Characterization of Atp1a3 mutant mice as a model of rapid-onset dystonia with parkinsonism.
Rapid-onset dystonia with parkinsonism (RDP) or DYT12 dystonia is a rare form of primary, generalized dystonia. Patients do not present with any symptoms until triggered by a physiological stressor. Within days, patients will show both dystonia and parkinsonism. Mutations resulting in a loss of function in the ATP1A3 gene have been identified as the cause of RDP. ATP1A3 encodes the α3 subunit of the Na(+)/K(+)-ATPase, which is exclusively expressed in neurons and cardiac cells. We have previously created a line of mice harboring a point mutation of the Atp1a3 gene (mouse homolog of the human ATP1A3 gene) that results in a loss of function of the α3 subunit. The Atp1a3 mutant mice showed hyperactivity, spatial learning and memory deficits, and increased locomotion induced by methamphetamine. However, the full spectrum of the motor phenotype has not been characterized in the mutant mice and it is not known whether triggers such as restraint stress affect the motor phenotype. Here, we characterized the motor phenotype in normal heterozygous Atp1a3 mutant mice and heterozygous Atp1a3 mutant mice that have been exposed to a restraint stress. We found that this type of trigger induced significant deficits in motor coordination and balance in the mutant mice, characteristic of other genotypic dystonia mouse models. Furthermore, stressed mutant mice also had a decreased thermal sensitivity and alterations in monoamine metabolism. These results suggest that the Atp1a3 mutant mouse models several characteristics of RDP and further analysis of this mouse model will provide great insight into pathogenesis of RDP.


General Synthesis of Secondary Alkylamines by Reductive Alkylation of Nitriles by Aldehydes and Ketones.
The development of C-N bond formation reactions is highly desirable due to their importance in biology and chemistry. Recent progress in 3d metal catalysis is indicative of unique selectivity patterns that may permit solving challenges of chemical synthesis. We report here on a catalytic C-N bond formation reaction-the reductive alkylation of nitriles. Aldehydes or ketones and nitriles, all abundantly available and low-cost starting materials, undergo a reductive coupling to form secondary alkylamines and inexpensive hydrogen is used as the reducing agent. The reaction has a very broad scope and many functional groups, including hydrogenation-sensitive examples, are tolerated. We developed a novel cobalt catalyst, which is nanostructured, reusable, and easy to handle. The key seems the earth-abundant metal in combination with a porous support material, N-doped SiC, synthesized from acrylonitrile and a commercially available polycarbosilane.


Branch retinal artery occlusion associated with directional coronary atherectomy after percutaneous transluminal coronary angioplasty.
To report a case of branch retinal artery occlusion after atherectomy. A 51-year-old man complained of visual loss in the right eye after directional coronary atherectomy, performed secondary to a complicated percutaneous transluminal coronary angioplasty. He underwent a full ophthalmologic examination, including fluorescein angiography and Doppler ultrasound. Visual Acuity was 20/30 with an inferior scotoma present in the right eye. There were three Hollenhorst plaques present inside the superotemporal vascular arcade. There is a small but definite risk of retinal microinfarctions after atherectomy.


Dataset on the antecedents of career adaptability among undergraduate students in Malaysia.
This data was obtained from a cross-sectional survey of 188 final year Bachelor of Business Administration (BBA) students in a Malaysian Public University. The survey was self-administered to final year BBA students undergoing seminar course prior to the commencement of their industrial training in the coming semester. A regression analysis was conducted in order to assess the link between students' self-esteem, pro-active personality, and social support with their career adaptability using the Statistical Package of the Social Sciences (SPSS) 20. Specifically, this data article provides data about the participants' demographic characteristics, as well as the mean, standard deviation and reliability of the measured constructs. It is believed by the authors that the dataset will guide policy makers on the choice of predictor(s) that could boost the level of students' career adaptability, most especially during the school to work transition, in this current volatile labour market.


Inter- and intragranular delta phase quantitative characterization in Inconel 718 by means of image analysis.
This paper describes an image processing method for discriminating the inter- and intragranular delta phase precipitates in Inconel 718 (IN 718). The successive practical operations and the motivations of their choices are presented in detail. The method was applied to IN 718 specimens heat treated with different parameters to produce microstructures containing various amounts of both types of precipitates. They were characterized by electron microscopy in backscattered electron imaging. The main difficulty arose from the fact that the brightness distributions of inter- and intragranular precipitates partially overlap. Additional information on their morphology and their spatial distribution had to be exploited in order to differentiate them. The shape and the orientation of the precipitates were evaluated using the structure tensor, an operator that quantifies the directionality of the intensity distribution in an image. The distance between parallel precipitates was also used as an additional property to identify clusters of intragranular precipitates.


Gender differences in patterns of spatial ability, environmental cognition, and math and English achievement in late adolescence.
Relationships were explored among three measures of spatial ability--the Embedded Figures Test (EFT), the Mental Rotations Test (MRT), and the Differential Aptitude Spatial Relations subtest (DAT)--an environmental cognition task (MAP), American College Testing (ACT) math and English achievement, and gender in a sample of 282 undergraduates. Variance attributable to gender among the spatial tasks ranged from 0.5% in the EFT to 12% in the MRT. Gender accounted for only 1% of the variance in the MAP task. Gender differences were noted in regression analyses; women's math and English achievement scores were both predictive of spatial ability, while for men, only math achievement was predictive of spatial ability. The results were interpreted as substantiating sex role socialization theory of cognitive abilities.


NK-1, but not NK-2, tachykinin receptors mediate plasma extravasation induced by antidromic C-fiber stimulation in rat hindpaw: demonstrated with the NK-1 antagonist CP-96,345 and the NK-2 antagonist Men 10207.
The effects of intradermal injection of CP-96,345 and Men 10207, selective antagonists for NK-1 and NK-2 tachykinin receptors, respectively, on the extravasation of plasma protein induced by antidromic stimulation of unmyelinated sensory fibers in the sciatic nerve was studied in rat hindpaw. Activation of unmyelinated fibers by antidromic sciatic nerve stimulation (1 Hz, 5 min) consistently evoked a localized plasma extravasation of Evans blue on the skin area of the hindpaw innervated by the sciatic nerve, which was not inhibited by intradermal injection of saline or Men 10207 (9 and 35 nmol). In contrast, CP-96,345 (3 and 9 nmol, but not 1 nmol), injected intradermally 15 min prior to nerve stimulation dose-dependently inhibited this response. Plasma extravasation induced by intravenously injected substance P was also inhibited by CP-96,345. Since CP-96,345 is a highly selective antagonist for NK-1 tachykinin receptors, it is suggested that the plasma extravasation induced by antidromic C-fiber stimulation and by systemically applied tachykinins is mediated by NK-1 tachykinin receptors.


Non-monotonic dose-response effect of bisphenol A on rare minnow Gobiocypris rarus ovarian development.
Bisphenol A (BPA) is widely spread in the environment, and can cause various reproductive disrupting effects on different organisms, including fish. Our previous published study showed that BPA has non-monotonic (inverted U-shaped) dose-response effect on rare minnow Gobiocypris rarus ovarian weight at different concentrations. To investigate the potential mechanism, we exposed female rare minnow to 1, 15 and 225 µg L(-1) BPA for 7 days in the present study. The levels of vitellogenin (Vtg), sex hormones, hydrogen peroxide (H2O2), glutathione (GSH) and triglyceride (TG) were measured. RNA-seq of ovary tissues was also performed. Result showed that Vtg, sex hormone and TG levels showed an inverted U-shaped increased response, while H2O2 and GSH levels showed a U-shaped inhibited response. RNA-seq data showed that many genes involved in lipid metabolism, oxidative stress, and proteolysis processes were altered. The change of Vtg, H2O2, GSH and TG levels was possibly related to the altered sex hormone levels. Sex hormone's direct effect, Vtg accumulation, TG accumulation and oxidative stress induced proteolysis may contribute to the change of ovary weight.


Circ_0000235 targets MCT4 to promote glycolysis and progression of bladder cancer by sponging miR-330-5p.
Warburg effect plays a crucial role in bladder cancer (Bca) development. However, the mechanism by which glycolysis is involved in Bca remains poorly understood. CircRNAs commonly play a regulatory role in tumor progression. Our study discovered and identified a novel circRNA, hsa_circ_0000235 (circ235), and investigated its role in the glycolytic process, which further results in the progression of Bca. We applied qRT-PCR to assess its clinicopathological relevance and evaluated its proliferation, migration, and glycolytic capacity. We investigated its mechanism using RNA immunoprecipitation, dual-luciferase reporters, and fluorescence in situ hybridization. The findings demonstrated that circ235 was dramatically increased in Bca tissues and was related to a worse prognosis. In vitro studies revealed that circ235 accelerated the rate of extracellular acidification and promoted glucose uptake and lactate manufacture in Bca cells. Additionally, it strengthened the proliferative and migratory capacities. Experiments on animals revealed that downregulating circ235 dramatically reduced carcinogenesis and tumor growth. Circ235 activates monocarboxylate transporter 4 (MCT4) by sponging miR-330-5p, which promotes glycolysis and tumor growth. In conclusion, these findings suggest that circ235 may be a viable molecular marker and therapeutic target for Bca.


Antiviral peptides against SARS-CoV-2: therapeutic targets, mechanistic antiviral activity, and efficient delivery.
The global pandemic of COVID-19 is a serious public health concern. Over 625 million confirmed cases and more than 6 million deaths have been recorded worldwide. Although several vaccines and antiviral medications have been developed, their efficacy is limited by the emerging new SARS-CoV-2 strains. Peptide-based therapeutics is a fast-growing class of new drugs and have unique advantages over large proteins and small molecules. Antiviral peptides (AVPs) are short polycationic antivirals with broad-spectrum effects, which have been shown to exert both prophylactic and therapeutic actions against reported coronaviruses. The potential therapeutic targets of AVPs are located either on the virus (e.g., E-protein and S-protein) to prohibit viral binding or host cells, particularly, those present on the cell surface (e.g., ACE2 and TMPRSS2). Despite AVPs having promising antiviral effects, their efficacy is limited by low bioavailability. Thus, nanoformulation is a prerequisite for prolonged bioavailability and efficient delivery. This review aimed to present an insight into the therapeutic AVP targets on both virus and host cells by discussing their antiviral activities and associated molecular mechanisms. Besides, it described the technique for discovering and developing possible AVPs based on their targets, as well as the significance of using nanotechnology for their efficient delivery against SARS-CoV-2.


Pre-conceptional and prenatal exposure to pesticides and pediatric neuroblastoma. A meta-analysis of nine studies.
Neuroblastoma is primarily an embryonal tumor of infancy. Recently, some toxicological agents used as pesticides have been associated with an increased incidence of this tumor. We intended to determine the potential association between prenatal exposure to pesticides and the incidence of neuroblastoma in children. Studies targeting the link between neuroblastoma and pesticides were searched in PUBMED, SCOPUS, and Google Scholar from January 1, 1960, through December 2020. We performed a PRISMA-based systematic review and meta-analysis. In addition, we took into consideration the IARC evaluation on pesticides issued in recent monographs. Prenatal pesticide exposure is associated with an increased risk of neuroblastoma with an OR of 1.6 (1.1-2.3; p = 0.013), while the OR is 1.0 (0.8-1.3; p = 0.723) for pesticide exposure after birth. There is a significant association between prenatal pesticide exposure and neuroblastoma. We emphasize the IARC conclusions evaluating the carcinogenicity of diazinon, glyphosate, malathion, parathion, and tetrachlorvinphos.


Prevalence, characteristics, and mortality of patients with transthyretin amyloid cardiomyopathy in the Nordic countries.
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive condition caused by deposition of transthyretin amyloid fibrils in the heart and is associated with poor quality of life and a shortened lifespan. This study aimed to describe the prevalence, clinical characteristics, and mortality of patients with ATTR-CM, using multiple national health registers in Denmark, Finland, Norway, and Sweden. Transthyretin amyloid cardiomyopathy patients were identified during 2008-2018 using a combination of diagnosis codes for amyloidosis and heart disease and were matched to patients with non-ATTR heart failure (HF). An identical study design was used in each country to facilitate comparison and aggregation of results. A total of 1930 ATTR-CM patients were identified from national health registers in the four countries. In 2018, prevalence of ATTR-CM per 100 000 inhabitants ranged from 1.4 in Denmark to 5.0 in Sweden; a steep increase over time was observed in Sweden and Norway. Median survival from diagnosis was 30 months for ATTR-CM patients and 67 months for matched HF patients. Survival was significantly lower for female than for male ATTR-CM patients (median survival: 22 and 36 months), while no significant difference was observed in the HF cohort. This study provides the first nationwide estimates of the prevalence, clinical characteristics, and mortality of patients with ATTR-CM, using identical study design across several countries. Findings corroborate previous case series showing high mortality in ATTR-CM, two-fold higher than for other HF patients and higher in women than men, highlighting the need for more precise and early diagnosis to reduce the disease burden.


Phosphohistidine and phospholysine phosphatase activities in the rat: potential protein-lysine and protein-histidine phosphatases?
We have detected phosphohistidine and phospholysine phosphatase activities in rat tissue extracts using partially phosphorylated, high-molecular-mass (> 10 kDa) polymers of histidine and lysine as substrates. Multiple phosphohistidine- and phospholysine-specific phosphatases were present in these extracts based on observed differences in heat stability, sensitivity to bivalent metal ions and thiol modifying reagents, and/or elution from DE-52 cellulose. The properties of these phosphohistidine and phospholysine phosphatases were distinct from those of the phosphomonoester-specific protein phosphatases or the N-P phosphohydrolases that act on the free phosphoamino acids phosphoarginine, 3-phosphohistidine or phospholysine.


The influence of a fall fumigation with ozone on the stomatal behavior of spruce and fir.
Clonal stock (grafts of 15-, 50-, and 100-year-old trees) of spruce (Picea abies (L.) Karst.) and fir (Abies alba Mill.) was exposed either to 150 ppb ozone (∼300 μgm-3) during 9 daylight hours or to carbon-filtered air on 35 days between 29 August and 21 October 1983. At the end of the fumigation the trees did not exhibit any visible signs of injury. Transpiration and leaf conductance in light and darkness, measured with a Licor porometer, revealed, however, stomatal sluggishness and - in spruce-increased transpiration.


In vitro function and in situ localization of Multidrug Resistance-associated Protein (MRP)1 (ABCC1) suggest a protective role against methyl mercury-induced oxidative stress in the human placenta.
Methyl mercury (MeHg) is an organic highly toxic compound that is transported efficiently via the human placenta. Our previous data suggest that MeHg is taken up into placental cells by amino acid transporters while mercury export from placental cells mainly involves ATP binding cassette (ABC) transporters. We hypothesized that the ABC transporter multidrug resistance-associated protein (MRP)1 (ABCC1) plays an essential role in mercury export from the human placenta. Transwell transport studies with MRP1-overexpressing Madin-Darby Canine Kidney (MDCK)II cells confirmed the function of MRP1 in polarized mercury efflux. Consistent with this, siRNA-mediated MRP1 gene knockdown in the human placental cell line HTR-8/SVneo resulted in intracellular mercury accumulation, which was associated with reduced cell viability, accompanied by increased cytotoxicity, apoptosis, and oxidative stress as determined via the glutathione (GSH) status. In addition, the many sources claiming different localization of MRP1 in the placenta required a re-evaluation of its localization in placental tissue sections by immunofluorescence microscopy using an MRP1-specific antibody that was validated in-house. Taken together, our results show that (1) MRP1 preferentially mediates apical-to-basolateral mercury transport in epithelial cells, (2) MRP1 regulates the GSH status of placental cells, (3) MRP1 function has a decisive influence on the viability of placental cells exposed to low MeHg concentrations, and (4) the in situ localization of MRP1 corresponds to mercury transport from maternal circulation to the placenta and fetus. We conclude that MRP1 protects placental cells from MeHg-induced oxidative stress by exporting the toxic metal and by maintaining the placental cells' GSH status in equilibrium.


Prostaglandin E1 and intrapulmonary shunt in cardiac surgical patients with pulmonary hypertension.
Unlike many other vasodilators, prostaglandin E1 may reduce pulmonary vascular resistance without changing intrapulmonary shunt in patients with adult respiratory distress syndrome. Whether the same is true for surgical patients with cardiogenic pulmonary hypertension but normal gas exchange remains unclear. Data from the intraoperative records of 8 patients with pulmonary hypertension and elevated pulmonary vascular resistance were used for the study. Hemodynamic variables had been monitored through radial arterial cannulas and pulmonary arterial catheters. Arterial and mixed venous oxygen tension, carbon dioxide tension, oxygen saturation, and hemoglobin level, as well as cardiac output and pulmonary capillary wedge pressure, had been determined in each patient before prostaglandin E1 infusion was started and again when the desired pulmonary vascular response had been achieved. Pulmonary and systemic vascular resistances and intrapulmonary shunt were calculated from standard formulas. Infusion rates of prostaglandin E1 ranged from 7 to 135 ng/kg/min. Prostaglandin E1 reduced mean pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary capillary wedge pressure but did not change intrapulmonary shunt. Heart rate and mean arterial and right atrial pressures were not changed, whereas systemic vascular resistance decreased and cardiac output increased. The present study shows that prostaglandin E1 reduces pulmonary arterial pressure and pulmonary vascular resistance without dramatic changes in intrapulmonary shunt in patients with pulmonary hypertension secondary to cardiac disease.


Intraoperative outflow resistance as a predictor of late patency of femoropopliteal and infrapopliteal arterial bypasses.
To evaluate the efficacy of intraoperative outflow resistance (OR) measurements in predicting late graft patency rates (PR) for femoropopliteal (FP) and femoroinfrapopliteal (FD) bypasses, we have reviewed 134 such cases performed during the past 3 years at our institution. Of these, 64 bypasses were FP (13 autogenous saphenous vein [ASV] and 51 polytetrafluoroethylene [PTFE]) and 70 were FD (43 ASV and 27 PTFE). Total and distal OR measurements (measured in millimeters of mercury per milliliter per minute) were divided into four groups each for all infrainguinal bypasses combined and for FP and FD bypasses separately. The relationship of PR to total and distal OR measurements were analyzed according to the product limit method. Overall 1- and 2-year PRs were 64% and 56%, respectively. For FP bypasses the same PRs were 78% and 67% whereas for FD bypasses, they were 52% and 45%, respectively. The 1-year PRs for FP and FD bypasses within each respective OR group were analyzed. For FP bypasses in the lowest to the highest total OR groups, the 1-year PRs were 86%, 75%, 78%, and 62% (NS), and for FD bypasses they were 72%, 89%, 23%, and 22% (p less than 0.001). Similar trends were observed when distal OR measurements were analyzed. For infrainguinal PTFE bypasses, both total and distal OR measurements were significant predictors of patency, whereas for those with ASV only distal OR measurements were predictive. These data reaffirm our early experience with OR measurements. Although a trend for predicting graft patency was noted for FP bypasses, OR measurements were highly predictive only for FD bypasses.


Epidural anesthesia in a parturient with neurofibromatosis type 2 undergoing cesarean section.
Neurofibromatosis type 2 (NF2) is a rare condition only recently recognized. We present a case describing successful regional analgesia in a parturient with NF2 after thorough imaging revealed no tumors within the epidural space. The presence of tumors within the spinal cord and nerve roots and their potential enlargement during pregnancy make routine neuraxial anesthesia hazardous in patients with NF2. Lumbosacral imaging before performing regional anesthesia is recommended.


Erythropoietin attenuates vascular calcification by inhibiting endoplasmic reticulum stress in rats with chronic kidney disease.
Previous studies suggested that endoplasmic reticulum (ER) stress induced-apoptosis promoted vascular calcification (VC). Interestingly, erythropoietin (EPO), an endogenous glycoprotein, exerts multiple tissue protective effects by inhibiting ER stress and apoptosis. We investigated the role and potential mechanism of EPO on VC in chronic kidney disease (CKD) rats and cultured vascular smooth muscle cells (VSMCs). The calcification model was established by subtotal nephrectomy in vivo or phosphate overload in vitro. The protein level of EPO receptor (EPOR) was increased in the calcified aortas of CKD rats. EPO prevented the reduction of VSMC phenotypic markers, and reversed the increased calcium content and calcium salt deposition in the aortas of CKD rats and cultured calcified VSMCs. The protein levels of activating transcription factor 4 (ATF4) and glucose-regulated protein 94 (GRP94) were upregulated in aortas and VSMCs under calcifying conditions, indicating ER stress activation. EPO treatment of CKD rats or calcified VSMCs downregulated the protein levels of ATF4 and GRP94. Furthermore, ER stress-mediated apoptosis, determined by the protein levels of CCAAT⁄enhancer-binding protein-homologous protein and cleaved caspase 12, was increased in tunicamycin or calcification media-treated VSMCs, but the increased effect was reversed in EPO-treated groups. The increased apoptotic cells in calcified VSMCs, as indicated by Hoechst staining and flow cytometry, were downregulated by the co-administration of EPO or 4-phenyl butyric acid. In conclusion, EPO might attenuate VC by inhibiting ER stress mediated apoptosis through EPOR signaling.


Changes in Health Care Spending, Use, and Clinical Outcomes After Nonfatal Firearm Injuries Among Survivors and Family Members : A Cohort Study.
Despite increasing awareness of firearm-related deaths, evidence on the clinical and economic implications of nonfatal firearm injuries is limited. To measure changes in clinical and economic outcomes after nonfatal firearm injuries among survivors and their family members. Cohort study. MarketScan Medicare and commercial claims data, 2008 to 2018. 6498 survivors of firearm injuries matched to 32 490 control participants and 12 489 family members of survivors matched to 62 445 control participants. Exposure to nonfatal firearm injury as a survivor or family member of a survivor. Changes in health care spending, use, and morbidity from preinjury through 1 year postinjury relative to control participants, on average and by type and severity of firearm injury. After nonfatal firearm injury, medical spending increased $2495 per person per month (402%) and cost sharing increased $102 per person per month (176%) among survivors relative to control participants (P < 0.001) in the first year after injury, driven by an increase in the first month of $25 554 (4122%) in spending and $1112 (1917%) in cost sharing per survivor (P < 0.001). All categories of health care use increased relative to the control group. Survivors had a 40% increase in pain diagnoses, a 51% increase in psychiatric disorders, and an 85% increase in substance use disorders after firearm injury relative to control participants (P < 0.001), accompanied by increased pain and psychiatric medications. Family members had a 12% increase in psychiatric disorders relative to their control participants (P = 0.003). These overall clinical and economic changes were driven by intentional firearm injuries and more severe firearm injuries. Precision of diagnostic codes and generalizability to other patient populations, including Medicaid and uninsured patients. In survivors, nonfatal firearm injuries led to increases in psychiatric disorders, substance use disorders, and pain diagnoses, alongside substantial increases in health care spending and use. In addition, mental health worsened among family members. National Institutes of Health.


Special considerations in bovine orthopedics and lameness.
This article discusses the features that make bovine orthopedics a unique area. Changes in methodology and design of internal fixation devices are considered, particularly as they differ in application to the different age and weight categories. Pediatric and economic considerations and the importance of client communications are reviewed in detail.


Evaluation of a telephone advice nurse in a nursing faculty managed pediatric community clinic.
Nurse-managed health centers face increasing obstacles to financial viability. Efficient use of clinic resources and timely and appropriate patient care are necessary for sustainability. A registered nurse with adequate education and support can provide high-quality triage and advice in community-based practice sites. The purpose of this program evaluation was to examine the effect of a telephone advice nurse service on parent/caregiver satisfaction and access to care. A quasi-experimental separate pre-post sample design study investigated parent/caregiver satisfaction with a telephone advice nurse in an urban pediatric nurse-managed health center. The clinic medical information system was used to retrieve client visit data prior to the service and in the first year of the program. Statistically significant differences were found on two items from the satisfaction with the advice nurse survey: the reason for calling (P < .05), and the importance of being involved in decision making (P < .05). A telephone advice nurse may increase both parent/caregiver and provider satisfaction and access to care.


Polydopamine particles as nontoxic, blood compatible, antioxidant and drug delivery materials.
Herein, the potential biomedical application of poly(3,4-dihyroxyphenyl)ethylamine, (poly(dopamine)-p(DA)) particles is reported. P(DA) particles with the size about 100 nm, 18.05 m2/g specific surface area, and mesoporous structure (7.19 nm pore width) were prepared and shown to be chemically modifiable using chlorosulfonic acid (CSA) and 3-CHloro-2 hydroxypropyl) trimethylammonium chloride solution (CHPACl) to obtain sulfonic acid and quaternary amine group containing modified p(DA) particles, m-p(DA)-CSA and m-p(DA)-CHPACl particles, respectively. The hydrolytic degradation of p(DA) particles at different pHs, including 1, 7.4 and 11, was carried out at 37.5 °C. These degradation studies revealed that p(DA) is slightly degradable at pH 1 and pH 7.4 with weight losses of 13.01 ± 0.08% and 7.26 ± 0.23% in 11 days, respectively. At pH 11, a sustained degradation that is almost linear degradation with time was observed for up to 30 days, with a total weight loss of 21.42 ± 0.88%. Furthermore, p(DA) particles were tested for cell toxicity against COS-1 cells and found non-toxic up to 50 μg/mL with 95.6 ± 4.5% cell viability as compared to 37.5 ± 0.03% for DA molecules. The p(DA) particles and DA were also compared for their ability to inhibit α-glucosidase; both inhibited α-glucosidase inhibition activity a concentration-dependent fashion: at concentrations of 500-4000 μg/mL, p(DA) provided 8.52-27.67% inhibition while DA inhibited 42.8-67.7% over the same concentration range. Furthermore, p(DA) particles were found to be blood compatible e.g., non-hemolytic with 1.87 ± 0.97% hemolysis ratio up to 50 μg/mL concentration and with 86.7% blood clotting index. Interestingly, p(DA) particle can be considered as an effective antioxidant with 33.5 ± 3.9 μg/ mL total phenol content in terms of gallic acid equivalency and 0.89 ± 0. 30 μmol/g trolox equivalent antioxidant capacity (TEAC). Finally, p(DA) particles and their modified forms, m-p(DA)-CSA, and m-p(DA)-CHPACl, were shown to be useful as active agent/drug delivery devices by using acyclovir as a model drug that can be readily loaded into particles and released at longer times at higher amounts for the modified p(DA) particles at physiological conditions.


Effect of mechanical thrombectomy with and without intravenous thrombolysis on the functional outcome of patients with different degrees of thrombus perviousness.
This study aimed to investigate the long-term functional outcome of patients with different degrees of thrombus perviousness (TP) undergoing mechanical thrombectomy alone and those undergoing combined intravenous thrombolysis (IVT) plus mechanical thrombectomy. We conducted a retrospective analysis of consecutive patients with acute ischemic stroke due to large vessel occlusion who underwent mechanical thrombectomy alone or bridging therapy between January 2016 and October 2020. TP was quantified by thrombus attenuation increase (TAI) on admission computed tomography angiography compared with non-contrast computed tomography. After dichotomization of TAI as higher or lower perviousness, Fisher exact tests were performed to estimate the associations of different therapies with favorable functional outcomes [Modified Ranking Scale score at 90 days (90-day mRS) of 0 to 2]. A total of 73 patients were included in our study. 35 (47.9%) thrombi were classified as higher-perviousness clots with TAI of ≥ 24 HU, and the other 38 thrombi were lower-perviousness clots. A favorable outcome with a 90-day mRS of 0 to 2 was observed in 32 patients. In patients with thrombi of lower perviousness, favorable outcome was more common in the bridging therapy group than in the thrombectomy-alone group (p = 0.013), whereas in patients with thrombi of higher perviousness, the long-term neurological outcome did not significantly differ between two therapy groups (p = 0.094). Patients with thrombi of lower perviousness were recommended to undergo intravenous alteplase followed by endovascular thrombectomy, and those with thrombi of higher perviousness could undergo thrombectomy alone.


Amoxapine cardiotoxicity.
Prolongation of the QRS interval, cardiopulmonary arrest, and death in a 31-year-old woman following an overdose of 2 g amoxapine, a tricyclic antidepressant, is reported. The patient's QRS interval prolonged to beyond 100 ms throughout hospitalization. Thirty-three hours after admission she suffered a bradycardiac-hypotensive event, followed by electromechanical dissociation and subsequent death. Cardiotoxicity has not been directly related to amoxapine; a 2-g acute ingestion is the lowest reported lethal dose.


Transoral lateral oropharyngectomy for squamous cell carcinoma of the tonsillar region: II. An analysis of the incidence, related variables, and consequences of local recurrence.
To determine the incidence of local and regional failure, distant metastasis, and overall survival following transoral lateral oropharyngectomy (TLO) and to determine factors associated with local recurrence. Retrospective case series throughout 20 years; mean follow-up of 10 years. Academic center. A total of 166 previously untreated patients with squamous cell carcinoma of the tonsil. A total of 131 (81.9%) of the 166 patients received preoperative induction chemotherapy. Fifty-one patients (30.7%) underwent postoperative radiation therapy. Local and regional recurrence, distant metastasis, second primary tumors, and survival. The 1- and 5-year Kaplan-Meier local control estimates were 91.2% and 82.1%, respectively. The 1- and 5-year Kaplan-Meier local control estimates were 98.3% and 89.0% for T1, 88.9% and 81.7% for T2, and 78.9% and 62.7% for T3 lesions, respectively (P = .02). In univariate analysis, 7 variables were significantly associated with an increased risk of local failure: increasing T classification; positive margins of resection; poor clinical response to induction chemotherapy; tumor spread to the posterior pillar, posterior pharyngeal wall, and contralateral soft palate; and invasion of the junction between the tonsil and soft palate. In a logistic regression model, spread to the posterior pillar was the only variable statistically associated with local failure (P = .02). The 1-, 3-, and 5-year Kaplan-Meier survival estimates were 87.9%, 67.2%, and 57.7%, respectively. The Kaplan-Meier survival estimate was significantly reduced (P = .009) in patients with local failure. Selected tonsillar squamous cell carcinoma can be managed with TLO with local control comparable to radiotherapy. Patient selection is critical and TLO is best suited for patients with anterior T1 to T2 squamous cell carcinoma of the tonsil, without posterior anatomic spread.


Development of a high efficiency dry powder inhaler: effects of capsule chamber design and inhaler surface modifications.
The objective of this study was to explore the performance of a high efficiency dry powder inhaler (DPI) intended for excipient enhanced growth (EEG) aerosol delivery based on changes to the capsule orientation and surface modifications of the capsule and device. DPIs were constructed by combining newly designed capsule chambers (CC) with a previously developed three-dimensional (3D) rod array for particle deagglomeration and a previously optimized EEG formulation. The new CCs oriented the capsule perpendicular to the incoming airflow and were analyzed for different air inlets at a constant pressure drop across the device. Modifications to the inhaler and capsule surfaces included use of metal dispersion rods and surface coatings. Aerosolization performance of the new DPIs was evaluated and compared with commercial devices. The proposed capsule orientation and motion pattern increased capsule vibrational frequency and reduced the aerosol MMAD compared with commercial/modified DPIs. The use of metal rods in the 3D array further improved inhaler performance. Coating the inhaler and capsule with PTFE significantly increased emitted dose (ED) from the optimized DPI. High efficiency performance is achieved for EEG delivery with the optimized DPI device and formulation combination producing an aerosol with MMAD < 1.5 μm, FPF<5 μm/ED > 90%, and ED > 80%.


Primary Care Physicians Practicing Preventive Medicine in the Outpatient Setting.
Preventive care is an important part of primary care medicine, yet much variation in its practice exists. The aim of this study is to assess physicians' perspectives of practicing preventive medicine and evaluate which topics are deemed most important. All primary care medicine providers at two separate academic medical centers (Mayo Clinic, MN and Mayo Clinic, FL) were surveyed via an E-mail questionnaire assessing physicians' perception of the role of preventive medicine during both acute/routine and yearly visits, physicians' perception of patients' response to preventive medicine topics, and which preventive medicine topics are commonly practiced. Of 445 providers meeting inclusion criteria, a total of 183 (41.1%) responded. Providers were more likely to engage patients in preventive medicine during yearly visits more so than acute visits (3.82 vs. 4.72, range 1-5 Likert Scale), yet providers were very likely to partake in such practices during both visits. Providers perceived that patients received the practice of preventive medicine very well (4.13 on 1-5 Likert Scale). No significant difference between provider practice and patient perception was noted between the two sites, although there was some variation based on clinical experience of the provider. Providers were found to most commonly practice topics recommended by the United States Preventive Services Task Force. Our study found a high predisposition to practicing preventive medicine. Providers seem to practice according to published evidence-based medicine recommendations.


The role of depressive symptoms and social support in the association of internet addiction with non-suicidal self-injury among adolescents: a cohort study in China.
Both internet addiction (IA) and non-suicidal self-injury (NSSI) are major public health concerns among adolescents, however, the association between IA and NSSI was not well understood. We aimed to investigate the association between IA and NSSI within a cohort study, and explore the mediated effect of depressive symptoms and the moderating effect of social support in the association. A total of 1530 adolescents aged 11-14 years who completed both the baseline (T1) and 14-month follow-up (T2) survey of the Chinese Adolescent Health Growth Cohort were included for the current analysis. IA, NSSI, depressive symptoms and social support were measured at T1; depressive symptoms and NSSI were measured again at T2. Structural equation models were employed to estimate the mediated effect of depressive symptoms and the moderating effect of social support in the association between IA and NSSI at T2. IA was independently associated with an increased risk of NSSI at T2, with the total effect of 0.113 (95%CI 0.055-0.174). Depressive symptoms mediated the association between IA and NSSI at T2, and social support moderated the indirect but not the direct effect of IA on NSSI at T2. Sex differences were found on the mediated effect of depressive symptoms and the moderated mediation effect of social support. Interventions that target adolescents' NSSI who also struggle with IA may need to focus on reducing depressive symptoms and elevating social support.


Treatment of higher risk acute lymphoblastic leukemia in young people (CCG-1961), long-term follow-up: a report from the Children's Oncology Group.
Children's Cancer Group CCG-1882 improved outcome for 1-21-year old with high risk acute lymphoblastic leukemia and Induction Day 8 marrow blasts ≥25% (slow early responders, SER) with longer and stronger post induction intensification (PII). This CCG-1961 explored alternative PII strategies. We report 10-year follow-up for patients with rapid early response (RER) and for the first time details our experience for SER patients. A total of 2057 patients were enrolled, and 1299 RER patients were randomized to 1 of 4 PII regimens: standard vs. augmented intensity and standard vs. increased length. At the end of interim maintenance, 447 SER patients were randomized to idarubicin/cyclophosphamide or weekly doxorubicin in the delayed intensification phases. The 10-year EFS for RER were 79.4 ± 2.4% and 70.9 ± 2.6% (hazard ratio = 0.65, 95% CI 0.52-0.82, p < 0.001) for augmented and standard strength PII; the 10-year OS rates were 87.2 ± 2.0% and 81.0 ± 2.2% (hazard ratio = 0.64, 95% CI 0.48-0.86, p = 0.003). Outcomes remain similar for standard and longer PII, and for SER patients assigned to idarubicin/cyclophosphamide and weekly doxorubicin. The EFS and OS advantage of augmented PII is sustained at 10 years for RER patients. Longer PII for RER patients and sequential idarubicin/cyclophosphamide for SER patients offered no advantage. CCG-1961 is the platform for subsequent COG studies.


Occult pyogenic liver abscess in an adolescent with type 2 diabetes.
Pyogenic liver abscess is a rare complication of diabetes, usually seen in adults greater than 50 years of age who have had diabetes for many years. We describe an 18-year-old male with type 2 diabetes found to have a pyogenic liver abscess caused by Klebsiella pneumoniae, and show accompanying images from his evaluation for fever of unknown origin (FUO). We conclude that in a child or adolescent with FUO and diabetes, occult pyogenic liver abscess must be considered.


Recurrence of Hepatocellular Carcinoma After Laparoscopic Hepatectomy: Risk Factors and Treatment Strategies.
To investigate the risk factors for recurrence and treatment strategies after patients with hepatocellular carcinoma (HCC) undergo total laparoscopic hepatectomy (LH). The study included 109 patients who underwent LH (laparoscopy resection [LR] group, n = 50) or open hepatectomy [OH] (open resection [OR] group, n = 59) for HCC in our hospital between March 2011 and June 2016. Perioperative outcomes, disease recurrence, survival, and risk factors for recurrence were analyzed. Patient characteristics did not significantly differ between groups. The 1- and 3-year survival rates were 90.7% and 78.1%, respectively, for the LR group and 83.1% and 74.4%, respectively, for the OR group (P = .71). The 1- and 3-year disease-free survival rates were 89.6% and 51.4%, respectively, for the LR group and 84.7% and 59.6%, respectively, for the OR group (P = .935). Tumor size, differentiation, vascular invasion, surgical bleeding, and surgical resection margin were risk factors for tumor recurrence after LH. LH for HCC did not increase the risk of recurrence compared with OH. Tumor size, differentiation, vascular invasion, surgical bleeding, and surgical resection margin were risk factors for tumor recurrence. Reducing bleeding during surgery and ensuring sufficient surgical margins were the most important measures to reduce postoperative recurrence of HCC.


Assessment of neonatal ventilation during high-frequency oscillatory ventilation.
To determine alterations in high-frequency oscillatory ventilation (HFOV) performance during clinical ventilator management. Clinical investigation. Two level III intensive care nurseries in Wilmington, Delaware, and Philadelphia, Pennsylvania. Thirty infants 1.49 +/- 1.01 kg with respiratory distress receiving HFOV. Due to the demonstrated benchtop load sensitivity of the HFOV (SensorMedics 3100), we hypothesized that measured tidal volume (Vt/kg) and high-frequency minute ventilation (HFMV) would vary inversely with respiratory rate adjustments and that ventilator performance will be affected with endotracheal tube (ETT) suctioning. Both Vt/kg and HFMV were recorded using a novel hot-wire anemometry technique at the time of ETT suctioning or changes in ventilator settings. During HFOV it was found that Vt/kg = 2.52 +/- 0.68 mL/kg and HFMV = 69 +/- 45 ([mL/kg]2 x Hz); effective ventilation was observed in the range of HFMV = 29-113 ([mL/kg]2 x Hz). HFMV decreased with an increase in breathing frequency. Although there was a significant increase in the mean Vt/kg after suctioning events, there was no difference in Vt/kg or HFMV after disconnection of the ETT alone. There were significant alterations in HFOV performance as a result of clinical adjustments in respiratory rate and suctioning. In addition, we found that measured Vt during clinically effective HFOV is at least equivalent to expected deadspace. Measurement of tidal volume and HFMV may be clinically important in optimizing HFOV performance both during ETT suctioning and adjustments to breathing frequency.


Evaluation of the pain resource nurse role: a resource for improving pediatric pain management.
Pain resource nurses (PRNs), who act as pain management coaches or mentors for their colleagues, can contribute to effective pain management. The PRN's role has not been well evaluated in the context of pediatric nursing. Therefore, the objective of this study was to examine the PRN's role in a pediatric setting and, more specifically, to describe the role in terms of the activities PRNs engage in, the challenges they face, and the supports that help them fulfill their role. This research was part of an evaluation of the implementation of a comprehensive pain management program in a pediatric hospital. Focus groups were conducted with 18 PRNs six months after implementation of the PRN role. The essence of the role is to provide support for best-practice pain management to nurses and the multidisciplinary team. The PRNs described seven components of their role and specific strategies to operationalize their role. In addition, the PRNs faced challenges, including feeling disappointed when their expectations for better pain management were not met, experiencing difficulty fitting the activities into their busy workdays, facilitating their colleagues' improved pain management without also alienating them, and maintaining their enthusiasm and energy for the role. Pediatric nursing staff can effectively fill the role of the PRN. The role is multifaceted, and maintaining the role required commitment and enthusiasm on the part of the nurses, as well as commitment by their related institutions.


Cognitive determinants of decisional capacity in neurodegenerative disorders.
Cognitive contributions to decisional capacity are complex and not well understood. Capacity to consent for research has been linked to executive function, but executive function assessment tools are imperfect. In this study, we examine the relationship between decisional capacity and a newly developed executive function composite score and determine whether cognitive performance can predict impaired decisional capacity. This is a cross sectional study of participants at the National Institutes of Health with frontotemporal dementia-amyotrophic lateral sclerosis spectrum disorders enrolled between 2017 and 2022. A structured interview tool was used to ascertain research decisional capacity. Study participant Uniform Data Set (v3.0) executive function (UDS3-EF) composite score, Clinical Dementia Rating Scale©, and Neuropsychiatric Inventory was determined. A decrease in UDS3-EF composite score significantly increased the odds of impaired decisional capacity (OR = 2.92, 95% CI [1.66-5.13], p = 0.0002). Executive function was most impaired in frontotemporal dementia (-2.86, SD = 1.26) and least impaired in amyotrophic lateral sclerosis (-0.52, SD = 1.25) participants. The UDS3-EF composite score was also strongly correlated to the Clinical Dementia Rating Scale©. Decisional capacity is intrinsically related to executive function in neurodegenerative disorders, and executive dysfunction may predict a lack of decisional capacity alerting investigators of the need for additional scrutiny during the informed consent process.


Semantic competition between hierarchically related words during speech planning.
There is overwhelming evidence that during speech planning semantically related words become lexically activated and compete for selection with the to-be-produced target word. The vast majority of this evidence stems from studies using the picture-word task, in which a distractor word (e.g., bird) drawn from the same semantic category as the target (e.g., fish) was shown to inhibit the picture-naming response more strongly than did an unrelated distractor word. By contrast, corresponding evidence from distractor words (e.g., carp) bearing a hierarchical relation to the target (e.g., fish) is sparse and inconclusive. In the present study, we investigated effects of subordinate-level distractors during basic-level naming and effects of basic-level distractors during subordinate-level naming. Hierarchically related distractors were found to inhibit the naming response in both situations. This pattern of results did not depend on whether the pictures were preferably named at the basic level or at the subordinate level. The results suggest that hierarchically related name alternatives compete for selection.


Blocking of in vitro translation of Paramecium messenger RNAs is due to messenger RNA primary structure.
Paramecium primaurelia mRNAs were translated in vitro in rabbit reticulocyte lysate and the products of translation were analyzed by their size. We show that the large majority of these products are of short but discrete sizes irrespective of the length of the mRNA which directs their synthesis. An illustrative example is given by the translation of mRNA of G surface antigen which directs the synthesis of a 50 kD polypeptide instead of the complete 250 kD protein. Control experiments suggest that the blocking is due to mRNA primary structure.


Protective role of anti-ribosomal P antibody in patients with lupus nephritis.
The aim of this study was to define clinical, histopathologic, and prognostic differences according to the presence of anti-ribosomal P antibody (anti-P) in Korean patients with biopsy-proven lupus nephritis (LN). We studied 79 patients who underwent kidney biopsies prior to the start of induction treatment, and who were subsequently treated with immunosuppressive drugs for at least 6 months and followed-up for more than 6 months. Anti-P was measured by immunoblot analysis at the time of renal biopsy. Of all patients, 35.4% were anti-P-positive. Such patients exhibited earlier LN onset, a higher Systemic Lupus Erythematosus Disease Activity Index 2000 score, and a higher estimated glomerular filtration rate at the time of renal biopsy, than did those without antibodies. Upon renal histopathological analysis, patients with anti-P exhibited less interstitial inflammation in terms of the activity index, less glomerular sclerosis, less tubular atrophy, and less interstitial fibrosis in terms of the chronicity index. Furthermore, anti-P was associated with lower chronicity scores. At a median follow-up time of 47 months, renal function was preserved in 27 of 28 patients who had anti-P, but only 38 of 51 patients without such antibodies did not progress to chronic renal disease. After multivariate logistic regression, we found that anti-P positivity was associated with a reduced rate of progression to chronic kidney disease after adjusting for gender, baseline creatinine, activity and chronicity score, and treatment response (odds ratio = 0.196, 95% CI: 0.039-0.989, P = 0.048). Anti-P was associated with better histological findings, and anti-P-positive patients had better renal outcomes than those without anti-P.


Histopathological findings of failed grafts following Descemet's stripping automated endothelial keratoplasty (DSAEK).
To study the histopathological findings of the early cases of failed DSAEK grafts and to analyze the causes of graft failure. Retrospective study of 13 failed DSAEK grafts (four grafts submitted alone with no host cornea) of 12 patients. The histopathologic features are correlated with the clinical and operative findings. Significant attenuation of the endothelial cells found in 10/13 cases (77%), retained recipient Descemet's membrane in 7/13 (54%), variability of graft thickness in 5/13 (38%) and two of these had stromal irregularity. Retrocorneal fibrous membrane along the donor's Descemet's membrane was found in 4/13 (31%) resulting in endothelial detachment in one case. Eight of the nine host cornea-graft specimens were found to have: total graft-cornea detachment (in one), subtotal in four and partial (⩽50% of graft length) in three. The detached flaps showed infection at the interface of the graft-host cornea in two, epithelial ingrowth and fibrous proliferation along the anterior stromal surface of the graft (one case each). An additional histopathological finding was secondary amyloid deposition within the host stroma (in one). Irregular or thick graft, graft-host interface fibrous/epithelial ingrowth, and infection all predispose to DSAEK failures related to graft detachment. Endothelial cells attenuation and retrocorneal fibrous membrane are major causes for primary graft failure.


Treatment outcome of extensor realignment for patellofemoral dysfunction.
Patellofemoral pain remains one of the most common musculoskeletal disorders encountered in orthopaedic practice. In this retrospective clinical study, 108 knees in 98 patients with patellofemoral pain due to malalignment were treated using a combined proximal and distal realignment technique. The results were evaluated at an average of 29.2 (1-9.2 years) months postoperatively. At final evaluation using the modified Trillat grading scale, good or excellent results were obtained in 88 (81.4%) of the knees treated. Second-look arthroscopy performed in 65 (60.2%) knees demonstrated good patellar tracking and Grade II articular changes were noted in 16 (14.8%) of the patellofemoral joints examined. Complications noted included anterior compartment syndrome with foot drop in one case and arthrofibrosis in another. We conclude that extensor realignment surgery with a combined proximal and distal realignment procedure is a reliable technique for patellofemoral pain secondary to malalignment.


Monitoring anesthesia depth with patient state index during pediatric surgery.
Monitoring anesthesia depth in children is challenging. Pediatric anesthesiologists estimate general anesthesia depth using indirect methods such as pharmacokinetic models and neurovegetative reflexes. The application of processed electroencephalography may help to identify the correct anesthesia depth (i.e., patient state index between 25 and 50). To determine the median values of patient state index and spectral edge frequency 95% in children undergoing general anesthesia conducted according to indirect evaluation of depth. The relationships between patient state index and spectral edge frequency 95% and indirect monitoring of anesthesia depth, type of anesthesia, age subgroups, and postoperative delirium were also assessed. A prospective observational study on children (aged 1-18 years) undergoing surgery longer than 60 min. The SedLine monitor and the novel SedLine pediatric sensors (Masimo Inc., Irvine California) were applied. Patient state index levels were recorded for the duration of the anesthesia until the discharge to the ward at predefined time points. In the 111 enrolled children, median patient state index level at the end of anesthesia induction was 25 (22-32) and ranged from 26 (23-34) to 28 (25-36) in the maintenance phase. Patient state index at extubation was 48 (35-60) and 69 (62-75) at discharge from the operatory room. Median right/left spectral edge frequency 95% values at the end of induction were 10 (6-14)/9 (5-14) Hz and median right/left spectral edge frequency 95% values in the maintenance phase ranged from 10 (6-14) to 12 (11-15) Hz in both hemispheres. At extubation, right/left spectral edge frequency 95% levels were 18 (15-21)/17 (15-21) Hz. We observed 39 episodes of burst suppression in 20 patients (19%). Median patient state index levels were not different between patients undergoing inhalational and intravenous anesthesia and between those undergoing general anesthesia and general anesthesia added to locoregional anesthesia. Children <2 years displayed significantly higher patient state index levels than older patients (p = .0004). The presence of a burst suppression episode was not associated with PAED levels (OR 1.58, 95% CI 0.14-16.74, p` = .18). NonpEEG-guided anesthesia in children led to median patient state index levels at the low range of recommended unconsciousness values with frequent episodes of burst suppression. Patient state index levels were generally higher in children below 2 years.


An unusual case of intraabdominal abscess and acute abdomen caused by axial torsion of a Meckel's diverticulum.
Meckel's diverticulum (MD), the most common congenital anomaly of the gastrointestinal tract, is a true diverticulum. MD is mostly seen in pediatric age groups but may be seen in adults as well. Is twice common in men than women. Surgical treatment is required in symptomatic MD patients. We present a 21-year-old female patient who was admitted with acute abdomen and underwent diverticulectomy with diagnosis of Meckel's diverticulum. The 21-year-old female patient was admitted to emergency service with abdominal pain, nausea and vomiting. Physical examination revealed abdominal distention, rebound tenderness and defense. Abdominal radiography revealed air-fluid levels. White blood cell count was high. In the exploration, torsion of MD was observed and diverticulectomy was performed. Histopathologic analysis indicated the presence of MD. The patient recovered without complication, and was uneventfully discharged. MD is found in 2% of the general population. Common complications of MD include gastrointestinal bleeding, intestinal obstruction, perforation and diverticulitis. However, axial torsion of MD is a rare complication. Simple diverticulectomy is sufficient in the treatment of most MD cases; however, ileal resection may be required in some cases. Diagnosis of MD is established by histopathologic analysis. Although MD is known as a pediatric disease, it is likely to occur in adults as well. Axial torsion of Meckel's diverticulum should be kept in mind the adults presenting with symptoms of acute abdomen.


A review of the application of anodization for the fabrication of nanotubes on metal implant surfaces.
Metal implants are the best choice for the long-term replacement of hard tissue, such as hip and knee joints, because of their excellent mechanical properties. Titanium and its alloys, due to their self-organized oxide layer, which protects the surface from corrosion and prevents ion release, are widely accepted as biocompatible metal implants. Surface modification is essential for the promotion of the osseointegration of these biomaterials. Nanotubes fabricated on the surface of metal implants by anodization are receiving ever-increasing attention for surface modification. This paper provides an overview of the employment of anodization for nanotubes fabricated on the surface of titanium, titanium alloys and titanium alloying metals such as niobium, tantalum and zirconium metal implants. This work explains anodic oxidation and the manner by which nanotubes form on the surface of the metals. It then assesses this topical research to indicate how changes in anodizing conditions influence nanotube characteristics such as tube diameters and nanotube-layer thickness.


Effect of dietary linoleate/alpha-linolenate balance on experimentally induced gastric injury in rats.
Rats were fed diets containing different ratios of linoleate (18:2 n-6) to alpha-linolenate (18:3 n-3), and the severity of gastric injury induced by ethanol, ischemia/reperfusion and water-immersion stress was compared. On decreasing the 18:2 n-6/18:3 n-3 ratios in the diets, the proportion of arachidonic acid (20:4 n-6) decreased and that of eicosapentaenoic acid (20:5 n-3) increased in the phospholipids of the gastric mucosa, which was associated with decreased mucosal prostaglandin E2 content. Mucosal injury in all the three experimental models was exacerbated significantly in the diet group fed 18:2 n-6/18:3 n-3 ratio of 0.25 (perilla oil) as compared with the groups fed dietary oils with 18:2 n-6/18:3 n-3 ratios of 2.7 (mixture of perilla and safflower oils) and 127 (safflower oil). This adverse effect induced by perilla oil diet was not observed when rats were pretreated with a mild irritant (20% ethanol) prior to challenge with a strong irritant (absolute ethanol). Furthermore, an 18:2 n-6/18:3 n-3 ratio of as low as 1 was found to be in a safe range in the water-immersion stress ulcer model. Thus, oils with very low n-6/n-3 ratios, for example perilla oil, could be used without the risk of the observed adverse effects on experimental gastric injury in people of industrialized countries ingesting foods with n-6/n-3 ratios of above 4. A decrease in the n-6/n-3 ratios to 2 or below is still recommended for the prevention of chronic diseases in the elderly related to atherosclerosis and inflammation.


The Commando procedure for pediatric patients: A case series.
The Commando procedure involves division of the intervalvular fibrous body, mitral valve replacement, and aortic valve replacement. It is considered a technically challenging procedure and traditionally has had high mortality. Five pediatric patients with combined left ventricular inflow and outflow obstruction were included in this study. There were no early or late deaths during follow-up, and no pacemakers were implanted. None of the patients required reoperation during follow-up, and none developed a clinically significant gradient across the mitral valve or aortic valve. The risks of this operation for patients with congenital heart disease undergoing multiple redo operations should be weighed against the benefits of normal-size mitral and aortic annular diameters and dramatically improved hemodynamics.


Impaired internal anal sphincter in a subgroup of patients with idiopathic fecal incontinence.
During multiport manometric recordings of the anorectum, 35 of 140 patients with idiopathic fecal incontinence had abnormally weak sphincters that did not relax during rectal distention, suggesting impaired function of the internal anal sphincter. This study documents this finding and compares anorectal function in these 35 patients with 25 matched normal subjects and the remaining 105 incontinent patients. Basal and squeeze pressures were significantly lower in the incontinent study group than in the other two groups. During rectal distention, 25 of 35 patients showed no anal relaxation at any volume, whereas 10 patients showed some relaxation after 60-ml distention because of the postinflation rebound in internal anal sphincter tone. The electrical responses of the external anal sphincter to rectal distention and to increases in intraabdominal pressure were greater in patients than in normal subjects, but the anal pressures were lower and anal leakage was common. Rectal sensations were not significantly different from normal subjects. These results indicate that 25% of patients with idiopathic fecal incontinence have markedly impaired function of the internal anal sphincter, but these patients also have extremely weak external sphincters.


MACHETE identifies interferon-encompassing chromosome 9p21.3 deletions as mediators of immune evasion and metastasis.
The most prominent homozygous deletions in cancer affect chromosome 9p21.3 and eliminate CDKN2A/B tumor suppressors, disabling a cell-intrinsic barrier to tumorigenesis. Half of 9p21.3 deletions, however, also encompass a type I interferon (IFN) gene cluster; the consequences of this co-deletion remain unexplored. To functionally dissect 9p21.3 and other large genomic deletions, we developed a flexible deletion engineering strategy, MACHETE (molecular alteration of chromosomes with engineered tandem elements). Applying MACHETE to a syngeneic mouse model of pancreatic cancer, we found that co-deletion of the IFN cluster promoted immune evasion, metastasis and immunotherapy resistance. Mechanistically, IFN co-deletion disrupted type I IFN signaling in the tumor microenvironment, leading to marked changes in infiltrating immune cells and escape from CD8+ T-cell surveillance, effects largely driven by the poorly understood interferon epsilon. These results reveal a chromosomal deletion that disables both cell-intrinsic and cell-extrinsic tumor suppression and provide a framework for interrogating large deletions in cancer and beyond.


Systemic thrombolysis in patients with acute stroke and active cancer: a systematic review and meta-analysis.
Cancer patients frequently have concomitant cerebrovascular diseases, which significantly worsen their prognosis. Prospective studies validating intravenous thrombolysis (IVT) safety profile in patients with acute ischemic stroke and active cancer are still lacking. Therefore, we aimed to evaluate IVT's efficacy and safety profile in acute ischemic stroke patients with comorbid active cancer. We included in a meta-analysis all relevant published studies, including patients with acute ischemic stroke with or without active cancer and receiving IVT, according to recommendations for IVT treatment for acute ischemic stroke. The primary outcomes were: any intracerebral hemorrhage, all-cause mortality, and good functional outcome reported as modified Rankin Scale (mRS) ≤ 2 at the end of the scheduled follow-up period. We included 11 studies in the meta-analysis. IVT was not associated with a significant increase in the incidence of intracerebral hemorrhage (OR 1.35; 95% CI 0.85-2.14; I2 76%), nor with a significant increase in death for any cause (OR 1.26; 95% CI 0.91-1.75; I2 71%); furthermore, IVT did not influence mRS between cancer and non-active cancer stroke patients (OR 0.72; 95% CI 0.35-1.49; I2 59%). IVT seems safe and effective in patients with ischemic stroke and concomitant cancer. Due to the low overall quality of the evidence, high-quality randomized controlled trials with adequate sample sizes are needed.


Primary suture of the perineal wound using constant suction and irrigation, following rectal excision for inflammatory bowel disease.
Thirty-four consecutive patients with inflammatory bowel disease underwent proctectomy with primary closure of the perineal wound. Throughout this period neither preoperative perineal sepsis nor intraoperative soiling was a contraindication to primary closure. An overall primary healing rate of 82% was obtained. It appears that the commonest cause of perineal wound breakdown is the inability of the suction catheter to drain all the serous fluid from the perineal space, resulting in discharge from the suture line and wound breakdown.


Fermentation liquid as a carbon source for wastewater nitrogen removal reduced nitrogenous disinfection byproduct formation potentials of the effluent.
Sludge alkaline fermentation liquid (SAFL) is an alternative to sodium acetate (NaAc) in enhancing wastewater nitrogen removal. Upon SAFL addition, dissolved organic nitrogen (DON) can be externally introduced or biologically synthesized during nitrogen removal, which is an important precursor to toxic nitrogenous disinfection by-products (N-DBPs). This study aims to evaluate the effects of different carbon source addition on effluent DON concentration, composition, and N-DBP formation potentials. A lab-scale A2O system treating real municipal wastewater was operated with NaAc or SAFL as external carbon sources. DON molecules and potential N-DBP precursors were identified by Orbitrap mass spectrometry. Subsequently, major microorganisms contributing to DON biosynthesis were suggested based on metagenomics. It was found that effluent DON was higher with SAFL as the carbon source than NaAc (1.51 ± 0.24 v.s. 0.56 ± 0.08 mg N/L, p < 0.05). Nevertheless, dichloroacetonitrile and nitrosamine formation potentials (7.14 ± 1.02 and 1.57 ± 0.07 μg/mg DON-N, respectively) of the effluent with SAFL addition were 42.79 ± 2.42% and 54.89 ± 1.70% lower than those of NaAc. Protein- and lignin-like compounds were the most abundant DON molecules in the effluent, where alanine, glycine and tyrosine were important precursors to N-DBPs. Azonexus and Flavobacterium spp. were positively correlated with these precursors, and possessed key genes involved in precursor synthesis. SAFL is a promising carbon source, not only for achieving efficient inorganic nitrogen and DON removals, but also for reducing N-DBP formation potentials of chlorinated effluent.


Physics-informed deep learning approach for modeling crustal deformation.
The movement and deformation of the Earth's crust and upper mantle provide critical insights into the evolution of earthquake processes and future earthquake potentials. Crustal deformation can be modeled by dislocation models that represent earthquake faults in the crust as defects in a continuum medium. In this study, we propose a physics-informed deep learning approach to model crustal deformation due to earthquakes. Neural networks can represent continuous displacement fields in arbitrary geometrical structures and mechanical properties of rocks by incorporating governing equations and boundary conditions into a loss function. The polar coordinate system is introduced to accurately model the displacement discontinuity on a fault as a boundary condition. We illustrate the validity and usefulness of this approach through example problems with strike-slip faults. This approach has a potential advantage over conventional approaches in that it could be straightforwardly extended to high dimensional, anelastic, nonlinear, and inverse problems.


The impact of FDA and EMEA guidelines on drug development in relation to Phase 0 trials.
An increase in the number of identified therapeutic cancer targets achieved through recent biomedical research has resulted in the generation of a large number of molecules that need to be tested further. Current development of (anticancer) drugs is a rather inefficient process that for an average new molecule takes around 10-15 years. It is also a challenging process as it is associated with high costs and a low rate of approval. It is known that less than 10% of new molecular entities entering clinical Phase I testing progress beyond the investigational programme and reach the market; this probability is even lower for anticancer agents. In 2003, the US Food and Drug Administration (US FDA) declared the urgent need for new toolkits to improve the critical development path that leads from scientific discovery to the patient. In this scenario, Phase 0 (zero) trials should allow an early evaluation in humans of pharmacokinetic and pharmacodynamic profiles of test compounds through administration of sub-pharmacological doses and for a short time period to a low number of humans. Typically, Phase 0 studies have no therapeutic or diagnostic intent. Owing to the low doses administered and the low risk of toxicity, shorter preclinical packages to support these studies are required. Phase 0 trials have been proposed to help in making an early selection of promising candidates for further evaluation in Phase I-III trials, providing a potentially useful instrument for drug discovery, particularly in the field of oncology. Phase 0 studies are expected to reduce costs of drug development, and to limit the preclinical in vitro and in vivo testing and the time period of drug development. However, there are also concerns about the utility and feasibility of Phase 0 studies. In January 2006, guidelines on exploratory investigational new drug studies in humans have been published by the US FDA, and currently a Phase 0 programme is ongoing at the National Cancer Institute to evaluate the impact (feasibility and utility) of Phase 0 studies on drug development. In Europe, a Position Paper produced by the Evaluation of Medicinal Products (EMEA) in 2004 raised the possibility of a reduced preclinical safety package to support early microdose clinical studies, and, as announced by a recent Concept Paper on medicinal products published by the committee for medicinal products for human use of the EMEA, EMEA's guidelines on Phase 0 studies are expected shortly. The true impact of Phase 0 studies on the drug development process as well as on the safety needs to be carefully explored.


Taurocholate-induced nitric oxide signaling and the ensuing production of reactive oxygen species lead to an increase in epithelial permeability in cultivated mouse gastric epithelium.
We have here elucidated whether ulcerogenic agents affect the production of NO and reactive oxygen species (ROS). The ulcerogenic agents dose dependently induced NO and ROS production in mouse gastric epithelial cells. Taurocholate (TC, 5 mM) exposure did not affect cell viability, but it increased inducible nitric oxide synthase (iNOS) expression, NO production, ROS production, and epithelial permeability. Epithelial permeability was inhibited with NOS inhibitors or antioxidants. Oxidative stress induced by acetylsalicylic acid (ASA) and ethanol was not inhibited with NOS inhibitors. ASA induced ROS production even at low concentrations (1 mM), which did not affect cell viability. Ethanol-induced ROS production was linked to cell viability, suggesting direct oxidative stress caused by ethanol. Taurocholate-induced NO signaling and the ensuing production of ROS might contribute to initiation of defensive or adaptive cellular mechanisms. ASA-induced ROS signaling might have similar effects, whereas ethanol induced direct oxidative stress, having an influence on cell viability.


A novel deep learning-based method for COVID-19 pneumonia detection from CT images.
The sensitivity of RT-PCR in diagnosing COVID-19 is only 60-70%, and chest CT plays an indispensable role in the auxiliary diagnosis of COVID-19 pneumonia, but the results of CT imaging are highly dependent on professional radiologists. This study aimed to develop a deep learning model to assist radiologists in detecting COVID-19 pneumonia. The total study population was 437. The training dataset contained 26,477, 2468, and 8104 CT images of normal, CAP, and COVID-19, respectively. The validation dataset contained 14,076, 1028, and 3376 CT images of normal, CAP, and COVID-19 patients, respectively. The test set included 51 normal cases, 28 CAP patients, and 51 COVID-19 patients. We designed and trained a deep learning model to recognize normal, CAP, and COVID-19 patients based on U-Net and ResNet-50. Moreover, the diagnoses of the deep learning model were compared with different levels of radiologists. In the test set, the sensitivity of the deep learning model in diagnosing normal cases, CAP, and COVID-19 patients was 98.03%, 89.28%, and 92.15%, respectively. The diagnostic accuracy of the deep learning model was 93.84%. In the validation set, the accuracy was 92.86%, which was better than that of two novice doctors (86.73% and 87.75%) and almost equal to that of two experts (94.90% and 93.88%). The AI model performed significantly better than all four radiologists in terms of time consumption (35 min vs. 75 min, 93 min, 79 min, and 82 min). The AI model we obtained had strong decision-making ability, which could potentially assist doctors in detecting COVID-19 pneumonia.


[Analysis of surgical-orthopaedic treatment of mandibular fractures in patients treated in the period 1984-1986].
During 3 years 1246 patients were treated for mandibular fractures, 828 of them were treated by conservative-orthopaedic methods while in 418 patients the displaced mandibular fragments were reduced and fixed surgically using various methods. The purpose of the assessment was a group of 319 patients in whom the fragments were reduced and fixed with ossous sutures. A good result of treatment was achieved after this operation in 291 cases (91.2%). In 28 patients (8.8%) postoperative complications developed requiring reoperation.


Occurrence and significance of prist-1-ene in kerogen pyrolysates.
A SERIES of acylic isoprenoid alkanes, of which pristane and phytane are typical, frequently occurs in crude oils, shales, coals, bitumens and so on. It is generally agreed that the primary source of these compounds is the phytyl side chain of chlorophyll(1,2) although the mechanisms of its incorporation into sediments and its subsequent diagenesis, are not completely understood. At present, little is known about the role of kerogen as a source, or sink, of isoprenoid moieties and we report here that the principal isoprenoid, obtained by the high temperature (600 degrees C) pyrolysis of kerogens has been identified as prist-1-ene.


Central and paracentral corneal pachymetry in patients with normal tension glaucoma and ocular hypertension.
The difference in central corneal thickness among subgroups of glaucoma patients, as well as its influence on Goldmann applanation tonometry, has been well documented in several clinical trials. In the present study, possible similarities and differences between central corneal thickness and corneal thickness of paracentral quadrants in patients with normal tension glaucoma (NTG) and ocular hypertension (OHT) were investigated. Central and paracentral corneal thickness was measured by optical slit scan pachymetry (Orbscan II). Fourteen patients (28 eyes) with NTG and 11 patients (22 eyes) with OHT were included in this study. t-Test was performed for statistical analysis. To evaluate overall corneal topography, the mean and SD values of the differences between the central corneal thickness and each peripheral quadrant were analysed. The following data was obtained (microm): (central, upper, temporal, nasal, inferior paracentral quadrant): OHT group 617-695-663-687-660. NTG group 568-629-593-612-616. Corneal thickness of all four paracentral quadrants differed significantly between the OHT and NTG groups. There was a more heterogeneous intraindividual pattern of overall corneal topography in the OHT group, and a more heterogeneous pattern of corneal topography among the individuals of the NTG group (interindividual heterogeneity). A comparison of central corneal thickness and paracentral corneal thickness revealed clinically relevant differences between the OHT and NTG groups. The presented data underlines the importance of correlating the site of applanation with the corresponding corneal thickness, especially in OHT patients. It further substantiates the necessity to obtain individual pachymetric data for each NTG patient.


Cellular and molecular events of inflammation induced transdifferentiation (EMT) and regeneration (MET) in mesenteric mesothelial cells.
In this review we summarize the cellular and molecular events of inflammation induced epithelial-to-mesenchymal (EMT) and mesothelial-to-macrophage transition (MET) during regeneration. Since the receptor transmits the environmental stimulus, downregulating or upregulating the process on an epigenetic level, the intracellular localization of receptors (signaling organelles: early endosomes or lysosomal degradation: late endosomes) plays a crucial role in the signaling events regulating inflammation and regeneration. Therefore, we focused on the internalization of the receptors as well as the intracellular compartmentalization of signaling molecules during EMT and MET. The review draws the reader's attention to the plasticity of mesothelial cells and supports the idea that during inflammation an ambient macrophage population might derive from mesothelial cells.


Roles of obesity in mediating the causal effect of attention-deficit/hyperactivity disorder on diabetes.
Previous observational studies have reported potential associations among attention-deficit/hyperactivity disorder (ADHD), obesity, and diabetes (including type 1 and type 2 diabetes mellitus [T1DM/T2DM]). However, whether the association between ADHD and diabetes is mediated by obesity is unknown. With two-sample Mendelian randomization, we analysed the causal effect of ADHD on T1DM and T2DM and six obesity-related traits [including body mass index, waist circumference (WC), hip circumference, waist-to-hip ratio (WHR), body fat percentage and basal metabolic rate] and the causal effect of these obesity-related traits on T1DM/T2DM. Finally, with multivariable Mendelian randomization, we explored and quantified the possible mediation effects of obesity-related traits on the causal effect of ADHD on T1DM/T2DM. Our results showed that ADHD increased the risk of T2DM by 14% [odds ratio (OR) = 1.140, 95% confidence interval (CI) = 1.005-1.293] but with no evidence of an effect on T1DM (OR = 0.916, 95% CI = 0.735-1.141, P = 0.433.). In addition, ADHD had a 6.1% increased causal effect on high WC (OR = 1.061, 95% CI = 1.024-1.099, P = 0.001) and an 8.2% increased causal effect on high WHR (OR = 1.082, 95% CI = 1.035-1.131, P = 0.001). In addition, a causal effect of genetically predicted high WC (OR = 1.870, 95% CI = 1.594-2.192, P < 0.001) on a higher risk of T2DM was found. In further analysis, WC mediated approximately 26.75% (95% CI = 24.20%-29.30%) of the causal association between ADHD and T2DM. WC mediates a substantial proportion of the causal effect of ADHD on the risk of T2DM, which indicated that the risk of T2DM induced by ADHD could be indirectly reduced by controlling WC as a main risk factor.


Affinity chromatography purification of type A botulinum neurotoxin from crystalline toxic complex.
Type A botulinum neurotoxin was purified from toxic crystals by adsorption to p-aminophenyl-beta-D-thiogalactopyranoside coupled to CH-Sepharose 4B. At pH 6.3, the toxic complex was held by the binding between the ligand and the hemagglutinin of the complex; the toxin is eluted selectively by dissociating the complex with buffer-saline of pH 7.9. The single-step affinity chromatography recovered 50 to 60% of applied toxicity as preparations of greater than 99% purity.


Heterobimetallic chalcogenidometallate strands: synthesis, structure, magnetism, and conductivity.
Two salts with one-dimensional, SiS(2)-type telluridostannate chain anions {[MSnTe(4)](2-)}(n), Rb(2)[HgSnTe(4)] (2) and (NMe(4))(2)[MnSnTe(4)] (3), were prepared by the reactions of [SnTe](4-) anions with Hg(2+) or Mn(2+) ions in solution. We present the crystal structures of 2 and 3, as well as the magnetic properties of the previously reported Cs(+) analogue Cs(2)[MnSnTe(4)] (1).


Changes in morphine self-administration after exposure to ionizing radiation: evidence for the involvement of endorphins.
Recent findings have implicated endogenous opiates in radiation-induced behavioral change. The present experiment further investigated this hypothesis by observing alterations in morphine self-administration after irradiation. Under the presumption that the release of endogenous opiates would decrease the need for exogenously supplied morphine, we hypothesized that after radiation exposure morphine-experienced mice would self-administer less of the opiate. C57BL/6J mice had continuous access to two drinking flasks which contained either water or morphine in saccharine water. Irradiated mice drank significantly less morphine than did sham-irradiated controls. This decrease was naloxone-reversible and could not be entirely attributed to a generalized radiogenic hypodipsia or taste aversion. These results are consistent with the hypothesis that radiation-induced behavioral changes may be due, in part, to the fluctuations of endogenous opiates.


Differential cytotoxic activity of pharmacological inhibitors of IGF1R-related pathways in JAK2V617F driven cells.
Myeloproliferative neoplasms (MPN) belong to a group of clonal diseases of hematopoietic stem cells characterized by aberrant proliferation of mature myeloid lineages. The constitutive activation of the JAK2/STAT signaling pathway is now well established to play a central role in MPN pathogenesis; however, accumulating evidence now indicates that the IGF1R-mediated signaling pathway contributes to the maintenance of the malignant phenotype. Studies using inhibitors of IGF1-mediated signaling have reported cytotoxic effects in cellular and murine models of MPN, but no consensus has been reached regarding the potency and efficacy of inhibitors of the IGF1R-related pathway in this context. In the present study, we compared the potency and efficacy of three inhibitors of IGF1R-related pathways in a JAK2V617F-driven cellular model. These inhibitors (NT157, OSI-906, and NVP-AEW54) present antineoplastic activity with similar efficacy in Ba/F3 JAK2V617F cells, with NT157 showing the greatest potency. Both the induction of apoptosis and reduction in cell proliferation were associated with the observed reduction in cell viability. Downregulation of JAK2/STAT signaling was an advantageous off-target effect of all three inhibitors. These preclinical studies reinforce the potential of the IGF1R-related pathway as a therapeutic target in MPN.


Vascular endothelial growth factor C expression is closely correlated with lymph node recurrence and poor prognosis in patients with early stage cervical cancer.
To detect vascular endothelial growth factor (VEGF)-C mRNA expression in surgically resected tissues of 'pathologic N0' (pN0) cervical cancer; to investigate the relevance of VEGF-C mRNA expression to clinicopathological factors, lymph node recurrence and prognosis in early stage cervical cancer. Patients with pN0 cervical cancer who successfully underwent radical hysterectomy with bilateral adnexectomy and bilateral pelvic lymphadenectomy were enrolled sequentially into this retrospective study. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to detect VEGF-C mRNA. Seventy-eight patients entered the study. VEGF-C mRNA was detected in 35 (44.87%) patients and was significantly correlated with tumour differentiation. VEGF-C mRNA expression was significantly associated with lymph node recurrence and poor overall survival 5 years after surgery. Multivariate analysis confirmed that VEGF-C mRNA expression was an independent predictor for lymph node recurrence and unfavourable overall survival. These findings indicate that detection of VEGF-C mRNA has clinical potential as a predictor for identifying patients with pN0 cervical cancer at high risk of lymph node recurrence and poor prognosis.


Acute pyloric perforation after prolonged crack smoking.
A 28-year-old homosexual man, previously healthy, presented with an acute abdomen on the fifth day of his crack binge. Abdominal free air was demonstrated by radiographic studies. Exploratory laparotomy discovered a clean, ulcer-free, pyloric perforation. This unusual case underscores the possibility of a life-threatening visceral perforation after cocaine use.


Liver elasticity in healthy individuals by two novel shear-wave elastography systems-Comparison by age, gender, BMI and number of measurements.
Establishing normal liver stiffness (LS) values in healthy livers is a prerequisite to differentiate normal from pathological LS values. Our aim was to define normal LS using two novel elastography methods head-to-head and to assess the number of measurements, variability and reproducibility. We evaluated shear wave elastography (SWE) methods integrated in Samsung RS80A and GE S8 by obtaining LS measurements (LSM) in 100 healthy subjects (20-70 years). Transient Elastography (TE) was used as reference method. Data were analyzed according to age, sex, BMI and 5 vs. 10 measurements. All subjects underwent B-mode ultrasound examination and lab tests to exclude liver pathology. Interobserver variation was evaluated in a subset (n = 24). Both methods showed excellent feasibility, measuring LS in all subjects. LSM-mean for GE S8 2D-SWE was higher compared to TE (4.5±0.8 kPa vs. 4.2±1.1, p<0.001) and Samsung RS80A (4.1±0.8 kPa, p<0.001). Both methods showed low intra- and interobserver variation. LSM-mean was significantly higher in males than females using 2D-SWE, while a similar trend for Samsung SWE did not reach significance. No method demonstrated statistical significant difference in LSM across age and BMI groups nor between LSM-mean based on 5 vs. 10 measurements. LSM was performed with high reproducibility in healthy adult livers. LSM-mean was significantly higher for GE S8 2D-SWE compared to Samsung RS80A and TE in healthy livers. Males had higher LSM than females. No method demonstrated statistical significant difference in LSM-mean across age- and non-obese BMI groups. Our results indicate that five LSM may be sufficient for reliable results.


Panic-agoraphobic spectrum symptoms in complicated grief.
Little is known about the presence and role of subclinical anxiety symptoms and traits in complicated grief (CG). Data from adults with CG (n=28) suggest that they experience more panic-spectrum symptoms (PSS) than bereaved controls (n=44), and that the presence of greater PSS is independently associated with poorer quality of life.


Nickel-catalyzed intermolecular oxidative Heck arylation driven by transfer hydrogenation.
The conventional oxidative Heck reaction between aryl boronic acids and alkenes typically involved the PdII/Pd0/PdII catalytic cycle incorporating an external oxidant and often suffered C=C bond isomerization for internal alkyl-substituted alkenes via chain-walking. Herein, we demonstrate that the regioselectivity (γ-selectivity vs. δ-selectivity) and pathway selectivity (hydroarylation vs. oxidative Heck coupling) of a directed Ni-catalyzed alkene arylation can be controlled by judicious tuning of the coordination environment around the nickel catalyst via optimization of an appropriate phosphine ligand and directing group. In this way, the Ni(0)-catalyzed oxidative Heck arylation that relies on transfer hydrogenation of an acceptor olefin is developed with excellent E/Z selectivity and regioselectivity. Mechanistic investigations suggest that the addition of the acceptor is crucial for lowering the energy for carbometalation and for enabling catalytic turnover.


Understanding the glucose tolerance of an archaeon β-glucosidase from Thermococcus sp.
β-glucosidase hydrolyzes the β-1,4 linkage of cellobiose, a product generated from the action of endoglucanase and cellobiohydrolase on cellulose, and generates glucose. Accumulated glucose during saccharification leads to product inhibition of β-glucosidase, which in turn cause an accumulation of cellobiose and inhibition of other cellulolytic enzymes. Thus, glucose tolerant and active β-glucosidase is required for the efficient saccharification of biomass. O08324 is a glucose tolerant β-glucosidase isolated from archaeon Thermococcus sp. which shows no loss in enzyme specific activity in the presence of up to 4 M glucose and is active at 78 °C. Since O08324 has such high glucose tolerance, knowing the rationale for glucose tolerance will be helpful in engineering glucose tolerant β-glucosidase. In the present study, we designed mutations at eleven sites across the gatekeeper, aglycone, and glycone region. Based on the kinetic studies of O08324 mutants, the gatekeeper residues at positions 160, 166, 167, 168, and the aglycone binding residue 156 were identified to play a role in glucose inhibition. However, only residues at the tunnel entrance, and not all gatekeeper residues contribute to glucose tolerance. This study sheds some light on the unusual glucose tolerance of O08321 archaeal GH1 β-glucosidase.


Binding of autoantibodies to the core region of tissue transglutaminase is a feature of paediatric coeliac disease.
Production of autoantibodies to the enzyme tissue transglutaminase (tTG) is a hallmark of coeliac disease (CD). We have previously demonstrated that the immumoglobulin (Ig) A response to tTG in adult CD specifically targets its catalytic core region, containing the active-site triad of amino acids. The aim of the present study was to investigate this phenomenon in paediatric patients with CD, and to elucidate the contribution of each active-site residue to epitopes recognised. The specificity of the IgG anti-tTG response was also investigated and compared with that of the IgA anti-tTG response, in both paediatric and adult patients with CD. Wild-type and novel variants of tTG were generated via site-directed mutagenesis and expressed as glutathione-S-transferase-fusion proteins in Escherichia coli BL-21. The mutagenic variants of tTG had substitutions of 1, 1, or all of the 3 of the catalytic triad amino acids. All of the recombinant tTGs were tested for their antigenicity in IgA and IgG enzyme-linked immunosorbent assays with cohorts of paediatric (n=63) and adult (n=30) CD sera. Substitution of even 1 amino acid in the catalytic triad resulted in a significant reduction of CD IgA and IgG anti-tTG binding, with all of the mutant proteins displaying diminished antigenicity compared with the wild-type protein. The core region of tTG is specifically targeted from early on in disease course by CD patient autoantibodies of both the IgA and IgG class.


Realigning the communication paradigm in nursing case management.
Communication underlies all of case management (CM), and better comprehension of the processes of communication within the context of the CM role may facilitate positive patient and organizational outcomes, and assist providers and policy makers in designing effective CM systems. Thus, the purpose of this qualitative, pilot project was to explore dimensions of communication of the nurse case manager role within a hospital setting. The results describe a "hub and spoke" model of communications and suggest the utility of this familiar model for understanding the communication dynamics for those who work as nursing case managers in hospital settings. Findings suggest that nurse case managers are at various times both advocates and mediators--communications roles that may encompass somewhat contradictory demands and perspectives.


Randomized clinical trial on continuous 7-days-a-week postoperative radiotherapy for high-risk squamous cell head-and-neck cancer: a report on acute normal tissue reactions.
To analyse acute mucosal reactions in patients treated with continuous accelerated postoperative irradiation (p-CAIR) compared to conventionally fractionated postoperative radiotherapy (p-CF). The patients were randomly assigned to receive 63 Gy in 1.8 Gy fractions 7-days-a-week given over a period of 5 weeks (n=88), or 63 Gy in 1.8 Gy fractions given 5-days-a-week over 7 weeks (n=87). It represents 65% of an overall trial size. Acute mucosal reactions were scored using modified Dische system. Polychotomous logistic regression was used to estimate the influence of the selected variables on maximum grade of mucositis, and percent of the body weight loss during radiotherapy. The average maximum Dische score and percent of the patients with confluent mucositis were higher in patients treated with p-CAIR, compared to p-CF (13.3 vs. 10.8 and 54 vs. 27%). Polychotomous logistic regression analysis revealed that fractionation scheme and tumour site have significantly influenced maximum Dische score. Tumour site (laryngeal vs. other) had even stronger influence on maximum Dische score than fractionation scheme. The average residual Dische score 8 weeks after radiotherapy was higher in p-CAIR compared to p-CF (2.1 vs. 1.4), and was, most frequently, related to persistent mucosal erythema (70 vs. 57% of pts.). No severe consequential toxicity of radiotherapy was observed, so far, in the trial. While the incidence, intensity and duration of mucosal reactions was higher in p-CAIR than in p-CF the accelerated treatment can be considered tolerable with respect to acute toxicity. In both arms of the trial slight or moderate mucosal erythema was the most frequent acute side effect, which did not completely subside within 8 weeks after irradiation.


Integrating and updating wildlife conservation in China.
China has about 11% of the world's total wildlife species, so strengthening China's wildlife conservation is of great significance to global biodiversity. Despite some successful cases and conservation efforts, 21.4% of China's vertebrate species are threatened by human activities. The booming wildlife trade in China has posed serious threat to wildlife in China and throughout the world, while leading to a high risk of transmission of infectious zoonotic diseases. China's wildlife conservation has faced a series of challenges, two of which are an impractical, separated management of wildlife and outdated protected species lists. Although the Wildlife Protection Law of China was revised in 2016, the issues of separated management remain, and the protected species lists are still not adequately revised. These issues have led to inefficient and overlapping management, waste of administrative resources, and serious obstacles to wildlife protection. In this article, we analyze the negative effects of current separated management of wildlife species and outdated protected species lists, and provide some suggestions for amendment of the laws and reform of wildlife management system.


Long-term efficacy of ureteral dilation for transplant ureteral stenosis.
Transluminal ureteral dilation was performed in 11 renal allograft recipients with transplant ureteral obstruction. Success was achieved in 5 patients (45 per cent) with a followup of 12 to 29 months (mean 19.6 months). All failures have been evident within 12 months of dilation. We conclude that ureteral dilation can provide long-term success in renal allograft recipients. However, continued close long-term monitoring of the anatomical and functional result is mandatory for patients treated in this manner.