Functional outcomes during inpatient rehabilitation for American Indian and Alaska Native children with traumatic brain injury.
American Indian/Alaska Native (AI/AN) people have the highest traumatic brain injury (TBI)-related mortality in the United States, but little is known about AI/AN children who survive traumatic brain injury (TBI). This study compares function and factors associated with discharge function between AI/AN and White children with TBI during inpatient rehabilitation. Retrospective national cohort study of 114 AI/AN and 7,267 White children aged 6 months-18 years who received inpatient TBI rehabilitation between 2002-2012 at facilities utilizing the Uniform Data System for Medical Rehabilitation\scriptsize®. The outcome measure was developmental functional quotients (DFQ is the FIM\scriptsize® or WeeFIM\scriptsize® score divided by age norms x 100) at discharge. AI/AN race was not associated with motor (regression coefficient (β) 0.18, 95% confidence interval (CI) -2.39, 2.76) or cognitive (β -1.54, 95% CI -3.75, 0.67) function. Among a subgroup with loss of consciousness > 24 hours (AI/AN n= 13, White n= 643), AI/AN race was associated with lower motor DFQ (β -12.83, 95% CI -25.39, -0.34). Overall, AI/AN race was not associated with inpatient rehabilitation function for children with TBI, but providers should not assume AI/ANs with more severe injuries have equitable outcomes.


Fibrous dysplasia of the mobile spine: report of 8 cases and review of the literature.
Eight cases of fibrous dysplasia (FD) of the mobile spine treated surgically at the same center were retrospectively reviewed. The study focuses on the issues concerning the diagnosis of FD and the outcome of conventional surgical techniques (resection or curettage) and vertebroplasty in the treatment of spinal FD lesions. Surgical excision or curettage is considered the standard treatment of spinal FD, whereas vertebroplasty is also performed occasionally. Between January 2005 and October 2010, 8 consecutive patients with spinal FD underwent conventional surgery (6 cases) or combined with vertebroplasty (2 cases). Before surgery, 4 patients underwent percutaneous computed tomography-guided biopsy, whereas 3 had incorrect histopathological diagnosis. In each of the 8 cases, the final pathological diagnosis was established after their open surgery. Pain relief was observed postoperatively in all patients. Three patients with neurological impairment became symptom-free after surgery. No cement extravasation was observed. Screw loosening and allograft resorption were observed in 1 case each. Signs of radiological improvement (filling of lytic lesions or thickening of the bone cortex surrounding the lesions) were not detected in any case. The radiological features of spinal FD may be atypical. The rate of correct preoperative pathological diagnosis by computed tomography-guided biopsy was low for patients with suspected spinal FD. Vertebroplasty is probably a valuable therapeutic option for spinal FD with pathological fractures. Limited decompression and stability with vertebroplasty might be recommended for patients with neurological deficits.


Bilateral peripapillary exophytic retinal hemangioblastomas.
A 14-year-old Iranian girl was referred for evaluation of bilateral elevation of the peripapillary retina. Fluorescein angiography was consistent with bilateral peripapillary exophytic retinal hemangioblastomas as seen in angiomatosis retinae (von Hippel's disease). Argon laser photocoagulation of the more severely affected left eye was performed with minimal effect upon the tumor.


Enhancing access to innovative cancer drugs: Cross-sector consensus on a way forward to benefit patients.
New discoveries and technologies are driving major advances in our understanding of cancer and underpinning a new era of precision medicine and immunotherapy. However, advances in treatment have been uneven: whereas survival rates for some common cancers are improving rapidly, for others there has been much less progress. In addition, healthcare systems are finding it difficult to provide access to expensive new treatments. There is an urgent need for imaginative policy solutions to incentivise the creation of novel therapies that address the full range of cancer-causing mechanisms. We have worked with organisations across the medical research community to develop consensus statements on how to enhance access to innovative cancer drugs. Here, we present our reflections on these statements.


Ventricular fibrillation following high potency intravenous vitamin injection.
A 67-year-old woman developed ventricular fibrillation following Parenterovite injection. Subsequent post-mortem revealed normal coronary arteries. It is postulated that the high potency vitamin injection caused the arrhythmia.


[Episodic bleeding events due to arteriovenous malformation (AVM) in the region of the distal ileum in a young male patient].
We report the case of a 32-year-old male patient who presented with episodic, self-limiting gastrointestinal bleeding events. After both esophagogastroduodenoscopy (EGD) and colonoscopy remained unremarkable, capsule endoscopy revealed an unexplained mucosal lesion that presented as an ulcerated process on spiral enteroscopy. Appropriate enteroscopic ink marking was followed by surgical partial resection of the distal ileum, with histopathology revealing evidence of an arteriovenous malformation (AVM). This case emphasizes the importance of deep enteroscopy both in the diagnosis and to facilitate therapeutic resection in rare gastrointestinal bleeding events affecting young people.


Endocytosis and intracellular processing of BODIPY-sphingomyelin by murine CATH.a neurons.
Neuronal sphingolipids (SL) play important roles during axonal extension, neurotrophic receptor signaling and neurotransmitter release. Many of these signaling pathways depend on the presence of specialized membrane microdomains termed lipid rafts. Sphingomyelin (SM), one of the main raft constituents, can be formed de novo or supplied from exogenous sources. The present study aimed to characterize fluorescently-labeled SL turnover in a murine neuronal cell line (CATH.a). Our results demonstrate that at 4°C exogenously added BODIPY-SM accumulates exclusively at the plasma membrane. Treatment of cells with bacterial sphingomyelinase (SMase) and back-exchange experiments revealed that 55-67% of BODIPY-SM resides in the outer leaflet of the plasma membrane. Endocytosis of BODIPY-SM occurs via caveolae with part of internalized BODIPY-fluorescence ending up in the Golgi and the ER. Following endocytosis BODIPY-SM undergoes hydrolysis, a reaction substantially faster than BODIPY-SM synthesis from BODIPY-ceramide. RNAi demonstrated that both, acid (a)SMase and neutral (n)SMases contribute to BODIPY-SM hydrolysis. Finally, high-density lipoprotein (HDL)-associated BODIPY-SM was efficiently taken up by CATH.a cells. Our findings indicate that endocytosis of exogenous SM occurs almost exclusively via caveolin-dependent pathways, that both, a- and nSMases equally contribute to neuronal SM turnover and that HDL-like particles might represent physiological SM carriers/donors in the brain.


Prenatal dinocap exposure alters swimming behavior in mice due to complete otolith agenesis in the inner ear.
Exposure to the fungicide dinocap during gestation produces behavioral abnormalities in the house mouse that are not apparent at birth but become obvious at weaning. Pregnant mice (CD-1) were exposed on Days 7 to 16 of gestation to dinocap at 0, 6, 12, or 25 mg/kg/day and the postnatal behavioral development of the offspring was assessed. Torticollis (head-tilting) appears in the treated offspring at 3 weeks of age (4.4% at 12 and 25.3% at 25 mg/kg/day) and, during a test of swimming ability, many of the mice (6.8% at 12 and 47.2% at 25 mg/kg/day) sink below the surface or are unstable and swim on their side in the water. These behavioral abnormalities are the result of agenesis of the otoliths in the inner ears. These were the only developmental defects noted in the 12 mg/kg/day dosage group. In this group 4.4% of the mice displayed torticollis, 9.2% did not swim normally, 19% were missing one or more whole otoliths (7.7% were missing all four otoliths), and partial agenesis of the crystalline material was seen in an additional 11.6% of the mice. The frequency of behavioral and inner ear defects increased in the higher dosage group, but the order of sensitivity of the effects did not change.


Time course of recovery of cytochrome p450 3A function after single doses of grapefruit juice.
Components of grapefruit juice may impair the activity of intestinal cytochrome P450 (CYP) 3A enzymes, sometimes resulting in clinically important drug interactions. The time course of recovery from CYP3A inhibition after a single exposure to grapefruit juice is not clearly established. Healthy volunteer subjects (N = 25) received a single 6-mg oral dose of the CYP3A substrate midazolam in the control condition without exposure to grapefruit juice. Two days later, midazolam was administered 2 hours after 300 mL of regular-strength grapefruit juice. Subjects were then randomly assigned to 3 different groups, receiving a third midazolam challenge at 26, 50, or 74 hours after exposure to grapefruit juice. The capacity of 6'7'-dihydroxybergamottin and bergamottin to inhibit human CYP3A was studied in vitro using human liver microsomes. The area under the plasma concentration curve (AUC) for midazolam increased by a factor of 1.65 (ratio compared with control) when midazolam was given 2 hours after grapefruit juice. At 26, 50, and 74 hours after grapefruit juice, the AUC ratios (mean AUC value at the indicated time divided by the mean control AUC on day 1) were 1.29, 1.29, and 1.06, respectively. The relationship of time after grapefruit juice exposure versus AUC increase over control indicated a recovery half-life estimated at 23 hours. The midazolam elimination half-life did not change significantly from the control value at any time after grapefruit juice exposure. 6'7'-Dihydroxybergamottin inhibited midazolam alpha-hydroxylation in vitro, with a mean 50% inhibitory concentration of 4.7 micro mol/L; preincubation of microsomes with 6'7'-dihydroxybergamottin greatly reduced the 50% inhibitory concentration to 0.31 micro mol/L, consistent with mechanism-based inhibition. Bergamottin itself had much weaker inhibitory potency compared to 6'7'-dihydroxybergamottin. A usual single exposure to grapefruit juice appears to impair the enteric, but not the hepatic, component of presystemic extraction of oral midazolam. Recovery is largely complete within 3 days, consistent with enzyme regeneration after mechanism-based inhibition. 6'7'-Dihydroxybergamottin was verified as a potent mechanism-based inhibitor of midazolam alpha-hydroxylation by CYP3A in vitro.


Engineering central metabolic modules of Escherichia coli for improving β-carotene production.
ATP and NADPH are two important cofactors for production of terpenoids compounds. Here we have constructed and optimized β-carotene synthetic pathway in Escherichia coli, followed by engineering central metabolic modules to increase ATP and NADPH supplies for improving β-carotene production. The whole β-carotene synthetic pathway was divided into five modules. Engineering MEP module resulted in 3.5-fold increase of β-carotene yield, while engineering β-carotene synthesis module resulted in another 3.4-fold increase. The best β-carotene yield increased 21%, 17% and 39% after modulating single gene of ATP synthesis, pentose phosphate and TCA modules, respectively. Combined engineering of TCA and PPP modules had a synergistic effect on improving β-carotene yield, leading to 64% increase of β-carotene yield over a high producing parental strain. Fed-batch fermentation of the best strain CAR005 was performed, which produced 2.1g/L β-carotene with a yield of 60mg/g DCW.


[Determination of meconium lead level of newborn by graphite furnace atomic absorption spectrometry].
To establish a method for the determination of lead in meconium from 144 samples of newborn through nitric acid digestion by means of graphite furnace atomic absorption spectrometry. after being baked for at least 12 h at 60 degrees C, 0.3 g of meconium was digested by nitric acid and hydrogen peroxide in turn at 80 degrees C under water-bath condition for 1h and then metered to the whole volume of to 2 mL. After correcting the background with D2 lamp, specimen basal corpuscle matched standard curve was used to detect the lead content. The mean lead content of 93 experimental samples was 1.934 microg x g(-1) with the standard deviation (SD) of 1.551, and that of the 51 control samples was 1.012 microg x g(-1), with the SD of 1.084. There was a significant difference in lead levels of in meconnt between the experimental group and control group (p = 0.000). The lead content of the experimental was significantly higher than that of the control group detected by this method. This method was stable and efficient.


Effects of an educational compact intervention in self-care - a mixed methods study with postgraduate trainees in primary care.
Multiple studies indicate that residents in family medicine (FM) are exposed to considerable stress and are particularly affected by burnout syndrome. Aim of the study was to specify the effects of a so-called "compact intervention" (i.e., a short intervention) in self-care on FM residents. The authors performed a concurrent and independent mixed-methods study with FM residents on the KWBW VerbundweiterbildungPLUS© program. FM residents could voluntarily take part in a two-day seminar including 270 min on self-care, which can be regarded as a compact intervention. Study participants completed a questionnaire before (T1) and ten to twelve weeks after the course (T2), with subsequent recruitment to interview. The main outcomes of the quantitative part were to evaluate (I) self-rated change of cognition and (II) change in behavior. The qualitative outcomes were all possible effects of the compact intervention on participants´ competencies as well as all sorts of induced behavioral changes. From a total of n = 307 residents, n = 287 FM residents (intervention group: n = 212; control group: n = 75) participated in the study. At T2, 111 post-intervention questionnaires were completed. 56% rated the intervention to be helpful for their well-being (n = 63/111). At T2, there was a significant increase in those willing to act in comparison to T1 (p = .01): 36% (n = 40/111) had changed their behavior and half of the study participants had passed on competencies to others (n = 56/111). From the intervention group, n = 17 participants additionally gave an interview. FM residents favored a trustful learning atmosphere, an interactive teaching concept and practical exercises. They described an encouraging stimulus to act and specified behavioral changes. A compact intervention in self-care could increase well-being, foster competencies and induce behavioral changes, if implemented into a training program with sufficient group cohesiveness. Further studies are required to specify long-term-results.


Activity of the antiestrogenic cajanin stilbene acid towards breast cancer.
Antiestrogenic therapy is a mainstay for estrogen receptor (ERα)-positive breast cancer. Due to the development of resistance to established antihormones such as tamoxifen, novel compounds are required. The low abundant cajanin stilbene acid (CSA) recently isolated by us from Pigeon Pea (Cajanus cajan) has structural similarities with estrogen. We analyzed the cytotoxic and anticancer activity of CSA in ERα-positive and -negative human breast cancer cells in vitro, in vivo and in silico. CSA exerts anticancer and antiestrogenic activities towards ERα-positive breast cancer, and it showed cytotoxicity towards tamoxifen-resistant MCF-7 cells, implying that CSA may be active against tamoxifen-resistant breast cancer cells. CSA showed low cytotoxicity in ERα-negative breast tumor cells as expected. Comparable cytotoxicity was observed towards p53 negative MCF-7 cells, implying that CSA is effective independent of the p53 status. Xenografted MCF-7 cells in nude mice were better inhibited by CSA than by cyclophosphamide. Testing of 8 primary cell cultures derived from human breast cancer biopsies showed that cell cultures from ER-positive tumors were more sensitive than from ER-negative ones. Dose-dependent decrease in ERα protein levels was observed upon CSA treatment. Synergistic effect with tamoxifen was observed in terms of increased p53 protein level. CSA affected pathways related to p53, cancer and cell proliferation. Gene promoter analyses supported the ERα regulation. CSA bound to the same site as 17β-estradiol and tamoxifen on ERα. In conclusion, CSA exerts its anticancer effects in ERα-positive breast cancer cells by binding and inhibiting ERα.


Tibial shock measured with bone and skin mounted transducers.
The purpose of this study was to assess the value of superficial transducer mounting to measure tibial shock during locomotion. Surface (SMT) and bone mounted transducers (BMT) simultaneously recorded axial tibial acceleration in five subjects who ran at 4.5 m s-1. SMT produced inconsistent recording across the subjects both in the time and frequency domains. In two subjects, SMT signals provided close approximation of BMT signals, some distortion occurred in one subject while severe distortions were observed in the other two subjects. The present results established that SMT could not be used directly to quantify the shock transmitted through the tibia during running. However, frequency transformation of SMT recordings produced encouraging results; the transformed SMT signals mimicked the signals recorded with the bone mounted transducer.


IL-18 gene therapy develops Th1-type immune responses in Leishmania major-infected BALB/c mice: is the effect mediated by the CpG signaling TLR9?
IL-18 regulates either Th1 or Th2 responses depending on the cytokine microenvironment. Administration of recombinant IL-18 (rIL-18) alone does not promote Th1 response, but rather induces Th2 response and exacerbates Leishmania major infection in susceptible BALB/c mice. Here, we treated BALB/c mice with an IL-18-expressing plasmid by using a gene gun weekly after L. major infection. This gene therapy resulted in improved pathogenic process and preferential induction of Th1 responses by inducing the expression of IL-12 p40, but treatment with rIL-18 did not. Notably, simultaneous administration of rIL-18 with an empty plasmid vector rendered BALB/c mice resistant to the infection, despite the fact that treatment with either rIL-18 alone or the plasmid vector alone did not influence the susceptibility. The synergistic role of the vector with rIL-18 was found to depend on CpG motifs, which enhanced expression of proinflammatory cytokines, especially IL-12, from APCs through Toll-like receptor (TLR) 9 ligation. Treatment with methylated plasmid vector in which CpG was disrupted could no longer prevent the disease development in coadministration with rIL-18. Taken together, IL-18 gene therapy was shown to develop Th1-type protective immunity in L. major-infected BALB/c mice without the requirement of exogenous IL-12, probably via CpG-TLR9 signaling pathway.


Sleep less and bite more: sleep disorders associated with occlusal loads during sleep.
Occlusal overload during sleep is a significant clinical issue that has negative impacts on the maintenance of teeth and the longevity of dental prostheses. Sleep is usually viewed as an 'out-of-functional' mode for masticatory muscles. However, orodental structures and prostheses are not free from occlusal loads during sleep since masticatory muscles can be activated at a low level within normal sleep continuity. Thus, an increase in masticatory muscle contractions, by whatever the cause, can be associated with a risk of increased occlusal loads during sleep. Among such conditions, sleep bruxism (SB) is a type of sleep-related movement disorders with potential load challenge to the tooth and orofacial structures. Patients with SB usually report frequent tooth grinding noises during sleep and there is a consecutive increase in number and strength of rhythmic masticatory muscle activity (RMMA). Other types of masticatory muscle contractions can be non-specifically activated during sleep, such as brief contractions with tooth tapping, sleep talking, non-rhythmic contractions related to non-specific body movements, etc.; these occur more frequently in sleep disorders. Studies have shown that clinical signs and symptoms of SB can be found in patients with sleep disorders. In addition, sleep becomes compromised with aging process, and a prevalence of most sleep disorders is high in the elderly populations, in which prosthodontic rehabilitations are more required. Therefore, the recognition and understanding of the role of sleep disorders can provide a comprehensive vision for prosthodontic rehabilitations when prosthodontists manage complex orodental cases needing interdisciplinary collaborations between dentistry and sleep medicine.


The E3 ligase COP1 promotes ERα signaling and suppresses EMT in breast cancer.
ERα signaling drives proliferation, survival and cancer initiation in the mammary gland. Therefore, it is critical to elucidate mechanisms by which ERα expression is regulated. We show that the tumor suppressor E3 ligase COP1 promotes the degradative polyubiquitination of the microtubule-associated protein HPIP. As such, COP1 negatively regulates estrogen-dependent AKT activation in breast cancer cells. However, COP1 also induces ERα expression and ERα-dependent gene transcription, at least through c-Jun degradation. COP1 and ERα levels are positively correlated in clinical cases of breast cancer. COP1 also supports the metabolic reprogramming by estrogens, including glycolysis. On the other hand, COP1 suppresses EMT in breast cancer cells. COP1 deficiency also contributes to Tamoxifen resistance, at least through protective autophagy. Therefore, COP1 acts as an oncogenic E3 ligase by promoting ERα signaling but also acts as a tumor suppressor candidate by preventing EMT, which reflects a dual role of COP1 in breast cancer.


Perinatal outcome of monochorionic twins with selective IUGR compared with uncomplicated monochorionic twins.
To evaluate the perinatal outcome of MC twins with selective IUGR (sIUGR). A prospective study, which included three groups of MC twins: Group A, uncomplicated MC twin pregnancies (n = 91); group B, sIUGR with normal umbilical artery Doppler (n = 19); and group C, sIUGR with abnormal (absence or reversed EDV) umbilical artery Doppler (n = 18). The latter were routinely hospitalized in the high-risk ward under strict surveillance. Neonatal outcome of fetuses complicated with sIUGR and normal Doppler was similar to controls. Neonates born to pregnancies complicated by sIUGR and abnormal Doppler had significantly increased incidence of CNS findings, RDS, NEC, sepsis, and neonatal death compared to controls. Adverse outcome in this group was independently associated only with gestational age at birth. The perinatal outcomes of MC twins complicated with sIUGR and normal Doppler are similar to uncomplicated MC pregnancies. MC twins with sIUGR and abnormal Doppler have reasonable outcomes, yet significantly more neonatal complications compared to non-complicated MC twins.


Optimized qRT-PCR Approach for the Detection of Intra- and Extra-Cellular SARS-CoV-2 RNAs.
The novel coronavirus SARS-CoV-2 is the causative agent of the acute respiratory disease COVID-19, which has become a global concern due to its rapid spread. Meanwhile, increased demand for testing has led to a shortage of reagents and supplies and compromised the performance of diagnostic laboratories in many countries. Both the World Health Organization (WHO) and the Center for Disease Control and Prevention (CDC) recommend multi-step RT-PCR assays using multiple primer and probe pairs, which might complicate the interpretation of the test results, especially for borderline cases. In this study, we describe an alternative RT-PCR approach for the detection of SARS-CoV-2 RNA that can be used for the probe-based detection of clinical isolates in diagnostics as well as in research labs using a low-cost SYBR green method. For the evaluation, we used samples from patients with confirmed SARS-CoV-2 infections and performed RT-PCR assays along with successive dilutions of RNA standards to determine the limit of detection. We identified an M-gene binding primer and probe pair highly suitable for the quantitative detection of SARS-CoV-2 RNA for diagnostic and research purposes.


Detection of human cytomegalovirus IgG antibody using automated immunoassay with recombinant antigens gives uniform results to established assays using whole virus antigens.
Serological testing for human cytomegalovirus (CMV) immunoglobulin G (IgG) continues to play a major role in the evaluation of tissue and organ transplant donors and recipients, screening blood donors and in estimating the risk of infection in pregnant women. In this study we evaluated the performance and technical characteristics of two semi-automated commercial CMV IgG immunoassays. One hundred consecutive sera submitted to a referral serology laboratory for CMV IgG antibody testing were assayed using two automated CMV IgG immunoassays: the Architect (Abbott Diagnostics) and Elecsys (Roche Diagnostics) immunoassays. Because this patient population has a high rate (∼87%) of seropostivity, we took a further 50 sera that were CMV IgG negative on Architect and tested on the Elecsys assay, in order to assess the specificity of the assays. The assays showed an excellent qualitative agreement with two (2%) discrepant results in the 100 patients tested initially, with all of the 50 additional sera negative on Architect also negative on the Elecsys. However, there was no correlation between the optical density of results generated by the instruments for the set of samples. Both Elecsys and Architect immunoassays are convenient for detection of CMV IgG antibody, with near identical qualitative results.


New evidence for the zoom lens model using the RSVP technique.
A main prediction from the zoom lens model for visual attention is that performance is an inverse function of the size of the attended area. The "attention shift paradigm" developed by Sperling and Reeves (1980) was adapted here to study predictions from the zoom lens model. In two experiments two lists of items were simultaneously presented using the rapid serial visual presentation technique. Subjects were to report the first item he/she was able to identify in the series that did not include the target (the letter T) after he/she saw the target. In one condition, subjects knew in which list the target would appear, in another condition, they did not have this knowledge, having to attend to both positions in order to detect the target. The zoom lens model predicts an interaction between this variable and the distance separating the two positions where the lists are presented. In both experiments, this interaction was observed. The results are also discussed as a solution to the apparently contradictory results with regard to the analog movement model.


Impact assessment of increasing renewable energy penetration on voltage instability tendencies of power system buses using a QV-based index.
This paper presents a QV-based approach called Critical Voltage-Reactive Power Ratio (CVQR) index to assess the voltage instability tendencies of power system buses with increase in renewable energy (RE) penetration within the power system. The buses are thus ranked according to the order in which they are impacted by increase in renewable energy penetration. Simulations were performed using DIgSILENT PowerFactory and result analyses were done with MATLAB. The developed CVQR index has been employed to assess the effect of increasing RE generation on grid voltage stability. This index provides information on the voltage instability tendencies of all non-slack buses of the RE-integrated grid and the buses are ranked from the weakest to the strongest. The rankings obtained from the developed CVQR has been compared with five commonly-used indices and the result of the comparison verifies the accuracy of the proposed index. IEEE 14-bus and IEEE 39-bus New England systems have been used to evaluate the proposed CVQR index and various scenarios of RE system combinations and placements have been considered. Voltage collapse condition is indicated whenever the CVQR index associated with any bus becomes positive (CVQR > 0). This index can as well be applied to other power system networks. The overall ranking of the buses based on the CVQR index can provide insights on the most appropriate location for large inductive loads or compensating devices, which can either absorb or inject reactive power into the power system, thereby influencing the system's voltage stability.


Cognitive function, drusen, and age-related macular degeneration: a cross-sectional study.
To examine the cross-sectional relationship between drusen, late age-related macular degeneration (AMD), and cognitive function. METHODS; We included 2149 stroke-free participants from the population-based Tromsø Study in Norway. Retinal photographs were graded for presence of drusen and AMD. Cognitive function was assessed using the verbal memory test (short verbal memory), digit-symbol coding test (processing speed), and the tapping test (psychomotor tempo). We assessed the relationship between drusen, late AMD, and cognitive test scores, adjusted for potential confounders. Late AMD was associated with decreased performance in the verbal memory test (standardized β=-0.23, 95% confidence interval (CI): -0.51 to -0.01). Intermediate and large drusen were associated with decreased performance in the digit-symbol coding test (standardized β=-0.14 and -0.19, 95% CIs: -0.23 to -0.05 and -0.29 to -0.09, respectively). Participants with large drusen were more likely to have test scores in the lowest quartile of the digit-symbol coding test (odds ratio (OR)=1.9, 95% CI: 1.1-3.5) and the tapping test (OR=1.6, 95% CI: 1.0-2.6), but not in the verbal memory test (OR=1.0, 95% CI: 0.6-1.6). The findings suggest a relationship between drusen deposition and reduced cognitive function. Although the relationships between drusen, late AMD, and the cognitive test results varied in strength and significance across the types of cognitive test, and may partly have been caused by residual confounding, it is not unlikely that a genuine but weaker relationship exists between drusen deposition and cognitive decline.


Cachexia-related long noncoding RNA, CAAlnc1, suppresses adipogenesis by blocking the binding of HuR to adipogenic transcription factor mRNAs.
Cancer-associated cachexia (CAC) is a devastating syndrome characterized by progressive losses of adipose tissue and skeletal muscle. CAC-related adipose tissue loss (CAL) occurs early and is associated with a shorter survival time. To explore potential regulatory long noncoding RNAs (lncRNAs) of CAL, RNA microarrays were used to analyze the transcriptomes of white adipose tissue from CAC mice vs. control mice. A set of differentially expressed lncRNAs was identified, and among them was CAAlnc1, which suppressed adipogenesis of C3H10 cells as demonstrated by gain-of-function and loss-of-function experiments. RNA immunoprecipitation and pull-down assays revealed Hu antigen R (HuR) was an important binding partner of CAAlnc1. The interaction between CAAlnc1 and HuR blocked the binding of HuR to adipogenic transcription factor mRNAs and further downregulated the expression of these transcription factors. This study generated a list of CAL-related lncRNAs and provided details of a functional lncRNA which may play an important role in CAL.


National Institutes of Health R01 Grant Funding Is Associated With Enhanced Research Productivity and Career Advancement Among Academic Cardiothoracic Surgeons.
National Institutes of Health (NIH) funding has declined among cardiothoracic surgeons. R01 grants are a well-known mechanism to support high-impact research, and we sought to clarify the association between NIH funding and academic achievement. We hypothesized that cardiothoracic surgeons who acquired R01 funding exhibit greater research output and faster career advancement. All cardiothoracic surgeons (n = 992) working at accredited United States cardiothoracic surgery training hospitals in 2018 were included. Institutional webpages, Scopus, and Grantome were utilized to collect publicly-available data regarding each surgeon's training and career history, research publications, and NIH funding. Seventy-eight (7.9%) surgeons obtained R01 funding as a principal investigator while 914 (92.1%) did not. R01-funded surgeons started their attending careers earlier (1998 vs 2005, P < 0.0001) and were more likely to have pursued dedicated research training (P < 0.0001). R01-funded surgeons authored 5.3 publications/year before their first R01 grant, 9.3 during the grant period, and 8.6 after the grant expired, all of which were greater than the publication rate of non-R01-funded surgeons at comparable career timepoints (2.0-3.0 publications/year, P < 0.0001). Among time-matched surgeons who completed medical school in 1998 or earlier (n = 73 R01-funded vs n = 602 non-funded), R01-funded surgeons have published more total publications (178.0 vs 56.5 papers, P < 0.0001) and exhibit a greater H-index (41.0 vs 19.0, P < 0.0001). These R01-funded surgeons have also advanced to higher academic ranks (P < 0.0001) and are more likely to be chiefs of their departments or divisions (42.5% vs 25.7%, P = 0.0035). Cardiothoracic surgeons who obtain R01 funding exhibit greater research productivity and faster career advancement.


Blunted ACTH response to hypoglycemic stress in depressed patients but not in patients with schizophrenia.
In this study, 7 hospitalized patients with major depression (MD), 5 hospitalized patients with schizophrenia (S), and 13 control subjects (C) were administered 0.15 units/kg of regular insulin at 1600 h by intravenous bolus infusion. ACTH, cortisol, and glucose levels were measured intermittently for 2h following infusion. Baseline ACTH, cortisol and glucose levels were similar in Cs, MDs, and Ss. The mean glucose nadir was equivalent for Cs, patients with MD, and patients with S. Patients with MD had a blunted ACTH response (F = 3.28; df = 12,126; p = .0004) and cortisol response (F = 4.20; df = 12,132; p = .0001) to hypoglycemia when compared to Cs and patients with S. Carroll Depression Rating Scale scores in patients with S (23 +/- 10) were similar to patients with MD (30 +/- 8) and significantly higher than in controls (1 +/- 2) (F = 55.2; df = 2.22; p = .0001). These findings suggest that patients with MD show different ACTH and cortisol responses to hypoglycemic stress which are not explained by negative feedback of baseline ACTH or cortisol, glucose nadir, or the number of depressive symptoms per se.


Vulnerability to sexually transmitted infections in women who sell sex on the route of prostitution and sex tourism in central Brazil.
to investigate knowledge on sexually transmitted diseases (STDs), STD-related risk behaviors, and signs/symptoms of STDs among female sex workers (FSWs). a cross-sectional study was conducted with a probabilistic sample comprising 395 women recruited using a respondent-driven sampling method between 2009 and 2010. The data were collected during face-to-face interviews. most of the participants were young adults, had a low educational level, and had poor knowledge on the transmission paths of the human immunodeficiency virus (HIV). Over one-third of the participants were not able to describe the signs/symptoms of STDs. The prevalence rates of vaginal discharge and wounds/ulcers were 49.0% and 8.6%, respectively, but 41.7% of the women had not sought treatment. the results indicate the need for public health policies focusing on the control and prevention of STDs in this population, especially for the FSWs who are active in an important prostitution and sex tourism route in central Brazil.


Seroprevalence of Toxoplasma gondii in Egyptian donkeys using ELISA.
A serological survey of Toxoplasma gondii was conducted using ELISA on 121 sera from adult donkeys from Monofia Province, Egypt. Antibodies to T. gondii were found in 65.6% of 121 donkeys.


Treatment of distal tibial fractures with the Ilizarov external fixator--a prospective observational study in 39 consecutive patients.
The management of displaced distal tibial fractures is still controversial. The different internal fixation techniques are often burdened by relatively high complication rates. Minimally invasive techniques with ring fixators have been introduced as an alternative allowing immediate reduction and stabilization, avoiding a staged protocol. The aim of this prospective study was to analyze the clinical and radiographic outcome the Ilizarov technique in patients with distal metaphyseal tibial fractures, with or without intra-articular involvement. Thirty-nine consecutive patients with isolated fractures treated with the Ilizarov technique were followed prospectively for one year. Depending on the type of fracture, 4 or 5 rings were used, in some cases with additional foot extension. Unrestricted weight-bearing was allowed in all cases. Pre- and post-operatively conventional radiographs, post-operative pain assessment and complications were evaluated. The function was evaluated clinically and with self-appraisal protocols: EQ-5D, NHP and FAOS. No patient developed compartment syndrome or deep venous thrombosis. Pin infections were frequent, but they were mostly superficial and were treated with antibiotics and/or the removal of isolated pins. Two patients required debridement. One of them had a deep infection and developed a residual deformity which was corrected and healed after re-operation. Another patient had a severe residual deformity. The fixator was removed after a median period of 16 weeks (range 11-30). The radiological results were poor in 5 patients but the overall self-appraisal showed satisfactory results in 36 patients. The Ilizarov method allowed early definitive treatment with a low complication rate and a good clinical outcome.


Transfer of inflammatory cytokines across the placenta.
The purpose of this study was to determine whether the placental transfer of interleukin (IL)-1alpha, IL-6, and tumor necrosis factor-alpha (TNF-alpha) occurs. Four normal-term placentas were perfused for maternal-fetal transfer of the cytokines, 2 placentas for fetal-maternal transfer, and 4 additional placentas were used for an endogenous control. The ex vivo isolated cotyledon human placental perfusion model was used. The reference compound antipyrine was used to determine the transport fraction and clearance index of the cytokines. The cytokines were added to either the maternal or fetal circulations, and samples were collected for 1 hour in a constant-flow open circulation. Cytokine levels were compared between the study and control placentas. Concentrations of the cytokines were measured by sandwich enzyme immunoassay. The clearance index for the maternal-fetal transfer of IL-1alpha and TNF-alpha was 0.001, suggesting minimal transfer to the fetal circulation. The clearance index for IL-6 was 0.30, indicating transfer to the fetal circulation. When the cytokines were added to the fetal circulation, the clearance index for IL-1alpha was 0.001, again indicating minimal transfer. The clearance index for TNF-alpha in the fetal-maternal study was not determined. IL-6 had a clearance index of 0.23, which was similar to that observed with maternal-fetal transfer. IL-6 concentrations in the study placentas were higher than the concentrations found in the controls. There appears to be bidirectional transfer of IL-6 in the healthy-term human placental perfusion model. II-2


Ternary SnS(2-x)Se(x) Alloys Nanosheets and Nanosheet Assemblies with Tunable Chemical Compositions and Band Gaps for Photodetector Applications.
Ternary metal dichalcogenides alloys exhibit compositionally tunable optical properties and electronic structure, and therefore, band gap engineering by controllable doping would provide a powerful approach to promote their physical and chemical properties. Herein we obtained ternary SnS(2-x)Se(x) alloys with tunable chemical compositions and optical properties via a simple one-step solvothermal process. Raman scattering and UV-vis-NIR absorption spectra reveal the composition-related optical features, and the band gaps can be discretely modulated from 2.23 to 1.29 eV with the increase of Se content. The variation tendency of band gap was also confirmed by first-principles calculations. The change of composition results in the difference of crystal structure as well as morphology for SnS(2-x)Se(x) solid solution, namely, nanosheets assemblies or nanosheet. The photoelectrochemical measurements indicate that the performance of ternary SnS(2-x)Se(x) alloys depends on their band structures and morphology characteristics. Furthermore, SnS(2-x)Se(x) photodetectors present high photoresponsivity with a maximum of 35 mA W(-1) and good light stability in a wide range of spectral response from ultraviolet to visible light, which renders them promising candidates for a variety of optoelectronic applications.


Transforming growth factor beta1, the dominant cytokine in murine prion disease: influence on inflammatory cytokine synthesis and alteration of vascular extracellular matrix.
Previous studies from our laboratory have shown the ME7 model of murine scrapie to be accompanied by an atypical inflammatory response that is characterized by marked astroglial and microglial activation but also by the lack of significant expression of the pro-inflammatory cytokines interleukin (IL)-1beta and IL-6. The aim of this study was to determine whether, in the absence of IL-1beta and IL-6, tumour necrosis factor (TNF)-alpha may play an equivalent pro-inflammatory role, or if an anti-inflammatory cytokine profile dominates. We have used competitive polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) to determine the levels of TNF-alpha, IL-10 and transforming growth factor (TGF)-beta1 in the ME7 model, using their expression in lipopolysaccharide (LPS)-induced acute inflammation as a positive control. Levels of mRNA were elevated for all three cytokines during acute inflammation, while TGF-beta1 mRNA alone was significantly elevated in ME7-injected brains. Similarly, by ELISA, we detected elevated IL-10, TNF-alpha and TGF-beta1 in LPS-injected animals but only significant elevation of TGF-beta1 in ME7-injected animals. An increase in laminin and collagen IV deposition around blood vessels was also observed and is consistent with up-regulation by active TGF-beta1. These findings suggest that TGF-beta1 may play a central role in maintenance of an atypical microglial phenotype and may also be involved in vascular and extracellular matrix changes.


Bilateral scapholunate dissociations with distal radial fractures and post-traumatic intercarpal fusion.
A patient with bilateral intraarticular distal radial fractures associated with scapholunate dissociation and post-traumatic lunotriquetral fusion on one side is described.


Tilted frames of reference have similar effects on the perception of gravitational vertical and the planning of vertical saccadic eye movements.
We investigated the effects of a tilted reference frame (i.e., allocentric visual context) on the perception of the gravitational vertical and saccadic eye movements along a planned egocentric vertical path. Participants (n = 5) in a darkened room fixated a point in the center of a circle on an LCD display and decided which of two sequentially presented dots was closer to the unmarked '6 o'clock' position on that circle (i.e., straight down toward their feet). The slope of their perceptual psychometric functions showed that participants were able to locate which dot was nearer the vertical with a precision of 1°-2°. For three of the participants, a square frame centered at fixation and tilted (in the roll direction) 5.6° from the vertical caused a strong perceptual bias, manifest as a shift in the psychometric function, in the direction of the traditional 'rod-and-frame' effect, without affecting precision. The other two participants showed negligible or no equivalent biases. The same subjects participated in the saccade version of the task, in which they were instructed to shift their gaze to the 6 o'clock position as soon as the central fixation point disappeared. The participants who showed perceptual biases showed biases of similar magnitude in their saccadic endpoints, with a strong correlation between perceptual and saccadic biases across all subjects. Tilting of the head 5.6° reduced both perceptual and saccadic biases in all but one observer, who developed a strong saccadic bias. Otherwise, the overall pattern and significant correlations between results remained the same. We conclude that our observers' saccades-to-vertical were dominated by perceptual input, which outweighed any gravitational or head-centered input.


Mental health and academic performance: a study on selection and causation effects from childhood to early adulthood.
An inverse relationship between mental health and academic achievement is a well-known phenomenon in the scientific literature. However, how and when this association develops is not fully understood and there is a lack of longitudinal, population-based studies on young children. Early intervention is important if associations are to be found already during childhood. The aim of the present study was to investigate the development of the association between mental health and academic performance during different developmental periods of childhood and adolescence. Data from a longitudinal birth cohort study of 1700 children were used. Child mental health was assessed through mother's reports at age 3, and self-reports at age 12 and 20. Academic performance was assessed through teacher reports on educational results at age 12 and final grades from compulsory school (age 15-16) and upper secondary school (age 18-19). The association between mental health and academic performance was assessed through regression models. The results indicate that social selection mechanisms are present in all three periods studied. Behavioral and emotional problems at age 3 were associated with performing below grade at age 12. Similarly, mental health problems at age 12 were associated with lack of complete final grades from compulsory school and non-eligibility to higher education. Academic performance at ages 15 and 19 did not increase the risk for mental health problems at age 20. Mental health problems in early childhood and adolescence increase the risk for poor academic performance, indicating the need for awareness and treatment to provide fair opportunities to education.


Transvenous (transjugular) liver biopsy. An experience based on 100 biopsies.
Transvenous (transjugular) liver biopsy consists in taking a liver specimen through a needle introduced into the liver parenchyma from the lumen of a hepatic vein. This procedure was attempted 104 times in 98 patients in whom percutaneous needle liver biopsy was contraindicated because of massive ascites and/or bleeding tendency. A liver specimen was obtained in 100 out of these 104 attempts; the tissue specimens were unfragmented and large enough to allow correct evaluation of liver architecture in 57 biopsies. The procedure was followed by no or only minor complications in all out patients except one who suffered a fatal intraperitoneal hemorrhage in relation to perforation of liver capsule; perforation was due to an excessive front rotation applied to the needle, a maneuver which therefore must be avoided. It is concluded that transvenous liver biopsy is a workable, efficient, and acceptably safe procedure for obtaining liver specimens in patients with massive ascites and/or bleeding tendency.


A fatal case of extensive gastrointestinal necrosis due to portal and mesenteric vein thrombosis in the post-acute phase of COVID-19.
Portal vein thrombosis (PVT) is considered a relatively rare thrombotic complication in coronavirus disease 2019 (COVID-19). Most reported cases of PVT develop within 2 weeks from COVID-19 onset. We report a fatal case of extensive gastrointestinal necrosis due to portal and mesenteric vein thrombosis approximately 6 weeks after the onset of critical COVID-19. Excessive elevation of his plasma D-dimer level had continued for weeks during the hospitalization contrary with improvement of respiratory failure. Thrombotic complication should be cautiously paid attention even in the post-acute phase of COVID-19, especially in patients with persistent elevation of plasma D-dimer level.


The effect of timing of antiretroviral therapy on CD4+ T-cell reconstitution in the intestine of HIV-infected patients.
Whether and to what extent gut mucosal CD4(+) T cells of HIV-infected patients can be restored by combination antiretroviral therapy (cART) is not yet fully resolved. We studied absolute numbers, differentiation, and activation of mucosal CD4(+) T cells at different stages of HIV infection and assessed the effect of timing of cART initiation on this cell population. Mucosal CD4(+) T-cell numbers were severely reduced at all stages of chronic infection, but normal in patients with acute infection. In patients with initiation of cART during chronic HIV infection, mucosal CD4(+) T cells restored to less than half of the numbers in controls. However, in patients who initiated cART during acute HIV infection, mucosal CD4(+) T-cell numbers were fully preserved and markers of microbial translocation and inflammation reversed to normal. The proportion of mucosal effector memory CD4(+) T cells normalized only if cART was initiated at >350 CD4(+) T cells per μl blood but not with delayed treatment. In conclusion, mucosal CD4(+) T-cell numbers can be preserved if cART is initiated in acute HIV infection. In chronically HIV-infected patients, early cART improves mucosal CD4(+) T-cell differentiation but cannot prevent the persistent lack of total CD4(+) T cells.


Effect of ochratoxin A (OTA) on the activity of some enzymes in developing eggs ofAscaris suum.
The studies focused on the effect of 1-ppm ochratoxin A solution on the activity of some enzymes during successive embryogenesis stages ofAscaris suum. As a result of OTA-affected incubation ofA suum eggs, inhibition of AcP reactions was observed throughout the embryonic development, reduction in of SDH and LDH activity during cleavage and gastrulation, and enhancement of the SDH and LDH activity was found in larvae. Moreover, inhibition of the processes of cleavage, gastrulation and organogenesis was recorded. The observed morphological and metabolic embryo disorders demonstrated teratogenic properties of the studied mycotoxin, and the presence of granules of various sizes in the developing eggs may indicate that OTA penetrated into the eggs.


The effects of excessive heat on heat-activated membrane currents in cultured dorsal root ganglia neurons from neonatal rat.
The effects of high temperature (53-61 degrees C) on membrane currents (I(heat)) or depolarization (V(heat)) induced by noxious heat were studied in cultured dorsal root ganglia neurons from neonatal rats using the whole cell patch clamp technique. I(heat) or V(heat) produced by 3 s ramps of increasing temperature between 43 and 50 degrees C exhibited a fast slope (Q10>10) that was similar both during rising and falling temperature (n=85). Temperatures exceeding 52 degrees C resulted in slowdown in the recovery of I(heat), and the threshold for inducing I(heat) was shifted to lower temperatures in successive trials. These high temperatures (54-60 degrees C) caused a linear and incomplete recovery of I(heat) (Q10 decreased to <5; 4.5 +/- 0.4; n=17) and in successive trials the threshold of I(heat) decreased to temperatures close to that in the bath. The neurons, however, remained sensitive to capsaicin and to decreased extracellular pH. It is suggested that exposure of nociceptive neurons to excessive noxious heat results in an irreversible decrease of the energy barrier between the resting and activated state of the protein structures responsible for generation of I(heat). This may explain the sensitization of nociceptors after heat injury.


Osteoporosis after spinal cord injury.
Immobilisation secondary to spinal cord injury (SCI) is associated with marked and rapid atrophy of trabecular bone. The purpose of this study was to evaluate bone mineral density (BMD) in both the upper and lower extremities following SCI sustained for various lengths of time and to correlate the BMD to the level of the lesion, time from injury, spasticity and serum calcium, phosphorus and alkaline phosphatase (ALP) levels. A study was undertaken in 41 SCI patients with a mean age of 35.8 +/- 12.7 years. A significant difference in BMD between upper and lower extremities of the paraplegics were found. BMD of upper and lower extremities were similar in tetraplegies. The BMD values were significantly different when the upper extremity scores of paraplegics and tetraplegics were compared but BMD scores of the lower extremities were similar in the two groups. The decrease in BMD was less in the spastic patients when compared to the flaccid group. There was a positive correlation between time from injury and the degree of BMD deficit in the paralysed areas. In the whole group of patients a significant positive correlation was found between the duration of SCI and serum ALP levels.


Enhancement of carcinoembryonic antigen expression by interferon.
Human interferon decreased DNA but not RNA synthesis in a human colon carcinoma cell line, WiDr; in addition, there was a two- to three-fold increase in the expression of a tumor-associated antigen, carcinoembryonic antigen. In contrast, interferon had no effect on a normal human diploid cell line, WI-38. Thus, in addition to its anti-cellular effect against tumor cells, interferon can also modulate tumor antigenicity.


Employee demand for health insurance and employer health plan choices.
Although most private health insurance in US is employment-based, little is known about how employers choose health plans for their employees. In this paper, I examine the relationship between employee preferences for health insurance and the health plans offered by employers. I find evidence that employee characteristics affect the generosity of the health plans offered by employers and the likelihood that employers offer a choice of plans. Although the results suggest that employers do respond to employee preferences in choosing health benefits, the effects of worker characteristics on plan offerings are quantitatively small.


Incidence and etiology of mortality in polytrauma patients: an analysis of material from Multitrauma Centre of the University Teaching Hospital no 1 in Szczecin, over a period of 3 years (2017-2019).
Introduction: The pattern of traumatic death is a subject of great interest in the worldwide literature. Most studies have aimed to improve trauma care and raise awareness of avoidable fatal complications.
Aim: The objective of the present study was an epidemiological and clinical analysis of causes of traumatic death of patients treated at the Multitrauma Centre of the University Teaching Hospital No 1 in Szczecin, over a period of 3 years (2017-2019).
Material and methods: The study material comprised medical data of 32 patients with a mean age of 63 years, who died due to polytrauma injury. The time of death form admission to the Multitrauma Centre, primary cause of death, spectrum and sites of injuries, as well as method of treatment (operative or conservative) were variables considered in the analysis.
Results: The predominant mechanisms of injury were traffic accidents - 22 cases (69%) followed by falls from a height 8 (25%) and other mechanism - 2 cases (6%). The most common primary cause of death was brain injury - 17 patients (53%) followed by pelvic or spinal fractures - 5 (16%). The predominant constituents of polytrauma were bony injuries (pelvis, spine and limbs) - 28 cases (87%), followed by head injuries - 25 (78%), chest - 24 (75%) and abdominal injuries - 17 (53%). Eighteen patients (56%) required operative treatment; craniotomy for brain injuries was the most commonly performed - in 11 patients, followed by laparotomy - in 5. Five other patients underwent an endovascular procedure - pelvic artery embolization. Twelve patients (38%) died in the first two days from admission to the trauma center, 5 (16%) in the first week and 15 over one week form admission.
Conclusions: Head injuries, pelvic fractures with associated retroperitoneal bleeding and severe injuries affecting several body parts were identified as the most dangerous for the survival of polytrauma patients. A trend to decrease mortality due to hemorrhagic shock was observed, but it remains unchanged for central nervous system injuries.


Phenotypic variability in induction of P-glycoprotein mRNA by aromatic hydrocarbons in primary human hepatocytes.
To determine whether human liver responds to treatment with aromatic hydrocarbons (AHs) with induction of the multidrug resistance (mdr) gene product P-glycoprotein and whether AH induction of mdr involves the Ah receptor, we compared induction of mdr mRNA with induction of cytochrome P450 (CYP)1A1 mRNA in AH-treated cultures of primary human hepatocytes. Hepatocytes from all 15 individuals tested responded to treatment with 3-methylcholanthrene (MC) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with induction of CYP1A1 mRNA. However, only 62% and 55% of the preparations responded to treatment with MC and TCDD, respectively, with induction of mdr mRNA. Indeed, in some individuals mdr mRNA was suppressed by MC and TCDD despite robust CYP1A1 induction. These studies provide the first evidence that not only does individual variation in mdr induction by AH exist but that AHs regulate mdr in humans by a novel mechanism distinguishable from the classical Ah receptor pathway. The dramatic variability in AH induction of mdr may be a predictive risk factor that will help to identify an individual's risk of AH-associated toxicities.


Acetabular fracture assessment in four different pelvic trauma centers: have the Judet views become superfluous?
The present study was designed to examine whether oblique radiographs (Judet views) in addition to 2D and 3D CT scans improved the intra- and interobserver reliability when assessing acetabular fractures. Four international orthopedic pelvic trauma centers reviewed the radiological images for 20 acetabular fracture patients. Three different image sets were made; one set containing plain radiographs including oblique (Judet) views and 2D axial CT scans. The second set contained an AP radiograph of the pelvis, without oblique views, 2D and 3D CT scans. The third set contained all the images. The image sets were evaluated in three separate sessions, for each session the raters were asked to classify the fracture according to Letournel, as well as record a number of other important radiological features concerning the fracture. The interobserver agreement for the Letournel classification was found to be moderate for all image sets. The image set without oblique views showed the best agreement with a kappa value of 0.60. The intra- and interobserver agreement for important modifiers were found to be substantial. The addition of oblique radiographs did not seem to increase the intra- or interobserver agreement for any of the factors evaluated except for the roof arc score. The moderate agreement found for the Letournel classification is to be expected given the complexity of the classification. The addition of oblique radiographs to the image sets does not seem to improve the reliability and thus its routine use for classification and decision making may be debated.


Neurological disorders in autism: A systematic review and meta-analysis.
Neurological disorders, such as epilepsy and cerebral palsy, have been reported to occur among individuals with autism beyond chance and may have an impact on daily living across the lifespan. Although there has been research investigating neurological disorders in autism, the findings are not always conclusive. Previous summaries of existing studies have not evaluated the full range of neurological disorders. This study aimed to comprehensively explore the neurological problems appearing in autism to provide updated information that is needed for better healthcare and support in this population. We looked at already published studies focusing on risk or frequency of neurological disorders in autism. Our results suggest that individuals with autism are more likely than the general population to have a range of neurological disorders, including epilepsy, macrocephaly, hydrocephalus, cerebral palsy, migraine/headache, and inborn abnormalities of the nervous system. In order to provide individualized healthcare and support of high quality to individuals diagnosed with autism, health care professionals and other support providers need to be attentive to neurological complications. To further improve our understanding about the link between autism and neurological disorders, future research should follow the neurological health of children who are diagnosed with or are at increased likelihood of autism.


Cancer therapy-related complications in the bowel and mesentery: an imaging perspective.
Cancer therapy-induced complications in the bowel and mesentery are fairly common. It is important for clinicians to be aware of these complications and the agents most frequently implicated. Cancer therapy is rapidly evolving and often encompasses both classic cytotoxic drugs and newer molecular targeted agents. Drugs from both broad classes can have numerous adverse effects on the bowel and mesentery that can be detected on imaging. These adverse effects include ileus, various forms of enterocolitis, gastrointestinal perforation, pneumatosis intestinalis, secretory diarrhea, and sclerosing mesenteritis. These complications are diverse and range from relatively benign to life threatening. The management is also variable, but many of these conditions are easily controlled and reversed with supportive care and cessation of the particular cancer therapy. The objective of this pictorial essay is to demonstrate some of the more common cancer therapy-induced complications of the bowel and mesentery, with a focus on the radiographic findings.


Comparative evaluation of two fully-automated real-time PCR methods for MRSA admission screening in a tertiary-care hospital.
We evaluated two fully-automated real-time PCR systems, the novel QIAGEN artus MRSA/SA QS-RGQ and the widely used BD MAX MRSA assay, for their diagnostic performance in MRSA admission screening in a tertiary-care university hospital. Two hundred sixteen clinical swabs were analyzed for MRSA DNA using the BD MAX MRSA assay. In parallel, the same specimens were tested with the QIAGEN artus MRSA/SA QS-RGQ. Automated steps included lysis of bacteria, DNA extraction, real-time PCR and interpretation of results. MRSA culture was additionally performed as a reference method for MRSA detection. Sensitivity values were similar for both assays (80 %), while the QIAGEN artus MRSA/SA QS-RGQ reached a slightly higher specificity (95.8 % versus 90.0 %). Positive (PPVs) and negative predictive values (NPVs) were 17.4 % and 99.4 % for the BD MAX MRSA assay and 33.3 % and 99.5 % for the QIAGEN artus MRSA/SA QS-RGQ, respectively. Total turn-around time (TAT) for 24 samples was 3.5 hours for both assays. In conclusion, both assays represent reliable diagnostic tools due to their high negative predictive values, especially for the rapid identification of MRSA negative patients in a low prevalence MRSA area.


The impact of antenatal and perinatal variables on cord blood haemopoietic stem/progenitor cell yield available for transplantation.
We investigated the impact of maternal and fetal variables on cord blood (CB) haemopoietic stem/progenitor cell content. These included maternal age, ethnic origin, parity, ABO and Rhesus D blood group, antenatal haemoglobin, alcohol and cigarette consumption at time of registration, mode of delivery, duration of the first and second stages of labour, gestational age, birth weight, cord pH and cord erythrocyte mean cell volume (MCV). Cord volumes and total nucleated cellularities (TNC) were recorded, the colony assay for granulocyte-macrophage colony-forming-cells (CFU-GM) was used to quantify the progenitor cells and the potential of CFU-GM to produce secondary colonies on replating was used as a measure of progenitor cell quality. We found: (1) significantly greater (P=0.04) volumes were collected from babies who weighed > or = 2.5kg versus babies with a birth weight <2.5kg; (2) significantly greater numbers of mononuclear cells (MNC) from mothers who drank 0-3 units versus those who drank > or = 4 units of alcohol weekly (P=0.03), and in babies with a cord pH < or = 7.1 v > 7.1 (P=0.02); (3) Significantly greater numbers of cord CFU-GM in mothers who drank 0-3 v > or = 4 units weekly (P=0.004) and smokers of > or = 10 v 0-9 cigarettes daily (P=0.02) and in spontaneous vaginal deliveries than assisted vaginal and caesarean deliveries (P=0.04), and (4) the potential of CFU-GM to produce secondary colonies was significantly greater in CB derived from Caucasians than from non-Caucasians ( P=0.02); in assisted vaginal delivery v spontaneous vaginal (P=0.02) and in deliveries with prolonged first stage of labour v short first stage of labour (P=0.04). We conclude that antenatal and perinatal variables may influence the CB stem/progenitor cell yield available for transplantation.


Immune induction of airway remodeling.
Airway remodeling is accepted to be a determining component within the natural history of asthma. It is a phenomenon characterized by changes in the airways structures that marches in parallel with and can be influenced by airway inflammation, floating at the interface between both natural and adaptive immunity and physical and mechanical cells behavior. In this review we aimed to highlight the comprehensive, yet not exhaustive, evidences of how immune cells induce, regulate and adapt to the recognized markers of airway remodeling. Mucous cell hyperplasia, epithelial dysfunction and mesenchymal transition, extracellular matrix protein synthesis and restructuration, fibroblast to myofibroblast transition, airway smooth muscle proliferation, bioactive and contractile properties, and vascular remodeling encompass complex physiopathological mechanisms that can be induced, suppressed or regulated by different cellular and molecular pathways. Growth factors, cytokines, chemokines and adhesion molecules expressed or derived either from the immune network of cells infiltrating the asthmatic airways and involving T helper lymphocytes, immune lymphoid cells, dendritic cells, eosinophils, neutrophils, mast cells or by the structural components such as epithelial cells, fibroblasts, myocytes, airway smooth muscle cells concur with protein cellular matrix component and metalloproteases in modifying the airway structure in a detrimental way. The consequences in lung function decline, fixed airway obstruction and clinical severity of the disease suggest the possibility of identify among the immune molecular pathway of remodeling some biological parameters or signal pathway to be either a good tracer for monitoring the disease evolution or a target for hypothetical phenotypes and endotypes. In the era of personalized medicine, a biomarker of remodeling might predict a response to small-molecule inhibitors or biologicals potentially targeting a fundamental aspect of asthma pathogenesis that impacts on the low responsiveness to airway inflammation directed treatments.


Metabolic activity and bioweathering properties of yeasts isolated from different supraglacial environments of Antarctica and Himalaya.
Yeasts have been frequently isolated from cold habitats, but their contribution to essential ecological processes such as the mineralization of organic matter in these environments is less known. Here, the diversity, metabolic capability, and extracellular enzyme profiles of yeasts from snow, blue ice and cryoconite hole environments from East Antarctica and cryoconite holes from a glacier in Western Himalaya were determined. Eighty-six yeast strains isolated were affiliated to the genera Glaciozyma, Goffeauzyma, Mrakia, Phenoliferia, and Rhodotorula. Variations in the abundance, diversity, physiological properties, extracellular enzyme and carbon substrate utilization patterns of the isolated yeasts, reflect the specific environmental conditions from which they were isolated. Overall, 20-90% of the yeasts across all habitat types and geographical locations produced extracellular enzymes to degrade proteins, esters, carbohydrates, pectin, cellulose, lignin, and tannin. About 10 and 29% of the yeasts also exhibited ability to solubilize rock-minerals like phosphate and silicate, respectively. Additionally, selected isolates were able to metabolize 28-93% of the carbon substrates comprising different compound classes on Biolog YT plates. Overall, the ability of yeasts to use diverse organic compounds prevalent on the glacier surface, points to their ecological significance in the decomposition of organic matter, cycling of nutrients, and in the weathering of minerals in supraglacial environments. Moreover, their wide metabolic capabilities suggest that they can colonize new niches and environments when meltwater export during the summer that enables links with surrounding ecosystems.


Kinetic isotope effects on thio-substituted biological phosphoryl transfer reactions from density-functional theory.
Primary and secondary kinetic and equilibrium isotope effects are calculated with density-functional methods for the dianionic methanolysis of the native (unsubstituted) and thio-substituted ethylene phosphates.


Hypofractionated radiation therapy versus standard fractionated radiation therapy with concurrent temozolomide in elderly patients with newly diagnosed glioblastoma.
Adjuvant hypofractionated radiation therapy (HRT) for elderly patients with newly diagnosed glioblastoma (GBM) is a reasonable option compared with standard fractionation radiation therapy (SFRT). Outcomes in patients receiving HRT in the presence of temozolomide (TMZ) compared with SFRT with TMZ are unclear. We examined HRT for GBM with TMZ in comparison to SFRT with TMZ. We conducted a retrospective analysis of patients ≥60 years of age with newly diagnosed GBM who received SFRT or HRT from 1994 to 2014 in the postoperative setting. Inclusion criteria included SFRT (60 Gy/30 fractions or 59.4 Gy/33 fractions) versus HRT (40 Gy/15 fractions). In this cohort, 158 patients were treated with SFRT versus 26 with HRT. Median survival in patients receiving SFRT compared with HRT was 430 and 475 days (P = .550), respectively. Ninety-five percent of the SFRT patients received TMZ versus 100% of those treated with HRT. Patients receiving HRT were older (median, 72 vs 66 years). All HRT patients were treated with the intensity modulated radiation therapy (IMRT) technique versus SFRT, in which 57% had IMRT. Multivariate Cox regression showed decreased overall survival (OS) associated with patient age >70 (hazard ratio [HR], 1.84), lower Karnofsky performance status (HR, 5.25), biopsy versus surgical resection (HR, 4.18), radiation therapy planning technique 3- or 2-dimensional planning versus IMRT (HR, 1.91; HR, 3.40, respectively). Analysis restricted to patients receiving IMRT-based planning showed no difference in OS between HRT and SFRT. For patients receiving TMZ, there was no survival difference between those treated with HRT and those treated with SFRT. Elderly GBM patients receiving HRT and those receiving SFRT had similar OS. Subset analysis patients receiving concurrent TMZ showed no difference in OS between the HRT and SFRT groups.


Predator: non-predator ratios in beetle assemblages.
In common with samples from less taxonomically constrained studies, significant correlations exist between the numbers of predatory and non-predatory species in assemblages of terrestrial beetles. Under logarithmic transformation the relationship can be described reasonably well by a straight line. Explanations for predator: non-predator relationships based on the dynamics of trophic interactions (e.g. competition for prey types or enemy-free space) seem insufficient to explain this pattern, because within beetle assemblages the necessary interactions are so few. Of other proposed determinants, those based on the relationship of local and regional species pools, on energetics, or on non-trophic factors seem the most plausible candidates for explaining proportionality amongst beetles. Much of the deviation from the overall pattern can be accounted for by sampling method and latitude. Temperate samples have a higher proportion of predatory species than tropical, whilst litter and pitfall trap samples have higher proportions of predatory species than Malaise trap and fogging samples.


Mechanisms of Skeletal Muscle Atrophy and Molecular Circuitry of Stem Cell Fate in Skeletal Muscle Regeneration and Aging.
Skeletal muscle is a complex and highly adaptable tissue. With aging, there is a progressive loss of muscle mass and function, known as sarcopenia, and a reduced capacity for regeneration and repair following injury. A review of the literature shows that the primary mechanisms underlying the age-related loss of muscle mass and the attenuated growth response are multi-factorial and related to alterations in multiple processes, including proteostasis, mitochondrial function, extracellular matrix remodeling, and neuromuscular junction function. Multiple factors influence the rate of sarcopenia, including acute illness and trauma, followed by incomplete recovery and repair. Regeneration and repair of damaged skeletal muscle involve an orchestrated cross-talk between multiple cell populations, including satellite cells, immune cells, and fibro-adipogenic precursor cells. Proof-of-concept studies in mice have demonstrated that reprogramming of this disrupted orchestration, resulting in the normalization of muscle function, may be possible using small molecules that target muscle macrophages. During aging, as well as in muscular dystrophies, disruptions in multiple signaling pathways and in the cross-talk between different cell populations contribute to the failure to properly repair and maintain muscle mass and function.


Pharmacological and immunological characterization of the Leu5 analogue of human beta-endorphin.
The potencies of beta h-endorphin, Met (O)5-beta h-endorphin, and synthetic Leu5-beta h-endorphin have been compared in three bioassays of opioid activity, and in two radioimmunoassays. In all assays, a peptide isolated from hemodialysates from a psychotic patient behaved like Leu5-beta h-endorphin; it has been distinguished unambiguously from beta h-endorphin and Met(O)5-beta h-endorphin. Leu5-beta h-endorphin was one-fifth as potent as beta h-endorphin in guinea pig ileum myenteric plexus, but was only slightly less active in mouse vas deferens and in guinea pig brain opiate receptor binding assay. The low cross-reactivity of Leu5-beta h-endorphin relative to beta h-endorphin with an antiserum raised to beta-endorphin suggests that the preferred solution conformations of these peptides are different. In all bioassays beta h-endorphin was 2- to 3-fold less potent than beta c-endorphin.


Studies of normal and nephritic rat glomerular basement membrane.
Solubilization of the normal glomerular basement membrane with various solvents revealed that the material is held together by hydrogen and disulfide linkages as well as ionic salt bridges which ionize at around pH 10.0. Pronase digestion indicated that differences in susceptibility to enzyme digestion exist between normal and nephritic membrane. Titration of a urea-insoluble material indicated that some alteration must have taken place in the association between various components of the nephritic basement membrane. Chemical analysis of alkali-solubilized fractions suggested that greater alkali susceptibility of the nephritic material may be present. A collagen-like material resembling both tendon and dog basement membrane collagen in its amino acid composition was isolated. It contained 10% hexose, but in addition to glucose and galactose, mannose was also detected. A glycopeptide fraction obtained by pronase and collagenase digestion has a carbohydrate composition similar to the collagen-like material above. These substances probably represent incompletely digested fragments of the basement membrane.


Prediction of rat liver transplantation outcomes using energy metabolites measured by microdialysis.
Warm ischemia jeopardizes graft quality and recipient survival in donation after cardiac death (DCD) transplantation. Currently, there is no system to objectively evaluate the liver quality from DCD. The present study tried to use energy metabolites to evaluate the donor liver quality. We divided 195 Sprague-Dawley rats into five groups: the control (n = 39), warm ischemic time (WIT) 15 min (n = 39), WIT 30 min (n = 39), WIT 45 min (n = 39), and WIT 60 min (n = 39) groups. Three rats from each group were randomly selected for pretransplant histologic evaluation of warm ischemia-related damage. The remaining 36 rats were randomly divided into donors and recipients of 18 liver transplantations, and were subjected to postoperative liver function and survival analyses. Between cardiac arrest and cold storage, liver energy metabolites including glucose, lactate, pyruvate, and glycerol were measured by microdialysis. The lactate to pyruvate ratio (LPR) was calculated. The changes in preoperative pathology with warm ischemia were inconspicuous, but the trends in postoperative pathology and aminotransferase levels were consistent with preoperative energy metabolite measurements. The 30-day survival rates of the control and WIT 15, 30, 45, and 60 min groups were 100%, 81.82%, 76.92%, 58.33%, and 25.00%, respectively. The areas under the receiver operating characteristic curves of glucose, lactate, glycerol, and LPR were 0.87, 0.88, 0.88, and 0.92, respectively. Glucose, lactate, glycerol, and LPR are predictors of graft quality and survival outcomes in DCD transplantation.


Effects of donepezil, nicotine and haloperidol on the central serotonergic system in mice: implications for Tourette's syndrome.
We have previously reported that acute and chronic donepezil and nicotine administration significantly attenuate DOI-induced head twitch response (HTR) in mice. This behavior, primarily mediated by stimulation of 5-HT2A receptors, has been proposed to model tic symptoms seen in Tourette's syndrome (TS). Haloperidol, a drug widely used to treat symptoms of TS, has also been reported to reduce DOI-induced head shakes in rodents when administered acutely. These findings suggest an inhibitory interaction of these drugs with 5-HT2A receptors. To test this hypothesis, we evaluated the effects of chronic donepezil, nicotine and haloperidol on expression levels of 5-HT2A mRNA and 5-HT2A receptor density in select brain regions. Initially, we established a dose-response relationship for the acute and chronic haloperidol and DOI-induced HTR. Male ICR mice were treated twice daily with donepezil (0.1 mg/kg), nicotine (0.5 mg/kg), and once daily with haloperidol (0.4 mg/kg) for 14 days and were sacrificed 16-18 h after the last injection. These drug regimens were chosen because of their significant effects on DOI-induced HTR. Donepezil significantly increased 5-HT2A mRNA level, but not the receptor density in the striatum. In the midbrain, donepezil significantly decreased the receptor density without affecting the 5-HT2A mRNA level. In the frontal cortex, only haloperidol significantly reduced the 5-HT2A receptor density. The cortex was the only area where donepezil, nicotine and haloperidol significantly reduced the 5-HT2A receptor density. The results suggest that the anti-tic properties of donepezil, nicotine and haloperidol in this paradigm might be due to antagonism of cortical 5-HT2A receptors. Thus, further investigation of involvement of cortical 5-HT2A receptors in TS as well as evaluation of selective 5-HT2A receptor antagonists in this disorder is warranted.


Tauroursodeoxycholic acid improves glucose tolerance and reduces adiposity in normal protein and malnourished mice fed a high-fat diet.
Early childhood malnutrition may facilitate the onset of obesity and diabetes mellitus in adulthood which, when established, makes it more resistant to therapeutic interventions. The beneficial effects of tauroursodeoxycholic acid (TUDCA) in glucose homeostasis and body fat accumulation were analyzed in protein-restricted mice fed a high-fat diet (HFD). C57BL/6 mice were fed a control (14% protein [C]) or a protein-restricted (6% protein [R]) diet for 6 weeks. Afterward, mice received an HFD or not for 12 weeks (C mice fed an HFD [CH] and R mice fed an HFD [RH]). In the last 15 days of this period, half of the mice fed a HFD received i.p. PBS (groups CH and RH) or 300 mg/kg TUDCA (groups CHT and RHT). RH mice developed obesity, as demonstrated by the increase in fat accumulation, liver steatosis, and metabolic inflexibility. Additionally, showed glucose intolerance and insulin hypersecretion. TUDCA reduced adiposity and improve metabolic flexibility through increased HSL phosphorylation and CPT1 expression in eWAT and BAT, and reduced ectopic fat deposition by activating the AMPK/HSL pathway in the liver. Also, improved glucose tolerance and insulin sensitivity, normalizing insulin secretion by reducing GDH expression and increasing insulin peripheral sensitivity by greater expression of the IRβ in muscle and adipose tissue and reducing PEPCK liver expression. Our data indicate that TUDCA reduces global adiposity and improves glucose tolerance and insulin sensitivity in protein malnourished mice fed a HFD. Therefore, this is a possible strategy to reverse metabolic disorders in individuals with the double burden of malnutrition.


Prophylactic anti-lipopolysaccharide freeze-dried plasma in major burns: a double blind controlled trial.
A double-blind controlled trial to test the efficacy of freeze-dried plasma containing a high titre of anti-lipopolysaccharide (anti-LPS) IgG in preventing or reducing sepsis in burns was carried out on 60 consecutive consenting adult burn victims with burns between 20 and 55 per cent of body surface area. Statistics failed to demonstrate a reduction in the mortality (P = 0.12) but did demonstrate a reduction in the incidence of burn wound infection (P = 0.0443), a fall in endotoxin levels in the first week (P = 0.041) and a rise in the anti-endotoxin levels after 5 units of anti-LPS plasma (P = 0.027). The logistics of carrying out such a trial are difficult but a larger patient population and modification of the original protocol might demonstrate a significant fall in mortality and morbidity. It was felt that some of the positive benefits of the high titre anti-LPS plasma might be due to factors other than the anti-LPS IgG.


Switchable hepatic organelles aberrations in DEN-induced mice under the influence of chemically characterized silk sericin.
Assessing the beneficial effects of silk sericin against hepatic injury induced by diethylnitrosamine (DEN). Aiming at promoting sericin as a natural product able to counteract the hazards of toxic elements, HPLC profile was conducted on the extracted sericin sample versus the standard one to qualitatively identify it. Following sericin treatment on human HepG2 liver cancer cells, many parameters were analyzed in vitro including cell viability, cell cycle, and cell apoptosis. Hepatic pro-inflammatory cytokines as well as histopathological and ultrastructure changes were evaluated in vivo in the different experimental groups. Sericin exhibited a dose-dependent cytotoxic effect on HepG2 cells with an IC50 of 14.12 + 0.75 μg/mL. The hepatotoxicity of DEN was manifested in mice by increased pro-inflammatory markers (IL-2, IL-6, and TNF-α), decreased IL-10, liver structure deterioration, and characteristic histopathological and ultrastructure changes. Sericin administration reversed most of the observed alterations inflected by DEN. Our results substantiate the sericin's powerful apoptotic impact in vitro. In experimental mice, combination treatment using sericin together with melatonin appears to be more potent in mitigating the adverse effects of DEN. However, further investigations are needed to identify the underlying mechanism of action and complement the knowledge about the expected medicinal values of sericin.


Recent advances in inorganic functional nanomaterials based flexible electrochemical sensors.
The flexible electrochemical sensor is a key component of the health monitoring system which can continuously track the physiological signals of the human body, while there is no obvious discomfort and invasiveness. Therefore, it has great potential in personalized medical testing. However, the development of flexible electrochemical sensors currently faces many difficulties, such as the limitations of conductive material properties and manufacturing methods, and the disadvantages of commonly used flexible substrates that are not resistant to high temperatures. In this work, inorganic nanomaterials commonly used to make flexible electrochemical sensors were classified to zero-dimensional (0D) nanomaterials, one-dimensional (1D) nanomaterials, two-dimensional (2D) nanomaterials, and hybrid nanomaterials according to their morphology. The fabrication method of the nanomaterials-based flexible electrochemical sensors was also introduced. Furthermore, the application of flexible electrochemical sensors for chemical and biological sensing and their detection performance were summarized. The detection targets were classified to ion, small molecule, biomacromolecule, and bacteria, respectively.


Prediabetes Is Associated with Unfavorable Outcome in Young Adult Patients with Ischemic Stroke.
Prediabetes has been associated with unfavorable short-term outcome in patients with ischemic stroke (IS). However, its effect in the subset of young adult patients has not been fully assessed. Our aim was to study the association between prediabetes and 3-month outcome in young adult patients with IS. This is a retrospective analysis of consecutive patients aged 18-55 years with a clinical diagnosis of acute IS between January 2010 and December 2016. According to their glucose profile, patients were divided in 3 groups: normal glucose metabolism, prediabetes, and diabetes. The outcome at 3 months was assessed by the modified Rankin Scale (mRS) and dichotomized as good (mRS score ≤2) and poor (mRS score >2) outcomes. A total of 247 patients were included, the median age was 49 years (interquartile range 42-53), and 144 (58.3%) were men. Prediabetes was diagnosed in 79 patients (32.0%) and diabetes was diagnosed in 45 patients (18.2%). Prediabetic (adjusted odds ratio [OR] 2.4, 95% confidence interval [CI] 1.1-5.1, P = .031) and diabetic (adjusted OR 2.8, 95% CI 1.3-6.1, P = .020) patients had a worse prognosis at 3 months. A statistical significant shift in the distribution of the mRS score at 3 months was found in prediabetic (adjusted OR 2.5, 95% CI .3-1.5, P = .002) and diabetic (adjusted OR 3.74, 95% CI .5-2.2, P = .002) patients. In young adults with IS, prediabetes and diabetes increase the risk of unfavorable outcome at 3 months.


Associations of small vessel disease and acute symptomatic seizures in ischemic stroke patients.
Cerebral microbleeds (CMBs), markers of small vessel disease are frequent in ischemic stroke, yet the association with acute symptomatic seizures (ASS) has not been well characterized. A retrospective cohort of hospitalized patients with anterior circulation ischemic stroke. The association of CMBs with acute symptomatic seizures was assessed using a logistic regression model and causal mediation analysis. Of 381 patients, 17 developed seizures. Compared with patients without CMBs, those with CMBs had a three-fold higher unadjusted odds of seizures (unadjusted OR: 3.84, 95% 1.16-12.71, p = 0.027). After adjusting for confounders such as stroke severity, cortical infarct location, and hemorrhagic transformation, the association between CMBs and ASS was attenuated (adjusted OR: 3.11, 95%CI: 0.74-11.03, p = 0.09). The association was not mediated by stroke severity. In this cohort of hospitalized patients with anterior circulation ischemic stroke, CMBs were more likely to be found in patients with ASS than those without ASS, an association that was attenuated when accounting for stroke severity, cortical infarct location, and hemorrhagic transformation. Evaluation of the long-term risk of seizures associated with CMBs and other markers of small vessel disease is warranted.


Uptake and release of transferrin and iron by mitogen-stimulated human lymphocytes.
Phytohaemagglutinin stimulation of human peripheral blood lymphocytes resulted in the expression of transferrin receptors and the uptake of iron into the cells. As assessed from the resistance of the 125I label to pronase, transferrin was rapidly bound and internalized at 37 degrees C, while at 4 degrees C 85% of the 125I label remained on the cell surface and was degraded by the pronase. Over 94% of the 125I label associated with and subsequently released from the cells was acid precipitable, indicating that transferrin was not degraded during its uptake and release. After reincubation for 1 h in fresh medium 70% of the cell associated 125I-transferrin was released. In contrast, less than 30% of the 59Fe was released, showing that iron was removed from transferrin and retained by the cells. Concentration dependent binding of 125I-transferrin estimated at 37 degrees C occurred with an apparent Ka of 5.7 +/- 1.1 X 10(7) l mol-1 (mean +/- SD, n = 4) indicating little variation between cells from different individuals, although the number of transferrin molecules associated with the cells varied greatly from 6.2 X 10(4)/cell to 1.4 X 10(5)/cell. The rate of iron uptake from 59Fe and 125I labelled transferrin at 37 degrees C by the cells from different subjects was also very variable, with a range between 0.46 and 2.27 pg Fe/min/10(6) cells (n = 6). However, iron uptake did not correlate with the amount of transferrin bound. This suggests that transferrin uptake and the release of iron from the transferrin to the interior of the cell are controlled independently.


GAP-43 closely interacts with BDNF in hippocampal neurons and is associated with Alzheimer's disease progression.
Growth-associated protein 43 (GAP-43) is known as a neuronal plasticity protein because it is widely expressed at high levels in neuronal growth cones during axonal regeneration. GAP-43 expressed in mature adult neurons is functionally important for the neuronal communication of synapses in learning and memory. Brain-derived neurotrophic factor (BDNF) is closely related to neurodegeneration and synaptic plasticity during the aging process. However, the molecular mechanisms regulating neurodegeneration and synaptic plasticity underlying the pathogenesis and progression of Alzheimer's disease (AD) still remain incompletely understood. Remarkably, the expressions of GAP-43 and BDNF perfectly match in various neurons in the Human Brain Atlas database. Moreover, GAP-43 and BDNF are highly expressed in a healthy adults' hippocampus brain region and are inversely correlated with the amyloid beta (Aβ), which is the pathological peptide of amyloid plaques found in the brains of patients with AD. These data led us to investigate the impact of the direct molecular interaction between GAP-43 and BDNF in hippocampal neuron fate. In this study, we show that GAP-43 and BDNF are inversely associated with pathological molecules for AD (Tau and Aβ). In addition, we define the three-dimensional protein structure for GAP-43 and BDNF, including the predictive direct binding sites via analysis using ClusPro 2.0, and demonstrate that the deprivation of GAP-43 and BDNF triggers hippocampal neuronal death and memory dysfunction, employing the GAP-43 or BDNF knock-down cellular models and 5XFAD mice. These results show that GAP-43 and BDNF are direct binding partners in hippocampal neurons and that their molecular signaling might be potential therapeutic targets for AD.


Regulation of telomeric repeat binding factor 1 binding to telomeres by casein kinase 2-mediated phosphorylation.
Telomere maintenance is essential for continued cell proliferation and chromosome stability. Telomeres are maintained by telomerase and a collection of associated proteins. The telomeric protein telomeric repeat binding factor 1 (TRF1) negatively regulates telomere length by inhibiting access of telomerase at telomere termini. Here we report that TRF1 interacts with the beta subunit of casein kinase 2 (CK2) and serves as a substrate for CK2. CK2-mediated phosphorylation is required for the efficient telomere binding of TRF1 in vitro and in vivo. Inhibition of CK2 by the CK2 inhibitor 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole decreased the ability of TRF1 to bind telomeric DNA. The resulting telomere-unbound form of TRF1 was then ubiquitinated and degraded by the proteasome. Partial knockdown of CK2 by small interfering RNA resulted in removal of TRF1 from telomeres and subsequent degradation of TRF1. Mapping of the CK2 target site identified threonine 122 as a substrate in TRF1. A threonine to alanine change at this position led to a diminished DNA binding due to reduced dimerization of TRF1. In addition, phosphorylation of threonine 122 seemed critical for TRF1-mediated telomere length control. Our findings suggest that CK2-mediated phosphorylation of TRF1 plays an important role in modulating telomere length homeostasis by determining the levels of TRF1 at telomeres.


A silver lining to higher prices at the pump? Gasoline prices and teen driving behaviors.
Existing literature shows negative relationships between gasoline price and motor vehicle crashes, particularly among teens. This paper extends that literature by evaluating the relationship between gasoline price and self-reported risky driving among teens. Observational study using multivariate empirical analysis, using pooled data from the Youth Risk Behavior Survey, waves 2003-2009. Secondary data from survey administered in private and public high schools across the United States. Students in grades 9 through 12, surveyed biennially from 2003 to 2009 (n = 58,749). Outcomes are (self-reported) driving without seatbelts, driving after consuming alcohol, and moderate physical activity (like walking or bicycling). State-level retail gasoline prices constitute the main predictor variable. Multivariate logistic models are estimated for the full sample, as well as by gender, race/ethnicity, and age. Individual characteristics, state unemployment, and state driving policies are controlled for. Standard errors are clustered at the state level. Results are reported in form of risk differences. Higher gasoline prices are negatively and significantly associated with driving without seatbelts. Associations are particularly strong for males and minorities. There are fewer statistical associations between gasoline prices and driving after drinking. Higher gasoline prices are positively associated with more moderate physical activity. Higher gasoline prices are associated with less risky driving behaviors among teens, and they may be associated with more active forms of transportation, like walking and bicycling. The study limitations are discussed.


Clinical Considerations for Immunoparesis in Multiple Myeloma.
Multiple myeloma is a relatively common clonal plasma cell disorder, comprising 17% of hematologic malignancies. One of the hallmark features of this disease is immunoparesis, which is characterized by the suppression of immunoglobulin polyclonality. Though not entirely elucidated, the mechanism behind this process can be attributed to the changes in the tumor microenvironment. All treating clinicians must consider potential complications related to immunoparesis in the management of multiple myeloma. Though not explicitly described in large data series, the increased risk of infection in multiple myeloma is likely, at least in part, due to immunoglobulin suppression. Additionally, the presence of immunoparesis serves as a prognostic factor, conveying poorer survival and a higher risk of relapse. Even in the era of novel agents, these findings are preserved, and immunoglobulin recovery also serves as a sign of improved outcome following autologous HSCT. Though not within the diagnostic criteria for multiple myeloma, the presence and degree of immunoparesis should be at diagnosis for prognostication, and immunoglobulin recovery should be tracked following myeloablative therapy and autologous HSCT.