosphatase that controls glycogen metabolism, by phosphorylating its regulatory subunit at a specific serine. Furthermore, the phosphorylation of this residue is stimulated by insulin in vivo. Increased and decreased phosphorylation of proteins by insulin can therefore be explained through the same basic underlying mechanism.


Preoperative Thrombocytosis Predicts Shortened Survival in Patients with Malignant Peritoneal Mesothelioma Undergoing Operative Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy.
This study was designed to determine the clinical significance of preoperative thrombocytosis in patients with malignant peritoneal mesothelioma (MPM) undergoing operative cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). CRS and HIPEC have been associated with prolonged survival in patients with MPM and is the preferred treatment in select patients. However, patient selection criteria remain ill-defined for this operation that is also associated with significant morbidity and mortality. Preoperative thrombocytosis has been associated with poor outcomes in various malignancies but never studied in MPM. Between January 2006 and December 2015, 100 patients with high-grade epithelioid MPM were evaluated and selected for CRS and HIPEC at our center (M: 53, F: 47; mean age: 54 years [range 17-81 years]). We analyzed various patient and treatment related factors potentially associated with overall survival (OS). The median actuarial overall survival was 32.8 months; the actuarial 1-, 3-, 5-year survivals were 70, 49, and 36%, respectively. On multivariate analysis, suboptimal resection (CCR > 1), high tumor burden (PCI > 20), and elevated preoperative platelet count (>367,000/mm3) were independently associated with shortened OS (P < 0.05). Median OS in patients with elevated versus normal platelet counts were 13 and 58 months, respectively (P < 0.001). Compared with patients with normal platelet counts, patients with elevated counts had significantly greater residual disease after operation (P = 0.008). Elevated preoperative platelet count is independently associated with poor outcome. Notably, thrombocytosis reflects aggressive tumor biology and should be considered a factor in patient selection for CRS and HIPEC.


Dissociated motor loss in the upper extremities. Clinical features and pathophysiology.
Dissociated motor loss occurring in the upper extremities with and without lower extremity myelopathy was evaluated in patients with cervical spondylosis. The presence of dissociated motor loss without attendant myelopathy was correlated with selected compression of the anterior nerve root in the lateral spinal canal, close to the intervertebral foramen. The clinical and radiologic feature differentiating these two dissociative syndromes were reviewed.


Elucidation of Piericidin A1 biosynthetic locus revealed a thioesterase-dependent mechanism of α-pyridone ring formation.
Piericidins are a class of α-pyridone antibiotics that inhibit mitochondrial respiratory chain and exhibit antimicrobial, antifungal, and antitumor activities. Sequential analysis of Streptomyces piomogeues var. Hangzhouwanensis genome revealed six modular polyketide synthases, an amidotransferase, two methyltransferases, and a monooxygenase for piericidin A1 production. Gene functional analysis and deletion results provide overview of the biosynthesis pathway. Furthermore, in vitro characterization of the terminal polyketide synthase module with the thioesterase domain using β-ketoacyl substrates was performed. That revealed a pathway where the α-pyridone ring formation is dependent on hydrolysis of the product β, δ-diketo carboxylic acid by the C-terminal thioesterase followed by amidation and cyclization. These findings set the stage to investigate unusual enzymatic mechanisms in α-pyridone antibiotics biosynthesis, provide a foundation for genome mining of α-pyridone antibiotics, and produce analogs by molecular engineering.


Impact of the Oklahoma IDeA Network of Biomedical Research Excellence research support and mentoring program for early-stage faculty.
The Oklahoma IDeA Network of Biomedical Research Excellence (OK-INBRE) provides a formalized mentoring program and grant awards to new and early-stage faculty throughout Oklahoma. The OK-INBRE Research Project Investigator (RPI) award program has supported 30 faculty from both research-intensive universities and primarily undergraduate institutions (PUIs) over the past 15 yr. To examine the impact of this program, we assessed the career trajectory of OK-INBRE RPI awardees and compared their productivity with a control group of applicants who applied for but did not receive an RPI award. A mixed-methods approach was employed to assess longitudinal programmatic impact. Regression analyses were conducted to estimate the effect of an RPI award on faculty productivity, controlling for institutional affiliation. Key informant interviews were conducted to capture qualitative information about satisfaction and additional outcomes. OK-INBRE RPI awardees had a higher number in total and mean number of publications. In achieving extramural funding, RPI awardees were 12.5 times (P = 0.005) as likely to receive a grant award of any type and 4.5 times (P = 0.06) as likely to receive a subsequent federal grant as those in the control group. Many RPI awardees attributed their career success to OK-INBRE, but they also helped to identify barriers to advancement or productivity associated with their specific home institutions. The combined data indicate that OK-INBRE plays a significant role in launching new and early-stage investigators on a path toward independent research careers, which will in turn have a positive impact on the future of the biomedical research enterprise in Oklahoma.NEW & NOTEWORTHY The Oklahoma IDeA Network of Biomedical Research Excellence (OK-INBRE) has been offering a formalized mentoring program and grant awards to new and early-stage faculty throughout Oklahoma for the past 15 yr. The program has been shown to play a significant role in launching participants on a path toward productive research careers, which will in turn be impactful on the biomedical research enterprise in Oklahoma.


Synthesis and antileukemic activity of 1-[(quinolizidinylalkyl)amino]4/7-R-thioxanthen-9-ones.
Fifteen 1-(quinolizidinylalkyl)amino derivatives of thioxanthenone bearing different substituents on position 4 and 7 were prepared and tested in mice against lymphocytic leukemia P 388. These compounds were inactive or displayed only borderline activity (compounds 1, 10, 15).


Respiratory symptoms and pulmonary function in coal miners: looking into the effects of simple pneumoconiosis.
Although severe impairment of pulmonary function is believed to occur commonly in complicated pneumoconiosis, the relationships of simple coal workers' pneumoconiosis (CWP) to pulmonary function and respiratory symptoms have remained under debate. The study aims to investigate if simple pneumoconiosis is associated with significant impairment of pulmonary function and increased risk of respiratory symptoms. Spirometry and diffusing capacity were performed in 205 miners with simple CWP and 289 without X ray evidence of pneumoconiosis, who were selected from a large underground coal mine in China. A questionnaire on occupational history and respiratory symptoms including breathlessness, chronic cough, and phlegm was administered. The presence or absence of emphysema on their X-ray films was also evaluated. Logistic regression and multiple linear regression analysis were applied to estimate the independent effect of CWP on respiratory symptoms and parameters of pulmonary function. On the average, the miners with CWP had lower values of pulmonary function and higher prevalences of respiratory symptoms, and emphysema than did those without. The simple CWP was associated with increased risk of the respiratory symptoms after adjusting for age, smoking, and years underground. Regression analysis showed that the CWP had significantly independent effects on parameters of pulmonary function. Even when the effects of emphysema, respiratory symptoms indicating chronic bronchitis were taken into consideration, the significant relationship between CWP and decrements in FVC and diffusing capacity remained. The findings of this study are consistent with simple CWP being a contributor to significant decrements in pulmonary function, and to increased risk of respiratory symptoms.


(-)Clausenamide facilitates synaptic transmission at hippocampal Schaffer collateral-CA1 synapses.
Clausenamide is a chiral compound isolated from leaves of the traditional Chinese herb Clausena lansium (lour) Skeels. It has been shown that (-)clausenamide, but not (+)clausenamide, improved learning and memory in amnesia animal models. However, the precise mechanism of clausenamide's actions remains unknown. Here we used an electrophysiological approach to observe the effect of (-)clausenamide on facilitating field excitatory postsynaptic potential (f-EPSP) in the CA1 area of hippocampal slices from rats. The results showed that (-)clausenamide enhanced synaptic transmission at doses 0.1, 1 and 10 μM. The increase of f-EPSP induced by (-)clausenamide was completely inhibited by preincubation with nimodipine (L-voltage-dependent calcium channel blocker, 10 μM), but there was no change when nimodipine was added after (-)clausenamide application. However, ryanodine (ryanodine receptors blocker, 100 μM) attenuated the slope of f-EPSP before or after (-)clausenamide incubation. The data suggested that (-)clausenamide promoted calcium influx to trigger intracellular calcium release which was responsible for potentiating synaptic transmission. Intracellular calcium release induced by (-)clausenamide promoted the activation of CaMKIIα at concentrations of 0.1, 1 and 10 μM, and pretreatment with KN93 (CaMKIIα inhibitor, 10 μM) completely blocked the enhancement of synaptic transmission induced by (-)clausenamide. cAMP response element-binding protein (CREB) was activated by (-)clausenamide and inhibited by KN93 preincubation, but H89 (PKA inhibitor, 10 μM) had no effect, indicating that (-)clausenamide facilitated synaptic transmission by a PKA-independent pathway. Collectively, (-)clausenamide facilitated synaptic transmission by promoting calcium influx to trigger intracellular calcium release, subsequently activating CaMKIIα-CREB signal pathway.


Sustainability considerations for organic electronic products.
The development of organic electronic applications has reached a critical point. While markets, including the Internet of Things, transparent solar and flexible displays, gain momentum, organic light-emitting diode displays lead the way, with a current market size of over $25 billion, helping to create the infrastructure and ecosystem for other applications to follow. It is imperative to design built-in sustainability into the materials selection, processing and device architectures of all of these emerging applications, and to close the loop for a circular approach. In this Perspective, we evaluate the status of embedded carbon in organic electronics, as well as options for more sustainable materials and manufacturing, including engineered recycling solutions that can be applied within the product architecture and at the end of life. This emerging industry has a responsibility to ensure a 'cradle-to-cradle' approach. We highlight that ease of dismantling and recycling needs to closely relate to the product lifetime, and that regeneration should be facilitated in product design. Materials choices should consider the environmental effects of synthesis, processing and end-product recycling as well as performance.


Benzo [a] pyrene-loaded aged polystyrene microplastics promote colonic barrier injury via oxidative stress-mediated notch signalling.
The adsorption of toxic substances on polystyrene microplastics (PSMPs) can modify their biological toxicity and exacerbate the threat to human health. The effects of benzo [a] pyrene (B (a) P)-loaded aged PSMPs on colonic barrier integrity remains unclear. Here, we showed that binding environmentally relevant concentrations of B (a) P alteredl̥ the physicochemical features and markedly enhanced the toxicity of PSMPs. Compared to pristine PSMP, PSMP@B (a) P promoted colonic barrier degradation, body weight loss, colon length shortening, oxidative stress (OS), autophagy, inflammation, and bacterial translocation. Microplastic (MP) exposure induced injury to the colon barrier, including tight junction (TJ) and mucosal barriers, via overactivation of the Notch signalling pathway under increased OS in mice and intestinal organoids. Notably, PSMP@B (a) P exposure exacerbated damage to TJ and the mucosal barrier via the overproduction of reactive oxygen species (ROS), which could be related to the release of B (a) P from PSMP@B (a) P induced by the acidic environment of autophagosomes, which in turn exert synergistic toxic effects with PSMPs. Our study elucidates some of the potential molecular mechanisms by which B (a) P enhances PSMP-related intestinal toxicity, which provides a potential therapeutic approach for diseases caused by PSMP@B (a)P and PSMP pollution.


Primary Hyperparathyroidism Secondary to Ectopic Parathyroid Adenoma: A Case Report.
Primary hyperparathyroidism (PHPT) secondary to parathyroid gland adenoma is mildly symptomatic and thus often incidentally diagnosed. In this report, we present a case of a 46-year-old man who was treated for hypertension and other nonspecific complaints. An elevated level of blood calcium led to the suspicion of parathyroid adenoma. Technetium-99m-methoxyisobutylisonitrile (99mTc-MIBI) planar and single-photon emission computed tomographic scintigraphy (SPECT/CT) confirmed the presence of a 10-mm-wide adenoma behind the sternal handle in the anterior mediastinum. The tumor was excised by Kocher's cervical access along with the right and left upper horns of the thymus gland and was histologically confirmed as being of parathyroid nature. However, blood parathyroid hormone and calcium remained persistently elevated. Repeated scintigraphy imaging revealed the presence of another retrosternal tracer focus at the level of Ludwig's angle. The patient was reoperated with the longitudinal sternotomy access, and thymus remnants, parathymic nodule, and fragments of mediastinal fat and right parietal pleura were removed. On the second postoperative day, parathyroid hormone and calcium reverted to normal values, but the patient remained hypertensive. Despite the successful surgical treatment, the patient remained hypertensive suggesting that the underlying reason was a familial hypertensive disease rather than parathyroid adenoma. In conclusion, this report underscores the need for diagnostic vigilance in the case of persisting hypercalcemia with hypertension and diagnostic and surgical difficulties in the management of ectopic PHPT secondary to parathyroid gland adenomas.


Visualization of bacterial polysaccharides by scanning transmission electron microscopy.
Highly purified capsular polysaccharides of Neisseria meningitidis groups A, B, and C have been visualized by high resolution Scanning Transmission Electron Microscopy (STEM). Spheroidal macromolecules approximately 200 A in diameter are characteristic of the Meningococcus A and C polysaccharides whereas filaments that are 400-600 A in length are found in Meningococcus B polysaccharide preparations. Filaments are occasionally found associated with the spheroidal Meningococcus A and C polysaccharides and it is proposed that these structures are composed of a long (1-4 microns) filament or filaments that are arranged in spheroidal molecules or micelles of high molecular weight. The Meningococcus B polysaccharide, by contrast, is a short flexuous filament or strand of relatively low molecular weight. A relationship between morphology and antigenicity is proposed.