Role of time-resolved-CTA in intracranial arteriovenous malformation evaluation at 128-slice CT in comparison with digital subtraction angiography.
Introduction The present study aimed to evaluate the accuracy of time-resolved-computed tomographic angiography (TR-CTA) on a 128-slice CT scanner vis-à-vis cerebral digital subtraction angiography (DSA) in defining the morphological and haemodynamic characteristics of cerebral arteriovenous malformation (AVM). Methods Twenty-one patients (age range 10-46, mean 24.8 years) with clinical suspicion of AVM and three patients (age range 23-35, mean 24.3 years) with diagnosed AVM who were on follow-up underwent DSA and TR-CTA, on average 1.5 days apart. Three independent neuroradiologists analysed both studies in a blinded fashion based on the following parameters: AVM location, arterial feeder territories, venous drainage pattern, nidus flow characteristics, venous outflow obstruction, arterial feeder enlargement, external carotid artery feeder, location of aneurysm if any, leptomeningeal and transdural recruitment, neoangiogenesis, and pseudophlebitic pattern. Results The TR-CTA correctly demonstrated AVM in all 21 positive cases. It concordantly detected location (21/21), venous drainage pattern (21/21), nidus flow characteristics (21/21), and the venous outflow obstruction (9/9). However, discordance was seen in the demonstration of the arterial feeder (2/45) ( p = 0.49), arterial enlargement (13/17) ( p = 0.103), external carotid artery feeder (0/1), aneurysmal location (3/5) ( p = 0.40), leptomeningeal recruitment (1/3) ( p = 0.40), neoangiogenesis (0/4) ( p = 0.028) and in the pseudophlebitic pattern (2/5) ( p = 0.167) demonstration. Conclusions The results suggest that TR-CTA can provide the important features of cerebral AVM which are required in patient management.


Single-Port Versus Multiport da Vinci System for Transoral Robotic Surgery of Hypopharyngeal and Laryngeal Carcinoma.
Da Vinci single port (SP) has been recently approved for transoral robotic surgery (TORS). Its characteristics make it particularly feasible for laryngeal and hypopharyngeal surgery. We report our experience comparing intra- and postoperative outcomes, technical advantages, and shortcomings of transoral laryngeal and hypopharyngeal resections performed with the da Vinci SP and the da Vinci Si/Xi systems. Retrospective database review. Single academic tertiary care hospital. Subjects included adult patients with laryngeal and hypopharyngeal carcinoma who underwent TORS between 2008 and 2022. The SP and multiport (MP) systems were compared in terms of intraoperative times, short-term postoperative outcomes, and TORS-related complications after a propensity score matching. A total of 185 patients were enrolled (56 SP vs 129 MP patients), and a cohort of 112 patients was analyzed after matching. The docking time was reduced in the SP group (8.84 ± 4.67 vs 6.45 ± 3.11 minutes; p = .003), as well as console time (53.91 ± 29.38 vs 42.70 ± 13.72 minutes; p = .035). Positive margins were more frequent in the MP group (52% vs 43%; p = .34). The mean decannulation time was 1.86 days longer in the SP group (p = .046). No significant differences emerged from the analysis of the duration of hospitalization, enteral feeding, and TORS-related complications. SP safety profile is comparable to that of previous models, while it showed advantages in terms of reduced docking times. Console times were also shortened due to improved maneuverability and field visualization.


Mechanical and infectious complications of central venous cannulation in children: lessons learned from a 10-year experience placing more than 1000 catheters.
We sought to better describe the expected incidence of mechanical and infectious complications associated with central venous cannulation of critically ill children. We undertook a retrospective analysis of a prospective data collection of 1056 consecutive percutaneous central venous catheters inserted under the supervision of an experienced surgeon. There were 245 (23%) subclavian (SC), 118 (11%) internal jugular (IJ), and 693 (66%) femoral (F) catheters placed in 289 children with an average age of 6.4 +/- 5.1 years (range, 4 weeks to 18 years) admitted to a burn intensive care unit. Catheter sepsis occurred in 7.4% of SC, 7.6% of IJ, and 4.9% of F catheters (NS, P = .25), for an overall sepsis rate of 5.8%. The number of catheter lumens did not impact infection rate. Infection rates increased in catheters left in situ more than 10 days, increasing to 37.5% at 14 days. Acute mechanical complications occurred in three insertions (0.3%), including two (0.8%) SC, zero (0%) IJ, and one (0.1%) F catheters (NS, P = .20). All three were arterial cannulations that were recognized and treated successfully without surgery. There were no pneumothoraces, vascular lacerations, acute thromboses, or catheter emboli. There were six (0.6%) cases of deep venous thrombosis that occurred in cannulated sites: one (0.4%) SC, two (1.6.%) IJ, and three (0.4%) F sites (NS, P = .23). Patient age did not influence complication rates. A total of 239 (23%) of the CVCs were placed in infants less than 24 months; 273 (26%) 2 to 5 years, 259 (25%) 6 to 10 years, and 285 (27%) >10 to 18 years. Catheter sepsis occurred in 6.7%, 5.9%, 6.2%, and 4.6%, respectively (NS, P = .75). There was no difference in rates of infection or mechanical complication between younger and older children. When closely supervised by an experienced surgeon, a low rate of infection (5.8%), acute mechanical complication (0.3%), and deep venous thrombosis (0.6%) accompanies central venous cannulation of critically ill children.


Evaluating the Efficacy of Activated Carbon in Minimizing the Risk of Heavy Metals Contamination in Spinach for Safe Consumption.
Toxicity induced by heavy metals is a major concern in agriculture as it decreases crops' growth and yield and leads to the deterioration of food quality. Recently, activated carbon has been identified as a possible solution. It can potentially improve crop nutrition and immobilize heavy metals in soil. That is why a glasshouse trial was conducted to investigate the effects of sugarcane bagasse-derived biochar on spinach growth and the availability of cadmium (Cd) and chromium (Cr) in artificially contaminated soil. The soil was placed in pots and contaminated with Cd and Cr at a rate of 10 mg kg-1. Biochar was added to the soil at concentrations of 0 (control), 0 (contaminated control), 100, 150, and 200 g, and 10-day-old nursery spinach plants were transplanted to the pots. The results showed that applying 200 g of biochar significantly increased shoot weight (235 g), soil pH, electrical conductivity, and organic matter. The highest levels of Cd (27.71 mg kg-1) and Cr (20.44 mg kg-1) were observed in the contaminated control pots, while the lowest levels of Cd (16.80 mg kg-1) and Cr (9.80 mg kg-1) were found in pots treated with 200 g of biochar (2%). Similarly, the highest levels of Cd (35.80 mg kg-1) and Cr (40.24 mg kg-1) in the roots were found in the contaminated control pots, while the lowest levels of Cd (19.26 mg kg-1) and Cr (21.34 mg kg-1) were observed in pots treated with 200 g of biochar. Biochar application at a rate of 2% can immobilize Cd and Cr in the soil and improve chlorophyll contents, carotenoids, photosynthetic rate, transpiration rate, and stomatal conductance in spinach in Cd- and Cr-contaminated soils. Further long-term field studies will be necessary to determine the feasibility of applying biochar as an organic amendment for enhancing spinach growth and reducing Cd and Cr bioavailability in contaminated soil.


Neuronal messenger ribonucleoprotein transport follows an aging Lévy walk.
Localization of messenger ribonucleoproteins (mRNPs) plays an essential role in the regulation of gene expression for long-term memory formation and neuronal development. Knowledge concerning the nature of neuronal mRNP transport is thus crucial for understanding how mRNPs are delivered to their target synapses. Here, we report experimental and theoretical evidence that the active transport dynamics of neuronal mRNPs, which is distinct from the previously reported motor-driven transport, follows an aging Lévy walk. Such nonergodic, transient superdiffusion occurs because of two competing dynamic phases: the motor-involved ballistic run and static localization of mRNPs. Our proposed Lévy walk model reproduces the experimentally extracted key dynamic characteristics of mRNPs with quantitative accuracy. Moreover, the aging status of mRNP particles in an experiment is inferred from the model. This study provides a predictive theoretical model for neuronal mRNP transport and offers insight into the active target search mechanism of mRNP particles in vivo.


The importance of oxytocin neurons in the supraoptic nucleus for breastfeeding in mice.
The hormone oxytocin, secreted from oxytocin neurons in the paraventricular (PVH) and supraoptic (SO) hypothalamic nuclei, promotes parturition, milk ejection, and maternal caregiving behaviors. Previous experiments with whole-body oxytocin knockout mice showed that milk ejection was the unequivocal function of oxytocin, whereas parturition and maternal behaviors were less dependent on oxytocin. Whole-body knockout, however, could induce the enhancement of expression of related gene(s), a phenomenon called genetic compensation, which may hide the actual functions of oxytocin. In addition, the relative contributions of oxytocin neurons in the PVH and SO have not been well documented. Here, we show that females with conditional knockout of oxytocin gene in both the PVH and SO undergo grossly normal parturition and maternal caregiving behaviors, while dams with a smaller number of remaining oxytocin-expressing neurons exhibit severe impairments in breastfeeding, leading to the death of their pups within 24 hours after birth. We also found that the growth of pups is normal even under oxytocin conditional knockout in PVH and SO as long as pups survive the next day of delivery, suggesting that the reduced oxytocin release affects the onset of lactation most severely. These phenotypes are largely recapitulated by SO-specific oxytocin conditional knockout, indicating the unequivocal role of oxytocin neurons in the SO in successful breastfeeding. Given that oxytocin neurons not only secrete oxytocin but also non-oxytocin neurotransmitters or neuropeptides, we further performed cell ablation of oxytocin neurons in the PVH and SO. We found that cell ablation of oxytocin neurons leads to no additional abnormalities over the oxytocin conditional knockout, suggesting that non-oxytocin ligands expressed by oxytocin neurons have negligible functions on the responses measured in this study. Collectively, our findings confirm the dispensability of oxytocin for parturition or maternal behaviors, as well as the importance of SO-derived oxytocin for breastfeeding.


Thromboprophylaxis for Patients with High-risk Atrial Fibrillation and Flutter Discharged from the Emergency Department.
Many patients with atrial fibrillation or atrial flutter (AF/FL) who are high risk for ischemic stroke are not receiving evidence-based thromboprophylaxis. We examined anticoagulant prescribing within 30 days of receiving dysrhythmia care for non-valvular AF/FL in the emergency department (ED). This prospective study included non-anticoagulated adults at high risk for ischemic stroke (ATRIA score ≥7) who received emergency AF/FL care and were discharged home from seven community EDs between May 2011 and August 2012. We characterized oral anticoagulant prescribing patterns and identified predictors of receiving anticoagulants within 30 days of the index ED visit. We also describe documented reasons for withholding anticoagulation. Of 312 eligible patients, 128 (41.0%) were prescribed anticoagulation at ED discharge or within 30 days. Independent predictors of anticoagulation included age (adjusted odds ratio [aOR] 0.89 per year, 95% confidence interval [CI] 0.82-0.96); ED cardiology consultation (aOR 1.89, 95% CI [1.10-3.23]); and failure of sinus restoration by time of ED discharge (aOR 2.65, 95% CI [1.35-5.21]). Reasons for withholding anticoagulation at ED discharge were documented in 139 of 227 cases (61.2%), the most common of which were deferring the shared decision-making process to the patient's outpatient provider, perceived bleeding risk, patient refusal, and restoration of sinus rhythm. Approximately 40% of non-anticoagulated AF/FL patients at high risk for stroke who presented for emergency dysrhythmia care were prescribed anticoagulation within 30 days. Physicians were less likely to anticoagulate older patients and those with ED sinus restoration. Opportunities exist to improve rates of thromboprophylaxis in this high-risk population.


Regulation of immunolabelled mu-opioid receptors and protein kinase C-alpha and zeta isoforms in the frontal cortex of human opiate addicts.
To assess the status of opioid receptors in the human brain during the process of opiate addiction, the abundance of immunoreactive mu-opioid receptors was quantitated in postmortem brains of chronic opiate addicts who had died of a heroin or methadone overdose. The immunoreactive levels of the associated enzyme protein kinase C (PKC-alpha and zeta isoforms) and G proteins (G alpha(i1/2) subunits) were also assessed in the same brains. In the frontal cortex of opiate addicts, the abundance of mu-opioid receptors was not different from that obtained in matched controls. The level of Ca2+-dependent PKC-alpha was decreased (25%), whereas that of the atypical PKC-zeta remained unchanged. The density of G alpha(i1/2) proteins also was found to be increased (40%). The results indicate that opiate addiction in humans does not appear to be associated with a reduced density of brain mu-opioid receptors. The sustained down-regulation of PKC-alpha in the brain of opiate addicts would allow the up-regulation of G alpha(i1/2) proteins aimed at compensating the postulated desensitization of the mu-opioid receptor system.


Duration of hospital admission and the need for empirical antipseudomonal therapy.
To reduce selective pressure for antimicrobial resistance, empirical use of antipseudomonal antibiotics is often reserved for patients with late-onset hospital-acquired infections. We examined the likelihood of isolating Pseudomonas aeruginosa as a function of time from hospital admission. We conducted a retrospective cohort study of all positive bacterial cultures in a tertiary-care hospital between March 2010 and November 2011. The primary outcome was the proportion of positive cultures yielding P. aeruginosa. Multivariable logistic regression was employed to assess the impact of time from admission on the likelihood of isolating P. aeruginosa, after adjusting for other important risk factors. A total of 7,668 positive cultures were obtained from 4,108 unique patients during the study interval, including 633 (8.3%) yielding P. aeruginosa. The probability of isolating P. aeruginosa increased linearly from 79/2,044 (3.9%) positive cultures obtained on admission to 153/664 (23%) in the 10th week of admission or beyond. The unadjusted odds ratio was 1.002/day (95% confidence interval [CI], 1.0016 to 1.0028; P < 0.0001); the adjusted odds ratio (aOR) was 1.0007/day (95% CI, 1.0001 to 1.0013; P = 0.02). Other important predictors of P. aeruginosa isolation included respiratory specimen type (aOR, 13.8; 95% CI, 9.1 to 21.1), recent hospital admission (aOR,1.8; 95% CI, 1.4 to 2.3), prior P. aeruginosa isolation during current admission (aOR, 4.9; 95% CI, 3.7 to 6.4), and prior antipseudomonal (aOR, 1.9; 95% CI, 1.4 to 2.5) or nonantipseudomonal (aOR, 1.8; 95% CI, 1.4 to 2.4) antibiotic exposure. It was determined that as time from admission increases, there is a linear increase in the likelihood of P. aeruginosa isolation. Any guidelines which distinguish early from late hospital-acquired infection must consider the implications of time point selection on the likelihood of inadequate P. aeruginosa empirical coverage.


Characterization of the transition state of protein unfolding by use of molecular dynamics: chymotrypsin inhibitor 2.
Temperature-induced unfolding of chymotrypsin inhibitor 2 in water was investigated by molecular dynamics simulations. The major transition state of unfolding was identified on the basis of structural and conformational changes in the protein during the unfolding reaction. The native tertiary contacts in the hydrophobic core were considerably disrupted in the transition state, whereas the secondary structure was partially intact. The extent of structural change of the protein around a particular residue was represented quantitatively by the ratio of the number of contacts the residue makes in the transition state relative to the native state, phi MD, which allows quantitative comparison with the experimentally determined phi F values. For the region of the unfolding trajectory that is identified as the transition state, the phi MD and phi F values are in good agreement, suggesting that the transition state identified in the unfolding simulation corresponds to that probed with protein engineering methods. Although speculative, the transition state identified in the simulation is consistent with available experimental data and provides an in-depth view of what the transition state of unfolding may look like.


Posterior glottic stenosis mechanism and surgical management.
Posterior glottic stenosis with arytenoid fixation is an uncommon complication of laryngeal injury. Though etiologies vary; the most common is prolonged intubation. Patients with this problem are tracheotomy dependent and have compromised voice production. There has been no acceptable approach to reconstruction of the larynx, the majority of patients being treated with some type of vocal fold lateralization. The success rate with this approach varies, and this procedure does not take advantage of the intact neuromuscular status of the larynx. Over the past 3 years we have utilized an alternative approach, to repair the stenosis and mobilize the arytenoids in 10 patients. Our surgical technique involves laryngeal exposure via a laryngofissure, the removal of posterior glottic cicatricial tissues, and the application of an autologous graft. Subsequently, all but one of the patients were able to be decannulated. Subjective postoperative voice analysis showed improved voice production. The pathophysiology for this disorder and a review of different treatment modalities are discussed.


Enrichment of Geogenic Ammonium in Quaternary Alluvial-Lacustrine Aquifer Systems: Evidence from Carbon Isotopes and DOM Characteristics.
Geogenic ammonium in groundwater owing to mineralization of natural organic matter (NOM) has been reported in different geologic settings, but detailed mechanisms responsible for high ammonium concentration levels are poorly understood. To this end, we chose Quaternary high ammonium aquifer systems in central Yangtze River basins and used carbon isotopes in both dissolved organic carbon and inorganic carbon together with characterization of dissolved organic matter (DOM) and groundwater chemistry to reveal mechanisms related to the genesis of ammonium. The results indicate that high levels of geogenic ammonium (up to 33.50 mg/L as N) occur due to long-term water-rock interactions in a relatively sluggish hydrogeological environment with abundant organic matter that is rich in both C and N. The stable carbon isotope data suggest that ammonium in the groundwater is released from intensive degradation of organic matter with higher contents of ammonium associated with methanogenesis. The optical signatures of DOM indicate ammonium in the groundwater is mostly associated with terrestrial humic-like components rather than protein-like components. Molecular characterization of DOM by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) shows that, compared to low ammonium groundwater, high ammonium groundwater has larger mass weights, greater abundance of CHO+N compounds, higher percentages of lignin- and condensed-hydrocarbon-like components, lower H/C ratios, higher nominal oxidation state of carbon (NOSC) values and more double bonds, rings, and aromatic structures. Strong degradation of NOM and preferential utilization of energetically more favorable, terrestrial humic-like components (lignin-like as the main class) with high NOSC values facilitates the formation of high ammonium groundwater. To the best of our knowledge, this is the first effort to use carbon isotopes and DOM characteristics to identify enrichment mechanisms for geogenic ammonium in alluvial-lacustrine aquifer systems.


Isotropic reorientational eigenmode dynamics complements NMR relaxation measurements for RNA.
(13)C NMR relaxation measurements alone are often not sufficient to describe the motions of small RNA molecules in solution. In the case where the global tumbling time of the RNA is on the same time scale as its internal motions, standard Lipari-Szabo analysis becomes inadequate, and other methods must be used to describe the dynamics. Here, molecular dynamics simulations of the iron-responsive element (IRE) RNA hairpin are analyzed using isotropic reorientational eigenmode dynamics (iRED) to provide a picture of the motions of the RNA. The results show that indeed there is no separability of global and internal motions, and thus the order parameters determined from experimental data cannot be quantitatively accurate. iRED analysis also identifies correlated motions, providing a new picture of the dynamics of the IRE loop.


Amitriptyline vs. lorazepam in the treatment of opiate-withdrawal insomnia: a randomized double-blind study.
Benzodiazepine use in the treatment of insomnia may cause benzodiazepine dependence, especially in opiate users. The aim of this study was to investigate the sedative-hypnotic effects of amitriptyline in treating opiate-withdrawal insomnia. A total of 27 patients with opiate withdrawal were given either amitriptyline or lorazepam in a randomized double-blind trial. Sleep was assessed by means of the Sleep Evaluation Questionnaire and three insomnia items of the Hamilton Depression Rating Scale. The scores of two sleep measures showed that all aspects of sleep, except for ease of awakening from sleep, in the two treatment groups were not significantly different. In conclusion, apart from the hangover effect, amitriptyline is as effective as lorazepam in the treatment of opiate-withdrawal insomnia.


Dietary compliance in a randomized double-blind infant feeding trial during infancy aiming at prevention of type 1 diabetes.
The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) tested the hypothesis whether extensively hydrolyzed casein-based versus regular cow's milk-based infant formula reduces the risk of type 1 diabetes. We describe dietary compliance in the trial in terms of study formula intake, feeding of nonrecommended foods, and serum cow's milk antibody concentration reflecting intake of cow's milk protein among 2,159 eligible newborn infants with a biological first-degree relative affected by type 1 diabetes and with HLA-conferred susceptibility to type 1 diabetes. The participating infants were introduced to the study formula feeding at the median age of 15 days with a median duration of study formula use of 63 days. During the intervention, 80% of the infants received study formula. Of these, 57% received study formula for at least 2 months. On average, 45.5 l of study formula were used per infant. Only 13% of the population had received a nonrecommended food by the age of 6 months. The dietary compliance was similar in the intervention and control arm. The reported cow's milk consumption by the families matched very well with measured serum casein IgA and IgG antibody concentration. To conclude, good compliance was observed in this randomized infant feeding trial. Compliance varied between the regions and those infants who were breastfed for a longer period of time had a shorter exposure to the study formula. High dietary compliance in infant feeding trial is necessary to allow accurate interpretation of study results.


Iron chelation regulates cyclin D1 expression via the proteasome: a link to iron deficiency-mediated growth suppression.
Iron (Fe) plays an important role in proliferation, and Fe deficiency results in G(1)/S arrest. Despite this, the precise role of Fe in cell-cycle control remains unclear. Cyclin D1 plays a critical function in G(1) progression by interacting with cyclin-dependent kinases. Previously, we examined the effect of Fe depletion on the expression of cell-cycle control molecules and identified a marked decrease in cyclin D1 protein, although the mechanism involved was unknown. In this study, we showed that cyclin D1 was regulated posttranscriptionally by Fe depletion. Iron chelation of cells in culture using desferrioxamine (DFO) or 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) decreased cyclin D1 protein levels after 14 hours and was rescued by the addition of Fe. Cyclin D1 half-life in control cells was 80 +/- 15 minutes (n = 5), while in chelator-treated cells it was significantly (P < .008) decreased to 38 +/- 3 minutes (n = 5). Proteasomal inhibitors rescued the Fe chelator-mediated decrease in cyclin D1 protein, suggesting the role of the proteasome. In Fe-replete cells, cyclin D1 was degraded in an ubiquitin-dependent manner, while Fe depletion induced a ubiquitin-independent pathway. This is the first report linking Fe depletion-mediated growth suppression at G(1)/S to a mechanism inducing cyclin D1 proteolysis.


Clinical benefits of intra-articular anakinra for arthrofibrosis.
Postoperative inflammation and stiffness, as well as the struggle to achieve full range of motion (ROM), following knee surgery is a significant clinical challenge. Interleukin-1 is a crucial mediator of the inflammatory response and development of pathological conditions leading to chronic inflammation. We hypothesized that intra-articular injection of intra-articular anakinra, an IL-1 antagonist, would result in sustained improvements of chronic refractory arthrofibrosis and limited arthrofibrosis of the knee joint. We retrospectively reviewed 8 patients who underwent injection of intra-articular anakinra, 200 mg. Four patients (3 women, 1 man) had intra-articular anakinra for treatment of chronic refractory arthrofibrosis, and 4 patients (4 women) had intra-articular anakinra for limited arthrofibrosis. All 4 of the refractory arthrofibrosis patients had failed conservative treatment with intensive physical therapy, corticosteroid injections, and anti-inflammatory medication. Three of the 4 patients had failed a prior manipulation under anesthesia with lysis of adhesions. All 4 reported improvement in ROM (10°-45°) and swelling, with 75% reporting improvement in pain. Seventy-five percent of these patients returned to prior activity level. All 4 of the limited arthrofibrosis also failed similar attempts at conservative treatment, and 2 of the 4 had failed a prior manipulation under anesthesia with lysis of adhesions. After intra-articular anakinra, all 4 reported improvement in ROM (20°-45°) and swelling, with 80% reporting improvement in pain. Seventy-five percent of these patients were able to return to prior activity level. We found intra-articular anakinra to be effective in this small cohort of patients with refractory arthrofibrosis and limited arthrofibrosis.


[Pharyngo-gastric anastomosis].
Thirteen cases of laryngo-pharyngo-cervical oesophagus carcinoma were treated by pharyngo-gastric anastomosis and total laryngectomy. All patients after operation could swallow. The five-year survival rate was 1/4, three-year survival rate was 3/7 and one-year survival rate 9/13. We suggest that resection of pharyngo-laryngo-esophageal, carcinoma with removal of all the pathological lesions and pharyngo-gastric anastomosis is the best way for the prophylaxis of recurrence when the carcinoma involves the cervical esophagus. Furthermore, due to the high tendency of metastasis to neck lymph nodes in the early stage of the carcinoma, neck dissection should be performed during operation. The advantages of pharyngo-gastric anastomosis are wide indication and good blood supply.


In vitro transcriptome analysis of two Chinese isolates of Streptococcus suis serotype 2.
The Streptococcus suis serotype 2 (S. suis 2) isolates 05ZYH33 and 98HAH33 have caused severe human infections in China. Using a strand-specific RNA-seq analysis, we compared the in vitro transcriptomes of these two Chinese isolates with that of a reference strain (P1/7). In the 89K genomic island that is specific to these Chinese isolates, a toxin-antitoxin system showed relatively high levels of transcription among the S. suis. The known virulence factors with high transcriptional activity in these two highly-pathogenic strains are mainly involved in adhesion, biofilm formation, hemolysis and the synthesis and transport of the outer membrane protein. Furthermore, our analysis of novel transcripts identified over 50 protein-coding genes with one of them encoding a toxin protein. We also predicted over 30 small RNAs (sRNAs) in each strain, and most of them are involved in riboswitches. We found that six sRNA candidates that are related to bacterial virulence, including cspA and rli38, are specific to Chinese isolates. These results provide insight into the factors responsible for the difference in virulence among the different S. suis 2 isolates.


Liposomal bupivacaine decreases pain following retropubic sling placement: a randomized placebo-controlled trial.
Midurethral slings are commonly used to treat stress urinary incontinence. Pain control, however, may be a concern. Liposomal bupivacaine is a local anesthetic with slow release over 72 hours, demonstrated to lower pain scores and decrease narcotic use postoperatively. The purpose of this study was to examine the impact of liposomal bupivacaine on pain scores and narcotic consumption following retropubic midurethral sling placement. This randomized, placebo-controlled trial enrolled women undergoing retropubic midurethral sling procedures with or without concomitant anterior or urethrocele repair. Subjects were allocated to receive liposomal bupivacaine (intervention) or normal saline placebo injected into the trocar paths and vaginal incision at the conclusion of the procedure. At the time of drug administration, surgeons became unblinded, but did not collect outcome data. Participants remained blinded to treatment. Surgical procedures and perioperative care were standardized. The primary outcome was the visual analog scale pain score 4 hours after discharge home. Secondary outcomes included narcotic consumption, time to first bowel movement, and pain scores collected in the mornings and evenings until postoperative day 6. The morning pain item assessed "current level of pain"; the evening items queried "current level of pain," "most intense pain today," "average pain today with activity," and "average pain today with rest." Likert scales were used to measure satisfaction with pain control at 1- and 2-week postoperative intervals. Sample size calculation deemed 52 subjects per arm necessary to detect a mean difference of 10 mm on a 100-mm visual analog scale. To account for 10% drop out, 114 participants were needed. One hundred fourteen women were enrolled. After 5 exclusions, 109 cases were analyzed: 54 women received intervention, and 55 women received placebo. Mean participant age was 52 years, and mean body mass index was 30.4 kg/m2. Surgical and demographic characteristics were similar, except for a slightly higher body mass index in the placebo group (31.6 vs 29.2 kg/m2; P=.050), and fewer placebo arm subjects received midazolam during anesthesia induction (44 vs 52; P=.015). For the primary outcome, pain score (millimeter) 4 hours after discharge home was lower in the intervention group (3.5 vs 13.0 millimeters; P=.014). Pain scores were also lower for subjects receiving liposomal bupivacaine at other time points collected during the first three postoperative days. Furthermore, fewer subjects in the intervention group consumed narcotic medication on postoperative day 2 (12 vs 27; P=.006). There was no difference in satisfaction with pain control between groups. Side-effects experienced, rate of postoperative urinary retention, and time to first bowel movement were similar between groups. Finally, no serious adverse events were noted. Liposomal bupivacaine decreased postoperative pain scores following retropubic midurethral sling placement, though pain was low in both the intervention and placebo groups. Participants who received liposomal bupivacaine were less likely to use narcotics on postoperative day 2. For this common outpatient surgery, liposomal bupivacaine may be a beneficial addition. Given the cost of this intervention, however, future cost-effective analyses may be useful.


Design of Deep Learning Model for Task-Evoked fMRI Data Classification.
Machine learning methods have been successfully applied to neuroimaging signals, one of which is to decode specific task states from functional magnetic resonance imaging (fMRI) data. In this paper, we propose a model that simultaneously utilizes characteristics of both spatial and temporal sequential information of fMRI data with deep neural networks to classify the fMRI task states. We designed a convolution network module and a recurrent network module to extract the spatial and temporal features of fMRI data, respectively. In particular, we also add the attention mechanism to the recurrent network module, which more effectively highlights the brain activation state at the moment of reaction. We evaluated the model using task-evoked fMRI data from the Human Connectome Project (HCP) dataset, the classification accuracy got 94.31%, and the experimental results have shown that the model can effectively distinguish the brain states under different task stimuli.


The Alzheimer's Prevention Clinic at Weill Cornell Medical College / New York - Presbyterian Hospital: Risk Stratification and Personalized Early Intervention.
In July 2013, Weill Cornell Medical College founded the first Alzheimer's Prevention Clinic (APC) in the United States, providing direct clinical care to family members of patients with Alzheimer's disease (AD) as part of the Weill Cornell Memory Disorders Program. At the APC, patients seeking to lower their AD risk undergo a comprehensive assessment, receive a personalized plan based on rapidly evolving scientific evidence, and are followed over time using validated as well as emerging clinical and research technologies. The APC approach applies the principles of pharmacogenomics, nutrigenomics and clinical precision medicine, to tailor individualized therapies for patients. Longitudinal measures currently assessed in the clinic include anthropometrics, cognition, blood biomarkers (i.e., lipid, inflammatory, metabolic, nutritional) and genetics, as well as validated, self-reported measures that enable patients to track several aspects of health-related quality of life. Patients are educated on the fundamental concepts of AD prevention via an interactive online course hosted on Alzheimer's Universe (www.AlzU.org), which also contains several activities including validated computer-based cognitive testing. The primary goal of the APC is to employ preventative measures that lower modifiable AD risk, possibly leading to a delay in onset of future symptoms. Our secondary goal is to establish a cohort of at-risk individuals who will be primed to participate in future AD prevention trials as disease-modifying agents emerge for testing at earlier stages of the AD process. The clinical services are intended to lower concern for future disease by giving patients a greater sense of control over their brain health.


Exposure of Bed Bugs to Metarhizium anisopliae at Different Humidities.
Bed bugs Cimex lectularius L. were exposed to conidia (spores) of the entomopathogenic fungus Metarhizium anisopliae by feeding, aerosol spray, or contact with a treated surface. Feeding experiments demonstrated that bed bugs were innately susceptible to this fungus. However, only at 98% humidity were mortality rates high, regardless of whether bed bugs were sprayed with a fungal solution or contacted a treated surface. Mortality in treated bed bugs at ambient humidity did not increase when these bed bugs were kept in aggregation with other bed bugs that had recently blood fed to repletion. Based on these laboratory studies, we conclude that M. anisopliae is a poor pathogen for use in control of bed bugs, particularly at humidities that would likely be encountered under field conditions.


Management of gastrointestinal lymphoma.
A study was made of 65 patients with primary gastrointestinal (GI) lymphoma. The occurrence was 40 (62%) in stomach, 15 (23%) in the small intestine, and 10 (15%) in colorectum. The majority of patients had their histology classified according to Rappaport's classification. Diffuse histiocytic type had the worst prognosis (median survival 13.8 months), and nodular histology had the best prognosis. A modified staging system proposed by Blackledge et al. was used. Patients who had their disease confined to one viscus (Stage I) or with spread to regional lymph nodes (Stage II) had an excellent prognosis, with a 5-year survival of 87 and 67%, respectively. However, those who had distant nodal involvement (Stage III, e.g., para-aortic nodes) or spread to adjacent organs within the abdomen (Stage IV) had worse prognosis, with 5-year survival of 40 and 13%, respectively. In Stage I, radiotherapy alone was as effective as surgical resection. None of the 11 patients treated by radiotherapy alone had perforation or bleeding. The 5-year disease-free survival was 51%.


Biochemical basis for enhanced binding of peptide dimers to X-linked inhibitor of apoptosis protein.
XIAP (X-linked inhibitor of apoptosis protein) is involved in the mediation of programmed cell death and, therefore, is a target for the development of cancer therapeutics. Peptide mimetics based upon Smac, the natural binding partner of XIAP, and specifically, dimeric peptides, have shown great promise in drug development. In the present work, the basis for enhanced dimer efficacy has been explored. Comparisons are made between the peptide binding site on the BIR3 domain of XIAP alone (residues 238-358) and a less truncated construct that includes both BIR2 and BIR3 domains (residues 151-350). This contingency differentially enhances the binding of dimeric tetrapeptides, potentially by providing additional hydrophobic binding surface. The effect of BIR2 on the BIR3 binding site is sustained, even if the BIR2 binding site is disrupted by mutagenesis, as shown by both a fluorescent competition assay and a polarity sensitive dye, badan. FRET measurements reveal an observed separation of >or=45 A between the BIR2 and BIR3 peptide binding pockets, thereby precluding a direct simultaneous interaction of the dimer molecules with both binding domains. Furthermore, variations in the linker length between dimeric tetrapeptides did not show a predictable trend in binding affinities, suggesting that local concentration effects were also an unlikely explanation for the enhanced dimeric affinities. Taken together, the results suggest that enhanced binding of dimeric peptides likely reflects the increased hydrophobic surface area on or near the BIR3 site and have significant ramifications for the design of therapeutics that target this class of proteins.


Exercise prescription: role of the physiatrist and allied health professional.
The prescription of exercise has advanced from an art to a science. The patient must first be examined by a physician to determine if there are contraindications to participating in an exercise program. This examination should include a graded exercise test to volitional fatigue to determine the normality of the electrocardiogram response to exercise and to assess the patient's capacity for exercise. Once the patient has received medical clearance, an exercise program is prescribed. This prescription is based on the individual's exercise capacity and includes a definition of the type, frequency, duration and intensity of exercise. Each of these four factors is discussed in detail and the potential role of the physiatrist, therapist, and allied health professional is defined.


A Mouse Immunogenicity Model for the Evaluation of Meningococcal Conjugate Vaccines.
The identification of an appropriate animal model for use in the development of meningococcal vaccines has been a challenge as humans are the only natural host for Neisseria meningitidis. Small animal models have been developed and are widely used to study the efficacy or immunogenicity of vaccine formulations generated against various diseases. Here, we describe the development and optimization of a mouse model for assessing the immunogenicity of candidate tetravalent meningococcal polysaccharide (MenACYW-TT) protein conjugate vaccines. Three inbred (BALB/c [H-2d], C3H/HeN [H-2k], or C57BL/6 [H-2b]) and one outbred (ICR [H-2g7]) mouse strains were assessed using serial two-fold dose dilutions (from 2 µg to 0.03125 µg per dose of polysaccharide for each serogroup) of candidate meningococcal conjugate vaccines. Groups of 10 mice received two doses of the candidate vaccine 14 days apart with serum samples obtained 14 days after the last dose for the evaluation of serogroup-specific anti-polysaccharide IgG by ELISA and bactericidal antibody by serum bactericidal assay (SBA). C3H/HeN and ICR mice had a more dose-dependent antibody response to all four serogroups than BALB/c and C57Bl/6 mice. In general, ICR mice had the greatest antibody dose-response range (both anti-polysaccharide IgG and bactericidal antibodies) to all four serogroups and were chosen as the model of choice. The 0.25 µg per serogroup dose was chosen as optimal since this was in the dynamic range of the serogroup-specific dose-response curves in most of the mouse strains evaluated. We demonstrate that the optimized mouse immunogenicity model is sufficiently sensitive to differentiate between conjugated polysaccharides, against unconjugated free polysaccharides and, to degradation of the vaccine formulations. Following optimization, this optimized mouse immunogenicity model has been used to assess the impact of different conjugation chemistries on immunogenicity, and to screen and stratify various candidate meningococcal conjugate vaccines to identify those with the most desirable profile to progress to clinical trials.


Measurement of In Vitro Single Cell Temperature by Novel Thermocouple Nanoprobe in Acute Lung Injury Models.
Energy metabolism may alter pattern differences in acute lung injury (ALI) as one of the causes but the detailed features at single-cellular level remain unclear. Changes in intercellular temperature and adenosine triphosphate (ATP) concentration within the single cell may help to understand the role of energy metabolism in causing ALI. ALI in vitro models were established by treating mice lung epithelial (MLE-12) cells with lipopolysaccharide (LPS), hydrogen peroxide (H2O2), hydrochloric acid (HCl) and cobalt chloride (CoCl2, respectively. 100 nm micro thermocouple probe (TMP) was inserted into the cytosol by micromanipulation system and thermoelectric readings were recorded to calculate the intracellular temperature based on standard curve. The total ATP contents for the MLE-12 cells were evaluated at different time intervals after treatments. A significant increase of intracellular temperature was observed after 10 or 20 μg/L LPS and HCl treatments. The HCl increased the temperature in a dose-dependent manner. On the contrary, H2O2 induced a significant decline of intracellular temperature after treatment. No significant difference in intracellular temperature was observed after CoCl2 exposure. The intracellular ATP levels decreased in a time-dependent manner after treatment with H2O2 and HCl, while the LPS and CoCl2 had no significant effect on ATP levels. The intracellular temperature responses varied in different ALI models. The concentration of ATP in the MLE-12 cells played part in the intracellular temperature changes. No direct correlation was observed between the intracellular temperature and concentration of ATP in the MLE-12 cells.


BETA-D-GLUCAN TESTING IN PATIENTS WITH FUNGAL ENDOPHTHALMITIS.
To review the literature on beta-D-glucan (BDG) testing in fungal endophthalmitis. Review of primary literature using PubMed through April 2017 and presentation of an illustrative case report. A total of 231 articles were identified and 43 were ultimately chosen for review based on relevance and presence of ophthalmologic examination and objective data. Beta-D-glucan is a major component of fungal cell walls. It is quantified using a calorimetry-based Fungitell assay based on modification of the limulus amebocyte lysate. Serum BDG levels are commonly used clinically in conjunction with other tests for early surveillance and diagnosis of invasive fungal infections. In the ophthalmic literature, elevated levels of BDG have been detected in vitreous fluid of patients undergoing vitrectomy for fungal endophthalmitis, tear fluid of patients with mycotic keratitis, and serum of a patient with bilateral endogenous subretinal abscesses. Elevated serum BDG levels appear to be highly associated with fungal endophthalmitis. Potential uses and considerations with regards to test limitations are discussed. Beta-D-glucan testing may be used as an adjunct to support a diagnosis, initiate pharmacologic therapy or surgical intervention, and optimize overall clinical management in patients diagnosed with or under clinical suspicion for invasive fungal infections, including endophthalmitis. Additional clinical studies are necessary to fully characterize the utility of BDG testing in patients with fungal endophthalmitis.


Influence of organic solvents on papain kinetics.
Papain activity was studied in water-organic solvent mixtures using the fluorogenic substrate Dabcyl-Lys-Phe-Gly-Gly-Ala-Ala-Edans. The increase of organic solvent (MeOH, EtOH, iPrOH, TFE, MeCN, (MeO)2Et and DMF) concentration in the mixture caused a substantial decrease the initial rate of papain-catalyzed hydrolysis. Moreover, the number of papain active sites decreased with the increase of DMF and MeOH concentration.


The Neural Control of Spinal Stability Muscles during Different Respiratory Patterns.
[Purpose] It is well-known that the muscles of spinal stability also play roles in respiration. The spinal stability muscles are divided into two subgroups, the local muscle group and the global muscle group. Appropriately coordinated activation of muscle groups are recommended for more efficient spinal stability. The indirect method of measuring coordination of muscle groups is the synergist ratio of local muscles to global muscles. The purpose of this study was to investigate the synergist ratios of the spinal stability muscles of different breathing patterns. [Subjects and Methods] Forty healthy subjects performed 4 different breathing patterns and 3 synergist ratios calculated from % maximal voluntary isometric contraction of 2 local group muscles and 3 global group muscles were analyzed. [Results] The results of this study show synergist ratios were consistent among the breathing patterns and there was a consistent muscle reliance pattern of synergist ratios during each breathing pattern. The synergist ratio of extensors stayed around 1. The results were consistent with those of previous studies of spinal stability exercises. [Conclusion] We suggest that different breathing patterns could be used as a component of spinal stability exercises, secondary to the similarities of muscle coordination with spinal stability exercises, commonly used in clinics.


Two new species of the spider Family Zodariidae from Laos.
Two new Zodariidae species, collected from the natural forest of Pakse City, Champasak Province, Laos, are described as Asceua adunca sp. nov. (male, female) and Mallinella renaria sp. nov. (male, female). Asceua torquata (Simon, 1909) and A. piperata Ono, 2004 are newly recorded from Laos, and the male of A. piperata is described and illustrated for the first time.


Community adjustment among older depressives.
Depression is the most common emotional disorder of later life, yet there is much confusion and clinical speculation about it. Adjustment of later-life depressives after psychiatric treatment is virtually an unknown area, as is the phenomenon of depression itself with this population. This study addressed these two issues. Community adjustment of younger and older clinically depressed patients after treatment was monitored. Also, adjustment differences in self and other ratings were compared between the two age groups. Results show that there are no significant differences in posttreatment adjustment ratings between the age groups. In addition, it was found that older depressives with a longer history of depression adjust less well than expected. Lastly, older depressives (relative to younger ones), particularly neurotic ones, show the following pattern of adjustment: Less alienation, less vigor, less confidence in skills, poorer work history, less abuse of alcohol or drugs, more social constriction, more agitation, and fewer household management skills.


How to improve vital sign data quality for use in clinical decision support systems? A qualitative study in nine Swedish emergency departments.
Vital sign data are important for clinical decision making in emergency care. Clinical Decision Support Systems (CDSS) have been advocated to increase patient safety and quality of care. However, the efficiency of CDSS depends on the quality of the underlying vital sign data. Therefore, possible factors affecting vital sign data quality need to be understood. This study aims to explore the factors affecting vital sign data quality in Swedish emergency departments and to determine in how far clinicians perceive vital sign data to be fit for use in clinical decision support systems. A further aim of the study is to provide recommendations on how to improve vital sign data quality in emergency departments. Semi-structured interviews were conducted with sixteen physicians and nurses from nine hospitals and vital sign documentation templates were collected and analysed. Follow-up interviews and process observations were done at three of the hospitals to verify the results. Content analysis with constant comparison of the data was used to analyse and categorize the collected data. Factors related to care process and information technology were perceived to affect vital sign data quality. Despite electronic health records (EHRs) being available in all hospitals, these were not always used for vital sign documentation. Only four out of nine sites had a completely digitalized vital sign documentation flow and paper-based triage records were perceived to provide a better mobile workflow support than EHRs. Observed documentation practices resulted in low currency, completeness, and interoperability of the vital signs. To improve vital sign data quality, we propose to standardize the care process, improve the digital documentation support, provide workflow support, ensure interoperability and perform quality control. Vital sign data quality in Swedish emergency departments is currently not fit for use by CDSS. To address both technical and organisational challenges, we propose five steps for vital sign data quality improvement to be implemented in emergency care settings.


Time-resolved immunofluorometric assay of human growth hormone.
We describe a time-resolved immunofluorometric assay (trIFMA) for human growth hormone (hGH), in which monoclonal antibody (mAb)-coated microtiter strip wells and a europium (Eu) chelate-labeled mAb are used. We compare the new trIFMA, in which two mAbs are used, with an immunoradiometric assay (IRMA) in which polyclonal antibodies are used. Serum samples (n = 185) from 36 children with various diagnoses were analyzed. In addition, 24-h profile samples (72 per child) from 39 children were analyzed. The trIFMA was more sensitive (detection limit, 0.03 mIU/L) than existing IRMAs. Both the intra- and interassay CVs were < or = 10.6% for hGH concentrations between 1 and 100 mIU/L. The trIFMA is technically simple and rapid, requires no centrifugation or separation reagent, and has a counting time of only 1 s per sample. In addition, the Eu label is nontoxic, presents no waste-disposal problems, and has a long shelf-life. Finally, the assay requires only small volumes of serum (25 muL), which is of considerable importance in pediatric use. The mAbs used for the trIFMA selectively bind the 22-kDa form of hGH, with the result that the assay detects about 80% of the amount detected by the polyclonal IRMA.


Importance of protein flexibility in molecular recognition: a case study on Type-I1/2 inhibitors of ALK.
Anaplastic lymphoma kinase (ALK) has been regarded as a promising target for the therapy of various cancers. A large number of ALK inhibitors with diverse scaffolds have been discovered, and most of them belong to Type-I inhibitors that only occupy the ATP-binding pocket. Recently, we reported a series of novel and potent Type-I1/2 inhibitors of ALK with the 1-purine-3-piperidinecarboxamide scaffold, which can bind to both the ATP-binding site of ALK and the adjacent hydrophobic allosteric pocket. In this study, the binding mechanisms of these Type-I1/2 ALK inhibitors were elucidated by multiple molecular modeling techniques. The calculation results demonstrate that the ensemble docking based on multiple protein structures and the MM/PB(GB)SA calculations based on molecular dynamics (MD) simulations yield better predictions than conventional rigid receptor docking (Glide, Surflex-Dock, and Autodock Vina), highlighting the importance of incorporating receptor flexibility in the predictions of binding poses and binding affinities of Type-I1/2 ALK inhibitors. Furthermore, the umbrella sampling (US) simulations and MM/GBSA binding free energy decomposition analyses indicate that Leu1122, Leu1198, Gly1202 and Glu1210 in the hinge region and Glu1197, Ile1171, Phe1174, Ile1179, His1247, Ile1268, Asp1270 and Phe1271 in the allosteric pocket of ALK are the key residues for determining the relative binding strength of the studied inhibitors. Besides, we found that the most potent inhibitor (001-017) tends to form stronger transient interactions with residues along the dissociation channel due to the high electronegativity of its bulky 4-(trifluoromethoxy) phenylamine tail. As a whole, both the stronger binding affinity and the higher energetic barrier (which may prolong the drug-target residence time) of 001-017 contribute to its excellent anti-proliferation activity against ALK-positive cancer cells.


Design and testing of a system for measuring high-frequency AC losses in superconducting wires and coils carrying DC and AC currents.
Development of high-power superconducting applications requires the accurate estimation of AC losses in the superconductor. In applications such as superconducting magnetic energy storage, the charge/discharge/persistent switching frequency of the coil, resulting from pulse width modulation control algorithms, is usually in the kilohertz regime. Therefore, a thorough investigation of the losses in the kilohertz regime of AC currents superimposed on large DC currents is essential in order to ensure the device stable operation at a predefined temperature. We describe here a unique experimental setup designed and built for characterizing AC losses in superconducting wires and coils under such special conditions. To minimize the eddy currents induced in the apparatus, a cryostat vacuum vessel was made of Delrin, an insulating synthetic polymer. The measurement setup allows driving DC currents up to 150 A and superimposed AC currents with amplitudes up to 10 Arms and frequencies up to 18 kHz. The system utilizes conduction cooling to reach a wide range of temperatures between 6 and 100 K and allows measurements of 10 cm long superconducting wires and coils with a diameter of 40 cm. The loss is measured by the electrical method, i.e., by direct voltage and current waveform measurement, achieving a resolution better than 100 nW. The system described here will assist in developing superconducting wires and coils for high-power applications.


Evaluation of hypersensitivity pneumonitis among workers exposed to metal removal fluids.
Hypersensitivity pneumonitis (HP) was identified among employees in an automobile parts manufacturing facility. Mycobacteria immunogenum (MI) was identified as a metal removal fluid (MRF) contaminant at this facility and had been identified as a contaminant in other facilities where HP had occurred. We therefore questioned whether measurement of MI-specific cell-mediated immunity would be associated with HP in this facility. We also questioned whether measures of cell-mediated immunity would be more informative about the presence of HP than evaluation of serum anti-MI antibody levels. Workers were categorized for exposure and disease status by questionnaire and review of medical records. Cell-mediated immunity to MI was assessed by measuring in vitro secretion of cytokines (interleukin 8, tumor necrosis factor alpha, and interferon-gamma) from peripheral blood mononuclear cells or anticoagulated whole blood induced by culture with MI antigen. Serum antibodies against MI were also measured. Six study participants met our survey definition for HP and 48 did not. As has been reported for various agents causing HP, serum antibody levels against MI were increased in both exposed workers and workers with HP. Serum antibodies did not distinguish between the two. When expressed as a percentage of secretion induced by lipopolysaccharide, MI induced a significant increase in interleukin-8 secretion in exposed participants' whole blood cultures. There were trends for increased MI-induced secretion of interferon-gamma by peripheral blood mononuclear cells from both exposed workers and workers with HP. However, these trends did not attain statistical significance. Thus, several measures of immunity to MI distinguished between exposed and unexposed workers but not between workers with and without HP. These evaluations of cell-mediated immunity were not more informative than measurement of serum antibodies. As was done at this facility, institution of a comprehensive safety and health plan for MRF is necessary to eliminate (or minimize) health effects related to occupational exposures in the machining environment.


Transport of finite size particles in confined narrow channels: diffusion, coherence, and particle separation.
Transport of the finite size spherical Brownian particles is investigated in confined narrow channels with varying cross-section width. Applying the Fick-Jacobs approximation, we obtain the expressions of the particle current, the effective diffusion coefficient, and the coherence level of Brownian transport (the Péclet number). For the case of the biased constant force, the dependencies of the nonlinear mobility, the effective diffusion coefficient, and the Péclet number on the particle size exhibit striking behaviors. The Péclet number decreases with increasing the radius of the particle which shows that the big sizes of the particles reduce the coherence level of Brownian transport. There exists an optimized value of the radius at which the effective diffusion coefficient is maximal. For the case of the asymmetric unbiased force, due to the competition between the spatial asymmetry and the temporal asymmetry, the transport directions of the particles depend very sensitively on the size of the particle. Particles larger than a given threshold radius move to the left, whereas particles smaller than that move to the right. Therefore, one can separate particles of different radii and make them move towards opposite directions.


No room for males in caves: Female-biased sex ratio in subterranean amphipods of the genus Niphargus.
Sex allocation theory predicts that the proportion of daughters to sons will evolve in response to ecological conditions that determine the costs and benefits of producing each sex. All else being equal, the adult sex ratio (ASR) should also vary with ecological conditions. Many studies of subterranean species reported female-biased ASR, but no systematic study has yet been conducted. We test the hypothesis that the ASR becomes more female-biased with increased isolation from the surface. We compiled a data set of ASRs of 35 species in the subterranean amphipod Niphargus, each living in one of three distinct habitats (surface-subterranean boundary, cave streams, phreatic lakes) representing an environmental gradient of increased isolation underground. The ASR was female-biased in 27 of 35 species; the bias was statistically significant in 12 species. We found a significant difference in the ASR among habitats after correction for phylogeny. It is most weakly female-biased at the surface-subterranean boundary and most strongly female-biased in phreatic lakes. Additional modelling suggests that the ASR has evolved towards a single value for both surface-subterranean boundary and cave stream-dwelling species, and another value for 9 of 11 phreatic lake dwellers. We suggest that a history of inbreeding in subterranean populations might lower inbreeding depression such that kin selection favours mating with siblings. This could select for a female-biased offspring sex ratio due to local mate competition among brothers. The observed patterns in sex ratios in subterranean species make them a group worthy of more attention from those interested in sex allocation theory.


Fabrication and MFM study of 60 nm track-pitch discrete track media.
Discrete track magnetic recording media with a 60 nm track pitch and prewritten servo patterns were fabricated and tested for read/write performance, and a feasibility analysis of the embedded servo was performed. The fabrication process consisted of ultraviolet nanoimprint lithography (UV-NIL) and sequential ion beam etching on a conventional perpendicular magnetic recording medium. Magnetic patterns were written to the fabricated tracks at 700 kilo flux changes per inch (kFCI) using a spin stand and were read using magnetic force microscopy (MFM), with a resulting signal-to-noise ratio (SNR) of 12.15 dB. The servo pattern was also visualized with MFM. These results demonstrated the feasibility of writing to a 30 nm wide discrete data track and the workability of the embedded servo pattern.


Health literacy, emotionality, scientific evidence: Elements of an effective communication in public health.
The importance of healthcare providers' communication abilities is still underestimated. Informing the population on the basis of documented evidence is essential but not enough to induce a change in the beliefs of who is doubtful or does not accept preventive interventions, such as vaccination. Lining up the offer of prevention to the knowledge of the citizens, also improving Health Literacy skills, is a critical step toward their empowerment and behavior change. The 2017 Erice Declaration was drafted to propose to the Institutions and the scientific community the main goals to improve communication and counteract Vaccine Hesitancy, at a very critical time, when mandatory vaccination was introduced in Italy.


Experience-dependent eye movements reflect hippocampus-dependent (aware) memory.
We investigated the relationship between experience-dependent eye movements, hippocampus-dependent memory, and aware memory. We measured eye movements in young adults, older adults, and memory-impaired patients with damage to the medial temporal lobe as they viewed 120 novel scenes and 120 previously viewed scenes. Participants indicated if each scene was old or new and also gave a confidence rating for the memory judgment. Young adults and older adults explored old scenes less than they explored new scenes, but the patients did not. For the young and older adults, this effect was observed only when participants were aware of the scene's familiar or novel status. In a second experiment, young adults viewed scenes that were either new, had been viewed previously, or had been viewed previously but had been changed (i.e., an object within the scene was either added or removed). The only instructions were to pay attention to the scenes and view each scene as it appeared, and there was no expectation that memory would be tested. Directly after the first altered scene was presented, participants were asked to classify the scene as new, old, or old but changed. Participants who were aware of the manipulation preferentially viewed the changed region, but participants who were unaware did not. These findings suggest that experience-dependent eye movements reflect hippocampus-dependent (and aware) memory, even when participants have no expectation that memory is being tested; and they are consistent with the view that awareness of what is learned is a fundamental characteristic of hippocampus-dependent memory.


Surgical electrocautery and the runaway pacemaker syndrome.
A case of a unipolar surgical electrocautery-induced runaway pacemaker is described. The single chamber ventricular pacemaker began firing at 140 beats/min with intermittent capture and the abnormal rhythm persisted after cessation of the electrocautery. Emergent explanation of the pulse generator was required.


Modification of the pigeon's visual startle reaction by the sensory environment.
A series of seven experiments related amplitude and latency of the pigeon's startle response, elicited by an intense visual stimulus, to antecedent auditory and visual events in the sensory environment. The data indicated that (a) within broad limits the amplitude of the reflex is a positive function of the intensity of the sensory background prevailing at the time of startle elicitation, (b) a change in the sensory environment occurring 15-2,000 msec prior to the startle-eliciting stimulus inhibits the amplitude of the response, and (c) a change in the sensory environment less than 10 msec prior to the startle-eliciting stimulus reduces the latency of the response. These findings are consistent with previous research on acoustic elicited startle in the rat. The overall configuration of the results suggests that a pathway including the reticulospinal tract and the bulbopontine reticular nuclei could be the major mediator of startle. In these terms, latency-reduction effects would occur because of partial activation of this pathway, amplitude inhibition would occur because of cerebellar influence, and amplitude facilitation would reflect cerebral or striatal influences.


[Medullary reaming in chronic osteomyelitis of the stable femur and tibia shaft].
Ten patients with chronic osteomyelitis of the femur or tibia shaft without bone instability were operated by intramedullary reaming. All patients but one had previous surgery, up to 12 operations with the average duration of the disease 10.5 years. After intramedullary reaming all patients received systemic antibiotics for 8 days and in 6 cases the intramedullary cannal was filled with gentamicin-PMMA chains which were removed in local anaesthesia 10 days after surgery. Eight patients who had severe pain at rest were promptly relieved by the operation. In 3 cases of chronic fistulation only one exacerbation was seen. This was because of insufficient reaming, the patient was subsequently reoperated with reaming from a distal approach. During the observation periode from the month 12 to 32 in no case was there a recurrence of pain or infection.


Lessons Learnt From the COVID-19 Pandemic.
The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has been characterized by unprecedented rates of spatio-temporal spread. Here, we summarize the main events in the pandemic's timeline and evaluate what has been learnt by the public health community. We also discuss the implications for future public health policy and, specifically, the practice of epidemic control. We critically analyze this ongoing pandemic's timeline and contrast it with the 2002-2003 SARS outbreak. We identify specific areas (e.g., pathogen identification and initial reporting) wherein the international community learnt valuable lessons from the SARS outbreak. However, we also identify the key areas where international public health policy failed leading to the exponential spread of the pandemic. We outline a clear agenda for improved pandemic control in the future.


Repair of partial patellar ligament avulsion during total knee arthroplasty using the Statak device.
Abstract The Statak is a suture anchor device used for attaching soft tissue to bone. This is a report on six knees in which this device was used to repair partial avulsion of the patellar ligament during total knee arthroplasty (TKA). The six patients were all women. The average age of the patients was 69 years. The diagnosis was osteoarthritis in three patients, rheumatoid arthritis in two, and steroid arthropathy in one. Three of the operations were revision arthroplasties. In all six cases, approximately half of the patellar ligaments were accidentally detached from the tibial tubercles during surgery, and were repaired using the Statak devices. The average length of follow-up was 3 years. The Knee Society knee score improved from an average of 15 points preoperatively to 87 points at the latest follow-up. The average total range of motion measured 104° before surgery and 108° at the latest follow-up. Three of the six knees operated on had no extensor lag. The suture anchor simplifies the secure fixation of the ligament to bone. The procedure can be performed easily and quickly. In our opinion, the Statak device has proven itself to be effective for the repair of partial patellar ligament avulsion during TKA.


Biological activities and medicinal properties of Asafoetida: A review.
Ferula asafoetida Linn. is a main source of asafoetida, a strong, tenacious and sulfurous odor, and oleo-gum resin of medicinal and nutritional importance. Asafoetida has been consumed as a spice and a folk medicine for centuries. Recent studies have shown several promising activities particularly relaxant, neuroprotective, memory enhancing, digestive enzyme, antioxidant, antispasmodic, hypotensive, hepatoprotective, antimicrobial, anticarcinogenic, anticancer, anticytotoxicity, antiobesity, anthelmintic and antagonistic effect. This review effectively deals with phytochemistry and various pharmacological and clinical studies of asafoetida.


Unilateral hypersecretion of aldosterone associated with adrenal hyperplasia as a cause of primary aldosteronism.
In 3 patients with longstanding hypertension and spontaneous or diuretic-induced hypokalemia, the diagnosis of primary aldosteronism was established by the dual criteria of non-suppressible plasma aldosterone level and suppressed plasma renin activity. Preoperative studies of the etiology for the hyperaldosteronism using the postural plasma aldosterone test and adrenal venous steroid measurements gave conflicting results. On the basis of the differential adrenal venous steroid content, which suggested an unilateral adrenal source for the aldosterone hypersecretion, presumed to be adrenal adenoma, each patient was operated upon. In each case the excised adrenal revealed adenomatous or macronodular hyperplasia. Reinvestigation of the patients 3 to 12 months after the adrenalectomy showed that the dynamics of the renin-aldosterone axis was now restored to the normal state even though the patients remained hypertensive. These findings indicate that unilateral hypersecretion of aldosterone associated with adrenal hyperplasia can occur in some patients with primary aldosteronism simulating that due to an aldosteronoma. Such observations also raise questions about the pathogenesis of the adrenal hyperplasia and seem to add further complexity to the evaluation of patients with hyperaldosteronism.


Myoglobin content in human skeletal muscle and myocardium: relation to fibre size and oxidative capacity.
Myoglobin, muscle fibre diameter, and citrate synthase activity were measured in leg muscle of untrained and trained men and in the myocardium from the apex of the left ventricle and from papillary muscle in patients subjected to open heart surgery. The citrate synthase (CS) activity was 60% higher in trained than in untrained skeletal muscle. In the myocardium it was around four times greater than in untrained skeletal muscle but there was no difference between the apex of the left ventricle and papillary muscle. The fibre diameter varied almost threefold between the different groups of muscles with the largest diameter in untrained skeletal muscle and the with the largest diameter in untrained skeletal muscle and the smallest in papillary muscle. The myoglobin content in trained skeletal muscle did not differ from that of untrained muscle. In the left ventricle it was only 40% of that found in untrained muscle while papillary muscle had almost twice as high a myoglobin content as did the left ventricle. The ratio between myoglobin and fibre diameter, however, was of similar magnitude in skeletal muscle and the left ventricle while it was twice as high in papillary muscle as in the other muscles. In conclusion, the diffusion distance in terms of fibre diameter decreased with increased oxidative capacity (CS activity), when comparing the statistical means of the four different groups. The capacity for oxygen diffusion in relation to oxygen demand measured as the ratio of myoglobin to fibre diameter appeared to be of similar magnitude in skeletal muscle and left ventricle but was higher in papillary muscle.


Alterations in fos-related antigen 2 and sigma1 receptor gene and protein expression are associated with the development of cocaine-induced behavioral sensitization: time course and regional distribution studies.
Repeated exposure to cocaine results in neuroadaptations that can alter the way the brain responds to subsequent stimuli. Earlier studies demonstrated that acute administration of cocaine up-regulates the immediate-early gene fos-related antigen 2 (fra-2) followed by a later up-regulation of sigma(1) receptor gene and protein levels in brain regions involved in addiction and reward. To test whether such alterations could have long-term consequences on behavior, the present study was undertaken. Using a cocaine-induced behavioral sensitization model coupled with gene and protein expression studies in mice, the results show that cocaine induces the expression of fra-2, which leads to a progressive increase in sigma(1) receptor gene and protein expression over a period of days. This progressive increase in sigma(1) expression corresponds to the steady increase in the locomotor response to repeated cocaine administration in mice. The cocaine-induced changes in fra-2 and sigma(1) receptor gene and protein expression occur in brain regions that subserve drug abuse, such as the cortex, striatum, and hippocampus, but not the cerebellum. Moreover, the prototypic sigma(1) receptor antagonist 1-[2-(3,4-dichloropheny)ethyl]-4-methylpiperazine (BD1063) significantly attenuates both the molecular adaptations and behavioral sensitization induced by cocaine. These data suggest that repeated exposure to cocaine elicits alterations in fra-2 and sigma(1) receptor-mediated mechanisms, which ultimately manifest as altered behavioral responses to cocaine.


Six new species of Macellicephala (Annelida: Polynoidae) from the Southern Ocean and south Atlantic with re-description of type species.
Increased sampling efforts in unexplored regions of the Southern Ocean (including depths >500 m) combined with the use of an epibenthic sledge resulted in a large collection of mobile, scale-bearing worms from the family Polynoidae Kinberg, 1856. The greatest taxonomic novelty was found in the genus Macellicephala McIntosh, 1885, the type genus of the exclusively deep-sea polynoid sub-family Macellicephalinae Hartmann-Schröder, 1971. Recently collected material from the Amundsen Sea led to discovery of four new species based on morphology and COI, 16S and 18S genes-Macellicephala gloveri sp. nov., M. linseae sp. nov., M. patersoni sp. nov. and M. brenesorum sp. nov. The holotype of type taxon Macellicephala mirabilis McIntosh, 1885 as well as historic material of Macellicephala collected from the Southern Ocean enabled comparison with the modern material. As a result, Macellicephala mirabilis is re-defined, and two new species, M. monroi sp. nov. and M. macintoshi sp. nov., are erected from the historic material previously ascribed to M. mirabilis. Additionally, DNA-suitable specimens assigned to M. monroi sp. nov. were collected from the Scotia Sea. Genetic data enabled the first test of the monophyly of Macellicephala. Based on current taxa coverage, these taxa form a well-supported monophyletic group as recovered by Bayesian and Maximum Likelihood analyses of our combined genetic dataset. In addition, the analysis shows strong support of a clade comprising Macellicephala and other exclusively deep-sea groups (including cave-dwelling taxa).


Clinical and endocrinological characteristics of adrenal incidentaloma in Osaka region, Japan.
The aim of this study was to investigate the clinical and endocrinological characteristics of adrenal incidentalomas in Osaka region, Japan. The study was a multicenter retrospective analysis of 150 patients with adrenal incidentalomas who underwent radiographic and endocrine evaluations between 2005 and 2013. Most adrenal incidentalomas were discovered by computed tomography (77.0%) and the rest were identified by abdominal ultrasonography (14.6%), magnetic resonance imaging (4.2%), or positron emission tomography (4.2%). Adrenal incidentalomas were more frequently localized on the left side than on the right. The average diameter of tumors was 21 ± 11 mm. On endocrinological evaluation, 14 patients were diagnosed with primary aldosteronism (9.3%), 10 with subclinical Cushing's syndrome (6.7%), 7 with pheochromocytoma (4.7%), 7 with Cushing's syndrome (4.7%), 2 with both subclinical Cushing's syndrome and primary aldosteronism (1.3%), and 110 with non-functioning tumors (73.3%). Patients with functioning tumors were significantly younger and had larger tumor diameters than those with non-functioning tumors. Except for hypertension, complications were comparable between patients with functioning and non-functioning tumors, including the presence of glucose intolerance, cardiovascular disease, and dyslipidemia. In conclusion, a higher prevalence of primary aldosteronism was observed compared with a previous report. Complications were comparable between patients with functioning and non-functioning tumors, including the frequencies of glucose intolerance, cardiovascular disease, and dyslipidemia. Long-term follow-up is required in patients with non-functioning tumors because the frequency of complications, such as glucose intolerance, cardiovascular disease, and dyslipidemia, was equal to that in patients with functioning tumors.


The influence of harvest time on essential oil composition, phenolic constituents and antioxidant properties of Turkish oregano (Origanum onites L.).
The aim of this research was to determine essential oil composition, phenolic constituents and antioxidant properties of Turkish oregano (Origanum onites L.) leaves harvested during the months of June to September. The maximum essential oil yield in the leaves appeared in the middle of July. The main components of oregano oil were carvacrol, thymol, gamma-terpinene, p-cymene, alpha-terpinene and alpha-pinene. Carvacrol was highest in the July harvest. The maximum extract yield was found in September. Oil distilled from early-season (June) harvested leaves had the highest antioxidant ability, expressed as low concentration providing 50% inhibition of free radical scavenging activity and high levels of reducing/antioxidant capacity. Twelve phenolic compounds of oregano extract were identified and the main components were found to be rosmarinic acid and acecetin. The maximum rosmarinic acid and acecetin were found in harvests of July and June, respectively. Total phenolic contents, free radical scavenging activities and reducing/antioxidant capacities were found to be highest in the July harvest. All yields, chemical compositions, free radical scavenging activities and reducing/antioxidant capacities of extracts and essential oils of Turkish oregano changed importantly depending on vegetative periods of growing season.


A novel real-time PCR assay for specific detection of Brucella melitensis.
Brucellosis is a zoonosis that occurs worldwide. The disease has been completely eradicated in livestock in Sweden in 1994, and all cases of confirmed human brucellosis are imported into Sweden from other countries. However, due to an increase in the number of refugees and asylum seekers from the middle-east to Sweden, there is a need to improve the current diagnostic methodology for Brucella melitensis. Whilst culture of Brucella species can be used as a diagnostic tool, real-time PCR approaches provide a much faster result. The aim of this study was to set up a species-specific real-time PCR for the detection of all biovars of Brucella melitensis, which could be used routinely in diagnostic laboratories. A Brucella melitensis real-time PCR assay was designed using all available genomes in the public database of Brucella (N = 96) including all complete genomes of Brucella melitensis (N = 17). The assay was validated with a collection of 37 Brucella species reference strains, 120 Brucella melitensis human clinical isolates, and 45 clinically relevant non-Brucella melitensis strains. In this study we developed a single real-time PCR for the specific detection of all biovars of Brucella melitensis. This new real-time PCR method shows a high specificity (100%) and a high sensitivity (1.25 GE/μl) and has been implemented in the laboratories of four governmental authorities across Sweden.


Usefulness of Volume Perfusion Computed Tomography in Differentiating Histologic Subtypes of Thymic Epithelial Tumors.
This study aimed to evaluate the usefulness of volume perfusion computed tomography (VPCT) parameters in differentiating the World Health Organization subtypes of thymic epithelial tumors. This study was approved by the local ethics committee, and informed written consent was obtained. Fifty-one thymic epithelial tumor patients confirmed by histopathological analysis underwent conventional CT and a 48-second VPCT scan of the tumor bulk before any treatment. The VPCT parameters (blood volume [BV], blood flow [BF], mean transit time [MTT], and permeability [PMB]) based on volume of interest (VOI) or region of interest (ROI) were compared for differences among low-risk thymomas (LRTs; types A, AB, and B1), high-risk thymomas (HRTs; types B2 and B3) and thymic carcinomas (TCs) by one-way analysis of variance. The BVVOI, PMBVOI, BVROI, and PMBROI values in LRT were significantly higher than the values from HRT and thymic carcinoma (BVVOI: 13.75, 6.17, and 5.48 mL/100 mL; PMBVOI: 22.47, 9.56, and 13.37 mL/100 mL/min; BVROI: 14.75, 6.87, and 6.06 mL/100 mL; PMBROI: 24.05, 9.79, and 15.63 mL/100 mL/min, respectively; all P < 0.05/3). However, the BFVOI, MTTVOI, BFROI, and MTTROI values did not differ between LRT and HRT or thymic carcinoma groups (P > 0.05/3). These results suggest that VPCT could be useful in differentiating LRTs from HRTs and TCs preoperatively.


Negative supercoiling increases the sensitivity of plasmid DNA to single-strand break induction by X-rays.
Negatively supercoiled topoisomers of the plasmid pIBI 30 were irradiated with 250 kV X-rays and assayed for strand scission by agarose gel electrophoresis. The survival of supercoiled molecules (Form I) decreased exponentially with increasing X-ray exposure and the dose required to reduce the fraction of DNA in Form I to 37% of its value in unirradiated controls (D37) decreased with increasing negative superhelicity. This enhanced radiation sensitivity of underwound DNA is tentatively attributed to the transient denaturation of the double helix that increases the susceptibility of individual strands to free radical attack.


Auditory spatial deficits following hemispheric lesions: dissociation of explicit and implicit processing.
Auditory spatial deficits occur frequently after hemispheric damage; a previous case report suggested that the explicit awareness of sound positions, as in sound localisation, can be impaired while the implicit use of auditory cues for the segregation of sound objects in noisy environments remains preserved. By assessing systematically patients with a first hemispheric lesion, we have shown that (1) explicit and/or implicit use can be disturbed; (2) impaired explicit vs. preserved implicit use dissociations occur rather frequently; and (3) different types of sound localisation deficits can be associated with preserved implicit use. Conceptually, the dissociation between the explicit and implicit use may reflect the dual-stream dichotomy of auditory processing. Our results speak in favour of systematic assessments of auditory spatial functions in clinical settings, especially when adaptation to auditory environment is at stake. Further, systematic studies are needed to link deficits of explicit vs. implicit use to disability in everyday activities, to design appropriate rehabilitation strategies, and to ascertain how far the explicit and implicit use of spatial cues can be retrained following brain damage.


Sources of Family Annoyance (SOFA): development, reliability, and validity.
The Sources of Family Annoyance (SOFA) is a brief questionnaire intended to measure chronic stressors experienced by fathers and mothers in the home. Two scales, Household Negatives and Child Negatives, were derived from factor analysis. Experiment 1 demonstrated that the instrument discriminated a group of parents of psychiatric clinic-referred children from nonreferred parents. Experiment 2 demonstrated that the instrument discriminated mothers who were receiving public assistance from mothers in a community sample. Results suggest that the SOFA is a reliable and valid brief parent stress assessment instrument that may be useful in family-based interventions to reduce stress and improve the course of pediatric illness.


Real-Time Segmentation of Unstructured Environments by Combining Domain Generalization and Attention Mechanisms.
This paper presents a focused investigation into real-time segmentation in unstructured environments, a crucial aspect for enabling autonomous navigation in off-road robots. To address this challenge, an improved variant of the DDRNet23-slim model is proposed, which includes a lightweight network architecture and reclassifies ten different categories, including drivable roads, trees, high vegetation, obstacles, and buildings, based on the RUGD dataset. The model's design includes the integration of the semantic-aware normalization and semantic-aware whitening (SAN-SAW) module into the main network to improve generalization ability beyond the visible domain. The model's segmentation accuracy is improved through the fusion of channel attention and spatial attention mechanisms in the low-resolution branch to enhance its ability to capture fine details in complex scenes. Additionally, to tackle the issue of category imbalance in unstructured scene datasets, a rare class sampling strategy (RCS) is employed to mitigate the negative impact of low segmentation accuracy for rare classes on the overall performance of the model. Experimental results demonstrate that the improved model achieves a significant 14% increase mIoU in the invisible domain, indicating its strong generalization ability. With a parameter count of only 5.79M, the model achieves mAcc of 85.21% and mIoU of 77.75%. The model has been successfully deployed on a a Jetson Xavier NX ROS robot and tested in both real and simulated orchard environments. Speed optimization using TensorRT increased the segmentation speed to 30.17 FPS. The proposed model strikes a desirable balance between inference speed and accuracy and has good domain migration ability, making it applicable in various domains such as forestry rescue and intelligent agricultural orchard harvesting.


Validation of a literature-based adherence score to Mediterranean diet: the MEDI-LITE score.
Numerous studies have demonstrated a relationship between adherence to Mediterranean diet and prevention of chronic degenerative diseases. The aim of this study was to validate a novel instrument to measure adherence to Mediterranean diet based on the literature (the MEDI-LITE score). Two-hundred-and-four clinically healthy subjects completed both the MEDI-LITE score and the validated MedDietScore (MDS). Significant positive correlation between the MEDI-LITE and the MDS scores was found in the study population (R = .70; p < .0001). Furthermore, statistically significant positive correlations were found for all the nine different food groups. According to the receiver operating characteristic (ROC) curve analysis, MEDI-LITE evidenced a significant discriminative capacity between adherents and non-adherents to the Mediterranean diet pattern (optimal cut-off point = 8.50; sensitivity = 96%; specificity = 38%). In conclusion, our findings show that the MEDI-LITE score well correlate with MDS in both global score and in most of the items related to the specific food categories.


Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology.
During myofibril assembly, thin filament lengths are precisely specified to optimize skeletal muscle function. Tropomodulins (Tmods) are capping proteins that specify thin filament lengths by controlling actin dynamics at pointed ends. In this study, we use a genetic targeting approach to explore the effects of deleting Tmod1 from skeletal muscle. Myofibril assembly, skeletal muscle structure, and thin filament lengths are normal in the absence of Tmod1. Tmod4 localizes to thin filament pointed ends in Tmod1-null embryonic muscle, whereas both Tmod3 and -4 localize to pointed ends in Tmod1-null adult muscle. Substitution by Tmod3 and -4 occurs despite their weaker interactions with striated muscle tropomyosins. However, the absence of Tmod1 results in depressed isometric stress production during muscle contraction, systemic locomotor deficits, and a shift to a faster fiber type distribution. Thus, Tmod3 and -4 compensate for the absence of Tmod1 structurally but not functionally. We conclude that Tmod1 is a novel regulator of skeletal muscle physiology.


Simultaneous in situ visualization and quantitation of dual antigens adsorbed on adjuvants using high content analysis.
Aim: Traditional antigenicity assay requires antigen recovery from the particulate adjuvants prior to analysis. An in situ method was developed for interrogating vaccine antigens with monoclonal antibodies while being adsorbed on adjuvants. Materials & methods: The fluorescence imaging-based high content analysis was used to visualize the antigen distribution on adjuvant agglomerates and to analyze the antigenicity for adsorbed antigens. Results: Simultaneous visualization and quantitation were achieved for dual antigens in a bivalent human papillomavirus vaccine with uniquely labeled antibodies. Good agreement was observed between the in situ multiplexed assays with well-established sandwich enzyme-linked immunosorbent assays. Conclusion: The streamlined procedures and the amenability for multiplexing make the in situ antigenicity analysis a favorable choice for in vitro functional assessment of bionanoparticles as vaccine antigens.


Atrophic rhinitis in a patient with anhidrotic ectodermal dysplasia.
We would like to present the rare case of a now 37-year old female patient with autosomal-recessively inherited anhidrotic ectodermal dysplasia being treated in our ENT department for atrophic rhinitis. The clinical appearance very much resembled the picture of an "empty nose" with distinct hypoplasia of the turbinates and extensively wide nasal cavities. We want to point out the possible existence of atrophic rhinitis against the background of an underlying syndromatic disease in adults and also the pediatric patient.


Molecular and phenotypical findings of a novel de novo SYNGAP1 gene variant in an 11-year-old Iranian boy with intellectual disability.
Intellectual developmental disorder (IDD) type 5 is an autosomal dominant (AD) disorder and is characterized by intellectual disability (ID), psychomotor developmental delay, variable autism phenotypes, microcephaly, and seizure. IDD can be caused by mutations in the SYNGAP1 gene, which encodes a Ras GTPase-activating protein. This study revealed a novel de novo nonsense variant in SYNGAP1. The identification of such variants is essential for genetic counseling in patients and their families. Exome sequencing implicated the causative variant. Sanger sequencing and cosegregation analyses were used to confirm the variant. Multiple in silico analysis tools were applied to interpret the variant using the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines. The de novo NM_006772.3(SYNGAP1):c.3685C>T variant was identified in an 11-year-old boy with severe intellectual disability, neurodevelopmental delay, speech disorder, ataxia, specific dysmorphic facial features, and aggressive behavior. The current study findings expand the existing knowledge of variants in SYNGAP1 that have been previously associated with nonsyndromic intellectual disability and autism, extending the spectrum of phenotypes associated with this gene. The data have implications for genetic diagnosis and counseling in similar phenotypic presentations.


Expression of the human papillomavirus type 18 E7 gene by a cassette-vector system for the transcription and translation of open reading frames in eukaryotic cells.
We have constructed and functionally tested a cassette-vector-system for the transcription and translation of open reading frames (ORFs) in cells of higher eukaryotes. The vectors are derived from the plasmid pBR322 and can be selected and amplified in Escherichia coli. Alternative eukaryotic promoters can be inserted between the restriction sites SphI and KpnI, translation initiation motifs between KpnI and BglII, linkers for the adjustment of the translation reading frame and the insertion of genes or gene segments between BglII and HindIII, followed by a HindIII-EcoRI segment with splicing and polyadenylation signals derived from SV40. A prototype vector system, pORFEX11, 12 and 13, contains the strong cytomegalovirus immediately early promoter and a 10-bp motif of the SV40 T-antigen translation start. Polylinkers derived from pUC18 permit the insertion of ATG-less ORFs downstream from the ATG of the vector. Either of the three alternative polylinkers adjusts the appropriate translation frame. A similar construct contains the regulatable promoter of the Drosophila heat shock gene 70. We inserted genes or gene segments, that code for the bacterial chloramphenicol acetyltransferase, the bacterial gene conferring resistance against hygromycin, and the ORF E7 of the human papillomavirus type 18 into these vectors. After transfection of mouse L fibroblasts, all proteins and functions were expressed in accordance with the prediction. In transiently transfected L cells, the E7 protein expressed from pORFEX12 constitutes approximately 2.0% of total cell protein. This E7 protein could be localized by immunocytochemistry as a cytoplasmic component.


Characterization of vascular permeability using a biomimetic microfluidic blood vessel model.
The inflammatory response in endothelial cells (ECs) leads to an increase in vascular permeability through the formation of gaps. However, the dynamic nature of vascular permeability and external factors involved is still elusive. In this work, we use a biomimetic blood vessel (BBV) microfluidic model to measure in real-time the change in permeability of the EC layer under culture in physiologically relevant flow conditions. This platform studies the dynamics and characterizes vascular permeability when the EC layer is triggered with an inflammatory agent using tracer molecules of three different sizes, and the results are compared to a transwell insert study. We also apply an analytical model to compare the permeability data from the different tracer molecules to understand the physiological and bio-transport significance of endothelial permeability based on the molecule of interest. A computational model of the BBV model is also built to understand the factors influencing transport of molecules of different sizes under flow. The endothelial monolayer cultured under flow in the BBV model was treated with thrombin, a serine protease that induces a rapid and reversible increase in endothelium permeability. On analysis of permeability data, it is found that the transport characteristics for fluorescein isothiocyanate (FITC) dye and FITC Dextran 4k Da molecules are similar in both BBV and transwell models, but FITC Dextran 70k Da molecules show increased permeability in the BBV model as convection flow (Peclet number > 1) influences the molecule transport in the BBV model. We also calculated from permeability data the relative increase in intercellular gap area during thrombin treatment for ECs in the BBV and transwell insert models to be between 12% and 15%. This relative increase was found to be within range of what we quantified from F-actin stained EC layer images. The work highlights the importance of incorporating flow in in vitro vascular models, especially in studies involving transport of large size objects such as antibodies, proteins, nano/micro particles, and cells.