Diet and cannibalism in plainfin midshipman Porichthys notatus.
The macroscopic and microscopic diversity of potential food items available in the nests of plainfin midshipman Porichthys notatus were quantified and compared with items that were found in the stomach and intestine (digestive tract) of the guarding males. In this species, males occur as one of two possible reproductive morphs: guarder males that care for young and sneaker males that parasitize the courtship and care of guarder males. Although it was predicted that guarder males would have fewer feeding opportunities due to their confinement to the nest, they in fact had more food items in their digestive tracts than did sneaker males and females. Date in the breeding season (a proxy of care duration) and body condition were not correlated with the amount of food consumed by guarder males. The main type of food consumed was P. notatus embryos; 69% of all guarder males sampled had cannibalized offspring. By comparing the diet of both sexes and tactics, this study sheds light on some of the strategies designed to cope with the costs of providing parental care.


Dual-energy computed tomography iodine uptake in differential diagnosis of inflammatory and malignant pulmonary nodules.
PURPOSE The aim of this study was to evaluate the diagnostic performance of iodine uptake parameters using dual-energy computed tomography (DECT) in discriminating inflammatory nodules from malignant tumors. METHODS This retrospective study included 116 solid pulmonary nodules from 112 patients who were admitted to our hospital between January and September 2018. All nodules were confirmed by surgery or puncture. The degree of enhancement of a single-section region of interest was evalu ated. After total tumor volume-of-interest segmentation, the mean iodine density of the whole tumor was measured. Meanwhile, iodine uptake parameters, including total iodine uptake vol ume, total iodine concentration, vital iodine uptake volume, and vital iodine concentration, were calculated, and a predictive model was established. The overall ability to discriminate between inflammatory and malignant nodules was analyzed using an independent samples t-test for normally distributed variables. The diagnostic accuracy and prognostic performance of DECT parameters were evaluated and compared using receiver operating characteristic curve analysis and logistic regression analysis. A multivariate logistic regression analysis was used to determine the prognostic factors and goodness-of-fit of the whole tumor mean iodine and iodine uptake parameters for discriminating malignant nodules. RESULTS There were 116 non-calcified nodules, including 64 inflammatory nodules and 52 malignant nodules. The degree of enhancement in malignant nodules was significantly lower than that in inflammatory nodules (P=.043). All iodine uptake parameters in malignant nodules were signifi cantly higher than those in inflammatory nodules (P < .001). The area under the receiver operat ing curve value, accuracy, sensitivity, and specificity of the established model based on iodine uptake parameters were 0.803, 76.72%, 82.69%, and 84.37%, respectively, which exhibited bet ter diagnostic performance than the degree of enhancement on weighted average images with respective values of 0.609, 59.48%, 61.54%, and 59.38%. CONCLUSION The iodine uptake parameters of DECT exhibited better diagnostic accuracy in discriminating inflammatory nodules from malignant nodules than the degree of enhancement on weighted average images.


Amygdala, medial prefrontal cortex, and hippocampal function in PTSD.
The last decade of neuroimaging research has yielded important information concerning the structure, neurochemistry, and function of the amygdala, medial prefrontal cortex, and hippocampus in posttraumatic stress disorder (PTSD). Neuroimaging research reviewed in this article reveals heightened amygdala responsivity in PTSD during symptomatic states and during the processing of trauma-unrelated affective information. Importantly, amygdala responsivity is positively associated with symptom severity in PTSD. In contrast, medial prefrontal cortex appears to be volumetrically smaller and is hyporesponsive during symptomatic states and the performance of emotional cognitive tasks in PTSD. Medial prefrontal cortex responsivity is inversely associated with PTSD symptom severity. Lastly, the reviewed research suggests diminished volumes, neuronal integrity, and functional integrity of the hippocampus in PTSD. Remaining research questions and related future directions are presented.


Sexual risk behaviour of Canadian participants in the first efficacy trial of a preventive HIV-1 vaccine.
Phase I and phase II HIV-1 vaccine trials have revealed increases in risky sexual activity among study subjects during the trials, perhaps because the subjects believe that the vaccine being tested is efficacious; subjects may thus suffer harm from their participation. We evaluated the sexual behaviour of Canadian men who have sex with men (MSM) who participated in the phase III Vax004 trial of an HIV-1 vaccine. Using self-reports of sexual behaviours during the 6 months before trial entry as a baseline, we determined changes in reported sexual behaviour after 6, 12 and 18 months of participation in the trial. Of 291 HIV-seronegative MSM enrolled from July to October 1999, 260 (89%) completed 18 months of follow-up, 19 (7%) experienced seroconversion, and 12 (4%) did not complete follow-up. Unprotected receptive anal intercourse during the previous 6 months with partners whose HIV-1 serostatus was positive or unknown was reported by 21% of men at enrollment and by 27% at any point during 18 months of follow-up. No increase in this behaviour from baseline was reported by participants, including among men who were motivated to enroll because of expected protection from HIV-1 infection, men who believed they had received the vaccine, men who believed that the vaccine had greater than 50% efficacy, or men who believed that they had received the vaccine and that vaccine efficacy was greater than 50%. MSM can be successfully enrolled in HIV-1 vaccine efficacy trials without evident increases in those sexual behaviours most associated with HIV-1 risk.


In vitro and in vivo experimental studies on trabecular meshwork degeneration induced by benzalkonium chloride (an American Ophthalmological Society thesis).
Long-term antiglaucomatous drug administration may cause irritation, dry eye, allergy, subconjunctival fibrosis, or increased risk of glaucoma surgery failure, potentially due to the preservative benzalkonium chloride (BAK), whose toxic, proinflammatory, and detergent effects have extensively been shown experimentally. We hypothesize that BAK also influences trabecular meshwork (TM) degeneration. Trabecular specimens were examined using immunohistology and reverse transcriptase-polymerase chain reaction. A trabecular cell line was stimulated by BAK and examined for apoptosis, oxidative stress, fractalkine and SDF-1 expression, and modulation of their receptors. An experimental model was developed with BAK subconjunctival injections to induce TM degeneration. Mass spectrometry (MS) imaging assessed BAK penetration after repeated instillations in rabbit eyes. Trabecular specimens showed extremely low densities of trabecular cells and presence of cells expressing fractalkine and fractalkine receptor and their respective mRNAs. Benzalkonium in vitro induced apoptosis, oxidative stress, and fractalkine expression and inhibited the protective chemokine SDF-1 and Bcl2, also inducing a sustained intraocular pressure (IOP) increase, with dramatic apoptosis of trabecular cells and reduction of aqueous outflow. MS imaging showed that BAK could access the TM at measurable levels after repeated instillations. BAK enhances all characteristics of TM degeneration typical of glaucoma-trabecular apoptosis, oxidative stress, induction of inflammatory chemokines-and causes degeneration in acute experimental conditions, potentially mimicking long-term accumulation. BAK was also shown to access the TM after repeated instillations. These findings support the hypothesis that antiglaucoma medications, through toxicity of their preservative, may cause further long-term trabecular degeneration and therefore enhance outflow resistance, reducing the impact of IOP-lowering agents.


Solution structure of the novel dispersin protein of enteroaggregative Escherichia coli.
Enteroaggregative Escherichia coli (EAEC), increasingly recognized as an important cause of infant and travelers' diarrhoea, exhibits an aggregative, stacked-brick pattern of adherence to epithelial cells. Adherence is mediated by aggregative adherence fimbriae (AAFs), which are encoded on the pAA virulence plasmid. We recently described a highly prevalent pAA plasmid-borne gene, aap, which encodes a protein (nicknamed dispersin) that is secreted to the bacterial cell surface. Dispersin-null mutants display a unique hyper-aggregating phenotype, accompanied by collapse of AAF pili onto the bacterial cell surface. To study the mechanism of this effect, we solved the structure of dispersin from EAEC strain 042 using solution NMR, revealing a stable beta-sandwich with a conserved net positive surface charge of +3 to +4 among 23 dispersin alleles. Experimental data suggest that dispersin binds non-covalently to lipopolysaccharide on the surface of the bacterium. We also show that the AAF organelles contribute positive charge to the bacterial surface, suggesting that dispersin's role in fimbrial function is to overcome electrostatic attraction between AAF and the bacterial surface.


[Invasive therapeutic procedures in monochorionic twins: clinical reality and pending questions].
Monochorionic twin pregnancies (MC) are associated with a higher risk of complications than their bichorionic equivalents. When two fetuses share the same placenta, the two fetal circulations are closely bound by omnipresent vascular anastomoses. The determination of the chorionicity is essential for an adequate management of these particular pregnancies. The twin-to-twin transfusion syndrome (TTTS) is one of the. possible complications and must be considered as an obstetrical emergency. Severe growth restriction of one twin occurs in 11% of MC pregnancies. Before the limit of viability, in some of the cases, selective foeticide using particular methods are mandatory to preserve the wellbeing of the healthy twin. The invasive procedures carried out at the time these complications occur proved their effectiveness, under the condition of being applied by experienced experts. Laser coagulation, TTTS gold standard treatment, is associated with a fetal survival rate equal or higher than 75%. Among MC twins, selective foeticide with bipolar cord coagulation allows an intact survival rate of the other twin in more than 75 to 80% of the cases.


Development of a Chest Wall Protector Effective in Preventing Sudden Cardiac Death by Chest Wall Impact (Commotio Cordis).
Commotio cordis, sudden death with chest impact, occurs clinically despite chest wall protectors worn in sports. In an experimental model of commotio cordis, commercially available chest wall protectors failed to prevent ventricular fibrillation (VF). The goal of the current investigation was to develop a chest wall protector effective in the prevention of commotio cordis. In the Tufts experimental model of commotio cordis the ability of chest protectors to prevent VF was assessed. Impacts were delivered with a 40-mph lacrosse ball, timed to the vulnerable period for VF. A chest wall protector or no chest wall protector (control) was randomly assigned to be placed over the chest. Four iterative series of 2 to 4 different chest wall material combinations were assessed. Materials included 3 different foams (Accelleron [Unequal Technologies, Glen Mills, PA], closed cell high density foam; Airilon [Unequal Technologies, Glen Mills, PA], closed cell low density soft foam; and an open cell memory foam) that were adhered to a layer of TriDur (Unequal Technologies, Glen Mills, PA), a flexible elastomeric coated aramid that was bonded to a semirigid polypropylene polymer (ImpacShield, Unequal Technologies, Glen Mills, PA). Induction of VF by chest wall impact was the primary outcome. Of 80 impacts without chest protectors, 43 (54%) resulted in VF. Ventricular fibrillation with chest protectors ranged from a high of 60% to a low of 5%. Of 12 chest protectors assessed, only 3 significantly lowered the risk of VF compared with impacts without chest protectors. These 3 chest protectors were combinations of Accelleron, Airilon, TriDur, and ImpacShield of different thicknesses. Protection increased linearly with the thicker combinations. Effective protection against VF with chest wall protection can be achieved in an experimental model of commotio cordis. Chest protector designs incorporating these novel materials will likely be effective in the prevention of commotio cordis on the playing field.


[Establishment and development of Tabebuia rosea (Bignoniaceae) seedlings in a semideciduous tropical forest under management, Pacific coast of Mexico].
We evaluated the effect of soil "scarification" and vegetation clearing treatments on the natural regeneration and initial development of Tabebuia rosea (Bertold) DC. seedlings in a moderate sized semideciduous tropical forest subjected to wood harvesting on the coast of Jalisco, Mexico. The treatments were applied under "seed" trees, and the number of germinated seedlings and their development were evaluated for nine months. Soil "scarification" promoted seed germination and initial seedling development, while the control of the competing vegetation increased the seedling growth and reduced their mortality. These results should be taken into account for the natural regeneration of this species, after clearing, to improve wood production, and should be incorporated into the silvicultural techniques currently developed in the region.


Pediatric Leprosy Profile in the Postelimination Era: A Study from Surabaya, Indonesia.
Children who live in leprosy-endemic areas are susceptible to infection due to early and frequent exposure to Mycobacterium leprae. Indonesia is on the verge of eliminating this disease (prevalence rate < 1/10,000 population), but pediatric leprosy continues to occur in low-endemic areas. This study aimed to evaluate pediatric leprosy over a decade in a tertiary hospital in Surabaya, Indonesia. A retrospective study of leprosy in children under 15 years old between 2010 and 2019 was conducted in the Morbus Hansen Division, Outpatient Clinic at Dr. Soetomo Hospital in Surabaya, Indonesia. Seventy pediatric leprosy cases were identified between 2010 and 2019, consisting of 58 multibacillary (MB)-type cases and 12 paucibacillary (PB)-type cases. Slit skin smear (SSS) was positive in 26 cases. There were two cases of grade-2 disability and 15 cases of leprosy reaction (erythema nodosum leprosum) in children at the time of diagnosis. There was an insignificant decline in the number of pediatric leprosy cases in the last 10 years. Cases and disabilities in children were found in some leprosy pocket areas even though the national elimination rate has been achieved. MB infections, disability, and treatment defaults were common problems in pediatric leprosy.


Cyclosporine treatment reduces oxygen free radical generation and oxidative stress in the brain of hypoxia-reoxygenated newborn piglets.
Oxygen free radicals have been implicated in the pathogenesis of hypoxic-ischemic encephalopathy. It has previously been shown in traumatic brain injury animal models that treatment with cyclosporine reduces brain injury. However, the potential neuroprotective effect of cyclosporine in asphyxiated neonates has yet to be fully studied. Using an acute newborn swine model of hypoxia-reoxygenation, we evaluated the effects of cyclosporine on the brain, focusing on hydrogen peroxide (H(2)O(2)) production and markers of oxidative stress. Piglets (1-4 d, 1.4-2.5 kg) were block-randomized into three hypoxia-reoxygenation experimental groups (2 h hypoxia followed by 4 h reoxygenation) (n = 8/group). At 5 min after reoxygenation, piglets were given either i.v. saline (placebo, controls) or cyclosporine (2.5 or 10 mg/kg i.v. bolus) in a blinded-randomized fashion. An additional sham-operated group (n = 4) underwent no hypoxia-reoxygenation. Systemic hemodynamics, carotid arterial blood flow (transit-time ultrasonic probe), cerebral cortical H(2)O(2) production (electrochemical sensor), cerebral tissue glutathione (ELISA) and cytosolic cytochrome-c (western blot) levels were examined. Hypoxic piglets had cardiogenic shock (cardiac output 40-48% of baseline), hypotension (mean arterial pressure 27-31 mmHg) and acidosis (pH 7.04) at the end of 2 h of hypoxia. Post-resuscitation cyclosporine treatment, particularly the higher dose (10 mg/kg), significantly attenuated the increase in cortical H(2)O(2) concentration during reoxygenation, and was associated with lower cerebral oxidized glutathione levels. Furthermore, cyclosporine treatment significantly attenuated the increase in cortical cytochrome-c and lactate levels. Carotid blood arterial flow was similar among groups during reoxygenation. Conclusively, post-resuscitation administration of cyclosporine significantly attenuates H(2)O(2) production and minimizes oxidative stress in newborn piglets following hypoxia-reoxygenation.


A dose-response study of OROS methylphenidate in children with attention-deficit/hyperactivity disorder.
OROS methylphenidate HCL (MPH) is a recently developed long-acting stimulant medication used to treat attention-deficit/hyperactivity disorder (ADHD). This study was conducted to examine dosage effects on ADHD symptoms and stimulant side effects and to explore potential moderating effects of ADHD subtype. Children with ADHD combined type (ADHD-CT) or predominantly inattentive type (ADHD-PI; n = 47), ages 5 to 16 years, underwent a placebo-controlled, crossover trial using forced titration with weekly switches at 3 dosage levels. Parent and teacher ratings of ADHD symptoms were used to evaluate efficacy. In addition, vital signs and standardized measures of stimulant side effects were obtained weekly. Parent ratings were more sensitive to treatment effects than teacher ratings. ADHD symptoms and Clinical Global Impressions Severity Index ratings at each dose condition differed significantly from placebo and baseline ratings, which did not differ from one another. For those with ADHD-CT, there was a clear linear dose-response relationship, with clinically significant reductions in ADHD Rating Scale-IV scores occurring in two thirds to three fourths of the subjects during either 36- or 54-mg dose conditions. Children with ADHD-PI, conversely, were more likely to respond optimally to lower doses and derived less benefit from higher doses, with 60% displaying significant improvement on the ADHD Rating Scale-IV at 36 mg or lower. Mild stimulant side effects were reported during placebo and at all dosage levels. With the exception of insomnia and decreased appetite, which were more common at higher doses, parent report of side effects was not related to dose. In addition, younger and smaller children were more likely to display sleep difficulties and decreased appetite at the higher dose levels Although pulse rate increased slightly with increasing dose, there were no dose effects on blood pressure. In children with ADHD-CT, the most common subtype of ADHD, increasing doses of stimulant medication were associated with increased improvement of inattention and hyperactivity symptoms. In children with ADHD-PI, symptom improvement occurred at lower doses and less benefit was derived from higher doses. In both ADHD subtypes, higher doses were associated with parent ratings of increased insomnia and decreased appetite.


Evaluation of early weight loss thresholds for identifying nonresponders to an intensive lifestyle intervention.
Weight losses in lifestyle interventions are variable, yet prediction of long-term success is difficult. The utility of using various weight loss thresholds in the first 2 months of treatment for predicting 1-year outcomes was examined. Participants included 2327 adults with type 2 diabetes (BMI:35.8 ± 6.0) randomized to the intensive lifestyle intervention (ILI) of the Look AHEAD trial. ILI included weekly behavioral sessions designed to increase physical activity and reduce caloric intake. 1-month, 2-month, and 1-year weight changes were calculated. Participants failing to achieve a ≥2% weight loss at Month 1 were 5.6 (95% CI:4.5, 7.0) times more likely to also not achieve a ≥10% weight loss at Year 1, compared to those losing ≥2% initially. These odds were increased to 11.6 (95% CI:8.6, 15.6) when using a 3% weight loss threshold at Month 2. Only 15.2% and 8.2% of individuals failing to achieve the ≥2% and ≥3% thresholds at Months 1 and 2, respectively, go on to achieve a ≥10% weight loss at Year 1. Given the association between initial and 1-year weight loss, the first few months of treatment may be an opportune time to identify those who are unsuccessful and utilize rescue efforts. clinicaltrials.gov Identifier: NCT00017953.


The impact of NaCl substitution with KCl on proteinase activities cell-free extract and cell-free supernatant at different pH levels and salt concentrations: Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus.
The effect of NaCl substitution with KCl at different pH levels (6.0, 5.5, and 5.0) and salt concentrations on proteinase activities of cell-free and supernatant of Lactobacillus delbrueckii ssp. bulgaricus 11824 (L. bulgaricus) and Streptococcus thermophilus MS (ST) was investigated. MRS broths were separately mixed with 4 salt treatments (NaCl only, 1NaCl:1KCl, 1NaCl:3KCl, and KCl only) at 2 different concentrations (5% and 10%) and incubated at 37 °C for 22 h. The cell pellets were used to prepare proteinase of cell-free extract and the cell-free supernatants were used as source of extracellular proteinases. The proteolytic activities and protein contents of both fractions were determined. The supernatants after incubation of both fractions with 3 milk caseins (α-, β-, κ-casein) were subjected to angiotensin-converting-enzyme inhibitory (ACE-inhibitory) activity and proteolytic activity by ortho-phthalaldehyde (OPA) method. Significant differences were observed in ACE-inhibitory activities and proteolytic (OPA) between salt treatments of cell-free extract and cell-free supernatant of L. bulgaricus and S. thermophilus at same salt concentration and same pH level. There was a significant effect of pH level and salt treatments interaction on ACE-inhibitory activity, OPA activity and azocasein activity. To reduce sodium concentration in cheese by substituting of NaCl with KCl, it was important to study the effect on starter culture proteinases which play a vital role in ripening and texture profile of cheese.


Vitamins E and K induce aryl hydrocarbon hydroxylase activity in human cell cultures.
Two fat soluble vitamins, Vitamins E and K, when added into culture medium, were found to increase aryl hydrocarbon hydroxylase activity in human cultured cells. The extent of induction in a hepatoma-derived cell line (Hep G2) by these vitamins is of similar magnitude to those cells receiving benz[a]anthracene; whereas in a mammary tumor-derived cell line (MCF-7), benz[a]anthracene is the best inducer for the hydroxylase activity. The increase of the hydroxylase activity is associated with increased levels of a specific mRNA coding for polynuclear aromatic hydrocarbons-induced form of cytochrome P-450 with Vitamins E and K treatment. The size of the induced mRNA is 3.3 kilobase which is the same as that of benz[a]anthracene treatment.


COVID-19 Pneumonia or Hypereosinophilic Syndrome?
Hypereosinophilic syndromes (HESs) are a group of disorders characterized by pathological proliferation of eosinophils. Diagnostic criteria include eosinophil count of 1,500/mm3 or higher, presence of organ involvement and exclusion of other causes of eosinophilia for at least 6 months. A 69-year-old male patient was referred to the pandemic clinic with a preliminary diagnosis of coronavirus disease 2019 (COVID-19) with fever and dyspnea. Computed tomography (CT) was compatible with COVID-19, nasopharyngeal swab polymerase chain reaction (PCR) was negative for two times. He had 20,000/mm3 eosinophilia and retrospective examinations showed that he have had eosinophilia for more than 1 year. Platelet-derived growth factor receptor alpha (PDGFRα) resulted positively. After starting parenteral methylprednisolone with a dose of 1 mg/kg, he was discharged with oral maintenance therapy. In outpatient follow-up, it was observed that eosinophilic pneumonia completely regressed. HES may occur with multiple system and organ involvement and findings. In the differential diagnosis of patients presenting with heart failure, pulmonary involvement and eosinophilia, HES must definitely be considered.


Removal of estrogens from primary settled sewage by repeated culture of Selenastrum capricornutum.
Biotransformation and biodegradation of estrogenic compounds by bacteria and even fungi have been reported widely, but the role of microalgae in the elimination of estrogens from municipal wastewater treatment plants and their interaction with other microorganisms in wastewater are not clear. This study reported the feasibility of repeatedly removing a mixture of 17β-estradiol (E2) and 17α-ethinylestradiol (EE2), each was 100 μg L-1, from primary settled municipal sewage by Selenastrum capricornutum (SC), a ubiquitous microalga, in four exposure cycles, each lasted 7 days, and how they interacted with the microbial consortium in sewage. Mixed estrogen in sewage stimulated the growth of SC, and the indigenous microorganisms in sewage also affected the microalgal growth. The indigenous microorganisms, particularly bacteria, could easily remove E2 (with 99.5% removal), so the role of SC was insignificant. On the contrary, EE2 was difficult to remove by indigenous microorganisms but the removal was significantly enhanced by SC, with almost all spiked EE2 being removed, even at the end of the fourth cycle (with 99.0% removal). These results indicated that SC, together with the indigenous microorganisms in wastewater, could be repeatedly used for simultaneous removal of E2 and EE2 from municipal sewage.


Mitigating human-wildlife conflict and monitoring endangered tigers using a real-time camera-based alert system.
The recovery of wild tigers in India and Nepal is a remarkable conservation achievement, but it sets the stage for increased human-wildlife conflict where parks are limited in size and where tigers reside outside reserves. We deployed an innovative technology, the TrailGuard AI camera-alert system, which runs on-the-edge artificial intelligence algorithms to detect tigers and poachers and transmit real-time images to designated authorities responsible for managing prominent tiger landscapes in India. We successfully captured and transmitted the first images of tigers using cameras with embedded AI and detected poachers. Notifications of tiger images were received in real time, approximately 30 seconds from camera trigger to appearing in a smart phone app. We review use cases of this AI-based real-time alert system for managers and local communities and suggest how the system could help monitor tigers and other endangered species, detect poaching, and provide early warnings for human-wildlife conflict.


Enhanced performance of dye-sensitized solar cells by utilization of an external, bifunctional layer consisting of uniform β-NaYF₄:Er³⁺/Yb³⁺ nanoplatelets.
Uniform β-NaYF(4):Er(3+)/Yb(3+) hexagonal nanoplatelets were synthesized via a modified hydrothermal route, and the nanoplatelets were applied as an external, bifunctional layer in a novel DSC configuration consisting of only one internal TiO(2) transparent layer. Approximately 10% enhancements of photocurrent and overall DSC efficiency are demonstrated by the addition of the external layer, which exhibits two functions of light reflecting and near-infrared (NIR) light harvesting. The novel DSC configuration not only simplifies the DSC fabrication process but also eliminates charge recombination induced by the conducting up-converting nanocrystals when used internally thus opening the path for other more efficient up-converting nanocrystals to be designed and applied.


Status of non-standard neutrino interactions.
The phenomenon of neutrino oscillations has been established as the leading mechanism behind neutrino flavor transitions, providing solid experimental evidence that neutrinos are massive and lepton flavors are mixed. Here we review sub-leading effects in neutrino flavor transitions known as non-standard neutrino interactions (NSIs), which is currently the most explored description for effects beyond the standard paradigm of neutrino oscillations. In particular, we report on the phenomenology of NSIs and their experimental and phenomenological bounds as well as an outlook for future sensitivity and discovery reach.


Wide-range high-resolution transmission electron microscopy reveals morphological and distributional changes of endomembrane compartments during log to stationary transition of growth phase in tobacco BY-2 cells.
Rapid growth of plant cells by cell division and expansion requires an endomembrane trafficking system. The endomembrane compartments, such as the Golgi stacks, endosome and vesicles, are important in the synthesis and trafficking of cell wall materials during cell elongation. However, changes in the morphology, distribution and number of these compartments during the different stages of cell proliferation and differentiation have not yet been clarified. In this study, we examined these changes at the ultrastructural level in tobacco Bright yellow 2 (BY-2) cells during the log and stationary phases of growth. We analyzed images of the BY-2 cells prepared by the high-pressure freezing/freeze substitution technique with the aid of an auto-acquisition transmission electron microscope system. We quantified the distribution of secretory and endosomal compartments in longitudinal sections of whole cells by using wide-range gigapixel-class images obtained by merging thousands of transmission electron micrographs. During the log phase, all Golgi stacks were composed of several thick cisternae. Approximately 20 vesicle clusters (VCs), including the trans-Golgi network and secretory vesicle cluster, were observed throughout the cell. In the stationary-phase cells, Golgi stacks were thin with small cisternae, and only a few VCs were observed. Nearly the same number of multivesicular body and small high-density vesicles were observed in both the stationary and log phases. Results from electron microscopy and live fluorescence imaging indicate that the morphology and distribution of secretory-related compartments dramatically change when cells transition from log to stationary phases of growth.


Colloidal and dissolved phosphorus in sandy soils as affected by phosphorus saturation.
Fertilization exceeding crop requirements causes an accumulation of phosphorus (P) in soils, which might increase concentrations of dissolved and colloidal P in drainage. We sampled soils classified as Typic Haplorthods from four fertilization experiments to test (i) whether increasing degrees of phosphorus saturation (DPS) increase concentrations of dissolved and colloidal P, and (ii) if critical DPS levels can be defined for P release from these soils. Oxalate-extractable concentrations of P, iron (Fe), and aluminum (Al) were quantified to characterize DPS. Turbidity, zeta potential, dissolved P, and colloidal P, Fe, Al, and carbon (C) concentrations were determined in water and KCl extracts. While concentrations of dissolved P decreased with increasing depth, concentrations of water-extractable colloidal P remained constant. In topsoils 28 +/- 17% and in subsoils 94 +/- 8% of water-extractable P was bound to colloids. Concentrations of dissolved P increased sharply for DPS > 0.1. Colloidal P concentrations increased with increasing DPS because of an additional mobilization of colloids and due to an increase of the colloids P contents. In addition to DPS, ionic strength and Ca(2+) affected the release of colloidal P. Hence, using KCl for extraction improved the relationship between DPS and colloidal P compared with water extraction. Accumulation of P in soils increases not only concentrations of dissolved P but also the risk of colloidal P mobilization. Leaching of colloidal P is potentially important for inputs of P into water bodies because colloidal P as the dominant water-extractable P fraction in subsoils was released from soils with relatively low DPS.


The E1E4 protein of human papillomavirus type 16 associates with a putative RNA helicase through sequences in its C terminus.
Human papillomavirus type 16 (HPV16) infects cervical epithelium and is associated with the majority of cervical cancers. The E1E4 protein of HPV16 but not those of HPV1 or HPV6 was found to associate with a novel member of the DEAD box protein family of RNA helicases through sequences in its C terminus. This protein, termed E4-DBP (E4-DEAD box protein), has a molecular weight of 66,000 (66K) and can shuttle between the nucleus and the cytoplasm. It binds to RNA in vitro, including the major HPV16 late transcript (E1E4. L1), and has an RNA-independent ATPase activity which can be partially inhibited by E1E4. E4-DBP was detectable in the cytoplasm of cells expressing HPV16 E1E4 (in vivo and in vitro) and could be immunoprecipitated as an E1E4 complex from cervical epithelial cell lines. In cell lines lacking cytoplasmic intermediate filaments, loss of the leucine cluster-cytoplasmic anchor region of HPV16 E1wedgeE4 resulted in both proteins colocalizing exclusively to the nucleoli. Two additional HPV16 E1E4-binding proteins, of 80K and 50K, were identified in pull-down experiments but were not recognized by antibodies to E4-DBP or the conserved DEAD box motif. Sequence analysis of E4-DBP revealed homology in its E4-binding region with three Escherichia coli DEAD box proteins involved in the regulation of mRNA stability and degradation (RhlB, SrmB, and DeaD) and with the Rrp3 protein of Saccharomyces cerevisiae, which is involved in ribosome biogenesis. The synthesis of HPV16 coat proteins occurs after E1E4 expression and genome amplification and is regulated at the level of mRNA stability and translation. Identification of E4-DBP as an HPV16 E1E4-associated protein indicates a possible role for E1E4 in virus synthesis.


Surveillance of obesity-related policies in multiple environments: the Missouri Obesity, Nutrition, and Activity Policy Database, 2007-2009.
The objective of this study was to develop the Missouri Obesity, Nutrition, and Activity Policy Database, a geographically representative baseline of Missouri's existing obesity-related local policies on healthy eating and physical activity. The database is organized to reflect 7 local environments (government, community, health care, worksite, school, after school, and child care) and to describe the prevalence of obesity-related policies in these environments. We employed a stratified nested cluster design using key informant interviews and review of public records to sample 2,356 sites across the 7 target environments for the presence or absence of obesity-related policies. The school environment had the most policies (88%), followed by after school (47%) and health care (32%). Community, government, and child care environments reported smaller proportions of obesity-related policies but higher rates of funding for these policies. Worksite environments had low numbers of obesity-related policies and low funding levels (17% and 6%, respectively). Sixteen of the sampled counties had high obesity-related policy occurrence; 65 had moderate and 8 had low occurrences. Except in Missouri schools, the presence of obesity-related policies is limited. More obesity-related policies are needed so that people have access to environments that support the model behaviors necessary to halt the obesity epidemic. The Missouri Obesity, Nutrition, and Activity Policy Database provides a benchmark for evaluating progress toward the development of obesity-related policies across multiple environments in Missouri.


Investigating associations between genetic risk for bipolar disorder and cognitive functioning in childhood.
Identifying phenotypic manifestations of genetic risk for bipolar disorder (BD) in childhood could increase our understanding of aetiological mechanisms. To examine whether BD genetic risk is associated with childhood (age 8 years) cognitive function. Using data from the Avon Longitudinal Study of Parents and Children, we examined associations between polygenic risk scores for BD (BD-PRS) derived using Psychiatric Genomics Consortium summary data at p-thresholds (PT) ≤0.01 (primary) and ≤0.5 (secondary) and several cognitive domains (sample sizes 5,613 to 5,936). We also examined whether associations were due to SNPs that have shared risk effects on schizophrenia (SZ). At PT≤0.01, the BD-PRS was associated with poorer executive functioning (ß= -0.03, 95%CI -0.06, -0.01; p = 0.013), and, more weakly with poorer processing speed (ß = -0.02, 95%CI -0.05, 0.02; p = 0.075). Evidence of association with both poorer processing speed (p = 0.016) and performance IQ (p = 0.018) was stronger at PT≤0.5. Associations with performance IQ and processing speed were primarily driven by genetic effects that are shared with SZ risk, but there was some evidence of bipolar-specific genetic effects on childhood executive functioning. The BD-PRS still explains only a small proportion of the variance for BD which will have reduced power to detect associations. Genetic risk for BD manifests as impaired cognition in childhood, and this is driven by risk SNPs that are also shared with SZ genetic risk. Further elucidation of which cognitive domains are most affected by genetic risk for BD could help understanding of aetiology and improve prediction of BD.


Mechanical strain drives exosome production, function, and miRNA cargo in C2C12 muscle progenitor cells.
Mesenchymal stem cells (MSCs) have been proven to promote tissue repair. However, concerns related to their clinical application and regulatory hurdles remain. Recent data has demonstrated the proregenerative secretome of MSCs can result in similar effects in the absence of the cells themselves. Within the secretome, exosomes have emerged as a promising regenerative component. Exosomes, which are nanosized lipid vesicles secreted by cells, encapsulate micro-RNA (miRNA), RNA, and proteins that drive MSCs regenerative potential with cell specific content. As such, there is an opportunity to optimize the regenerative potential of MSCs, and thus their secreted exosome fraction, to improve clinical efficacy. Exercise is one factor that has been shown to improve muscle progenitor cell function and regenerative potential. However, the effect of exercise on MSC exosome content and function is still unclear. To address this, we used an in vitro culture system to evaluate the effects of mechanical strain, an exercise mimetic, on C2C12 (muscle progenitor cell) exosome production and proregenerative function. Our results indicate that the total exosome production is increased by mechanical strain and can be regulated with different tensile loading regimens. Furthermore, we found that exosomes from mechanically stimulated cells increase proliferation and myogenic differentiation of naïve C2C12 cells. Lastly, we show that exosomal miRNA cargo is differentially expressed following strain. Gene ontology mapping suggests positive regulation of bone morphogenetic protein signaling, regulation of actin-filament-based processes, and muscle cell apoptosis may be at least partially responsible for the proregenerative effects of exosomes from mechanically stimulated C2C12 muscle progenitor cells.


Special quasirandom structures for gadolinia-doped ceria and related materials.
Gadolinia doped ceria in its doped or strained form is considered to be an electrolyte for solid oxide fuel cell applications. The simulation of the defect processes in these materials is complicated by the random distribution of the constituent atoms. We propose the use of the special quasirandom structure (SQS) approach as a computationally efficient way to describe the random nature of the local cation environment and the distribution of the oxygen vacancies. We have generated two 96-atom SQS cells describing 9% and 12% gadolinia doped ceria. These SQS cells are transferable and can be used to model related materials such as yttria stabilized zirconia. To demonstrate the applicability of the method we use density functional theory to investigate the influence of the local environment around a Y dopant in Y-codoped gadolinia doped ceria. It is energetically favourable if Y is not close to Gd or an oxygen vacancy. Moreover, Y-O bonds are found to be weaker than Gd-O bonds so that the conductivity of O ions is improved.


Potential failure of the International Normalized Ratio (INR) System in the monitoring of oral anticoagulation in patients with lupus anticoagulants.
Patients with antiphospholipid antibody syndrome (APS) experience a higher rate of recurrence of thrombosis than the general population of patients with thrombotic disease. Based on a retrospective analysis, it has been suggested that patients with APS should be kept on prolonged anticoagulation aiming at international normalised ratio (INR) values > 3.0. To evaluate whether the requirement for more intense anticoagulation depends on the variable sensitivity of thromboplastin reagents to the influence of aPLA, we monitored oral anticoagulant treatment in 10 patients with persistent lupus anticoagulants (LA) and venous thromboembolic disease using two thromboplastin reagents: Pro-IL-Complex (Instrumentation Laboratory, combined) and Recombiplastin (Ortho, recombinant). Acenocoumarol dosage was always assigned based on INR values obtained with the combined thromboplastin using diluted (1:20) test plasma, aiming at an INR interval of 2.0 to 3.0. Single INR determinations with both reagents were obtained throughout the study period for 110 aPLA-free patients on stable oral anticoagulation. Using the manufacturer's instrument-certified international sensitivity index (ISI) values, INR obtained with the recombinant reagent were significantly higher than those obtained with the combined reagent in LA-positive patients, but they were lower in LA-negative patients. After correction for local ISI calibration in LA-negative patients, INR values of 3.1 and 4.6 with Recombiplastin corresponded, respectively, to INR values of 2.0 and 3.0 with Pro-IL-Complex. These results indicate the thromboplastin-dependency of INR values in patients with LA, thereby questioning the validity of the INR system for the monitoring of oral anticoagulant treatment in these patients.


Comparison between direct use and PLGA nanocapsules containing drug of traditional Chinese medicine, Tiaojing Zhixue, in treatment of dysfunctional uterine bleeding.
Dysfunctional uterine bleeding is menstrual bleeding in abnormal volume, duration, or time, and it is a common problem in women. A wide range of drug therapies, with varying efficacy, is available for women with dysfunctional uterine bleeding. The use of herbal and traditional medicine is one of the ways to treat this disease, which has fewer side effects than chemical drugs. On the other hand, these medicines have less effect on treatment than chemical drugs. Therefore, increasing their effectiveness in the treatment of diseases has always been important. For this purpose, in this study, a comparison was done between direct use and PLGA nanocapsules containing Tiaojing Zhixue, in the treatment of dysfunctional uterine bleeding. First, PLGA nanocapsules containing Tiaojing Zhixue were synthesized by the electrospray technique. Then 80 women with dysfunctional uterine bleeding were treated with this medicine. These people were divided into two groups of 40 people. The first group was treated with 20mg of Tiaojing Zhixue and the other group was treated with PLGA nanocapsules containing Tiaojing Zhixue for eight months. The duration and frequency of bleeding from one month before the start of treatment and during the eight months after the start of treatment (second, fourth, and eighth month) were assessed in two groups. The two groups were homogeneous in terms of mean frequency of bleeding and mean duration of bleeding before starting treatment. The positive response in the PLGA nanocapsules treatment group (75%) was higher than the direct use drug treatment group (42.5%) (P < 0.01). The rate of side effects was the same in each group. Due to the effectiveness of PLGA nanocapsules in the treatment of dysfunctional uterine bleeding and the lack of side effects, it can be considered as an alternative medicine for the treatment of this disorder.


Multi-component immunoaffinity subtraction chromatography: an innovative step towards a comprehensive survey of the human plasma proteome.
In order to discover novel protein markers indicative of disease processes or drug effects, the proteomics technology platform most commonly used consists of high resolution protein separation by two-dimensional electrophoresis (2-DE), mass spectrometric identification of proteins from stained gel spots and a bioinformatic data analysis process supported by statistics. This approach has been more successful in profiling proteins and their disease- or treatment-related quantitative changes in tissue homogenates than in plasma samples. Plasma protein display and quantitation suffer from several disadvantages: very high abundance of a few proteins; high heterogeneity of many proteins resulting in long charge trains; crowding of 2-DE separated protein spots in the molecular mass range between 45-80 kD and in the isoelectric point range between 4.5 and 6. Therefore, proteomic technologies are needed that address these problems and particularly allow accurate quantitation of a larger number of less abundant proteins in plasma and other body fluids. The immunoaffinity-based protein subtraction chromatography (IASC) described here removes multiple proteins present in plasma and serum in high concentrations effectively and reproducibly. Applying IASC as an upfront plasma sample preparation process for 2-DE, the protein spot pattern observed in gels changes dramatically and at least 350 additional lower abundance proteins are visualized. Affinity-purified polyclonal antibodies (pAbs) are the immunoaffinity reagents used to specifically remove the abundant proteins such as albumin, immunoglobulin G, immunoglobulin A, transferrin, haptoglobin, alpha-1-antitrypsin, hemopexin, transthyretin, alpha-2-HS glycoprotein, alpha-1-acid glycoprotein, alpha-2-macroglobulin and fibrinogen from human plasma samples. To render the immunoaffinity subtraction procedure recyclable, the pAbs are immobilized and cross-linked on chromatographic matrices. Antibody-coupled matrices specific for one protein each can be pooled to form mixed-bed IASC columns. We show that up to ten affinity-bound plasma proteins with similar solubility characteristics are eluted from a mixed-bed column in one step. This facilitates automated chromatographic processing of plasma samples in high throughput, which is desirable in proteomic disease marker discovery projects.


Effects of Olive Oil Phenolic Compounds on Inflammation in the Prevention and Treatment of Coronary Artery Disease.
Coronary artery disease (CAD) is responsible for more than 7 million deaths worldwide. In the early stages of the development of atherosclerotic plaques, cardiovascular risk factors stimulate vascular endothelial cells, initiating an inflammatory process, fundamental in the pathogenesis of CAD. The inclusion of potentially cardioprotective foods, such as olive oil, to the diet, may aid in the control of these risk factors, and in the reduction of cytokines and inflammatory markers. The present review aims to address the interaction between phenolic compounds present in olive oil, and inflammation, in the prevention and treatment of CAD. In vitro and in vivo studies suggest that phenolic compounds, such as hydroxytyrosol, tyrosol, and their secoiridoid derivatives, may reduce the expression of adhesion molecules and consequent migration of immune cells, modify the signaling cascade and the transcription network (blocking the signal and expression of the nuclear factor kappa B), inhibit the action of enzymes responsible for the production of eicosanoids, and consequently, decrease circulating levels of inflammatory markers. Daily consumption of olive oil seems to modulate cytokines and inflammatory markers related to CAD in individuals at risk for cardiovascular diseases. However, clinical studies that have evaluated the effects of olive oil and its phenolic compounds on individuals with CAD are still scarce.


A simple scoring system to improve clinical assessment of acute otitis media.
To evaluate an easy to use 10-point scoring system in clinical assessment of acute otitis media (AOM). Study design. Symptoms of AOM observed by validated otoscopists were tabulated and scored with a 10-point and a 30-point system at acute onset of illness and at the test-of-cure (TOC) 3 weeks later. A total of 330 children (mean age = 13.1 months) with AOM were studied. At AOM onset, the mean 10-point and 30-point scores; were highly correlated (P < .001). At TOC, 256 children were cured, 69 failed, and 5 were lost to follow-up. The 10-point scores were 0.5 and 4.4 for children with cure and failure. The 10-point score had a sensitivity of 87%, specificity of 98%, positive predictive value of 91%, and negative predictive value of 97% compared with the diagnosis by validated otoscopists. A simple, easy-to-use 10-point AOM scoring system was shown to discriminate AOM cure and failure at TOC.


Probing the essential catalytic residues and substrate affinity in the thermoactive Bacillus stearothermophilus US100 L-arabinose isomerase by site-directed mutagenesis.
The L-arabinose isomerase (L-AI) from Bacillus stearothermophilus US100 is characterized by its high thermoactivity and catalytic efficiency. Furthermore, as opposed to the majority of l-arabinose isomerases, this enzyme requires metallic ions for its thermostability rather than for its activity. These features make US100 L-AI attractive as a template for industrial use. Based on previously solved crystal structures and sequence alignments, we identified amino acids that are putatively important for the US100 L-AI isomerization reaction. Among these, E306, E331, H348, and H447, which correspond to the suggested essential catalytic amino acids of the L-fucose isomerase and the L-arabinose isomerase from Escherichia coli, are presumed to be the active-site residues of US100 L-AI. Site-directed mutagenesis confirmed that the mutation of these residues resulted in totally inactive proteins, thus demonstrating their critical role in the enzyme activity. A homology model of US100 L-AI was constructed, and its analysis highlighted another set of residues which may be crucial for the recognition and processing of substrates; hence, these residues were subjected to mutagenesis studies. The replacement of the D308, F329, E351, and H446 amino acids with alanine seriously affected the enzyme activities, and suggestions about the roles of these residues in the catalytic mechanism are given. The mutation F279Q strongly increased the enzyme's affinity for L-fucose and decreased the affinity for L-arabinose compared to that of the wild-type enzyme, showing the implication of this amino acid in substrate recognition.


In vivo expression of B7-1 and B7-2 by follicular lymphoma cells can prevent induction of T-cell anergy but is insufficient to induce significant T-cell proliferation.
Expression of B7 family costimulatory molecules on B cells defines their capacity to function as antigen presenting cells (APCs). B cells that do not express B7 costimulatory molecules induce T-cell tolerance. Therefore, the expression of B7 costimulatory molecules on malignant B cells might be critical for their recognition by anti-tumor-specific T cells. Here we show that virtually all germinal center (GC)-derived B-cell lymphomas including follicular lymphoma (FL) and diffuse large cell lymphoma, but not mantle cell lymphoma or small lymphocytic lymphomas (SLL/CLL), express B7-1 (CD80) and B7-2 (CD86) on their cell surface in situ, although at extremely low levels. Despite their expression of low levels of B7-1 and B7-2, FL cells could not induce significant allogeneic T-cell proliferation. However, B7 costimulatory molecules on FL appeared to be functional because they were capable of increasing T-cell proliferation of preactivated T cells in a secondary allogeneic mixed lymphocyte response. Moreover, low B7 expression was sufficient to prevent the induction of alloantigen-specific anergy in vitro. Therefore, we postulate that whereas low-level expression of B7 is not sufficient to initiate a productive antilymphoma T-cell response, it might be sufficient to prevent T-cell tolerance in vivo.


Renal hemodynamic effects of glucagon-like peptide-1 agonist are mediated by nitric oxide but not prostaglandin.
The incretin hormone, glucagon-like peptide-1 (GLP-1), is known for responding to dietary fat and carbohydrate. It elicits effects on pancreas, gut, and brain to stabilize blood glucose levels. We have previously reported that the GLP-1 agonist, exenatide, vasodilates the kidney and suppresses proximal reabsorption. The present study was undertaken to determine whether the renal effects of exenatide are mediated by nitric oxide (NO) and/or prostaglandins. Inulin clearance (glomerular filtration rate, GFR) and urine flow rate (UV) were measured in anesthetized rats before and during exenatide infusion (1 nmol/h iv). Animals were pretreated with cyclooxygenase (COX) inhibitor (meclofenamate), NO synthase (NOS) inhibitor (NG-monomethyl-l-arginine, l-NMMA), NO clamp (l-NMMA + sodium nitroprusside), or placebo. Effectiveness of COX inhibition was tested by measuring urinary prostaglandin E2 (UPGE2). Effectiveness of NOS blockade and NO clamp was determined by urinary NO degradation products (UNOx). Exenatide increased GFR, UV, UPGE2, and UNOx. Pretreatment with meclofenamate reduced UPGE2 by 75% and reduced the effect of exenatide on UPGE2 by 30% but did not modify the effects of exenatide on GFR or UV. Pretreatment with l-NMMA reduced UNOx and the impact of exenatide on GFR and UV by 50%. Pretreatment by NO clamp did not prevent UNOx from increasing during exenatide but blunted the effects of exenatide on GFR and UV. In conclusion, exenatide is a potent renal vasodilator and diuretic in the rat. These effects of exenatide are insensitive to COX inhibition but are mediated, in part, by NO.


Treatment of brachymetatarsia by distraction osteogenesis.
Metatarsal lengthening by distraction osteogenesis was performed on 17 brachymetatarsia patients with 39 metatarsal bones. To lengthen the first metatarsal in an attempt to prevent development of varus deformity of the hindfoot after lengthening, horizontal lengthening in the anterior direction was performed rather than lengthening through the anatomical axis. In addition, care was taken to ensure that the fourth metatarsal bone screw did not interpose with the fifth extensor tendon during the fourth metatarsal lengthening. Lengthening was successful except in 1 case with mean lengthening of 19.5 mm (48.8%) for the first metatarsal and 17.1 mm (36.2%) for the fourth metatarsal. Because of joint stiffness, plantar capsulotomy was performed on 7 cases, 6 of which had been previously operated on bilaterally. Varus deformity of the hindfoot after the first metatarsal lengthening and entrapment of the fifth extensor tendon after the fourth metatarsal lengthening was not detected in any case.


[Endoscopic sclerosis with pneumatic distension for pyriform sinus fistula treatment].
Classic treatment for pyriform sinus fistula (PSF) has been surgical excision; however, less invasive therapeutic alternatives whose aim is the obliteration of the sinus have been described subsequently. The authors present a technical modification of endoscopic sclerosis with diathermy (ESD): continuous infusion of air flow through the flexible endoscope was used to distend the pyriform sinus and facilitate recognition of the fistula opening. The sinus obliteration was performed with a wire guide and diathermy. In the last 15 years, 9 patients were diagnosed of suffering from PSF in our institution. Initial treatment was antibiotics therapy associated in some cases to cervical abscess drainage. Fistulectomy was performed in 4 cases and ESD in 4. The ninth patient received both treatments, performing electrocauterization after a surgical recurrence. Three of the patients who underwent surgery relapsed; none treated by ESD did, or had any complications. In our experience, endoscopic sclerosis with pneumatic distension is a simple technique, reproducible, not invasive and very effective; hence we consider it might become a first line therapy for PSF.


Samp1 is functionally associated with the LINC complex and A-type lamina networks.
The transmembrane inner nuclear membrane (INM) protein Samp1 is required for anchoring centrosomes near the nuclei. Using high-resolution fluorescence microscopy we show that Samp1 is distributed in a distinct and characteristic pattern in the nuclear envelope (NE), where it partially colocalizes with the LINC complex protein Sun1. By studying the localization of Samp1 deletion mutants and fusion proteins, we conclude that the cysteine-rich N-terminal half of Samp1 is nucleoplasmically exposed and is responsible for targeting to the INM. It contains four conserved CxxC motifs with the potential to form zinc fingers. The distribution of cysteine-to-alanine substitution mutants, designed to prevent zinc finger formation, showed that NE localization of Samp1 depends on intact CxxC motifs. Overexpression of Samp1 zinc finger mutants produced an abnormal dominant phenotype characterized by disrupted organization of a selective subset NE proteins, including emerin, Sun1, endogenous Samp1 and, in some cases, lamin A/C, but not lamin B, Sun2 or nucleoporins. Silencing of Samp1 expression showed that emerin depends on Samp1 for its correct localization in the NE. Our results demonstrate that Samp1 is functionally associated with the LINC complex protein Sun1 and proteins of the A-type lamina network.


Innovative designs for trials informing the care of cardiac surgical patients: Part II.
This review examines advances in clinical trial methodologies relevant to cardiac anesthesia. It focuses on innovative approaches, including factorial randomization, composite outcomes, and cluster randomized trials, which enhance the efficiency, practical relevance, and generalizability of trial outcomes. Factorial randomization is becoming popular because the approach allows investigators to simultaneously evaluate two or more interventions. Furthermore, factorial designs can evaluate interactions among treatments, which is highly relevant information that cannot be obtained from separate trials. Composite outcomes are also increasingly utilized, combining multiple individual outcomes into a single measure, which increases statistical power and can better represent relevant physiology. Designing valid composites requires careful consideration of component outcome severity and incidence. Cluster randomized trials, including stepped wedge and multiple crossover designs, are addressing the challenges of group-level effects and shared environments. The evolution of clinical trial designs is marked by a shift towards methodologies that enhance efficiency and provide more nuanced insights into treatment effects. These include factorial designs for simultaneous intervention assessment, composite outcomes for comprehensive physiological representation, and cluster trials for group-level effect analysis. Such advancements are shaping the future of clinical research, making it more relevant, efficient, and broadly applicable.


Tool morphology constrains the effects of tool use on body representations.
What factors constrain whether tool use modulates the user's body representations? To date, studies on representational plasticity following tool use have primarily focused on the act of using the tool. Here, we investigated whether the tool's morphology also serves to constrain plasticity. In 2 experiments, we varied whether the tool was morphologically similar to a target body part (Experiment 1, hand; Experiment 2, arm). Participants judged the tactile distance between pairs of points applied to their tool-using target body surface and forehead (control surface) before and after tool use. We applied touch in 2 orientations, allowing us to quantify how tool use modulates the representation's shape. Significant representational plasticity in hand shape (increase in width, decrease in length) was found when the tool was morphologically similar to a hand (Experiment 1A), but not when the tool was arm-shaped (Experiment 1B). Conversely, significant representational plasticity was found on the arm when the tool was arm-shaped (Experiment 2B), but not when hand-shaped (Experiment 2A). Taken together, our results indicate that morphological similarity between the tool and the effector constrains tool-induced representational plasticity. The embodiment of tools may thus depend on a match-to-template process between tool morphology and representation of the body.


Heteroscorpionate rare-earth initiators for the controlled ring-opening polymerization of cyclic esters.
A series of neutral rare-earth metal amides containing different achiral and chiral heteroscorpionate ligands was synthesized and characterized and these compounds were employed in the polymerization of cyclic esters. Thus, treatment of [Ln{N(SiHMe(2))(2)}(3)(thf)(2)] (Ln = Nd, Sm) with acetamide or thioacetamide heteroscorpionate ligands for 2 h at 0 °C afforded the α-agostic silylamido dimeric rare-earth compounds [Ln{N(SiHMe(2))(2)}(NNE)](2) (Ln = Nd and Sm; NNE = heteroscorpionate ligands, E = O, S) (1-8), some as enantiopure complexes. Complexes 1-8 contain dianionic heteroscorpionate pseudoallyl ligands resulting from C-H activation of the bridging methine group of the bis(pyrazol-1-yl)methane moiety and subsequent coordination to the metal center. However, when the reaction was carried out for 1 h at lower temperature new bis(silylamido) dimeric lanthanide compounds [Ln{N(SiHMe(2))(2)}(2)(NNE)](2) (Ln = Nd and Sm; E = O) (9 and 10) were obtained. The structures of the complexes were determined by spectroscopic methods and the X-ray crystal structures of 1, and 4 were also established. Neodymium complexes are active initiators for the ring-opening polymerization (ROP) of lactide (LA) and lactones, giving rise to medium-high molar mass polymers under mild conditions and with narrow polydispersities. These complexes were well suited for achieving well-controlled polymerization through an insertion-coordination mechanism. Achiral and racemic complexes did not affect stereocontrol in the polymerizarion of rac-LA but the enantiomerically pure complex 1 was found to exhibit a homosteric preference for one of the two enantiomers of rac-LA at low conversions.


Recent Advances in Anthocyanin Analysis and Characterization.
Anthocyanins are a class of polyphenols responsible for the orange, red, purple and blue colors of many fruits, vegetables, grains, flowers and other plants. Consumption of anthocyanins has been linked as protective agents against many chronic diseases and possesses strong antioxidant properties leading to a variety of health benefits. In this review, we examine the advances in the chemical profiling of natural anthocyanins in plant and biological matrices using various chromatographic separations (HPLC and CE) coupled with different detection systems (UV, MS and NMR). An overview of anthocyanin chemistry, prevalence in plants, biosynthesis and metabolism, bioactivities and health properties, sample preparation and phytochemical investigations are discussed while the major focus examines the comparative advantages and disadvantages of each analytical technique.


Self-rated health predicts healthcare utilization in heart failure.
Heart failure (HF) patients experience impaired functional status, diminished quality of life, high utilization of healthcare resources, and poor survival. Yet, the identification of patient-centered factors that influence prognosis is lacking. We determined the association of 2 measures of self-rated health with healthcare utilization and skilled nursing facility (SNF) admission in a community cohort of 417 HF patients prospectively enrolled between October 2007 and December 2010 from Olmsted County, MN. Patients completed a 12-item Short Form Health Survey (SF-12). Low self-reported physical functioning was defined as a score ≤ 25 on the SF-12 physical component. The first question of the SF-12 was used as a measure of self-rated general health. After 2 years, 1033 hospitalizations, 1407 emergency department (ED) visits, and 19,780 outpatient office visits were observed; 87 patients were admitted to a SNF. After adjustment for confounding factors, an increased risk of hospitalizations (1.52 [1.17 to 1.99]) and ED visits (1.48 [1.04 to 2.11]) was observed for those with low versus moderate-high self-reported physical functioning. Patients with poor and fair self-rated general health also experienced an increased risk of hospitalizations (poor: 1.73 [1.29 to 2.32]; fair: 1.46 [1.14 to 1.87]) and ED visits (poor: 1.73 [1.16 to 2.56]; fair: 1.48 [1.13 to 1.93]) compared with good-excellent self-rated general health. No association between self-reported physical functioning or self-rated general health with outpatient visits and SNF admission was observed. In community HF patients, self-reported measures of physical functioning predict hospitalizations and ED visits, indicating that these patient-reported measures may be useful in risk stratification and management in HF.


A model of persistent partial hindlimb ischemia in the rabbit.
An animal model of resting limb ischemia in the rabbit was developed and studied. Anesthetized rabbits underwent unilateral common iliac artery (CIA) division, allowing comparisons between an experimental (ischemic) and the contralateral control limb in the same animal. The time course and severity of the ischemic insult were measured by quantitating muscle blood flow in seven muscle groups using 57Co-radiolabeled microspheres, limb femoral arteriovenous oxygen differences (AVDO2), and limb arterial pressure. Nine of 20 animals had objective evidence of functional limb impairment judged by abnormal resting posture and/or abnormal gait. Muscle blood flow in the experimental limbs became significantly less than blood flows of corresponding contralateral muscle groups (P less than 0.05) when measured at 1 week after CIA division. By 17 days, mean muscle blood flow had returned to within 82.5% of that of the control limb. AVDO2 increased from 4.8 +/- 0.99 to 8.13 +/- 2.26 ml O2/dl blood following CIA division and remained persistently greater than the control limb value until Day 31. Limb arterial pressure decreased markedly after CIA division and remained significantly depressed beyond 6 weeks when the study was terminated. The reasons for the differential time courses of these parameters of blood flow are discussed. Common iliac artery division in the rabbit appears to produce persistent, partial ischemia at least 17 days in duration, allowing in-depth study of the effects of persistent limb ischemia on muscle cell function in the laboratory setting, as well as permitting the assessment of various therapeutic manipulations for the treatment of prolonged muscle ischemia.


Disruption of Cytosolic Folate Integrity Aggravates Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Modulates Metastatic Properties in Non-Small-Cell Lung Cancer Cells.
Patients with advanced-stage non-small-cell lung cancer (NSCLC) are susceptible to malnutrition and develop folate deficiency (FD). We previously found that folate deprivation induces drug resistance in hepatocellular carcinoma; here, we assessed whether disrupted cytoplasmic folate metabolism could mimic FD-induced metastasis and affect the sensitivity of NSCLC cells to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). We examined whether cytosolic folate metabolism in NSCLC cells was disrupted by FD or the folate metabolism blocker pemetrexed for 1-4 weeks. Our results revealed an increase in NF-κB overexpression-mediated epithelial-mesenchymal transition biomarkers: N-cadherin, vimentin, matrix metalloproteinases (MMPs), SOX9, and SLUG. This finding suggests that the disruption of folate metabolism can drastically enhance the metastatic properties of NSCLC cells. Cytosolic FD also affected EGFR-TKI cytotoxicity toward NSCLC cells. Because SLUG and N-cadherin are resistance effectors against gefitinib, the effects of SLUG knockdown in folate antagonist-treated CL1-0 cells were evaluated. SLUG knockdown prevented SLUG/NF-κB/SOX9-mediated invasiveness and erlotinib resistance acquisition and significantly reduced pemetrexed-induced gelatinase activity and MMP gene expression. To summarize, our data reveal two unprecedented adverse effects of folate metabolism disruption in NSCLC cells. Thus, the folic acid status of patients with NSCLC under treatment can considerably influence their prognosis.


PROBLEMS WITH "SOFT" POLYTOMIES.
Abstract- The "soft" assumption attributes polytomies to lack of data, not simultaneous cladogenesis (the "hard" assumption). Most systematists prefer the first interpretation, but most parsimony programs implicitly use the second. Results can thus be inconsistent with initial assumptions. Under certain circumstances that seem especially typical for large data sets treating higher taxa, it may be valid to eliminate both compatible and incompatible polytomous trees from consideration. Consistent treatment of soft polytomies can reduce the ambiguity of cladistic solutions and improve the resolution, and testability, of phylogenetic hypotheses.


Industrial hygiene survey in a university art department.
Analysis of air samples indicated that concentrations of respirable free silica from sandblasting equipment used inside an unventilated painting room greatly exceeded the current OSHA standard and NIOSH recommended criteria. Lack of ventilation in the design materials studio resulted in excessive wood dust concentrations; levels averaged 29 mg/m3 which was well above the evaluation criteria of 5 mg/m3. Noise levels measured in the woodworking area of the design materials studio, and near the melting furnace located in the foundry of the ceramics studio, exceeded the 100-dBA limit recommended by NIOSH for a 2 hr continuous exposure. Lack of proper ventilation in the design materials painting room and in the printmaking darkroom resulted in exposures to toxic concentrations of toluene (from spray painting) and methyl cellosolve acetate (from KPR photo etching chemicals). Results of atmospheric sampling indicate that exposure to wood dust, crystalline silica, methyl cellosolve acetate, and toluene were excessive, and capable of producing both acute and long term health effects.


Combining spatial and scale-space techniques for edge detection to provide a spatially adaptive wavelet-based noise filtering algorithm.
New methods for detecting edges in an image using spatial and scale-space domains are proposed. A priori knowledge about geometrical characteristics of edges is used to assign a probability factor to the chance of any pixel being on an edge. An improved double thresholding technique is introduced for spatial domain filtering. Probabilities that pixels belong to a given edge are assigned based on pixel similarity across gradient amplitudes, gradient phases and edge connectivity. The scale-space approach uses dynamic range compression to allow wavelet correlation over a wider range of scales. A probabilistic formulation is used to combine the results obtained from filtering in each domain to provide a final edge probability image which has the advantages of both spatial and scale-space domain methods. Decomposing this edge probability image with the same wavelet as the original image permits the generation of adaptive filters that can recognize the characteristics of the edges in all wavelet detail and approximation images regardless of scale. These matched filters permit significant reduction in image noise without contributing to edge distortion. The spatially adaptive wavelet noise-filtering algorithm is qualitatively and quantitatively compared to a frequency domain and two wavelet based noise suppression algorithms using both natural and computer generated noisy images.


Uniform growth of high-quality oxide thin films on graphene using a CdSe quantum dot array seeding layer.
Graphene displays outstanding properties as an electrode and a semiconducting channel material for transistors; however, the weak interfacial bond between graphene and an inorganic oxide material-based insulator presents a major constraint on these applications. Here, we report a new approach to improving the interface between the two materials using a CdSe quantum dot (QD)-based seeding layer in an inorganic material-graphene junction. CdSe QDs were electrochemically grown on graphene without degrading the properties of the graphene layer. The graphene structure was then used as the electrode in an oxide semiconductor by depositing a zinc oxide thin film onto the graphene coated with a QD seed layer (QD/G). The zinc oxide film adhered strongly to the graphene layer and provided a low contact resistance. A high-k dielectric layer in the form of an HfO2 film, which is an essential element in the fabrication of high-performance graphene-based field effect transistors, was also uniformly formed on the QD/G sheet using atomic layer deposition. The resulting transistors provided a relatively good performance, yielding hole and electron mobilities of 2600 and 2000 cm(2)/V·s.


Effects of Cardiovascular Fitness and Body Composition on Maximal Core Temperature in Collegiate Football Players During Preseason.
McClelland, JM, Godek, SF, Chlad, PS, Feairheller, DL, and Morrison, KE. Effects of cardiovascular fitness and body composition on maximal core temperature in collegiate football players during preseason. J Strength Cond Res 32(6): 1662-1670, 2018-This study evaluated the effects of body mass index (BMI) and aerobic fitness (V[Combining Dot Above]O2max) on maximal core temperature values (Tcmax) in 17 National Collegiate Athletic Association Division III football players during preseason. The subjects included 9 backs (BKs) and 8 linemen (LM). V[Combining Dot Above]O2max testing was performed 1 week before preseason. Core temperature was monitored by ingestible sensor every 10 minutes during practices on day 4 (D1), day 5 (D2), day 7 (D3), and postacclimatization on day 14 (D4). Wet bulb globe temperature (WBGT) was recorded on each collection day. Independent, paired t-tests and Pearson's correlations were performed (α = 0.05). There were no significant correlations between V[Combining Dot Above]O2max and Tcmax on D1 (WBGT = 29.07° C) or D2 (WBGT = 30.93° C), but on D3 (WBGT = 31.39° C) there was a nonsignificant moderate negative correlation (r = -0.564, p = 0.090). There were no significant correlations between BMI and Tcmax on D1 or D2, but on D3 there was a nonsignificant moderate positive correlation (r = 0.596, p = 0.069). Paired t-tests revealed that overall Tcmax (D1-3) (38.56 ± 0.32° C) was statistically higher (p = 0.002) than D4 (38.16 ± 0.30° C). Independent t-tests between groups showed that the Tcmax values during preacclimatization (D1-D3) were significantly higher in LM (38.50 ± 0.37° C) than BKs (38.16 ± 0.35° C) (p = 0.007). V[Combining Dot Above]O2max was significantly lower (p = 0.006) in LM (36.89 ± 6.40 ml·kg·min) than BKs (47.44 ± 7.09 ml·kg·min), and BMI was significantly higher (p = 0.019) in LM (35.59 ± 4.00 kg·m) than BKs (28.68 ± 3.38 kg·m). The results of this study demonstrate that LM are significantly less fit than BKs and have a greater BMI. When WBGT was the highest on D3, the results suggest that those with lower V[Combining Dot Above]O2max and higher BMI experienced a higher Tcmax.


Disease trajectories in older adults with non-AD pathologic change and comparison with Alzheimer's disease pathophysiology: A longitudinal study.
Based on the 'AT(N)' system, individuals with normal amyloid biomarkers but abnormal tauopathy or neurodegeneration biomarkers are classified as non-Alzheimer's disease (AD) pathologic change. This study aimed to assess the long-term clinical and cognitive trajectories of individuals with non-AD pathologic change among older adults without dementia, comparing them to those with normal AD biomarkers and AD pathophysiology. Analyzing Alzheimer's Disease Neuroimaging Initiative data, we evaluated clinical outcomes and conversion risk longitudinally using mixed effects models and multivariate Cox proportional hazard models. We found that compared to individuals with A-T-N-, those with abnormal tauopathy or neurodegeneration biomarkers (A-T + N-, A-T-N + , and A-T + N + ) had a faster rate of cognitive decline and disease progression. Individuals with A-T + N + had a faster rate of decline than those with A-T + N-. Additionally, in individuals with the same baseline tauopathy and neurodegeneration biomarker status, the presence of baseline amyloid could accelerate cognitive decline and clinical progression. These findings provide a foundation for future studies on non-AD pathologic change and its comparison with AD pathophysiology.


Amiodarone and its desethyl metabolite: tissue distribution and morphologic changes during long-term therapy.
The pharmacokinetic characteristics of amiodarone suggest extensive tissue deposition. We confirmed this by measuring tissue concentrations of the drug and of its major metabolite, desethylamiodarone, in human tissues. These were obtained at autopsy (n = 9), surgery (n = 7), or biopsy (n = 2) from 18 patients who had been treated with amiodarone for varying periods of time. High concentrations of amiodarone were found in fat (316 mg/kg wet weight in autopsy specimens, 344 mg/kg wet weight in biopsy specimens). Amiodarone and desethylamiodarone concentrations (mg/kg wet weight, autopsy samples) were also high in liver (391 and 2354), lung (198 and 952), adrenal gland (137 and 437), testis (89 and 470), and lymph node (83 and 316). We also found high concentrations of amiodarone (306 mg/kg wet weight) and desethylamiodarone (943 mg/kg wet weight) in abnormally pigmented ("blue") skin from patients with amiodarone-induced skin pigmentation. These values were 10-fold higher than those in unpigmented skin from the same patients. These high concentrations were associated with lysosomal inclusion bodies in dermal macrophages in the pigmented skin. The inclusion bodies were intrinsically electron dense and were shown to contain iodine by energy dispersive x-ray microanalysis. Lysosomal inclusion bodies shown by electron microscopy to be multilamellar were seen in other tissues. These tissues included terminal nerve fibers in pigmented skin, pulmonary macrophages, blood neutrophils, and hepatocytes and Kupffer cells. These characteristic ultrastructural findings occur in both genetic lipidoses and lipidoses induced by other drugs, e.g., perhexiline. We conclude that during therapy with amiodarone, widespread deposition of amiodarone and desethylamiodarone occurs. This leads to ultrastructural changes typical of a lipidosis. These changes are seen clearly in tissues associated with the unwanted effects of amiodarone, e.g., skin, liver and lung.


Interleukin-6 CpG Methylation and Body Weight Correlate Differently in Type 2 Diabetes Patients Compared to Obese and Lean Controls.
Diabetes mellitus type 2 (DMT2) is accompanied by systemic low-grade inflammation with elevated levels of interleukin-6 (IL-6), which is encoded by a gene (IL-6) previously shown to be regulated by DNA methylation. We investigated seven CpG sites in IL-6 in individuals with DMT2, obese individuals and lean controls. Further, the DMT2 group received the glucagon-like peptide 1 agonist liraglutide. Blood samples were taken at the beginning of the study and after 4 months. The DNA methylation was assessed using pyrosequencing. Methylation levels at the CpG sites -664, -628 and +13 at the first sampling time point (T1) and at -666 and -664 at the second sampling time point (T2) correlated negatively with initial body weight in the DMT2 group. We found positive correlations for the obese and the lean control group. In the obese group, CpG +27 methylation at T1 correlated with initial body weight (r = 0.685; p = 0.014). In the lean group, CpG -664 at T1 (r = 0.874; p = 0.005) and CpG -628 at T2 (r = 0.632; p = 0.050) correlated with initial body weight. These findings are an informative basis for further studies to elucidate epigenetic mechanisms underlying DMT2. Additionally, our results might provide starting points for the development of biomarkers for prevention and therapy strategies.


The Effects of a Comprehensive Care Management Program on Readmission Rates After Acute Exacerbation of COPD at a Community-Based Academic Hospital.
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is one of the leading causes of hospitalization in the United States. Prior investigations suggest clinical and physiological parameters are important determinants for AECOPD readmissions. Strategies aimed at addressing these factors have not resulted in a major reduction of readmissions. We compared patients readmitted after an index AECOPD admission with non-readmitted patients. Patients' age, gender, body mass index, comorbidities (obstructive sleep apnea, chronic hypercapnia, congestive heart failure, lung cancer, pulmonary arterial hypertension, pneumonia, interstitial lung disease, atrial fibrillation, musculoskeletal disorders, cognitive disorders, and anxiety disorders), substance abuse and smoking status were assessed. Some 272 patients were included: 20 patients were readmitted within 30 days of their index hospitalization; 252 patients were not readmitted within 30 days of their index admission. Readmitted patients were significantly more likely to have pneumonia than non-readmitted patients (30.0% versus 13.1%, p<0.05). No statistically significant difference was seen with respect to other clinical comorbidities. Patients readmitted within 30 days were significantly more likely than non-readmitted patients to have safety issues at home (80.0% versus. 39.3%, p<0.001), anxiety (60.0% versus 29.8%, p<0.01), and lack of transportation (35.0% versus 15.5%, p<0.05). Implementation of a comprehensive care management program (CCMP) was associated with a reduction in readmissions from 21.5% to 13.6% (p<0.01, 95% confidence interval [CI] 2.08-12.45). A CCMP can reduce readmissions through attention to social variables, optimization of in-hospital care, improved coordination of pre- and post-discharge, a system to better identify problems after discharge, and an office setup that accommodates same-day visits.


Comparison of amino terminal region of three isoenzymes of phospholipases A2 (TFV PL-Ia, TFV PL-Ib, TFV PL-X) from Trimeresurus flavoviridis (habu snake) venom and the complete amino acid sequence of the basic phospholipase, TFV PL-X.
Three phospholipases (PLA2s) isolated from Japanese habu snake (Trimeresurus flavoviridis) venom differ from each other in the physiological symptoms induced in animals. The amino acid compositions and amino terminal sequences of these isoenzymes have been compared. TFV PL-Ia and TFV PL-Ib resemble each other very closely, but TFV PL-X has a distinctly different amino acid composition and amino terminal region. The complete amino acid sequence of the basic PLA2, TFV PL-X, was determined by sequencing the four peptides obtained by the cleavage of Asp-Pro bonds. The overlapping peptide was obtained by cleaving tryptophanyl bond and the carboxy terminal region was determined by sequencing the chymotryptic peptide. TFV PL-X consisted of a single chain of 122 amino acid residues, including 14 half-cystine residues. It is a group II A PLA2 and is homologous with the phospholipase super family. However, it has a distinctly different sequence compared with the other PLA2s from the venom of Trimeresurus species.


The C-terminal region of serotonin transporter is important for its trafficking and glycosylation.
We investigated the effects of brefeldin A and ilimaquinone, inhibitors of membrane trafficking, using serotonin transporter (SERT)-expressing COS-7 cells. Both drugs significantly inhibited the serotonin uptake activity of SERT and caused SERT to be retained in the endoplasmic reticulum (ER), indicating that membrane trafficking is an important factor for SERT functional regulation. In agreement with previous reports, a C-terminal-deletion mutant of SERT (SERTDeltaCT) mostly localized to the ER and completely lacked serotonin uptake activity. To further elucidate the role of the C-terminus of SERT, we investigated whether overexpression of FLAG-tagged SERT C-terminus (FLAG-SERT-CT) affected the serotonin uptake activity and glycosylation of SERT. Interestingly, when concomitantly expressed with full-length FLAG-SERT in COS-7 cells, FLAG-SERT-CT increased the serotonin uptake activity and mature glycosylation of FLAG-SERT. These results indicate that the C-terminal region of SERT plays a crucial role in the functional regulation of SERT via membrane trafficking and glycosylation. In addition, proteasome inhibitors induced apparent ER stress, significantly decreased the serotonin uptake activity and mature glycosylation of SERT and caused SERT to be localized to the ER, suggesting that SERT function would be attenuated via membrane trafficking in pathological states that trigger ER stress.


A human case of Clinostomum complanatum infection in Korea.
A 33-year-old Korean man visited a medical clinic with complaints of throat discomfort and pain for one week. The symptoms occurred one day after eating raw brackish water fish, perch. Endoscopy revealed a fluke, about 5 mm in length, attaching to and peristaltically moving on the surface of the mucosa at the arytenoid region of the larynx. Microscopically, the testes were triangular, tandem, and separated by the uterus. The ovary and cirrus pouch were placed apart from median line between testes. Numerous blood cells were observed in the ceca. The worm was identified to be Clinostomum complanatum. This is the second human case of clinostomiasis in Korea.


Supramolecular ssDNA templated porphyrin and metalloporphyrin nanoassemblies with tunable helicity.
Free-base and nickel porphyrin-diaminopurine conjugates were formed by hydrogen-bond directed assembly on single-stranded oligothymidine templates of different lengths into helical multiporphyrin nanoassemblies with highly modular structural and chiroptical properties. Large red-shifts of the Soret band in the UV/Vis spectroscopy confirmed strong electronic coupling among assembled porphyrin-diaminopurine units. Slow annealing rates yielded preferentially right-handed nanostructures, whereas fast annealing yielded left-handed nanostructures. Time-dependent DFT simulations of UV/Vis and CD spectra for model porphyrin clusters templated on the canonical B-DNA and its enantiomeric form, were employed to confirm the origin of observed chiroptical properties and to assign the helicity of porphyrin nanoassemblies. Molar CD and CD anisotropy g factors of dialyzed templated porphyrin nanoassemblies showed very high chiroptical anisotropy. The DNA-templated porphyrin nanoassemblies displayed high thermal and pH stability. The structure and handedness of all assemblies was preserved at temperatures up to +85 °C and pH between 3 and 12. High-resolution transition electron microscopy confirmed formation of DNA-templated nickel(II) porphyrin nanoassemblies and their self-assembly into helical fibrils with micrometer lengths.


Geomagnetic Intensity: Changes during the Past 3000 Years in the Western Hemisphere.
A series of archeomagnetic measurements have been carried out on archeologic materials from Arizona and Mexico which can be compared with results from Europe and Asia. This comparison shows a westward drift of geomagnetic intensity at a rate of about 0.24 degree per year. Furthermore, an apparent coincidence between changes in the earth's magnetic moment and changes in the production rate of radiocarbon is observed.


A Prospective, Median 15-Year Comparison of Ponseti Casting and Surgical Treatment of Clubfoot.
In 2010, 2 authors of this current study reported the results of Ponseti treatment compared with primary posteromedial release (PMR) for congenital talipes equinovarus in a cohort of 51 prospective patients. This current study shows outcomes recorded at a median of 15 years after the original treatment. Patient health records were available for all 51 patients at a median of 15 years (range, 13 to 17 years) following treatment of congenital talipes equinovarus with either the Ponseti method (25 patients [38 feet]) or PMR (26 patients [42 feet]). Thirty-eight of 51 patients could be contacted, and 33 patients (65%) participated in the clinical review, comprising patient-reported outcomes, clinical examination, 3-dimensional gait analysis, and plantar pressures. Sixteen (42%) of 38 Ponseti-treated feet and 20 (48%) of 42 PMR-treated feet had undergone a further surgical procedure. The PMR-treated feet were more likely to undergo osteotomies and intra-articular surgical procedures (15 feet) than the Ponseti-treated feet (5 feet) (p < 0.05). Of the 33 patients reviewed with multimodal assessment, the Ponseti group, compared with the PMR group, demonstrated better Dimeglio scores (5.8 compared with 7.0 points; p < 0.05), Disease Specific Instrument (80.7 compared with 65.6 points; p < 0.05), Functional Disability Inventory (1.1 compared with 5.1; p < 0.05), and American Academy of Orthopaedic Surgeons (AAOS) Foot and Ankle Outcomes Questionnaire scores (52.2 compared with 46.6 points; p < 0.05), as well as improved total sagittal ankle range of motion in gait and ankle plantar flexion range at toe-off. The PMR group with clinical hindfoot varus displayed higher pressures in the lateral midfoot and the forefoot. Although the numbers of repeat surgical interventions following Ponseti treatment and primary PMR were similar, the PMR-treated feet had greater numbers of osteotomies and intra-articular surgical procedures. Functional outcomes were improved at a median of 15 years for feet treated with the Ponseti method compared with feet treated with PMR, with advantages seen in the Ponseti group over several domains. This study provides the most comprehensive evaluation of outcomes close to skeletal maturity in prospective cohorts, reinforcing the Ponseti method as the initial treatment of choice for idiopathic clubfeet. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.


Mother-infant interactions with infants with congenital visual impairment and associations with longitudinal outcomes in cognition and language.
This study investigated mother-infant interactions, including maternal maintaining of infant attentional focus and sensitivity, with infants with congenital severe and profound visual impairment (VI) and the association with developmental trajectories from one to three years. Fifty-five infants and mothers were video-recorded playing together with a standard set of toys at Time 1 (T1) mean age 12.95 months (8.13-17.05 months). Maintain was categorized as the mother following and maintaining the child's focus, and Sensitivity, the mother's responsiveness and contingency to infant behaviour. Vision level was measured using the Near Detection Scale. Cognition and language were measured at T1, 12 months later (T2) and 24 months later (T3) using the Reynell-Zinkin Scales. Cross-sectional analyses showed that mothers of infants with severe VI (basic form vision) produced higher rates of Maintain compared to those with children with profound VI (light perception at best). Linear mixed-effects models examining developmental progression from T1 to T3 (controlling for vision level) showed an average increase of 5 DQ points (CI 95%: 1.03-9.08) in verbal comprehension for higher Sensitivity. No significant findings were found for Maintain. The findings suggest that mother-infant interactions (maternal Maintain) are associated with level of vision at infancy, but only maternal Sensitivity has a long-term positive association with advances in verbal comprehension from infancy to about three years. They highlight the need for incorporating strategies related to parent-infant interactions, including increased sensitivity, into early intervention for children with visual impairment.


Sugammadex, the Guardian of Deep Muscle Relaxation During Conventional and Robot-Assisted Laparoscopic Surgery: A Narrative Review.
High intra-abdominal pressure induced by artificial pneumoperitoneum can obviously impair respiratory and circulatory functions and has a negative effect on the prognosis of patients undergoing conventional and robot-assisted laparoscopic surgery. The application of deep neuromuscular blockade during the operation is reported to lower the intra-abdominal pressure and improve patients' outcome. However, concern lies in the risks of postoperative residual muscular paralysis with the use of deep neuromuscular blockade. Sugammadex, a specific antagonist for aminosteroids muscle relaxants, can effectively and rapidly reverse rocuronium and vecuronium induced neuromuscular blockade of different depths. Thus, sugammadex allows the ability to safeguard the application of deep neuromuscular blockade in laparoscopic operations and helps to alleviate the adverse complications associated with pneumoperitoneum. Here, we review the application of deep neuromuscular blockade in different laparoscopic surgeries and discuss the benefits and possible risks of sugammadex administration in the reversal of deep neuromuscular blockade in these operations.


Distinct effects of testosterone on plasma and cerebrospinal fluid amyloid-beta levels.
The effect of testosterone on the levels of the Alzheimer's disease amyloid-beta peptide (Abeta) was investigated in guinea pigs. Castrated guinea pigs (GPX) were administered testosterone at two different dosages, following which plasma and cerebrospinal fluid (CSF) Abeta_{40} levels were measured. Plasma Abeta_{40} levels were reduced in GPX in the early stages of low-dose testosterone treatment, whereas CSF Abeta_{40} levels were only reduced by the time circulating testosterone had returned to untreated GPX levels. The supraphysiological testosterone dose did not reduce CSF Abeta_{40} levels significantly until circulating testosterone was back to uncastrated levels, whereas plasma Abeta_{40} levels significantly increased over time in these animals. These results indicate that the extent of testosterone-induced changes to Abeta_{40} levels and their response rates depend on both the tissue examined and testosterone dosage.


Functional Deficits in the Less-Impaired Arm of Stroke Survivors Depend on Hemisphere of Damage and Extent of Paretic Arm Impairment.
Background. Previous research has detailed the hemisphere dependence and specific kinematic deficits observed for the less-affected arm of patients with unilateral stroke. Objective. We now examine whether functional motor deficits in the less-affected arm, measured by standardized clinical measures of motor function, also depend on the hemisphere that was damaged and on the severity of contralesional impairment. Methods. We recruited 48 left-hemisphere-damaged (LHD) participants, 62 right-hemisphere-damaged participants, and 54 age-matched control participants. Measures of motor function included the following: (1) Jebsen-Taylor Hand Function Test (JHFT), (2) Grooved Pegboard Test (GPT), and (3) grip strength. We measured the extent of contralesional arm impairment with the upper-extremity component of the Fugl-Meyer (UEFM) assessment of motor impairment. Results. Ipsilesional limb functional performance deficits (JHFT) varied with both the damaged hemisphere and severity of contralesional arm impairment, with the most severe deficits expressed in LHD participants with severe contralesional impairment (UEFM). GPT and grip strength varied with severity of contralesional impairment but not with hemisphere. Conclusions. Stroke survivors with the most severe paretic arm impairment, who must rely on their ipsilesional arm for performing daily activities, have the greatest motor deficit in the less-affected arm. We recommend remediation of this arm to improve functional independence in this group of stroke patients.