Characterization of a Recombinant Trehalose Synthase from Arthrobacter chlorophenolicus and its Unique Kinetics Indicating a Substrate Cooperativity.
Trehalose is a non-reducing disaccharide with beneficial physiological properties and commercial potential. Trehalose synthase (EC 126.96.36.199) catalyzes the reversible conversion between maltose and trehalose. A recombinant trehalose synthase from Arthrobacter chlorophenolicus SK 33.001 (ACTS) was cloned, expressed, and characterized. The recombinant enzyme encoded a protein of 598 amino acids with a molecular mass of 66 kDa. Gel filtration showed that ACTS is a tetramer in sodium phosphate buffer. The enzyme was metal ion independent and exhibited maximal activity in sodium phosphate buffer (pH 7.5) at 30 °C. The kinetic investigations resulted in a KM value of 120.5 ± 4.5 mM for maltose and a KM value of 343.1 ± 13.8 mM for trehalose. The catalytic efficiency (Vmax/KM) for maltose and trehalose were 0.2 and 0.15 U mg-1 mM-1, respectively. In addition, a cooperative substrate binding was found displayed by the determined Hill coefficients (nH) of 2.8 for maltose and 2.1 for trehalose as a substrate, respectively. The final trehalose yield of various maltose concentrations (50-1000 mM) was constant between 58 and 59%, implying that substrate concentration had no inhibitory influence on ACTS activity.


"Healthy immigrant effect" among individuals experiencing homelessness in Spain?: Foreign-born individuals had higher average age at death in 15-year retrospective cohort study.
Individuals experiencing homelessness (IEHs) suffer from severe health inequities. Place of origin is linked to health and mortality of IEHs. In the general population the "healthy immigrant effect" provides a health advantage to foreign-born people. This phenomenon has not been sufficiently studied among the IEH population. The objectives are to study morbidity, mortality, and age at death among IEHs in Spain, paying special attention to their origin (Spanish-born or foreign-born) and to examine correlates and predictors of age at death. Retrospective cohort study (observational study) of a 15-year period (2006-2020). We included 391 IEHs who had been attended at one of the city's public mental health, substance use disorder, primary health, or specialized social services. Subsequently, we noted which subjects died during the study period and analyzed the variables related to their age at death. We compared the results based on origin (Spanish-born vs. foreign-born) and fitted a multiple linear regression model to the data to establish predictors of an earlier age at death. The mean age at death was 52.38 years. Spanish-born IEHs died on average almost nine years younger. The leading causes of death overall were suicide and drug-related disorders (cirrhosis, overdose, and chronic obstructive pulmonary disease [COPD]). The results of the linear regression showed that earlier death was linked to COPD (b = - 0.348), being Spanish-born (b = 0.324), substance use disorder [cocaine (b =-0.169), opiates (b =.-243), and alcohol (b =-0.199)], cardiovascular diseases (b = - 0.223), tuberculosis (b = - 0.163), high blood pressure (b =-0.203), criminal record (b =-0.167), and hepatitis C (b =-0.129). When we separated the causes of death for Spanish-born and foreign-born subjects, we found that the main predictors of death among Spanish-born IEHs were opiate use disorder (b =-0.675), COPD (b =-0.479), cocaine use disorder (b =-0.208), high blood pressure (b =-0.358), multiple drug use disorder (b =-0.365), cardiovascular disease (b =-0.306), dual pathology (b =-0.286), female gender (b =-0.181), personality disorder (b =-0.201), obesity (b =-0.123), tuberculosis (b =-0.120) and having a criminal record (b =-0.153). In contrast, the predictors of death among foreign-born IEHs were psychotic disorder (b =-0.134), tuberculosis (b =-0.132), and opiate (b =-0.119) or alcohol use disorder (b =-0.098). IEHs die younger than the general population, often due to suicide and drug use. The healthy immigrant effect seems to hold in IEHs as well as in the general population.


Qinghaosu, dietary vitamin E, selenium, and cod-liver oil: effect on the susceptibility of mice to the malarial parasite Plasmodium yoelii.
Young female mice were fed torula-yeast-based diets deficient in vitamin E or selenium or supplemented with cod-liver oil to determine the effect of host antioxidant status on the therapeutic efficacy of the Chinese traditional antimalarial drug qinghaosu (QHS), a sesquiterpene endoperoxide. Vitamin E deficiency enhanced the antimalarial action of QHS against Plasmodium yoelii, both in terms of decreased parasitemia and improved survival but Se deficiency did not. A vitamin E-deficient diet containing 5% cod-liver oil had such strong antimalarial activity in itself that no additional therapeutic benefit of QHS could be demonstrated. Hematocrit values in parasitized mice treated with QHS or fed the cod-liver-oil-supplemented, vitamin E-deficient diet were normal. Nutritional manipulation of host antioxidant status may provide a promising prophylactic and/or therapeutic tool for the control of malaria.


Hereditary spastic paraparesis in adults associated with inborn errors of metabolism: a diagnostic approach.
Spastic paraparesis is a general term describing progressive stiffness and weakness in the lower limbs caused by pyramidal tract lesions. This clinical situation is frequently encountered in adult neurology. The diagnostic survey is usually limited to searching for acquired causes (spinal cord compression, inflammatory, metabolic, infectious diseases) and the so-called 'hereditary spastic paraparesis'. Although poorly recognized by neurologists, spastic paraparesis is also one of the multiple presentations of inborn errors of metabolism (IEMs) in children and adults. Pyramidal signs are usually included in a diffuse neurological or systemic clinical picture; however, in some cases spastic paraparesis remains the only symptom for years. Since these metabolic causes are often treatable, it is essential to include them in the general diagnostic approach to spastic paraparesis. Here we review IEMs causing paraparesis in adults.


Legionnaires' disease after heart transplantation.
The cases of 8 heart transplant recipients with legionnaires' disease are reviewed. The diagnosis in each patient was made by fluorescent antibody stains or direct culture of the sputum, transtracheal aspirate, or fine needle aspirate of the lung. All patients were successfully treated with erythromycin alone or in combination with rifampin. Radiographic and clinical variations of legionnaires' disease as seen in the immunocompromised host are presented.


The effectiveness of positive airway pressure therapy in reducing postoperative adverse outcomes in surgical patients with obstructive sleep apnea: A systematic review and meta-analysis.
Obstructive sleep apnea (OSA) is prevalent in surgical patients and is associated with an increased risk of adverse perioperative events. To determine the effectiveness of positive airway pressure (PAP) therapy in reducing the risk of postoperative complications in patients with OSA undergoing surgery. Systematic review and meta-analysis searching Medline and other databases from inception to October 17, 2021. The search terms included: "positive airway pressure," "surgery," "post-operative," and "obstructive sleep apnea." The inclusion criteria were: 1) adult patients with OSA undergoing surgery; (2) patients using preoperative and/or postoperative PAP; (3) at least one postoperative outcome reported; (4) control group (patients with OSA undergoing surgery without preoperative and/or postoperative PAP therapy); and (5) English language articles. Twenty-seven studies included 30,514 OSA patients undergoing non-cardiac surgery and 837 OSA patients undergoing cardiac surgery. PAP therapy MAIN RESULTS: In patients with OSA undergoing non-cardiac surgery, PAP therapy was associated with a decreased risk of postoperative respiratory complications (2.3% vs 3.6%; RR: 0.72, 95% CI: 0.51-1.00, asymptotic P = 0.05) and unplanned ICU admission (0.12% vs 4.1%; RR: 0.44, 95% CI: 0.19-0.99, asymptotic P = 0.05). No significant differences were found for all-cause complications (11.6% vs 14.4%; RR: 0.89, 95% CI: 0.74-1.06, P = 0.18), postoperative cardiac and neurological complications, in-hospital length of stay, and in-hospital mortality between the two groups. In patients with OSA undergoing cardiac surgery, PAP therapy was associated with decreased postoperative cardiac complications (33.7% vs 50%; RR: 0.63, 95% CI: 0.51-0.77, P < 0.0001), and postoperative atrial fibrillation (40.1% vs 66.7%; RR: 0.59, 95% CI 0.45-0.77, P < 0.0001). In patients with OSA undergoing non-cardiac surgery, PAP therapy was associated with a 28% reduction in the risk of postoperative respiratory complications and 56% reduction in unplanned ICU admission. In patients with OSA undergoing cardiac surgery, PAP therapy decreased the risk of postoperative cardiac complications and atrial fibrillation by 37% and 41%, respectively.


Patients with coronary artery- or chronic obstructive pulmonary disease walk with mechanical inefficiency.
Patients with chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) are associated with exercise intolerance. Whether exercise intolerance and reduced mechanical efficiency are due to inactivity alone or to disease related muscular abnormalities is not clear. The aim was to find out whether two patient groups with different limitations for exercise had the same mechanical inefficiency. CAD and COPD patients were compared to a healthy age matched reference group in walking and cycling mechanical efficiency. Both patient groups showed a similar mechanical inefficiency when walking (COPD 16.9 +/- 6.4%, CAD 19.2 +/- 4.1%) compared to healthy controls (24.7 +/- 6.4%). No differences were found when bicycling. VO2peak (mL x kg(-1) x min-1) was significantly reduced in both patient groups compared to the healthy controls (COPD = 23.1+/- 5.3, CAD = 27.9 +/- 3.6, Healthy controls = 36.2 +/- 7.1). Both COPD and CAD patients show mechanical inefficiencies when walking compared to healthy controls. Inactivity is a common feature between the two patient groups, whereas the exercise limitations are quite different. These findings indicate that the mechanical inefficiency might primarily be caused by inactivity.


VEP-based acuity assessment in low vision.
Objective assessment of visual acuity (VA) is possible with VEP methodology, but established with sufficient precision only for vision better than about 1.0 logMAR. We here explore whether this can be extended down to 2.0 logMAR, highly desirable for low-vision evaluations. Based on the stepwise sweep algorithm (Bach et al. in Br J Ophthalmol 92:396-403, 2008) VEPs to monocular steady-state brief onset pattern stimulation (7.5-Hz checkerboards, 40% contrast, 40 ms on, 93 ms off) were recorded for eight different check sizes, from 0.5° to 9.0°, for two runs with three occipital electrodes in a Laplace-approximating montage. We examined 22 visually normal participants where acuity was reduced to ≈ 2.0 logMAR with frosted transparencies. With the established heuristic algorithm the "VEP acuity" was extracted and compared to psychophysical VA, both obtained at 57 cm distance. In 20 of the 22 participants with artificially reduced acuity the automatic analysis indicated a valid result (1.80 logMAR on average) in at least one of the two runs. 95% test-retest limits of agreement on average were ± 0.09 logMAR for psychophysical, and ± 0.21 logMAR for VEP-derived acuity. For 15 participants we obtained results in both runs and averaged them. In 12 of these 15 the low-acuity results stayed within the 95% confidence interval (± 0.3 logMAR) as established by Bach et al. (2008). The fully automated analysis yielded good agreement of psychophysical and electrophysiological VAs in 12 of 15 cases (80%) in the low-vision range down to 2.0 logMAR. This encourages us to further pursue this methodology and assess its value in patients.


Bio-inspired synthesis and biological evaluation of a colchicine-related compound library.
A bio-inspired investigation of the reactions of substrates of type 1 with VOF(3) and PIFA [phenyliodine(III) bis(trifluoroacetate)] led to a collection of colchicine-like compounds 2-5 and related systems. Biological evaluation revealed that some of the synthesized products had significant cytotoxic properties against the colon cancer cell line HT-29.


Glycogen accumulation in synaptic boutons in Clarke's nucleus neuropil after sciatic nerve crush at birth. An electron microscopic study.
Glycogen accumulation in the Clarke's nucleus neuropil of young adult rats whose sciatic nerves were crushed in the first postnatal day was investigated with the electron microscope. Glycogen was observed in synaptic boutons and in small myelinated axons. In some terminals, glycogen accumulated in membrane-bound structures resembling mitochondria and formed large multigranular bodies which were entirely separated from the axoplasm. The multigranular body reached the size of 1.3 micron. Glycogen was present as single beta particles of about 25-40 nm in diameter and in aggregations of large alpha clusters. The astrocytic glycogen distribution was almost similar to that of the control specimens. Glycogen was not observed in other glial cells. It is probable that glycogen accumulation in synaptic terminals of partially deafferentiated Clarke's nucleus may result from impaired glycolysis due to deficient resupply of the distal axon with glycolytic enzymes caused by a defect in axoplasmic transport from the hypoplastic sensory neuronal perikarya.


Thoracic Endografting for Aortic Occlusion after Coarctation Surgery.
Acute occlusion of the descending thoracic aorta (DTA) is rare and associated with high morbidity and mortality. In the case described here, rescue thoracic endovascular aortic repair (TEVAR) was successful in a 59-year-old man with acute occlusion of the DTA accompanied by lower body hypoperfusion after two previous open repairs for aortic coarctation.


The effect of the benzothiazepine diltiazem on force and Ca2+ current in isolated frog skeletal muscle fibres.
1. The action of the D-cis and L-cis isomers of the benzothiazepine derivative diltiazem on isometric force and L-type Ca2+ inward current in short muscle fibres from toe muscles of the frog (Rana esculenta and R. temporaria) was investigated under voltage clamp control with two internal microelectrodes. The experiments were performed at 10 degrees C in TEA-sulphate solution, in which the concentration of ionized Ca2+ was about 4 mM. 2. In the presence of diltiazem (D-cis, 0.25-30 microM; L-cis, 5-100 microM) normal Ca2+ currents and phasic contractures could be elicited by a depolarizing voltage step. However, after long-lasting depolarizations both the Ca2+ channel and the force controlling system (voltage sensor) remained refractory for minutes instead of seconds as under control conditions, i.e. they were 'paralysed'. L-cis diltiazem was about 20 times less effective in comparison with the D-cis isomer. 3. Speed of restoration of force and Ca2+ current was retarded by up to two orders of magnitude, depending on the applied concentration of diltiazem. 4. The steady state potential dependence of force restoration (V0.5 = -49 mV; the potential at which half of the voltage sensors are restored) and that of Ca2+ current restoration (V0.5 = -57 mV) were not altered by diltiazem. 5. The time course of the transition to paralysis, which was quite slow under control conditions, could be accelerated by diltiazem in a concentration-dependent manner. 6. Paralysis developed at the same speed when the fibre was depolarized from -90 mV to -30 mV or to +30 mV. 7. The voltage dependence of Ca2+ current inactivation (inactivation curve; conditioning pulses of 2 min duration) was shifted by about 14 mV to more negative potentials (V0.5 = -31 mV; V'0.5 = -45 mV) under the influence of 1 microM-D-cis diltiazem. It is assumed that no steady state was reached during the conditioning pulse. 8. The voltage dependence of force activation (V0.5 = -45 mV) was not altered by diltiazem. 9. Since the effects of both isomers of diltiazem could only be disclosed during the adjustment of a new steady state and since the drugs acted in a similar way on the inactivation kinetics of force and Ca2+ current, it is concluded that, in depolarized fibres, the drug facilitates the transition to a stabilized inactivated form of the voltage sensor/Ca2+ channel molecule.


Benchmarking Eliminative Radiomic Feature Selection for Head and Neck Lymph Node Classification.
In head and neck squamous cell carcinoma (HNSCC) pathologic cervical lymph nodes (LN) remain important negative predictors. Current criteria for LN-classification in contrast-enhanced computed-tomography scans (contrast-CT) are shape-based; contrast-CT imagery allows extraction of additional quantitative data ("features"). The data-driven technique to extract, process, and analyze features from contrast-CTs is termed "radiomics". Extracted features from contrast-CTs at various levels are typically redundant and correlated. Current sets of features for LN-classification are too complex for clinical application. Effective eliminative feature selection (EFS) is a crucial preprocessing step to reduce the complexity of sets identified. We aimed at exploring EFS-algorithms for their potential to identify sets of features, which were as small as feasible and yet retained as much accuracy as possible for LN-classification. In this retrospective cohort-study, which adhered to the STROBE guidelines, in total 252 LNs were classified as "non-pathologic" (n = 70), "pathologic" (n = 182) or "pathologic with extracapsular spread" (n = 52) by two experienced head-and-neck radiologists based on established criteria which served as a reference. The combination of sparse discriminant analysis and genetic optimization retained up to 90% of the classification accuracy with only 10% of the original numbers of features. From a clinical perspective, the selected features appeared plausible and potentially capable of correctly classifying LNs. Both the identified EFS-algorithm and the identified features need further exploration to assess their potential to prospectively classify LNs in HNSCC.


Effect of calcination temperatures on the performance of rectorite for cadmium immobilization in soil: Freeze-thaw, plant growth, and microbial diversity.
The immobilization of cadmium (Cd(II)) in soil using calcined rectorite (REC) was investigated in this research. The results of immobilization show that a small amount of REC calcined at 700 °C (REC-700 °C) could effectively immobilize 90% of Cd(II) in soil, while the immobilization efficiency of REC only reached 42%. Moreover, the immobilization efficiency of REC calcined at 300 °C and 500 °C (REC-300 °C and REC-500 °C) were lower than REC. To investigate the mechanism, the materials before and after immobilization were fully analyzed by Fourier transform infrared spectroscopy (FT-IR), powdery X-ray diffraction analysis (XRD), and scanning electron microscopy (SEM). The results indicate that the structure of REC has been changed after calcination at different temperatures and Cd(II) was successfully immobilized on materials. Losing free water, structural water and OH groups respectively, the layer spacing of REC-300 °C and REC-500 °C was shrunk. However, the crystal structure of REC was destroyed after calcination at 700 °C, resulting in the generation of new phases. According to the XRD result, more cadmium hydroxide (Cd(OH)2) were produced on REC-700 °C, indicating that more OH groups were formed during immobilization. Furthermore, Tessier test demonstrates that Cd(II) in soil changed from exchangeable state and water soluble state to carbonate bound state and iron manganese oxide bound state during immobilization. The result of microbial community indicates that REC-700 °C can restore the microbial composition of Cd(II)-contaminated soil. The effects of pH, freeze-thaw, REC dosage, and initial heavy metal concentration were also evaluated to provide a theoretical basis for the subsequent application of the material in the remediation of contaminated soil.


New clusters of serum electrolytes aid in stratification of diabetes and metabolic risk.
Serum electrolytes were found to associate with type 2 diabetes. Our study aimed to stratify nondiabetes by clusters based on multiple serum electrolytes and evaluate their associations with risk of developing diabetes and longitudinal changes in glucose and lipid metabolic traits. We performed a data-driven cluster analysis in 4937 nondiabetes individuals aged ≥40 years at baseline from a cohort follow-up for an average of 4.4 years. Cluster analysis was based on seven commonly measured serum electrolytes (iron, chlorine, magnesium, sodium, potassium, calcium, and phosphorus) by using the k-means method. A total of 4937 nondiabetes individuals were classified into three distinct clusters, with 1635 (33.1%) assigned to Cluster A, 1490 (30.2%) to Cluster B, and 1812 (36.7%) to Cluster C. Individuals in Cluster A had higher serum chlorine, were older, and more were women. Individuals in Cluster B had higher serum iron and body mass index (BMI). Individuals in Cluster C had higher serum phosphorus, were younger, and had lower BMI. Cluster B had 1.41-fold higher risk of developing diabetes and Cluster C's risk was 1.33-fold higher compared with Cluster A. Over an average follow-up of 4.4 years, Cluster A showed a moderate and stable BMI, Cluster B showed an accelerated deterioration in glucose metabolism, and Cluster C showed the most sharply increased serum low-density lipoprotein cholesterol level. Clusters based on seven common serum electrolytes differed in diabetes risk and progression of glucose and lipid metabolic traits. Serum electrolytes clusters could provide a powerful tool to differentiate individuals into different risk stratification for developing type 2 diabetes.


Generating orally active galanin analogues with analgesic activities.
The endogenous neuropeptide galanin has anticonvulsant and analgesic properties mediated by galanin receptors expressed in the central and peripheral nervous systems. Our previous work showed that by combining truncation of the galanin peptide with N- and C-terminal modifications afforded analogues that suppress seizures or pain upon intraperitoneal (i.p.) administration. To generate orally active galanin analogues, the previously reported lead compound Gal-B2 (NAX 5055) was redesigned by 1) central truncation, (2) introduction of D-amino acids, and 3) addition of backbone spacers. Analogue D-Gal(7-Ahp)-B2, containing 7-aminoheptanoic acid as a backbone spacer and an oligo-D-lysine motif at the C terminus, exhibits anticonvulsant and analgesic activity post-i.p. administration. Oral administration of D-Gal(7-Ahp)-B2 demonstrates analgesic activity with decreases in both acute and inflammatory pain in the mouse formalin model of pain at doses as low as 8 mg kg(-1) .


Demyristoylation of the major substrate of protein kinase C (MARCKS) by the cytoplasmic fraction of brain synaptosomes.
Myristoylated alanine-rich C kinase substrate (MARCKS) is a major substrate of protein kinase C, whose interaction with the plasma membrane is dependent on its phosphorylation by protein kinase C and on its N-terminal myristoylation. We describe a hitherto undescribed demyristoylation activity of the protein in cytoplasmic fraction of synaptosomes from bovine brain. The activity is dependent on ATP but independent from calcium. The formation of the demyristoylated form, characterized by an increased mobility on SDS gel (70 kDa instead of 85 kDa), was confirmed by mass spectrometry and amino acid sequencing. The molecular mass of the demyristoylated protein as well as the incorporation of radioactive phosphate from [gamma-32P]ATP indicated that one phosphoryl group was incorporated during the demyristoylation process. Calmodulin, which binds to the protein kinase C phosphorylation domain of MARCKS, inhibited the reaction in a calcium-dependent manner. These data suggest that the demyristoylation is regulated by the signal transduction pathways and that the two conserved domains of the protein, namely the N-terminal myristoylated region and the phosphorylation site domain, are functionally interdependent. The localization of MARCKS in the cells may be regulated not only by its phosphorylation with protein kinase C but also by a reversible myristoylation of the protein in situ.


Extra-anatomic bypass: a closer view.
The results of 60 femorofemoral, 27 axillobifemoral, and 15 axillounifemoral bypasses were analyzed. Considered in this order, the operative mortality rate was zero, 11%, and 13%, respectively; initial hemodynamic failure was 7%, 13%, and 9%, respectively; 5-year overall primary patency rate was 67%, 62%, and 19%, respectively; and the secondary patency rate was 74%, 82%, and 37%, respectively. However, axillobifemoral patency was made to seem better by including six cases (12 graft limbs) performed because of nonocclusive disease (aneurysm or failure of graft performed for aneurysm). Excluding these, axillobifemoral primary and secondary patency decreased to 47% and 69%, respectively. Femorofemoral bypass results were made worse by cases performed because of unilateral failure of an aortic bifurcation graft. Exclusion of these bypasses increased primary and secondary patency rates to 74% and 82%, respectively. Occlusion of the major outflow artery (superficial femoral) markedly affected long-term patency of all three bypasses. Thus, "good" and "poor" runoff primary patencies were, respectively, for femorofemoral bypass 79% and 53%, for axillobifemoral bypass 92% and 41%, respectively (occlusive disease only), and for axillounifemoral bypass 54% and zero, respectively. This detailed breakdown of results explains the wide variances in the reported results for these extra-anatomic bypasses and provides a better perspective for their application in different clinical settings.


Transoral robotic resection of advanced recurrent nasopharyngeal carcinoma involving the internal carotid artery.
Transoral robotic surgery (TORS) is a reliable, minimally invasive approach for treating recurrent nasopharyngeal carcinoma (rNPC). However, tumours involving the internal carotid artery (ICA) are considered to be unsuitable for TORS. This paper presents the first case of transoral robotic resection of advanced rNPC involving the ICA. This case is a 55 year-old male patient who received radiotherapy 27 years ago. This patient underwent a standard TORS resection 2 weeks after ipsilateral ICA embolization. Postoperative Magnetic resonance imaging and biopsy results indicated total resection. During the 2 month follow-up, no severe complications were found, and the primary site was tumour-free. This study preliminarily presents the feasibility and efficiency of advanced rNPC resection with TORS. TORS can potentially provide better quality of life for patients as a less invasive approach than current endoscopic surgery. Even so, the surgical approach should be selected strictly according to the tumour's location.


Forty-one cases of round ligament varicosities that are easily misdiagnosed as inguinal hernias.
To demonstrate the benefit and safety of conservative therapy for round ligament varicosities (RLVs) that are easily misdiagnosed as inguinal hernias. We retrospectively analyzed clinical materials of 41 consecutive cases of RLVs diagnosed by ultrasound in a single hospital from January 2011 to December 2015. Misdiagnosis rate, clinical and sonographic features, management after diagnosis and prognosis were recorded. All forty-one cases were pregnant females in their second or third trimester. Twenty-eight cases were first misdiagnosed as inguinal hernias (68.3%). Thirty cases presented as reducible swelling in the inguinal area (73.2%), and twenty-five of which were painful (61.0%). Four cases only felt pain in the inguinal area without swelling (9.7%). Seven cases had no obvious discomfort (17.1%). All cases were diagnosed as RLVs by gray-scale and color Doppler ultrasonography and justified a wait-and-see strategy. Thirty-seven cases were followed until total recovery after delivery (follow-up rate 90.2%). Swelling with or without pain disappeared spontaneously postpartum. RLVs are easily misdiagnosed as inguinal hernias and color Doppler of the inguinal area is the best examination for making the correct diagnosis. Conservative therapy for RLV is beneficial and safe when assured by color Doppler.


Synergistic effect of PKC activation and actin filament disruption on carbonate apatite-facilitated lymphocyte transfection.
Leukemia and lymphoma cells are potential targets for genetic manipulation in cancer therapy. On the other hand, genetically modified autologous lymphocytes expressing a chimeric antigen against a receptor overexpressed in tumor cells or tumor vasculature are promising cell-based therapeutics for cancer.However, the lack of a smart device for efficient transgene delivery to the lymphocytes poses the major obstacle to the successful clinical applications of these attractive approaches. Recently, we developed a carbonate apatite-based nanocarrier system for effective intracellular delivery and release of DNA molecules, achieving very high level of transgene expression in both primary and cancer cells. Although its efficacy in human T leukemia cells is relatively poor, immobilization of fibronectin and/or chimeric E-cadherin-Fc on particle surface could enhance transgene delivery in presence of an actin filament disrupter. Here, we report for the first time that simultaneous stimulation of human T leukemia cells by a protein kinase C (PKC) activator, a Ca(2+) ionophore and an actin filament disrupter dramatically accelerated carbonate apatite-mediated transgene delivery in the cells, resulting in over 100-fold more efficacy than commcercially available lipofectamine.


Free living amoebae isolation in irrigation waters and soils of an insular arid agroecosystem.
The use of freshwater in agricultural systems represents a high percentage of total water consumption worldwide. Therefore, alternative sources of water for irrigation will need to be developed, particularly in arid and semi-arid areas, in order to meet the growing demand for food in the future. The use of recycled wastewater (RWW), brackish water (BW) or desalinated brackish water (DBW) are among the different non-conventional water resources proposed. However, it is necessary to evaluate the health risks for humans and animals associated with the microbiological load of these waters. Protozoa such as free-living amoebae (FLA) are considered an emerging group of opportunistic pathogens capable to cause several diseases in humans (e.g. cutaneous and ocular infections, lung, bone or adrenal gland conditions or fatal encephalitis). In the present study we evaluate FLA presence in three different irrigation water qualities (RWW, BW and DBW) and its survival in irrigated agricultural soils of an extremely arid insular ecosystem (Fuerteventura, Canary Islands, Spain). Samples were cultured on 2% Non-Nutrient Agar (NNA) plates covered with a thin layer of heat killed E. coli and checked daily for the presence of FLA. According to the prevalence of FLA, Vermamoeba vermiformis (53,8%), Acanthamoeba spp. (30,8%), Vahlkampfia avara (7,7%) and Naegleria australiensis (7,7%) were detected in the analysed water samples, while Acanthamoeba (83,3%), Cercozoa spp. (8,3%) and Vahlkampfia orchilla (8,3%) were isolated in irrigated soils. Only Acanthamoeba strains were isolated in no irrigated soils used as control, evidencing the capability of these protozoa to resist environmental harsh conditions. Additionally, all analysed water sources and the irrigated soils presented growth of several pathogenic bacteria. Therefore, the coexistence in water and soils of pathogenic bacteria and FLA, can mean an increased risk of infection in agroecosystems.


Adaptive motion artifacts reduction using 3-axis accelerometer in e-textile ECG measurement system.
The electro-conductive fabric (e-textile or e-fabric) as an electrode for ECG measurement is one of the best application for ubiquitous healthcare system. However, it is difficult to measure the bio-signal due to its sensitivity variation caused by impedance change, especially by motion of the subject. In this paper, adaptive motion artifacts reduction using motion information from 3-axis accelerometer is proposed and analyzed in quantitative manner.


SHORT Syndrome: an Update on Pathogenesis and Clinical Spectrum.
This review describes the unique pathogenesis of SHORT syndrome, a rare genetic form of insulin resistance syndrome, and recent advances in understanding the underlying mechanisms. SHORT syndrome results from dysfunction of PI3K, but the mechanisms behind the clinical manifestations are not entirely understood. Elucidating these mechanisms may contribute to the understanding of the roles of insulin signaling and PI3K signaling in humans. There are paucity of data on treatment and outcomes. The clinical spectrum of the disorder appears wider than previously understood, and overlaps with other clinical syndromes. PI3K malfunction is associated with insulin resistance, decreased lipogenesis, increased energy expenditure, and possible IGF1 resistance. SHORT syndrome may be underdiagnosed, and should be considered in individuals with growth failure, craniofacial dysmorphism, and lipodystrophy. Much is still unknown about the optimal management and long-term outcomes.


Optimizing the clinical utility of PCA3 to diagnose prostate cancer in initial prostate biopsy.
PCA3 has been included in a nomogram outperforming previous clinical models for the prediction of any prostate cancer (PCa) and high grade PCa (HGPCa) at the initial prostate biopsy (IBx). Our objective is to validate such IBx-specific PCA3-based nomogram. We also aim to optimize the use of this nomogram in clinical practice through the definition of risk groups. Independent external validation. Clinical and biopsy data from a contemporary cohort of 401 men with the same inclusion criteria to those used to build up the reference's nomogram in IBx. The predictive value of the nomogram was assessed by means of calibration curves and discrimination ability through the area under the curve (AUC). Clinical utility of the nomogram was analyzed by choosing thresholds points that minimize the overlapping between probability density functions (PDF) in PCa and no PCa and HGPCa and no HGPCa groups, and net benefit was assessed by decision curves. We detect 28% of PCa and 11 % of HGPCa in IBx, contrasting to the 46 and 20% at the reference series. Due to this, there is an overestimation of the nomogram probabilities shown in the calibration curve for PCa. The AUC values are 0.736 for PCa (C.I.95%:0.68-0.79) and 0.786 for HGPCa (C.I.95%:0.71-0.87) showing an adequate discrimination ability. PDF show differences in the distributions of nomogram probabilities in PCa and not PCa patient groups. A minimization of the overlapping between these curves confirms the threshold probability of harboring PCa >30 % proposed by Hansen is useful to indicate a IBx, but a cut-off > 40% could be better in series of opportunistic screening like ours. Similar results appear in HGPCa analysis. The decision curve also shows a net benefit of 6.31% for the threshold probability of 40%. PCA3 is an useful tool to select patients for IBx. Patients with a calculated probability of having PCa over 40% should be counseled to undergo an IBx if opportunistic screening is required.


EEG as a possible prognostic tool in phenylketonuria.
Clinical EEG and biochemical data were recorded in 10 children with classical PKU and 5 with variant forms of hyperphenylalaninaemias during the first year of life. A semiquantitative evaluation of the EEG showed a high correlation between epileptiform abnormalities and phenylalanine blood levels in the first 90 days of life and therefore with the delay before dietary therapy in PKU children. Although performed on a limited population, such an approach may indicate an additional non-computerized EEG tool for the clinical management of hyperphenylalaninaemias, and suggest some criteria for neurophysiological risk evaluation during the first year of life.


Could tau-PET imaging contribute to a better understanding of the different patterns of clinical progression in Alzheimer's disease? A 2-year longitudinal study.
Monitoring the progression of Tau pathology makes it possible to study the clinical diversity of Alzheimer's disease. In this 2-year longitudinal PET study, we aimed to determine the progression of [18F]-flortaucipir binding and of cortical atrophy, and their relationships with cognitive decline. Twenty-seven AD patients at the mild cognitive impairment/mild dementia stages and twelve amyloid-negative controls underwent a neuropsychological assessment, 3 T brain MRI, and [18F]-flortaucipir PET imaging (Tau1) and were monitored annually over 2 years with a second brain MRI and tau-PET imaging after 2 years (Tau2). We analyzed the progression of tau standardized uptake value ratio (SUVr) and grey matter atrophy both at the regional and voxelwise levels. We used mixed effects models to explore the relations between the progression of SUVr values, cortical atrophy, and cognitive decline. We found an average longitudinal increase in tau SUVr values, except for the lateral temporoparietal cortex where the average SUVr values decreased. Individual analyses revealed distinct profiles of SUVr progression according to temporoparietal Tau1 uptake: high-Tau1 patients demonstrated an increase in SUVr values over time in the frontal lobe, but a decrease in the temporoparietal cortex and a rapid clinical decline, while low-Tau1 patients displayed an increase in SUVr values in all cortical regions and a slower clinical decline. Cognitive decline was strongly associated with the progression of regional cortical atrophy, but only weakly associated with SUVr progression. Despite a relatively small sample size, our results suggest that tau-PET imaging could identify patients with a potentially "more aggressive" clinical course characterized by high temporoparietal Tau1 SUVr values and a rapid clinical progression. In these patients, the paradoxical decrease in temporoparietal SUVr values over time could be due to the rapid transition to ghost tangles, for which the affinity of the radiotracer is lower. They could particularly benefit from future therapeutic trials, the neuroimaging outcome measures of which deserve to be discussed.


Rapid formation of human immunodeficiency virus-like particles.
Understanding the molecular mechanisms involved in the assembly of viruses is essential for discerning how viruses transmit from cell to cell and host to host. Although molecular aspects of assembly have been studied for many viruses, we still have little information about these events in real time. Enveloped viruses such as HIV that assemble at, and bud from, the plasma membrane have been studied in some detail using live cell fluorescence imaging techniques; however, these approaches provide little information about the real-time morphological changes that take place as viral components come together to form individual virus particles. Here we used correlative scanning ion conductance microscopy and fluorescence confocal microscopy to measure the topological changes, together with the recruitment of fluorescently labeled viral proteins such as Gag and Vpr, during the assembly and release of individual HIV virus-like particles (VLPs) from the top, nonadherent surfaces of living cells. We show that 1) labeling of viral proteins with green fluorescent protein affects particle formation, 2) the kinetics of particle assembly on different plasma membrane domains can vary, possibly as a consequence of differences in membrane biophysical properties, and 3) VLPs budding from the top, unimpeded surface of cells can reach full size in 20 s and disappear from the budding site in 0.5 to 3 min from the moment curvature is initially detected, significantly faster than has been previously reported.


Minimizing the risk of small-for-size syndrome after liver surgery.
Primary and secondary liver tumors are not always amenable to resection due to location and size. Inadequate future liver remnant (FLR) may prevent patients from having a curative resection or may result in increased postoperative morbidity and mortality from complications related to small-for-size syndrome (SFSS). This comprehensive review analyzed the principles, mechanism and risk factors associated with SFSS and presented current available options in the evaluation of FLR when planning liver surgery. In addition, it provided a detailed description of specific modalities that can be used before, during or after surgery, in order to optimize the conditions for a safe resection and minimize the risk of SFSS. Several methods which aim to reduce tumor burden, preserve healthy liver parenchyma, induce hypertrophy of FLR or prevent postoperative complications help minimize the risk of SFSS. With those techniques the indications of radical treatment for patients with liver tumors have significantly expanded. The successful outcome depends on appropriate patient selection, the individualization and modification of interventions and the right timing of surgery.


Clinical characteristics and prognosis of amyotrophic lateral sclerosis with autoimmune diseases.
The occurrence of autoimmune diseases (AIDs) in amyotrophic lateral sclerosis (ALS) patients is widely reported, but little is known about the associated clinical phenotype. This study aims to evaluate the clinical features and prognosis of ALS patients with AID. This retrospective study was based on the ALS Registry dataset of Peking Union Medical College Hospital from 2013 to 2020. Clinical features and inflammatory biomarkers at registration were compared between ALS patients with coexisting AIDs and those without (controls). The medical records of immunotherapy were also collected. The Kaplan-Meier method and Cox proportional hazard model were used to study the survival of ALS patients. There are 26 (1.6%) ALS patients with AIDs in our database. The ALS patients with AIDs had older ages at onset and poorer respiratory function than controls (p<0.05). After propensity score matching by sex, onset age, and disease duration, the difference in respiratory function remained significant between groups. We found no differences in overall survival between ALS patients with and without AIDs before and after matching (p = 0.836; p = 0.395). Older age at onset, rapid disease progression, and lower erythrocyte sedimentation rate (ESR) were associated with shorter survival (p<0.05). Among ALS patients with AIDs, 8 (30.8%) had a history of immunotherapy and showed slightly prolonged survival compared with those without immunotherapy, but the results did not reach statistical significance (p = 0.355). Patients with coexisting ALS and AIDs had older onset age and poorer respiratory function but similar overall survival than those with pure ALS.


Structural organization of a 67-kilobase streptococcal conjugative element mediating multiple antibiotic resistance.
The molecular organization of the conjugative cat-erm-tet region of Streptococcus agalactiae B109 was examined by cloning large contiguous portions of the strain B109 chromosome, using a cosmid vector system. The organization of this region was compared with pDP5, a plasmid which acquired this resistance element by transposition. Both the chromosomal copy and the transposed copy of the resistance region were found to be 67-kilobases long, although sequences at the boundary of the transposed copy of the element showed some rearrangement. In addition to the stable chromosomal state, we present evidence which suggests the presence of a circular form of the element.


Levels of aspartate aminotransferase (AST) in saliva of patients with different periodontal conditions.
The purpose of this study was to evaluate the relationship between aspartate aminotransferase (AST) levels in saliva measured by Reflotron trade mark System of Diagnosis and periodontal condition indicated by Community Periodontal Index of Treatment Needs (CPITN). Fifteen patients were assigned to one of four groups C0, C1, C3 and C4, based on their largest CPITN code among the examined sites, totaling 60 participants. About 1.0 ml of non-stimulated saliva was collected from the individuals after a mouth rinse with water. Biochemical analyses of saliva samples were carried out using the proposed system in order to quantify their AST concentration. There were no significant differences between levels (U/ml) of AST (median; interquartile range) from groups C0 (30.9; 14.7-41.7), C1 (30.3; 19.5-39.4) and C3 (35.1; 27.0-63.5). However, group C4 (106.2; 84.4-129.7) differed statistically from the others (p<0.001) and presented AST levels as high as 284.2 U/ml. Gingival bleeding and suppuration were observed in three individuals with concentrations higher than 125.0 U/ml. Levels of AST in saliva from patients presenting CPITN code 4 were higher than from patients coded lower and could be detected by the evaluated diagnostic system. Periodontal destruction such as periodontal pockets, gingival bleeding and suppuration seems to be related to higher AST levels in saliva.


Association of Food Deserts and Food Swamps With Obesity-Related Cancer Mortality in the US.
Obesity-related cancers account for 40% of all cancers in the US. Healthy food consumption is a modifiable factor shown to reduce obesity-related cancer mortality, but residing in areas with less access to grocery stores (food deserts) or higher access to fast food (food swamps) reduces healthy food access and has been understudied. To analyze the association of food deserts and food swamps with obesity-related cancer mortality in the US. This cross-sectional ecologic study used US Department of Agriculture Food Environment Atlas data from 2012, 2014, 2015, 2017, and 2020 and Centers for Disease Control and Prevention mortality data from 2010 to 2020. A total of 3038 US counties or county equivalents with complete information on food environment scores and obesity-related cancer mortality data were included. An age-adjusted, generalized, mixed-effects regression model was performed for the association of food desert and food swamp scores with obesity-related cancer mortality rates. Data were analyzed from September 9, 2022, to September 30, 2022. Food swamp score was calculated as the ratio of fast-food and convenience stores to grocery stores and farmers markets. Higher food swamp and food desert scores (20.0 to ≥58.0) indicated counties with fewer healthy food resources. Obesity-related cancer (based on the International Agency for Research on Cancer evidence between obesity and 13 types of cancer) mortality rates were categorized as high (≥71.8 per 100 000 population) vs low (<71.8 per 100 000 population) per county. A total of 3038 counties or county equivalents with high obesity-related cancer mortality rates had a higher percentage of non-Hispanic Black residents (3.26% [IQR, 0.47%-26.35%] vs 1.77% [IQR, 0.43%-8.48%]), higher percentage of persons older than 65 years (15.71% [IQR, 13.73%-18.00%] vs 15.40% [IQR, 12.82%-18.09%]), higher poverty rates (19.00% [IQR, 14.20%-23.70%] vs 14.40% [IQR, 11.00%-18.50%]), higher adult obesity rates (33.00% [IQR, 32.00%-35.00%] vs 32.10% [IQR, 29.30%-33.20%]), and higher adult diabetes rates (12.50% [IQR, 11.00%-14.20%] vs 10.70% [IQR, 9.30%-12.40%]) compared with counties or county equivalents with low obesity-related cancer mortality. There was a 77% increased odds of having high obesity-related cancer mortality rates among US counties or county equivalents with high food swamp scores (adjusted odds ratio, 1.77; 95% CI, 1.43-2.19). A positive dose-response relationship among 3 levels of food desert and food swamp scores and obesity-related cancer mortality was also observed. The findings of this cross-sectional ecologic study suggest that policy makers, funding agencies, and community stakeholders should implement sustainable approaches to combating obesity and cancer and establishing access to healthier food, such as creating more walkable neighborhoods and community gardens.


Methodological considerations when measuring and analyzing auditory steady-state responses with multi-channel EEG.
The auditory steady-state response (ASSR) has been traditionally recorded with few electrodes and is often measured as the voltage difference between mastoid and vertex electrodes (vertical montage). As high-density EEG recording systems have gained popularity, multi-channel analysis methods have been developed to integrate the ASSR signal across channels. The phases of ASSR across electrodes can be affected by factors including the stimulus modulation rate and re-referencing strategy, which will in turn affect the estimated ASSR strength. To explore the relationship between the classical vertical-montage ASSR and whole-scalp ASSR, we applied these two techniques to the same data to estimate the strength of ASSRs evoked by tones with sinusoidal amplitude modulation rates of around 40, 100, and 200 Hz. The whole-scalp methods evaluated in our study, with either linked-mastoid or common-average reference, included ones that assume equal phase across all channels, as well as ones that allow for different phase relationships. The performance of simple averaging was compared to that of more complex methods involving principal component analysis. Overall, the root-mean-square of the phase locking values (PLVs) across all channels provided the most efficient method to detect ASSR across the range of modulation rates tested here.


Synergistic induction of interleukin-6 by tumor necrosis factor and lithium chloride in mice: possible role in the triggering and exacerbation of psoriasis by lithium treatment.
One of the side effects of treatment of manic depressive disease with lithium salts is the triggering or aggravation of psoriasis. In a murine model, subcutaneous (s.c.) injection of a combination of tumor necrosis factor (TNF) and lithium chloride (LiCl) induces a psoriasiform inflammatory reaction. Recent studies suggest that interleukin (IL)-6 and its inducer TNF may play an important role in the pathophysiology of psoriasis. To understand the mechanism involved in the exacerbation of psoriasis by lithium salts, the IL-1, IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in murine skin injected with TNF in combination with LiCl were studied. IL-6 levels in skin extracts of mice treated s.c. with a combination of TNF and LiCl were considerably increased as compared to the levels found in skin extracts from mice treated with TNF or LiCl alone. In contrast, in the same skin extracts IL-1 levels were not changed and GM-CSF was even not detectable. Although less pronounced, increased IL-6 levels could also be found in the sera of mice treated s.c. with TNF and LiCl. Injection with IL-1, interferon-gamma, lipopolysaccharide, or phorbol 12-myristate 13-acetate also induced IL-6 in murine skin. However, these IL-6 levels were not enhanced by co-treatment with LiCl. Likewise, on inflammatory reaction could be seen in mice treated with these agents. These results suggest a role for endogenous TNF and IL-6 in the triggering or aggravation of psoriasis in lithium-treated patients.


Inhibition of 14-3-3ε by K50 acetylation activates YAP1 to promote cholangiocarcinoma growth.
14-3-3 proteins are ubiquitous adapters combining with phosphorylated serine/threonine motifs to regulate multiple cellular processes. As a negative regulator, 14-3-3 proteins could sequester the phosphorylated YAP1 in cytoplasm to inhibit its activity. In this study, we identified the K50 acetylation (K50ac) of 14-3-3ε protein and investigated its roles and mechanism in cholangiocarcinoma progression. The NAD (+)-dependent protein deacetylases inhibitor, NAM treatment significantly up-regulated the K50ac of 14-3-3ε. K50R mutation resulted in the decrease of K50ac of 14-3-3ε. The K50ac of 14-3-3ε was reversibly mediated by PCAF acetyltransferase and sirt1 deacetylases. K50ac had no obvious effect on the protein stability of 14-3-3ε, but inhibited the combination of 14-3-3ε with phosphorylated YAP1, which resulted in the activation of YAP1 in cholangiocarcinoma. K50R significantly decreased cholangiocarcinoma cell proliferation in vitro and the growth of tumor xenograft in vivo compared with WT (wild type) 14-3-3ε. The level of K50ac were higher in cholangiocarcinoma tissues accompanied by the accumulation of YAP1 in nuclear than para-carcinoma tissues. Our study revealed the underlying mechanism of K50ac of 14-3-3ε and its roles in cholangiocarcinoma, providing a potential targeting for cholangiocarcinoma therapy.


Structure-function studies of the eighth hydrophobic domain of a serotonin receptor.
The most prominent structural feature of the G protein-coupled receptor superfamily is their seven hydrophobic domains, which are postulated to form membrane-spanning alpha helices. Some members of the G protein-coupled receptor family, specifically several serotonin (5-HT) receptors, possess eight hydrophobic domains. The importance of this extra hydrophobic domain, located at the N terminus of the receptor, is unknown. This question was addressed by deleting the extra hydrophobic region from the 5-HT2C receptor and comparing its function and topology with those of the wild-type receptor. Immunofluorescence microscopy was used to determine the location of the N terminus of the epitope-tagged wild-type and mutant receptors. The N terminus of both receptors was extracellular, suggesting that the extra hydrophobic domain does not change the topology of this receptor and is unlikely to be a membrane-spanning alpha helix. Radioligand-binding studies in transfected cells and expression studies in Xenopus oocytes demonstrated that seven hydrophobic domains were sufficient for normal function in these assays. Interestingly, the mutant receptor, now containing seven hydrophobic domains, is expressed at higher levels in transfected cells than the wild-type receptor containing eight hydrophobic domains, suggesting that the extra hydrophobic domain does impact the activity of this receptor by regulating its expression.


Application of Contrast-Enhanced Sonography for Diagnosis of Space-Occupying Lesions in the Extrahepatic Bile Duct: Comparison With Conventional Sonography and Contrast-Enhanced Computed Tomography.
To investigate the application of contrast-enhanced sonography compared with conventional sonography and contrast-enhanced computed tomography (CT) for diagnosis of space-occupying lesions in the extrahepatic bile duct. Seventy-two patients with pathologic diagnoses of space-occupying lesions in the extrahepatic bile duct were retrospectively recruited. All patients underwent conventional sonography, contrast-enhanced sonography, and contrast-enhanced CT. The sensitivity, specificity, and diagnostic accuracy were compared. Among the 72 patients, 11 cases were benign, and 61 were malignant. The diagnostic accuracy rates for conventional sonography, contrast-enhanced sonography, and contrast-enhanced CT were 66.67% (48 of 72), 90.28% (65 of 72), and 88.89% (64 of 72), respectively. The Youden index showed that contrast-enhanced sonography (0.811) was comparable with contrast-enhanced CT (0.720) and better than conventional sonography (0.159). There were significant differences in accuracy between conventional and contrast-enhanced sonography (P= .001) and conventional sonography and contrast-enhanced CT (P = .001); however, there was no significant difference between contrast-enhanced sonography and contrast-enhanced CT (P = .785). There were significant differences in sensitivity between conventional and contrast-enhanced sonography (P= .006) and conventional sonography and contrast-enhanced CT (P = .006) but no significant difference between contrast-enhanced sonography and contrast-enhanced CT (P > .99). There were no significant differences in specificity among the techniques (P > .05). There was a significant difference in the number of lesions with clear boundaries displayed: 16 on conventional sonography and 56 on contrast-enhanced sonography (P = .006). Contrast-enhanced sonography can show the dynamic blood supply in space-occupying pathologic regions of the extrahepatic bile duct. The diagnostic accuracy of contrast-enhanced sonography in the extrahepatic bile duct was higher than that of conventional sonography and comparable with that of contrast-enhanced CT. Therefore, contrast-enhanced sonography may be a promising imaging technique for diagnosis of space-occupying lesions in the extrahepatic bile duct.


Possible stimulation of Na+-K+-ATPase by NO produced from sodium nitrite by ultraviolet light in mouse gastric fundal strip.
1. In the present study, we investigated the roles of Na+-K+-ATPase and extracellular Na+ or Ca2+ ions in ultraviolet (UV) light-induced photorelaxation of methacholine-contracted mouse isolated gastric fundus in the presence of NaNO2 (50 microM). 2. Ouabain (1-500 microM), sodium vanadate (10 microM to 3 mM) and amiloride (1-100 microM) completely inhibited the photorelaxation in a concentration-dependent manner. 3. Metabolic inhibitors, sodium azide (10-100 microM), 2,4-dinitrophenol (100 microM to 1 mM) and sodium fluoride (100 microM to 1 mM) significantly reduced photorelaxation. 4. Substitution of sucrose, lithium or KCl with extracellular Na+ completely abolished the photorelaxant responses. 5. Replacement of all extracellular CaCl2 with BaCl2 also completely inhibited UV-induced relaxation. 6. Verapamil (1-10 microM) decreased UV-induced relaxation significantly. 7. These results suggest that nitric oxide produced from NaNO2 by UV-light in mouse gastric fundus probably stimulates Na+-K+-ATPase activity, and photorelaxation of gastric smooth muscle is dependent on extracellular Na+ and Ca2+ ions.


Using WeChat to guide preparation before transthoracic echocardiography reduces anxiety and improves satisfaction of parents of infants with congenital heart disease.
To explore the effect of using WeChat to guide preparation before transthoracic echocardiography (TTE) on reducing anxiety and improving the satisfaction of parents of infants with congenital heart disease (CHD). This study was a retrospective study conducted in a children's hospital. The clinical data of 44 patients and the anxiety and satisfaction data of their parents who received WeChat guidance were collected between December 2021 and January 2022 (the WeChat group). The corresponding data of 47 patients and their parents who received educational brochure guidance were collected between September 2021 and November 2021 (the routine group). Guidance was used to help the parents prepare for TTE performed by medical professionals. The State-Trait Anxiety Inventory scale and the Patient Satisfaction Questionnaire-18 (PSQ-18) were used. The data of the two groups were compared and analyzed. The comparison of parental anxiety between the two groups showed that the scores of state anxiety and trait anxiety in the WeChat group were significantly lower than those in the routine group (p < 0.05). The comparison of the results of the PSQ-18 showed that the scores for general satisfaction, interpersonal manner, communication, time spent with the physician, and accessibility and convenience in the WeChat group were significantly higher than those in the routine group (p < 0.05). Using WeChat to guide preparation before TTE for infants with CHD can effectively reduce the anxiety of their parents and improve their parents' satisfaction with medical treatment.


Adapting prehospital care to a large rural geographic area: a review of the Emergency Health Services Nova Scotia implementation.
Nova Scotia is building a system of prehospital care based on four principles: "Fail Safe" government ownership; "Full Service" advanced life support capable; "High Performance" resource efficiency; and "Fiscally Responsible" performance goals, incentives and penalties. Emergency Health Services Nova Scotia exercises funding and regulatory control through service provided by a private contractor. Benefits include improved fleet and equipment management, information systems, 911 dispatch and performance tracking, medical control and paramedic care, and public accountability. Problems include rural dispatch, budget costs, labour issues and stakeholder communication.


Scintigraphic photopenia in sacrococcygeal chordoma.
A case with a photon deficient or cold lesion on bone scintigraphy due to sacrococcygeal chordoma is presented. The proposed mechanism is also explained.


Building abstinent networks is an important resource in improving quality of life.
To investigate changes in social network and quality of life of a substance use disorder cohort as they progressed through treatment. Multi-site, prospective, observational study of 338 adults entering substance use disorder treatment. Patients at 21 facilities across Norway contributed baseline data when they initiated treatment, and follow-up data was collected from them one year later. The cohort was divided into those who completed, dropped out, and remained in treatment one year after treatment initiation. For each treatment status group, general linear models with repeated measures analyzed global and social quality of life with the generic QOL10 instrument over time. The between-group factor was a change in social network variable from the EuropASI. Those who gained an abstinent network reported the largest quality of life improvements. Improvements were smallest or negligible for the socially isolated and those who were no longer in contact with the treatment system. Developing an abstinent network is particularly important to improve the quality of life of those in substance use disorder treatment. Social isolation is a risk factor for impaired quality of life throughout the treatment course.


Functional conservation of the glycosyltransferase gene GT47A in the monocot rice.
Glucuronoarabinoxylan is the major hemicellulose in grass cell walls, yet the mechanism of xylan synthesis in monocot plants is still unclear. Unraveling the genes involved in the biosynthesis of xylan in rice will be very important for the utilization of rice straw as a source of bioenergy in the future. In this report, we investigated the functional role of a rice gene homologous to Arabidopsis IRREGULAR XYLEM10 (IRX10), belonging to the glycosyl transferase (GT) gene family 47 (GT47), in the biosynthesis of xylan. The protein sequence of OsGT47A from rice exhibits a 93.49% similarity to IRX10, which is involved in the biosynthesis of glucuronoxylan in Arabidopsis. Phylogenetic analysis of the GT47 glycosyl transferase family in the rice genome revealed that OsGT47A is a closely related homolog of IRX10 and IRX10L. Expression pattern analysis showed that the OsGT47A gene is highly expressed in the rice stem. Overexpression of OsGT47A in the irx10 irx10L double mutant rescued the plant growth phenotype and restored secondary wall thickness. Analysis of monosaccharides indicated that the rescued plants had levels of xylose identical to those of the wild type plants, and the fluorescence signals were restored in the complementation plants by xylan immunolocalization. The OsGT47A complementation under the native promoter of Arabidopsis IRX10L (ProIRX10L) partially rescued the double mutant, indicating that OsGT47A is functionally equivalent to IRX10L. Together, these results suggest that the IRX10 homolog OsGT47A exhibits functional conservation and is most likely involved in xylan synthesis in rice.


Effect of Extended 30 μg Ethinyl Estradiol with Continuous Low-Dose Ethinyl Estradiol and Cyclic 20 μg Ethinyl Estradiol Oral Contraception on Adolescent Bone Density: A Randomized Trial.
To compare changes in lumbar spine bone mineral density after 12 months of a 91-day extended regimen or 28-day combined oral contraceptive with those in a healthy reference group not using hormonal contraceptives. Phase 2, multicenter, open-label, randomized, controlled study. Forty-five academic centers, clinical research centers, and community practices in the United States. Eight hundred twenty-nine postmenarcheal adolescent girls aged 12-18 years. Adolescents were randomly assigned to 91-day levonorgestrel (LNG)/ethinyl estradiol (EE) extended regimen (84 days of LNG 150 μg/EE 30 μg with 7 days of EE 10 μg [LNG/EE extended regimen]) or 28 days of LNG/EE (21 days of LNG 100 μg/EE 20 μg with 7 days of placebo [LNG/EE 21/7]) for 12 months. A reference group not seeking hormonal contraception was also evaluated. The primary end point was mean percent change in lumbar spine bone mineral density measured using dual-energy x-ray absorptiometry. Of 1361 adolescents randomized/enrolled, 829 were included in the primary analysis. Mean changes in lumbar spine bone mineral density were +2.26% with LNG/EE extended regimen, +1.45% with LNG/EE 21/7, and +2.50% in the reference group. Noninferiority of the LNG/EE extended regimen compared with the reference group was shown. A statistically significant treatment difference was found between LNG/EE 21/7 and the reference group (1.05%; 95% confidence interval, 0.61%-1.49%) but not between LNG/EE extended regimen and the reference group (0.23%; 95% confidence interval, -0.20% to 0.67%). No new safety signals were noted. Compared with the reference group, bone accrual was statistically significantly lower among LNG/EE 21/7 users but not among LNG/EE 30-μg extended regimen users. Additional research is needed to clarify the clinical relevance of these findings.


Prognostic performance of critical care scores in patients undergoing transcatheter aortic valve implantation.
Critical care management of patients undergoing transcatheter aortic valve implantation (TAVI) is a major determinant of their outcome. The aim of this study was to compare the prognostic performance of four general scoring systems [Acute Physiology and Chronic Health Evaluation (APACHE), Simplified Acute Physiology Score (SAPS), Sequential Organ Failure Assessment (SOFA), and MultiOrgan Dysfunction (MOD) scores] in TAVI patients. Between 1 June 2008 and 30 June 2014, 75 patients (81.2 ± 6.4 years old, 36 men and 39 women) who underwent TAVI were scored during the first 24 h of their stay at the intensive care unit (ICU). The outcome measures were in-hospital and 30-day mortality and in-hospital and 30-day morbidity defined as myocardial infarction, implantation of permanent pacemaker, stroke, tamponade, major bleeding, vascular access site complications and prolonged ventilation. Four patients (5.3%) died in ICU and one more during follow-up, indicating a 30-day mortality rate of 6.6%. Regarding in-hospital mortality, the area under the ROC curve (AUC) was 0.92 for SAPS II, 0.88 for APACHE II, 0.73 for MODS and 0.74 for SOFA. Regarding 30 day-mortality, SAPS II and APACHE II performed equally higher (AUC = 0.88) than the other two scores (0.79 for MODS and 0.80 for SOFA). SAPS II had the best calibration among all four scores for in-hospital and 30-day mortality (χ2 = 3.06 and χ2 = 3.29, respectively). AUCs for in-hospital and 30-day morbidity were above 0.7 for SAPS II and APACHE II. SAPS II and APACHE II are reliable mortality and morbidity risk stratification models for TAVI patients with high calibration and discrimination.


Clinical management of iron overload.
HHC is a common inherited disorder, characterized by iron accumulation in the liver, heart, pancreas, and other organs. The clinical consequences of systemic iron loading are diverse and not always improved with iron reduction therapy. The most important prognostic factor at the time of diagnosis is the presence or absence of hepatic fibrosis or cirrhosis. Those without significant hepatic fibrosis may be expected to have a normal life expectancy with phlebotomy therapy. The availability of genetic testing for HHC has significantly changed the diagnostic approach to this disorder. Although liver biopsy remains vital to determining prognosis, genetic testing is increasingly used in the diagnosis and family screening of patients with HHC.


Enzymatic decolorization of spent textile dyeing baths composed by mixtures of synthetic dyes and additives.
The effects of different components of real dyeing bath formulations, such as the equalizing and fixing additives-acids, salts, and surfactants-on the decolorization catalyzed by Funalia trogii enzymatic extracts, were investigated to understand their influence on the recalcitrance to biodegradation of this type of wastewater. The decolorization of selected dyes and dye mixtures after tissue dyeing was performed in the presence/absence of auxiliary compounds. All spent dyeing baths were enzymatically decolorized to different extents, by the addition of extracts containing laccase only or laccase plus cellobiose dehydrogenase. Whereas surfactant auxiliaries, in some instances, inhibit the decolorization of spent dyeing baths, in several occurrences the acid/salt additives favor the enzymatic process. In general, the complete spent dyeing formulations are better degraded than those containing the dyes only. The comparison of extracellular extracts obtained from spent straws from the commercial growth of Pleurotus sp. mushrooms with those from F. trogii reveals similar decolorization extents thus allowing to further reduce the costs of bioremediation.


Does Malrotation of the Tibial and Femoral Components Compromise Function in Kinematically Aligned Total Knee Arthroplasty?
Internal and external malrotation of the femoral and tibial components is associated with poor function after total knee arthroplasty (TKA). We determined the degree of malrotation for both components in kinematically aligned TKA and whether this malrotation compromised function. Seventy-one patients (mean age 68 years) were followed after TKA. Malrotation was measured. Simple regression determined the association between malrotation and function. Even though the range of malrotation of the tibial component can be greater than that of the femoral component, the malrotation of the femoral and tibial components bounded by the ranges reported in this study is compatible with a well-functioning TKA.


Redox-dependent impairment of vascular function in sickle cell disease.
The vascular pathophysiology of sickle cell disease (SCD) is influenced by many factors, including adhesiveness of red and white blood cells to endothelium, increased coagulation, and homeostatic perturbation. The vascular endothelium is central to disease pathogenesis because it displays adhesion molecules for blood cells, balances procoagulant and anticoagulant properties of the vessel wall, and regulates vascular homeostasis by synthesizing vasoconstricting and vasodilating substances. The occurrence of intermittent vascular occlusion in SCD leads to reperfusion injury associated with granulocyte accumulation and enhanced production of reactive oxygen species. The participation of nitric oxide (NO) in oxidative reactions causes a reduction in NO bioavailability and contributes to vascular dysfunction in SCD. Therapeutic strategies designed to counteract endothelial, inflammatory, and oxidative abnormalities may reduce the frequency of hospitalization and blood transfusion, the incidence of pain, and the occurrence of acute chest syndrome and pulmonary hypertension in patients with SCD.


Evaluating preferences for profiles of GLP-1 receptor agonists among injection-naïve type 2 diabetes patients in the UK.
To use a discrete choice experiment (DCE) to evaluate preferences for the actual treatment features and overall profiles of two injectable glucagon-like peptide-1 receptor agonists (dulaglutide and liraglutide) among patients with type 2 diabetes mellitus (T2DM) in the UK. In-person interviews were conducted in the UK to administer a DCE to patients with self-reported T2DM, naïve to treatment with injectable medications. The DCE examined six attributes of T2DM treatment each described by two levels: "dosing frequency," "hemoglobin A1c change," "weight change," "type of delivery system," "frequency of nausea," and "frequency of hypoglycemia." Part-worth utilities were estimated using random effects logit models and were used to calculate relative importance (RI) values for each attribute. A chi-square test was used to determine differences in preferences for dulaglutide versus liraglutide profiles. A total of 243 participants [mean age: 60.5 (standard deviation 10.9) years; 76.1% male; mean body mass index: 29.8 (standard deviation 5.4) kg/m(2)] completed the study. RI values for the attributes in rank order were: "dosing frequency" (41.6%), "type of delivery system" (35.5%), "frequency of nausea" (10.4%), "weight change" (5.9%), "hemoglobin A1c change" (3.6%), and "frequency of hypoglycemia" (3.0%). Significantly more participants preferred the dulaglutide profile (83.1%) compared with the liraglutide profile (16.9%; P<0.0001). This study elicited patients' preferences for attributes and levels representing the actual characteristics of two specific glucagon-like peptide-1 medications. In this context, dosing frequency and type of delivery system were most important, accounting for over 75% of the RI. While previous studies have identified efficacy as highly important in T2DM medication decisions, this study suggests that when differences in efficacy between medications are small, other treatment features (eg, dosing frequency and delivery system) are of much greater importance to patients.


Studies on the metabolism of the lipoprotein Lp (a) in man.
Lp(a) was isolated and labeled by reductive alkylation. Radioactivity only entered the protein moiety of the lipoprotein. No change in the immunological or physicochemical properties of Lp(a) was noted after the radiomethylation. After incubation of labeled Lp(a) with whole serum for 24 h in vitro, more than 99% of the radioactivity of the incubated sample was found in Lp(a). In 4 subjects Lp(a) was injected intravenously. A linear decline of the specific activity of Lp(a) in the serum was found when it was plotted semilogarithmically against time. Half-lives of Lp(a) in the serum were 35, 38, 53 and 58 h. In one subject, the "soluble" and the "insoluble" apoproteins of Lp(a) showed the same half-life as the whole Lp(a) molecule. This suggests that no exchange of Lp(a) apoproteins with lipoproteins of other density classes took place. At different times after the injection of Lp(a), 3--8% of the radioactivity of the serum was found in Lp B, and less than 2% of the radioactivity was detectable in VLDL and the fraction having a density of greater than 1.110 g/ml.


Excellent low-temperature NH3-SCR NO removal performance and enhanced H2O resistance by Ce addition over the Cu0.02Fe0.2CeyTi1-yOx (y = 0.1, 0.2, 0.3) catalysts.
In the present work, a serial of Cu0.02Fe0.2CeyTi1-yOx catalysts are prepared by sol-gel method and applied for NH3-SCR of NO, meanwhile Cu0.02Fe0.2Ce0.2Ti0.8Ox shows good low-temperature NH3-SCR performance with/without water and an outstanding water resistance. The bulk structure, redox ability, surface acidity and surface species of Cu0.02Fe0.2CeyTi1-yOx are measured and discussed by series of characterization in details to illuminate the reasons for the good low-temperature activity and water resistance. The Ce modification can tune the surface acidic distribution, improve the surface oxygen content and surface oxidation reduction cycle (Ce4+ + Fe2+ ↔ Ce3+ + Fe3+), which contribute the good activity. In addition, the effect of water on NH3-SCR performance over Cu0.02Fe0.2TiOx and Cu0.02Fe0·2Ce0·2Ti0.8Ox are investigated emphatically by in situ DRIFTS.


The involvement of CD14 in stimulation of cytokine production by uronic acid polymers.
In this study the molecular mechanisms behind the stimulatory activities of the uronic acid polymers poly mannuronic acid (poly M), high M alginate and oxidized cellulose (C60XY) were investigated and compared with lipopolysaccharide (LPS). The cytokine-inducing abilities of the uronic acid polymers and LPS were examined on CD14-positive human monocytes and CD14-negative U373 astrocytoma cells. It was found that LPS induced monocytes and U373 cells to produce tumor necrosis factor (TNF) and interleukin(IL)-6, respectively, by different mechanisms. The poly uronic acids induced monocytes to produce TNF, but with 100-1000 times less potency compared to LPS. On U373 cells, LPS at concentrations > or = 32 ng/ml resulted in a dose-related IL-6 production, whereas the poly uronic acids had negligible effects even at 1 mg/ml. The binding data demonstrate that only the CD14-positive monocytes in the peripheral blood mononuclear cells population bound poly M. Furthermore, poly M was found to bind to CD14 in the presence of serum. Antibodies against CD14 also inhibited the TNF-inducing activity of the three uronic acid polymers tested. In conclusion, these results demonstrate that uronic acid polymers induce TNF production through mechanisms which involve CD14.


Brachial neuritis or Parsonage-Turner syndrome: A problem of liability. A presentation of 3 cases.
Neuralgic amyotrophy, brachial neuritis or Parsonage-Turner syndrome is a rare neuromuscular involvement of unknown aetiology. When it onsets in connection with a health care act, such as childbirth or surgery, a malpractice argument is often used as a cause of adverse outcome, usually due to an incorrect position of the patient on the operating table, a circumstance which directly involves the anesthesia area. Three cases are presented of Parsonage-Turner syndrome following very different surgery, with different results as regards prognosis. A review and discussion of bibliography is presented on the possibility that such circumstances are the subject of malpractice claims. Special emphasis is placed on the most currently accepted aetiopathogenic theories, and the relationship of this syndrome with the surgical act as a determining medico-legal aspect. Valuation parameters are proposed.


Good Functional Outcomes and Low Infection Rates in Total Hip Arthroplasty in HIV-Positive Patients, Provided There Is Strict Compliance With Highly Active Antiretroviral Therapy.
Patients with HIV are more likely to require a total hip arthroplasty (THA) because of an increase in life expectancy and complications with HIV. The purpose of this study is to describe the mid-term outcomes of THA in HIV-positive patients and risk factors for postoperative infections and poor outcomes. This is a single-center retrospective review of nonhemophiliac HIV-positive patients who underwent THA. We reviewed the short- and mid-term readmission and complication rates. Eighty-seven patients underwent 102 THAs. The average age was 58 years (24-73 years). The average body mass index was 31.6 (18-55). The average CD4+ count was 569 cells per cubic millimeter (mm3) (51-1480), and the mean viral load was <40 copies/mL (undetectable-380 000). The mean follow-up time was 6.7 years (24 months- 8.3 years). Four patients had postoperative complications within 30 days. Seven patients had postoperative complications after 30 days; 5 of which had septic loosening of implants and had either not been initiated on or were noncompliant with their highly active antiretroviral therapy. The average postoperative Harris Hip Score was 81 (41-100) and Oxford Hip Score was 43.43 (34-48). There was no correlation the between CD4+ count and viral load with complications. Low rate of complications and revision is achievable in the HIV-positive, nonhemophilic arthroplasty population contrary to published literature. An important factor ensuring good long-term outcomes in HIV-positive patients undergoing THA was the initiation of highly active antiretroviral therapy before the procedure and ensuring patient compliance with therapy after joint arthroplasty.


Immunoglobulins, autoantibodies and other serum protein fractions in psychiatric disorders.
The levels of IgM, IgG and IgA were measured in the serum of 337 psychiatric inpatients (92 patients with bipolar depression, 150 patients with unipolar depression and 95 schizophrenics) and compared to 150 healthy subjects. A significantly higher level of IgM was found in all psychiatric groups compared with the controls, and IgM levels were more elevated in female patients than in male patients for the bipolar and unipolar groups. There were no differences for the other immunoglobulins (IgG, IgA) among the groups studied. In 51 of the patients (17 bipolar, 34 unipolar), other measurements were performed (C-reactive protein, antinuclear antibodies, lymphocyte antibodies, thyroid antibodies, complement and the third and fourth factors of complement). The unipolar group showed a significant rise of C-reactive protein values and the presence of antinuclear antibodies. Interestingly all patients with antinuclear antibodies were females. No difference was found between psychiatric patients and controls in lymphocyte antibodies, thyroid antibodies and values of complement.


Light and electron microscopic immunocytochemical analysis of the noradrenaline innervation of the rat visual cortex.
Immunocytochemistry with an antiserum against noradrenaline was used to examine the organization and morphology of noradrenergic axons in the rat visual cortex. Observations with the light microscope confirmed earlier reports concerning the distribution pattern of noradrenergic fibres, and provided some further clues about their intracortical organization. Particularly striking was the finding of fibres which followed an oscillating course within the boundaries of layers II-IV as they ran in the mediolateral direction. Examination of the morphological characteristics of noradrenaline-containing axon terminals in serial ultrathin sections has provided further evidence that the vast majority (87.6%) form conventional synapses in the visual and frontoparietal cortex, and has given clues about the postsynaptic elements involved in these synaptic contacts; they are, in decreasing frequency, spines, dendritic shafts of various diameters, and pyramidal and non-pyramidal somata. In addition, a few labelled terminals were visualized in close association with intracerebral capillaries.


Application of the white rot fungus Phanerochaete chrysosporium in biotreatment of bagasse effluent.
Biotreatment of bagasse effluent using Phanerochaete chrysosporium (white rot fungus) is investigated. This study confirmed that lignin is the major pollutant component in this effluent followed by different carbohydrates. The treatment conditions must be very proper, especially in terms of biomass culture to achieve a successful treatment. The best conditions of temperature, biomass concentration, pH and duration for biotreatment of this effluent were 35°C, 552 mg l(-1), 6 and 5 to 9 days, respectively. Under these conditions, a 9 days long treatment reduced by 98.7% the original biochemical oxygen demand (of 2,780 mg l(-1)) and by 98.5% the dissolved chemical oxygen demand (initial 4,200 mg l(-1)). Moreover, fungal treatment reduced total dissolved solids from 3,950 to 575 mg l(-1) and color from 560 mg l(-1) PtCo to 111 mg l(-1) PtCo.


NO-donating genistein prodrug alleviates bone loss in ovariectomised rats.
To find a more potent alternative with less oestrogen-related side effects for hormone replacement therapy (HRT) in postmenopausal osteoporosis, we designed and synthesized a NO-releasing prodrug of genistein (NO-G) according to the structure of NONSAIDs. The purpose of this study was to evaluate the effects of the prodrug on bone in ovariectomised (OVX) rats. Forty-eight adult Sprague-Dawley female rats were ovariectomised and treated with vehicle, 9 mg/kg genistein and 4.5, 9 or 18 mg/kg NO-G by oral administration daily. The bioassays were performed in terms of bone mineral density (BMD), mechanical testing, bone formation markers, bone alkaline phosphatase (b-ALP) and osteocalcin (OCN) and bone resorption marker urine deoxypyridinoline (DPD). In addition, the effects of the drugs on uterus and body weight were examined. After treatment for 12 weeks, the BMD of whole femur and tibia in the NO-G (9 and 18 mg/kg) groups were 12.1% and 12.2% higher than that of OVX group (P<0.01); the bending strength of the femur was 11.2% and 12.2% higher than OVX group (P<0.01). The OVX-induced increase of serum b-ALP, OCN and urinary DPD were markedly attenuated. The prodrug showed no side effects on uterus and body weight. The NO-releasing prodrug of genistein improves the bone loss in OVX rats without stimulatory effects on the uterus, which suggests that the product could potentially be used for the prevention and treatment of postmenopausal osteoporosis.


Adjuvant Chemotherapy Is Associated with Improved Survival for Stage III Colon Cancer When Initiated Beyond 8 Weeks.
The National Comprehensive Cancer Network (NCCN) guidelines recommend adjuvant chemotherapy (AC) within 6-8 weeks of surgical resection for patients with stage III colon cancer. However, postoperative complications or prolonged surgical recovery may affect the receipt of AC. The aim of this study was to assess the utility of AC for patients with prolonged postoperative recovery. We queried the National Cancer Database (2010-2018) for patients with resected stage III colon cancer. Patients were categorized as having either normal or prolonged length of stay (PLOS: >7 days, 75th percentile). Multivariable Cox proportional hazard regression and logistic regressions were used to identify factors associated with overall survival and receipt of AC. Of the 113,387 patients included, 30,196 (26.6%) experienced PLOS. Of the 88,115 (77.7%) patients who received AC, 22,707 (25.8%) initiated AC more than 8 weeks after surgery. Patients with PLOS were less likely to receive AC (71.5% vs. 80.0%, OR: 0.72, 95%CI=0.70-0.75) and displayed inferior survival (75 vs. 116 months, HR: 1.39, 95%CI=1.36-1.43). Receipt of AC was also associated with patient factors such as high socioeconomic status, private insurance, and White race (p<0.05 for all). AC within and after 8 weeks of surgery was associated with improved survival for patients with both normal LOS and PLOS (normal LOS: <8 weeks HR: 0.56, 95% CI: 0.54-0.59, >8 weeks HR: 0.68, 95% CI: 0.65-0.71; PLOS: <8 weeks HR: 0.51, 95% CI: 0.48-0.54, >8 weeks HR: 0.63, 95% CI 0.60-0.67). AC was associated with significantly improved survival if initiated up to 15 weeks postoperatively (normal LOS: HR: 0.72, 95%CI=0.61-0.85; PLOS: HR: 0.75, 95%CI=0.62-0.90), and very few patients (<3.0%) initiated AC beyond this time. Receipt of AC for stage III colon cancer may be affected by surgical complications or otherwise prolonged recovery. Timely and even delayed AC (>8 weeks) are both associated with improved overall survival. These findings highlight the importance of delivering guideline-based systemic therapies, even after complicated surgical recovery.


Molecular characterization and immunological properties of Echinococcus granulosus sensu stricto (G1) ADK1 and ADK8.
Adenylate kinases (ADKs) are one of the important enzymes regulating adenosine triphosphate (ATP) metabolism in Echinococcus granulosus sensu lato. The objective of the present study was to explore the molecular characteristics and immunological properties of E. granulosus sensu stricto (G1) adenylate kinase 1 (EgADK1) and adenylate kinase 8 (EgADK8). EgADK1 and EgADK8 were cloned and expressed, and the molecular characteristics of EgADK1 and EgADK8 were analyzed through different bioinformatics tools. Western blotting was used to examine the reactogenicity of recombinant adenylate kinase 1 (rEgADK1) and recombinant adenylate kinase 8 (rEgADK8) and to evaluate their diagnostic value. The expression profiles of EgADK1 and EgADK8 in 18-day-old strobilated worms and protoscoleces were analyzed by quantitative real-time PCR, and their distribution in 18-day-old strobilated worms, the germinal layer, and protoscoleces was determined by immunofluorescence localization. EgADK1 and EgADK8 were successfully cloned and expressed. Bioinformatics analysis predicted that EgADK1 and EgADK8 have multiple phosphorylation sites and B-cell epitopes. Compared with EgADK8, EgADK1 and other parasite ADKs have higher sequence similarity. In addition, both cystic echinococcosis (CE)-positive sheep sera and Cysticercus tenuicollis-infected goat sera could recognize rEgADK1 and rEgADK8. EgADK1 and EgADK8 were localized in protoscoleces, the germinal layer, and 18-day-old strobilated worms. EgADK1 and EgADK8 showed no significant difference in their transcription level in 18-day-old strobilated worms and protoscoleces, suggesting that EgADK1 and EgADK8 may play an important role in the growth and development of E. granulosus sensu lato. Since EgADK1 and EgADK8 can be recognized by other parasite-positive sera, they are not suitable as candidate antigens for the diagnosis of CE.


Multimodal intraoperative monitoring during intramedullary spinal cord tumor surgery.
The aim of this work is to evaluate the utility of multimodal intraoperative monitoring (IOM) during intramedullary spinal cord tumor (IMSCT) surgery in our institution, and to investigate which IOM events are likely to be encountered during critical surgical phases. Twenty-five patients who underwent IMSCT surgery with IOM were included in this study. Our multimodal IOM assessment included SSEP, mMEP, and fEMG monitoring. Positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity were assessed 24 h and 1 month after surgery. The IOM events during three main surgical phases were also investigated. For mMEP assessment, two warning criteria (>50 % decrease in mMEP amplitude and all-or-none mMEP amplitude presence) were employed. Long-term outcome prediction was better when the all-or-none criterion was applied than when the >50 % amplitude decrease criterion was applied. Based on the all-or-none criterion, the PPV, NPV, sensitivity, and specificity were 60, 100, 100, and 91 %. Frequent IOM events were observed during the three major main surgical phases. Seven (29 %) patients showed SSEP events during opening of the spinal cord. During tumor removal, 21 of 25 patients (84 %) had IOM events, and 13 of 18 (72 %) of the fEMG events occurred prior to the mMEP events. Based on the association of fEMG events with upcoming mMEP events during tumor removal, we recommend inclusion of fEMG monitoring in IOM. Multimodal IOM provides useful electrophysiological information during IMSCT surgery, especially during the main surgical phases.


On-line sample preconcentration by sweeping and poly(ethylene oxide)-mediated stacking for simultaneous analysis of nine pairs of amino acid enantiomers in capillary electrophoresis.
This study proposes a sensitive method for the simultaneous separation and concentration of 9 pairs of amino acid enantiomers by combining poly(ethylene oxide) (PEO)-based stacking, β-cyclodextrin (β-CD)-mediated micellar electrokinetic chromatography (MEKC), and 9-fluoroenylmethyl chloroformate (FMOC) derivatization. The 9 pairs of FMOC-derivatized amino acid enantiomers were baseline separated using a discontinuous system, and the buffer vials contained a solution of 150 mM Tris-borate (TB), 12.5% (v/v) isopropanol (IPA), 0.5% (w/v) PEO, 35 mM sodium taurodeoxycholate (STDC), and 35 mM β-CD, and the capillary was filled with a solution of 1.5 M TB, 12.5% (v/v) IPA, 35 mM STDC, and 35 mM β-CD. Based on the difference in viscosity between the sample zone and PEO solution and because of the STDC sweeping, the discontinuous system effectively stacked 670 nL of the 9 pairs of FMOC-derivatized amino acid enantiomers without losing chiral resolution. Consequently, the limits of detection for the 9 pairs of FMOC-derivatized amino acid enantiomers were reduced to 40-60 nM. This method was successfully used to determine d-Tryptophan (Trp), l-Trp, d-Phenylalanine (Phe), l-Phe, d-Glutamic acid (Glu), and l-Glu in various types of beers.


Reevaluation of the presence of the major antigen Ca++ complex in Bernard-Soulier syndrome platelets. Elastase degradation of the complex in Bernard-Soulier syndrome platelet preparations.
Crossed immunoelectrophoresis of human platelet membranes reveals a major antigen GPIIb-GPIIIa-Ca++ complex which is absent to decreased in Glanzmann's thrombasthenia. In our initial report, we also noted its absence in two patients with Bernard-Soulier syndrome associated with the presence of two neoantigens, and postulated that this may be due to endogenous proteolysis. It now appears that this observation is due to exogenous proteolysis from granulocyte-elastase contamination in the platelet membrane preparation. Purified elastase is capable of degrading the major antigen-Ca++ complex, particularly in its dissociated form, to the pattern initially reported for Bernard-Soulier platelets. Of particular interest is the observation that the elastase-degraded dissociated complex can be reassociated in the presence of Ca++. This indicates that the elastase-sensitive antigenic determinants recognized by the rabbit anti-human platelet membrane antibody are not required for the bonds which reassociate the complex.


Prevention of smoking in young children in Holland: education and changing attitudes.
The Dutch Foundation on Smoking and Health is executor of the Dutch governmental information policy to discourage smoking. Although smoking prevalences have steadily decreased from 60% in 1967 to 33% in 1989, much needs to be done to continue to eliminate this dangerous habit. The main priority of the Foundation is to prevent young people from taking up the habit of smoking. To this end, we use two different education and prevention campaigns: 1) "Don't play with fire," a school program aimed at children 10-12 years old. It consists of a teachers manual and six worksheets for each pupil and gives information about seven different aspects of the smoking habit; 2) a continuing approach, via posters, advertisements in youth media and school materials to young adolescents 13-19 years old. In 1983 the campaign "I don't smoke, I play sports"; in 1986 "Smoking . . . why should I"; and in 1989 "Smoking? Why should you?" Both programs led to increased knowledge, changed attitudes, and decreased smoking habits among both target groups.


Complications of submucous resections of the nasal septum.
We studied retrospectively 263 patients, who had previously undergone submucous resection of their nasal septa. Unsatisfactory septal corrections, perforations, and dorsal saddling were looked for and could be correlated with the skills of the ten surgeons who performed the procedures. Three of the surgeons were attending physicians, while the other seven were resident trainees at different stages of their specialty education. From the total number of the patients, 17 (6.4%) were noted to have persistent septal perforations, 10 (3.8%) had residual deviations of their nasal septa, and 1 (0.4%) had a saddle nose deformity. These findings differed significantly among the different surgeons. The incidence varied from 0% to 30.4% in septal perforations, from 0% to 10.4% in unsatisfactory corrections of the septum, and from 0% to 2.6% in saddle nose. Our findings show that a well-executed submucous resection of the nasal septum by a skilled surgeon yields a low incidence of complications, while in unskilled hands, it may carry a high incidence of complications.


[Medial pancreatectomy: results of a series of 11 patients].
To report a new series of medial pancreatectomy (MP), with analysis of early and long-term results. From 1990 to 1999, 11 patients (mean age = 53 years, extremes: 28-70)--including 10 non-diabetic--underwent MP for neuroendocrine tumor (n = 5), intraductal papillary mucinous tumor (IPMT) (n = 3), serous cystadenoma, metastasis from renal cell carcinoma, and focal pancreatitis. The procedure included medial resection of variable extent, frozen section, and suture of the cephalic stump. The caudal stump was either anastomosed to the posterior gastric wall (n = 9), or closed when atrophic or very small (n = 2). The mean length of resection was 7 cm (extremes: 4-15). The diagnosis suspected preoperatively was confirmed in 10 cases. In one patient, a suspected adenocarcinoma was actually a focal pancreatitis. No postoperative death occurred. Seven patients experienced complications: one delayed gastric emptying and 6 pancreatic fistulas (54%), including 3 associated with intraabdominal collection. Two patients were reoperated to drain a pancreatic fistula. The mean hospital stay was 14 days (extremes: 10-21) without complications, and 30 days (extremes: 11-90) after complications. After a mean follow-up of 45 months (extremes: 7-130), only one patient initially non-diabetic experienced post-operative diabetes and needs enzyme therapy after a 15 cm-resection for IPMT. No patient developed isolated intrapancreatic recurrence. MP preserves efficiently pancreatic function and is associated with a low risk of intrapancreatic recurrence. Conversely, MP is associated with an high risk of pancreatic fistula.