Vitamin K1 As A Potential Molecule For Reducing Single-Walled Carbon Nanotubes-Stimulated α-Synuclein Structural Changes And Cytotoxicity.
Different kinds of vitamins can be used as promising candidates to mitigate the structural changes of proteins and associated cytotoxicity stimulated by NPs. Therefore, the structural changes of α-syn molecules and their associated cytotoxicity in the presence of SWCNTs either alone or co-incubated with vitamin K1 were studied by spectroscopic, bioinformatical, and cellular assays. Intrinsic and ThT fluorescence, CD, and Congo red absorption spectroscopic approaches as well as TEM investigation, molecular docking, and molecular dynamics were used to explore the protective effect of vitamin K1 on the structural changes of α-syn induced by SWCNTs. The cytotoxicity of α-syn/SWCNTs co-incubated with vitamin K1 against SH-SY5Y cells was also carried out by MTT, LDH, and caspase-3 assays. Fluorescence spectroscopy showed that vitamin K1 has a significant effect in reducing SWCNT-induced fluorescence quenching and aggregation of α- syn. CD, Congo red adsorption, and TEM investigations determined that co-incubation of α- syn with vitamin K1 inhibited the propensity of α-syn into the structural changes and amorphous aggregation in the presence of SWCNT. Docking studies determined the occupation of preferred docked site of SWCNT by vitamin K1 on α- syn conformation. A molecular dynamics study also showed that vitamin K1 reduced the structural changes of α- syn induced by SWCNT. Cellular data exhibited that the cytotoxicity of α- syn co-incubated with vitamin K1 in the presence of SWCNTs is less than the outcomes obtained in the absence of the vitamin K1. It may be concluded that vitamin K1 decreases the propensity of α- syn aggregation in the presence of SWCNTs and induction of cytotoxicity.


Isolation, characterization of melanin derived from Ophiocordyceps sinensis, an entomogenous fungus endemic to the Tibetan Plateau.
Melanins are pigments of high molecular weight formed by oxidative polymerization of phenolic or indolic compounds. In this present study, a black pigment was isolated from the fermentation broth of Ophiocordyceps sinensis, an entomogenous fungus which is endemic to the Tibetan Plateau by alkaline extraction, acid hydrolysis, and repeated precipitation. It was designed as melanin since the physical and chemical properties including its ultraviolet (UV) and infrared (IR) spectra of the black pigment conformed to the characteristic of melanin and similar to the commercial synthetic melanin. The antioxidant activity of melanin derived from O. sinensis was evaluated. They showed much stronger scavenging abilities on 1,1-diphenyl-2-picrylhydrazyl (DPPH•) and the chelating ability on ferrous ions than that of the water extract from the mycelia of O. sinensis, with IC(50) value 18.51 ± 0.85 μg/ml and 2.58 ± 0.26 μg/ml, separately. This is the first report of melanin from O. sinensis and will be helpful for the study on the physiology and the artificial cultivation of this fungus, an endangered species.


High Diversity of Drosophilidae in High-Altitude Wet Forests in Northeastern Brazil.
The high-altitude wet forests of northeastern Brazil, locally known as "Brejos de Altitude," are enclaves of the Atlantic Forest situated above 500 m, surrounded by dryland vegetation, the Caatinga. The aim of this study was to characterize drosophilid communities in these upland forests, since few ecological studies on drosophilid communities have been conducted in northeastern Brazil. Four sites were investigated in three different times of the year throughout standardized traps. The results reveal the presence of 55 different species in a total of 13,064 specimens collected. The data were evaluated using ecological diversity measurements and compared with those obtained for other environments in the same geographic region. As for species composition, the Bonito upland forest, in a boundary forest location, stood out as having high species richness.


Rotavirus Serum IgA Immune Response in Children Receiving Rotarix Coadministered With bOPV or IPV.
Vaccine schedules including bivalent oral and inactivated poliovirus vaccines will replace trivalent oral poliovirus vaccines in 2016. We evaluated rotavirus immunoglobulin A seroresponses when the second dose of Rotarix at 16 weeks was given concomitantly with inactivated or bivalent oral poliovirus vaccines. Rotavirus immunoglobulin A seroresponse rate at week 28 was 15% lower in recipients of bivalent oral poliovirus vaccines compared with inactivated poliovirus vaccines. Bivalent oral poliovirus vaccine decreases rotavirus IgA seroresponse rates when coadministered at 16 weeks of age.


Perineal-abdominal cystourethrectomy with pelvic node dissection: a new 2-stage procedure for selected cases.
An ileal conduit diversion followed 7 to 14 days later by cystourethrectomy with pelvic node dissection was done on 20 patients with carcinoma of the bladder. Two types of patients were selected for this operation: 1) those with an advanced stage of carcinoma involving the bladder neck, prostatic urethra or prostate, primarily cases suspected of having focal metastatic disease in the urethra, and 2) patients who had had a previous pelvic operation with resultant dense adhesions and scarring. The cystourethrectomy with pelvic node dissection is begun perineally. After the specimen, consisting of the urethra, part of the urogenital diaphragm, seminal vesicles, prostate and bladder is dissected, mobilized and, finally, pushed into the pelvis the perineum is closed and the operation is completed abdominanlly through a Pfannenstiel incision.


Electrochemical and electrochemiluminescence study of Ru(bpy)(2+)3-doped silica nanoparticles with covalently grafted biomacromolecules.
Spherical Ru(bpy)(2+)(3)-doped silica (RuSi) nanoparticles were prepared via a water-in-oil microemulsion approach. The electrochemical and electrochemiluminescent properties of the RuSi nanoparticles immobilized on an indium tin oxide (ITO) electrode were investigated. Further, electrochemiluminescence (ECL) of the RuSi nanoparticles with covalently coated biomacromolecules was studied. By covalent cross-linking with glutaraldehyde, gamma-(aminopropyl) triethoxysilane (APTES)-pretreated RuSi nanoparticles were coupled with different concentrations of bovine serum albumin (BSA), hemoglobin, and myoglobin, respectively. ECL from these biomacromolecule-coated RuSi nanoparticles decreased with the increase of the loading of biomacromolecules. Moreover, the ECL of coreactants with different sizes was studied. The ECL decrease could be assigned to the steric hindrance and limited diffusion of coreactant molecules into the RuSi nanoparticles after biomacromolecule conjugation. Since tens of thousands of Ru(bpy)(2+)(3) molecules are contained in the silica particles and the RuSi nanoparticle surface modification could improve their biocompatibility, the biomacromolecule-coated RuSi nanoparticles could be readily used as efficient and stable ECL tag materials in the future.


A weak blood group A phenotype caused by a new mutation at the ABO locus.
A number of alleles have been described for ABO encoding for common and rare ABO blood group phenotypes. Critical mutations in the coding sequence of ABO that may confer the different specificity and activity of the glycosyltransferases encoded by this gene locus have been identified. Three unrelated patients from Germany, Turkey, and Bosnia who were diagnosed as having variant A subgroups were subjected to extended ABO typing. Serologic investigations were performed with standard methods. The genetic basis of the ABO phenotypes was determined by haplotype-specific sequence analysis of the last two exons (exons 6 and 7) of ABO and the intervening intron. The RBCs of all three patients showed serologic A characteristics being similar to subgroup A(x). The serum of all three patients contained weakly reactive anti-A. In all three patients, sequence analysis indicated an A allele with a nucleotide sequence identical to ABO(*)A101 except for a single-base substitution in exon 7 at position 502, where C was replaced by G. This point mutation resulted in an amino acid exchange from arginine to glycine at position 168. The nucleotide sequence of intron 6 of the A allele was found to be identical to the ABO(*)A101 sequence in each patient. This study suggests that a variant A phenotype can arise from the new R168G polymorphism, reflecting the importance of this region for the ABO transferase efficiency.


Capsule function following anterior dislocation: implications for diagnosis of shoulder instability.
During shoulder dislocation, the glenohumeral capsule undergoes non-recoverable strain, leading to joint instability. Clinicians use physical exams to diagnose injury and direct repair procedures; however, they are subjective and do not provide quantitative information. Our objectives were to: (1) determine the relationship between capsule function following anterior dislocation and non-recoverable strain; and (2) identify joint positions at which physical exams can be used to detect non-recoverable strain in specific capsule regions. Physical exams were simulated at three joint positions including external rotation (ER) using robotic technology before and after anterior dislocation. The resulting joint kinematics, strain distribution in the capsule, and non-recoverable strain were determined. Following dislocation, anterior translation increased by as much as 48% (0° ER: p = 0.03; 30° ER: p = 0.03; 60° ER: p < 0.01). Capsule sub-regions with less non-recoverable strain required more ER to detect differences in the strain ratios between the intact and injured joint. Strain ratio changes on the humeral side of the posterior axillary pouch (0.31 ± 0.32) were significant at all joint positions (0° ER: p = 0.03; 30° ER: p = 0.048; 60° ER: p = 0.04), whereas strain ratio differences on the humeral side of the anterior axillary pouch (0.18 ± 0.21) were significant only at 60° of ER (p = 0.03). Therefore, standardizing physical exams for joint position could help surgeons identify specific locations of non-recoverable strain that may have been ignored.


Derivation, maintenance, and characterization of rat embryonic stem cells in vitro.
The in vitro differentiation of mouse embryonic stem (ES) cells into different somatic cell types such as neurons, endothelial cells, or myocytes is well established, and many mouse ES cell lines have been created so far. The establishment of rat ES cell lines, however, has proven to be difficult. Most attempts to culture rat ES cell lines and maintain them in an undifferentiated state have failed, so researchers were forced to abandon this system and use mouse ES cells. This chapter describes the long-term cultivation of an alkaline phosphatase-positive rat embryonic stem cell-like line (RESC) and their differentiation into neuronal, endothelial, and hepatic lineages. The RESCs can be characterized by typical growth in single cells as well as embryoid bodies when cultivated in the presence of leukemia inhibitory factor. RESC expressed stage-specific-embryonic antigen 1 and the major histocompatibility class 1 molecule. Neuronal differentiation is achieved by standard retinoic acid treatment and endothelial differentiation can be reproducibly induced by growth on or within Matrigel for 14 d. To induce expression of hepatocyte-specific antigens, RESCs were either grown in hepatocyte-conditioned media or in media containing different combinations of growth factors. The characterization of differentiated cells was done primarily by immunohistochemistry, enzyme-linked immunosorbent assay, and polymerase chain reaction.


Improved survival of patients with stage II melanoma of the extremity using hyperthermic isolation perfusion with 1-phenylalanine mustard.
Between 1964 and 1983, 65 patients with Stage II extremity melanoma were treated in a nonrandomized fashion with wide local excision, lymph node dissection, and hyperthermic perfusion with 1-phenylalanine mustard at 1.0-1.5 mg/kg. Southwest Oncology Group Stage II criteria were used, including IIA (node positive), IIB/C (recurrent local/regional), or both. During the study interval, literature reports of 5-year survival for Stage II melanoma ranged from 6% to 50% and averaged approximately 26% to 30%. In this study group, 40% of patients had recurrent disease confined to regional lymph nodes, 33% had recurrent cutaneous disease, and 26% had recurrent disease in both locations. Survival for all Stage II patients at 5 years was 56.6%, and 40% at 10 years. When recurrent disease was confined to regional nodes only (IIA), survival at 5 years was 70.5%, and 40% at 10 years. Survival for patients with Stage IIB/C disease at 5 and 10 years was 58% and 43.7%. When recurrent melanoma was present in both skin and nodes, 5-year survival was 29%. The present study indicates that aggressive treatment of Stage II extremity melanoma, which includes hyperthermic isolation perfusion, can prolong survival in these high-risk patients.


Brittle nail syndrome: a pathogenesis-based approach with a proposed grading system.
Brittle nail syndrome is a heterogeneous abnormality, characterized by increased fragility of the nail plate. Brittle nails affect about 20% of the population and women are affected twice as frequently as men. The vast majority of patients experience brittle nails as a significant cosmetic problem and a substantial number indicate that these nail abnormalities are painful, impair daily activities, and may have a negative impact on occupational abilities. Pathogenic factors leading to brittle nails are factors that impair intercellular adhesion of the corneocytes of the nail plate or factors that cause a pathologic nail formation by involving the matrix. Clinical features of brittle nail syndrome are onychoschizia and onychorrhexis: the impairment of intercellular adhesive factors of the nail plate is expressed as onychoschizia, whereas the involvement of the nail matrix is expressed as onychorrhexis. Although impairment of life quality has not been evaluated for patients with brittle nail syndrome, the reduction of life quality in other nail problems has been studied and is evident. A proposed scoring system of key features of brittle nails is presented, and therapeutic approaches focussed on the pathogenic factors are discussed.


Neonatal alloimmune neutropenia attributed to maternal immunoglobulin G antibodies against the neutrophil alloantigen HNA-1c (SH): a report of five cases.
Neonatal alloimmune neutropenia (NAN) occurs when maternal immunoglobulin G (IgG) antibodies enter fetal circulation and destroy neonatal neutrophils. Whether antibodies specific for the neutrophil antigen HNA-1c (SH) can cause NAN is uncertain, because in three of four reported cases, other neutrophil-specific antibodies were present. In this report, we describe five cases of NAN, in which only anti-HNA-1c was detected in maternal serum. HNA-1c antibodies were detected with flow cytometry immunofluorescence (FCI) and the monoclonal antibody (MoAb) immobilization of granulocyte antigens (MAIGA) assay. Genotyping for HNA-1c was performed by allele-specific polymerase chain reaction amplification of DNA. All five maternal serum samples contained IgG antibodies with specificity for HNA-1c detected in both FCI and MAIGA assay. Of CD16-specific MoAbs evaluated, only MBC238.7 was optimal for detection of antibody by MAIGA assay. Recombinant human granulocyte-colony-stimulating factor (rHuG-CSF) was effective in raising neutrophil counts in the two infants treated in this manner. Severe NAN can be caused by maternal antibodies specific for HNA-1c (SH) alone. Use of an appropriate MoAb is critical for detection of anti-HNA-1c by MAIGA assay. rHuG-CSF is an effective therapy in infants with NAN caused by anti-HNA-1c.


The use of a personal digital assistant for wireless entry of data into a database via the Internet.
Researchers typically record data on a worksheet and at some later time enter it into the database. Wireless data entry and retrieval using a personal digital assistant (PDA) at the site of patient contact can simplify this process and improve efficiency. A surgeon and a nurse coordinator provided the content for the database. The computer programmer created the database, placed the pages of the database on the PDA screen, and researched and installed security measures. Designing the database took 6 months. Meeting Health Insurance Portability and Accountability Act of 1996 (HIPAA) requirements for patient confidentiality, satisfying institutional Information Services requirements, and ensuring connectivity required an additional 8 months before the functional system was complete. It is now possible to achieve wireless entry and retrieval of data using a PDA. Potential advantages include collection and entry of data at the same time, easy entry of data from multiple sites, and retrieval of data at the patient's bedside.


The effect of propranolol on the rise in plasma ammonia during modest exercise.
Changes in plasma ammonia in response to exercise with and without pretreatment with propranolol have been studied. A standardised submaximal treadmill exercise test was used to assess the effects of placebo or propranolol 40 mg, 80 mg, or 160 mg twice daily given in random order for 3 days, the last dose being taken 90 min before exercise. After placebo the mean incremental rise in plasma ammonia in response to exercise was 16 mumol X 1(-1). The corresponding rise after propranolol 40 mg was 56 mumol X 1(-1) (p less than 0.01). All three doses of propranolol produced similar effects on plasma ammonia and exercise heart rates.


Glioblastoma Multiforme: A Rare Case of Spinal Drop Metastasis.
The occurrence of spinal drop metastasis in patients diagnosed with glioblastoma multiforme (GBM) is rare. In previous reports, this diagnosis occurred after surgical resection of GBM, which was believed to increase the likelihood of tumor seeding. Diagnosis of spinal drop metastasis prior to surgery remains rare. We report a 57-year-old woman with a brief history of confusion, altered behavior, and agitation without any other significant past medical history. Computed tomography and magnetic resonance imaging (MRI) of the head demonstrated an intra-axial lesion of the right temporal lobe as well as evidence of leptomeningeal disease around the medulla. A spine MRI scan revealed spinal drop metastases at the level of C1 and T6/T7. Subsequent biopsy confirmed WHO-2016 grade IV GBM. The awareness of the possibility of spinal drop metastasis prior to surgical resection of GBM is important. The use of routine MRI of the whole neuroaxis in patients diagnosed with GBM can aid in prognosis and management options.


Evolving variation in the extent of surgery for low-risk papillary thyroid cancer in the United States.
The continued debate over total thyroidectomy versus lobectomy and declining favor for prophylactic central neck dissection for patients with clinically node-negative papillary thyroid cancer ≤4 cm is ongoing after the 2015 guideline updates from the American Thyroid Association. This study aimed to evaluate contemporary trends in the extent of surgery in this low-risk cohort. Retrospective data from the National Cancer Database were used to identify adult patients with clinically node-negative papillary thyroid cancer ≤4 cm who underwent resection from 2012 to 2020. The primary outcome was the extent of surgery (lobectomy or total thyroidectomy, with or without prophylactic central neck dissection). Multivariable regression was performed to identify characteristics associated with variation in the extent of surgery. Of 83,464 included patients, 79.3% were female patients with a median age of 51 years. The majority underwent total thyroidectomy either with prophylactic central neck dissection (39.1%) or without (37.5%) versus lobectomy with prophylactic central neck dissection (7.2%) or without (16.2%). Lobectomy rates increased from 18.3% in 2012 to 29.9% in 2020. Prophylactic central neck dissection rates also increased (42.9% to 52.1%). Patients who were male sex, Asian American, had smaller tumors or were treated at community cancer programs had a decreased likelihood of total thyroidectomy. Patients who were older, male sex, Black race, with smaller tumors, or were treated at community cancer programs or mid- or low-volume facilities had decreased likelihood of prophylactic central neck dissection. Proportional use rates of operative approaches for low-risk, clinically node-negative papillary thyroid cancer have changed in recent years after the American Thyroid Association guideline changes, including increasing overall rates of lobectomy as well as prophylactic central neck dissection, with differences noted based on patient- and facility-level factors.


Air swallowing as a tic.
The authors present a patient with Gilles de la Tourette syndrome who developed abdominal distension and bloating due to air swallowing. We suggest that this air swallowing may have been due to a tic.


Essential oil of Sicilian Prangos ferulacea (L.) Lindl. and its major component, β-ocimen, affect contractility in rat small and large intestine.
Prangos ferulacea (L.) Lindl is an Apiaceae plant, widely used in traditional medicine. Recently, chemical composition and biological activities of its essential oil (Prangroil) have been reported, but there are no studies on possible effects on intestinal contractility. We investigated the effects of essential oil Sicilian Prangoil on the contractility of rat small (duodenum) and large (colon) intestine and the related action mechanism. Responses to Prangoil and to its major component β-ocimen in intestinal segments were assessed in vitro as changes in isometric tension. Prangoil, induced in duodenum, depending upon doses, contraction and/or muscular relaxation. Instead, in colon Prangoil only reduced the phasic contractions and induced muscular relaxation. β-ocimen, in both segments, produced only reduction of the spontaneous contractions without affecting basal tone. Prangoil contractile effects were abolished by ω-conotoxin, neural N-type Ca2+ channels blocker, atropine, muscarinic receptor antagonist, neostigmine, acetylcholinesterase (AChE) inhibitor, suggesting that Prangoil-induced contraction would be the result of an increase in neuronal cholinergic activity. Prangoil and β-ocimen inhibitory effects were unaffected by ω-conotoxin, L-NAME, blocker of the NO synthase, ODQ, soluble guanylate cyclase inhibitor, excluding involvement of neurotransmitter release or NO synthesis in the inhibitory effects. Potassium channel blocker did not affect Prangoil or β-ocimen inhibitory responses. Prangoil or β-ocimen inhibited the Ca2+ and high-KCl solution -induced contractions and the Carbachol-induced contractions in calcium free solution. Prangoil affects the contractility of small and large intestine in rat, with regional differences, via potentiation of neural cholinergic activity, blockade of L-type voltage-gated calcium channel and reduction of Ca2+ release from the intracellular store. The Prangroil main components, β-ocimen, contributes to the inhibitory effects.


Ungulate biomass in relation to feeding strategy within Amazonian forests.
The relationship between diet and biomass was examined in the Amazonian ungulates (red brocket deer, grey brocket deer, collared peccary, white-lipped peccary, and lowland tapir) of Northeastern Peru. Tropical forest ungulates have lower biomasses than savanna or grassland ungulates, because in tropical forests the majority of primary production occurs in the canopy, well out of reach from terrestrial herbivores. Within the Amazonian ungulates, species that supplement their diet with animal material, namely the peccaries, obtain a greater crude and metabolic biomass, and higher reproductive rates than the purely herbivorous species. Omnivory appears to help terrestrial herbivores inhabiting closed canopy forests overcome some effects of food limitation.


Early identification of 'at-risk' students by the parents of paediatric patients.
Assessment of medical student clinical skills is best carried out using multiple assessment methods. A programme was developed to obtain parent evaluations of medical student paediatric interview skills for feedback and to identify students at risk of poor performance in summative assessments. A total of 130 parent evaluations were obtained for 67 students (parent participation 72%, student participation 58%). Parents completed a 13-item questionnaire [Interpersonal Skills Rating Scale (IPS) maximum score 91, higher scores = higher student skill level]. Students received their individual parent scores and de-identified class mean scores as feedback, and participants were surveyed regarding the programme. Parent evaluation scores were compared with student performance in formative and summative faculty assessments of clinical interview skills. Parents supported the programme and participating students valued parent feedback. Students with a parent score that was less than 1 standard deviation (SD) below the class mean (low IPS score students) obtained lower faculty summative assessment scores than did other students (mean +/- SD, 59% +/- 5 versus 64% +/- 7; P < 0.05). Obtaining 1 low IPS score was associated with a subsequent faculty summative assessment score below the class mean (sensitivity 0.38, specificity 0.88). Parent evaluations combined with faculty formative assessments identified 50% of students who subsequently performed below the class mean in summative assessments. Parent evaluations provided useful feedback to students and identified 1 group of students at increased risk of weaker performance in summative assessments. They could be combined with other methods of formative assessment to enhance screening procedures for clinically weak students.


A data-driven approach to quantify disparities in power outages.
This research proposes a data-driven approach to identify possible disparities in a utility's outage management practices. The approach has been illustrated for an Investor-Owned Utility located in the Midwest region in the U.S. Power outage data for approximately 5 years between March 2017 and January 2022 was collected for 36 ZIP/postal codes located within the utility's service territory. The collected data was used to calculate the total number of outages, customers affected, and the duration of outages during those 5 years for each ZIP code. Next, each variable was normalized with respect to the population density of the ZIP code. After normalizing, a K-means clustering algorithm was implemented that created five clusters out of those 36 ZIP codes. The difference in the outage parameters was found to be statistically significant. This indicated differential experience with power outages in different ZIP codes. Next, three Generalized Linear Models were developed to test if the presence of critical facilities such as hospitals, 911 centers, and fire stations, as socioeconomic and demographic characteristics of the ZIP codes, can explain their differential experience with the power outage. It was found that the annual duration of outages is lower in the ZIP codes where critical facilities are located. On the other hand, ZIP codes with lower median household income have experienced more power outages, i.e., higher outage counts in those 5 years. Lastly, the ZIP codes with a higher percentage of the White population have experienced more severe outages that have affected more customers.


Maternal-reported behavioral and emotional problems in Taiwanese preschool children.
There has been limited epidemiologic information concerning preschoolers' behavioral and emotional problems in Eastern societies. This study was therefore aimed to investigate behavioral and emotional problems in a large sample of Taiwanese preschoolers using the Child Behavior Checklist for Ages 1.5-5 (CBCL/1.5-5). The CBCL/1.5-5 was scored by mothers of 645 Taiwanese preschoolers aged 24-71 months. Psychometric features of the scale as well as the raw scores and prevalence rates of behavioral problems of Taiwanese preschoolers were compared with those of American counterparts. Several demographic variables with the Total Problems and syndromes scores were also examined. The CBCL/1.5-5 was found to have good to excellent levels of reliability (internal consistency, test-retest reliability and inter-parent agreement) and an acceptable model fit of seven-syndrome factor structure (root mean square error of approximation=0.055) when used with Taiwanese preschoolers. The prevalence rate of Total Problems, Internalizing syndrome and Externalizing syndrome score in the clinical range was 25.1%, 11.2% and 25.4%, respectively. Cross-cultural comparisons showed that Taiwanese preschoolers had higher scores in six narrow-band syndromes (effect size d=0.17-0.43, all p's<0.005) and prevalence rates of four Internalizing-related syndromes and Sleep Problems than American sample (odds ratio=2.4-4.9, all p's<0.005). Analyses of behavioral correlates revealed associations of first birth order with higher Internalizing, Externalizing and Total Problems scores (all p's<0.05). Furthermore, younger ages (24-47 months) and male gender were associated with higher Externalizing and Total Problems scores (all p's<0.05). Our data have provided important epidemiologic information to assist in clinical assessment and management of preschoolers' behavioral and emotional problems in an Eastern society.


Evaluation of three force-position hybrid control methods for a robot-based biological joint-testing system.
Robot-based joint-testing systems (RJTS) can be used to perform unconstrained laxity tests, measuring the stiffness of a degree of freedom (DOF) of the joint at a fixed flexion angle while allowing the other DOFs unconstrained movement. Previous studies using the force-position hybrid (FPH) control method proposed by Fujie et al. (J Biomech Eng 115(3):211-7, 1993) focused on anterior/posterior tests. Its convergence and applicability on other clinically relevant DOFs such as valgus/varus have not been demonstrated. The current s1tudy aimed to develop a 6-DOF RJTS using an industrial robot, to propose two new force-position hybrid control methods, and to evaluate the performance of the methods and FPH in controlling the RJTS for anterior/posterior and valgus/varus laxity tests of the knee joint. An RJTS was developed using an industrial 6-DOF robot with a 6-component load-cell attached at the effector. The performances of FPH and two new control methods, namely force-position alternate control (FPA) and force-position hybrid control with force-moment control (FPHFM), for unconstrained anterior/posterior and valgus/varus laxity tests were evaluated and compared with traditional constrained tests (CT) in terms of the number of control iterations, total time and the constraining forces and moments. As opposed to CT, the other three control methods successfully reduced the constraining forces and moments for both anterior/posterior and valgus/varus tests, FPHFM being the best followed in order by FPA and FPH. FPHFM had root-mean-squared constraining forces and moments of less than 2.2 N and 0.09 Nm, respectively at 0° flexion, and 2.3 N and 0.14 Nm at 30° flexion. The corresponding values for FPH were 8.5 N and 0.33 Nm, and 11.5 N and 0.45 Nm, respectively. Given the same control parameters including the compliance matrix, FPHFM and FPA reduced the constraining loads of FPH at the expense of additional control iterations, and thus increased total time, FPA taking about 10 % longer than FPHFM. The FPHFM would be the best choice among the methods considered when longer total time is acceptable in the intended clinical applications. The current results will be useful for selecting a force-position hybrid control method for unconstrained laxity tests using an RJTS.


Regulating Back Electron Transfer through Donor and π-Spacer Alterations in Benzothieno[3,2-b]indole-based Dye-sensitized Solar Cells.
Three metal-free organic D-π-A dyes with benzothieno[3,2-b]indole as electron donor, cyanoacrylic acid as both electron acceptor and anchoring group with benzene (BID-1), thiophene (BID-2) and furan (BID-3) as π-spacers were designed and synthesized for application in dye-sensitized solar cells (DSSCs). A planar and electron-rich heterocycle such as benzothieno[3,2-b]indole offers better backbone rigidity and improves charge transport properties in comparison to indolo[3,2-b]indole donor, previously reported from our group. Additionally, we synthesized a benzothieno[3,2-b]indole donor grafted with longer alkyl chains which efficiently prevented the approach of oxidized species in the electrolyte coming closer to semiconductor thereby arresting recombination. A power conversion efficiency of 4.11 % was achieved for dye-sensitized solar cells based on the furan π-spacer benzothieno[3,2-b]indole dye BID-3 in comparison to the corresponding indolo[3,2-b]indole dye (IID-3) having an efficiency of 1.71 %. Detailed interfacial electrical measurements along with theoretical calculations disclosed the mechanism of back electron transfer and improvement in photovoltaic performance with respect to variation in both donor and π-spacer.


Effects of kola-nut extract administration on the liver, kidney, brain, testis and some serum constituents of the rat.
Kola-nut extract induced a number of overt neurotoxicological signs in male albino rats. A decrease in the total body weight and an increase in the absolute weights of the liver, kidney, brain and testis were observed after 18 weeks oral administration of kola-nut extract to the rats. Total protein, RNA and DNA of these organs were significantly depressed. The activity of beta-glucuronidase and beta-galactosidase was induced only in the kidney, brain and testis of treated animals. While the levels of serum phosphomonoesterases and total cholesterol were significantly enhanced due to kola-nut intake, serum total and conjugated bilirubin levels were significantly decreased.


Decoy receptor 3 analogous supplement protects steatotic rat liver from ischemia-reperfusion injury.
For steatotic livers, pharmacological approaches to minimize the hepatic neutrophil and macrophage infiltration, and cytokine and chemokine release in ischemia-reperfusion (IR) injury are still limited. Tumor necrosis factor (TNF)-α superfamily-stimulated pathogenic cascades and M1 macrophage/Kupffer cells (KC) polarization from Th1 cytokines are important in the pathogenesis of IR liver injury with hepatic steatosis (HS). Conversely, anti-inflammatory M2 macrophages produce Th2 cytokine (interleukin-4), which reciprocally enhances M2 polarization. Toll-like receptor 4-activated KCs can release proinflammatory mediators, skew M1 polarization and escalate liver IR injury. Decoy receptor 3 (DcR3) could be potential agents simultaneously blocking the IR liver injury-related pathogenic changes and extend the survival of steatotic graft. Rats were fed with methionine and choline-deficient high-fat diet (MCD HFD) for 6 weeks to induce HS. Preliminary experiments with HS group and IR group were conducted, and either immunoglobulin G Fc protein or DcR3 analogue was treated for 14 days in all groups to evaluate the severity. In the Zucker rat-focused experiments, various serum and hepatic substances, M1 polarization, and hepatic microcirculation were assessed. We found that serum/hepatic DcR3 levels were lower in nonalcoholic fatty liver disease patients with HS. DcR3a protected Zucker rats with HS from IR liver injury. The beneficial effects of DcR3a supplement were mediated by inhibiting hepatic M1 polarization of KCs, decreasing serum/hepatic TNFα, nitric oxide, nitrotyrosine, soluble TNF-like cytokine 1A, Fas ligand, and interferon-γ levels, neutrophil infiltration, and improving hepatic microcirculatory failure among rats with IR-injured steatotic livers. Additionally, downregulated hepatic TNF-like cytokine 1A/Fas-ligand and toll-like receptor 4/nuclear factor-κB signals were found to mediate the DcR3a-related protective effects of steatotic livers from IR injury. Using multimodal in vivo and in vitro approaches, we found that DcR3a analogue was a potential agent to protect steatotic liver against IR injury by simultaneous blockade of the multiple IR injury-related pathogenic changes.


Robust quantum control by a single-shot shaped pulse.
Considering the problem of the control of a two-state quantum system by an external field, we establish a general and versatile method allowing the derivation of smooth pulses which feature the properties of high fidelity, robustness, and low area. Such shaped pulses can be interpreted as a single-shot generalization of the composite pulse-sequence technique with a time-dependent phase.


Midbrain neurocysticercosis presenting as isolated pupil sparing third cranial nerve palsy.
Brainstem alone is involved very infrequently in patients with neurocysticercosis; usually, it occurs in association with disseminated form of the disease. Isolated involvement of the third nerve is commonly due to vascular causes. We are reporting a case due to cysticercus lesion presenting as isolated third-nerve involvement with sparing of the pupil. The diagnosis of neurocysticercosis was established by the presence of characteristic granulomatous lesions in the midbrain along with positive ELISA for cysticercal antigen in the cerebrospinal fluid. The patient responded well to corticosteroids with almost complete recovery. A follow-up MRI scan showed a significant decrease in the size of the lesion.


Two distinct strio-nigral substance P pathways in the rat: an experimental immunohistochemical study.
Re-examination of the strio-nigral substance P (SP) tract by means of an experimental immunohistochemical method in the rats demonstrated the presence of two distinct pathways from the nucleus caudatus putamen (CP) to the substantia nigra (SN). Destruction of the posterior portion of the CP resulted in the disappearance of SP-positive fibers in the SN pars lateralis but not in the SN pars compacta or reticulata. On the other hand, destruction of the ventrolateral portion of the anterior portion of the CP caused the disappearance of SP-positive fibers in the SN pars compacta and pars reticulata but not in the SN pars lateralis. In addition, destruction of the dorsal portion of the anterior portion of the CP, where 3-6 cell islets of SP-positive cells are located, failed to decrease SP-positive fibers in any of the subdivisions of the SN. These findings strongly suggest that SP-positive neurons in the posterior portion of the CP project to the SN pars lateralis (posterior strio-nigral SP tract), SP-positive cells in the lateroventral part of the anterior portion of the CP extend to the SN pars compacta and pars reticulata, but SP-positive cells in the dorsal part of the anterior portion of the CP do not innervate the SN.


The Mini-Open Wiltse Approach with Pedicle Screw Fixation Versus Percutaneous Pedicle Screw Fixation for Treatment of Neurologically Intact Thoracolumbar Fractures: A Systematic Review and Meta-Analysis.
The purpose of the present study was to compare the clinical outcomes and complications between the mini-open Wiltse approach with pedicle screw fixation (MWPSF) and percutaneous pedicle screw fixation (PPSF) in treating neurologically intact thoracolumbar fractures. We comprehensively searched PubMed, Web of Science, Embase, and the Cochrane Library and performed a systematic review and meta-analysis of all randomized controlled trials and retrospective comparative studies assessing these important indexes of the 2 methods using Review Manager, version 5.4. The clinical outcomes are presented as the risk difference for dichotomous outcomes and the mean difference for continuous outcomes with the 95% confidence intervals. Heterogeneity was assessed using the χ2 test and I2 statistics. The study was registered with PROSPERO (CRD 42021290078). Two randomized controlled trials and six retrospective cohort studies were included in the present analysis. The percutaneous approach was associated with less intraoperative blood loss compared with the mini-open Wiltse approach. No significant differences were found in the total length of the incisions, hospitalization time, postoperative visual analog scale scores, postoperative Oswestry disability index, postoperative Cobb angle, postoperative Cobb angle correction, postoperative Cobb angle correction loss, accuracy rate of pedicle screw placement, and postoperative complications between MWPSF and PPSF. However, the incidence of facet joint violation was significantly higher in the PPSF group. In addition, MWPSF was associated with a shorter operative time, shorter intraoperative fluoroscopy time, lower hospitalization costs, better postoperative vertebral body angle and percentage of vertebral body height compared with PPSF. Both MWPSF and PPSF are safe and effective treatments of neurologically intact thoracolumbar fractures. Nevertheless, our results have indicated that MWPSF might be the better choice, because it has a shorter learning curve and decreased facet joint violation, operative time, hospitalization costs, and radiation exposure. In addition, MWPSF was associated with better improvement of the postoperative vertebral body angle and percentage of vertebral body height.


The effect of fraction size on control of early glottic cancer.
A retrospective analysis of 600 patients treated for head and neck malignancy at the Cooper Hospital/University Medical Center was undertaken. Patients who had surgical intervention (excluding biopsy) were withdrawn from this review. Fifty-eight patients with Stage I Glottic Laryngeal Carcinoma were identified and constitute the basis of this report. Various parameters were analyzed to assess their impact on local control. These include age, sex, serum hemoglobin, tumor bulk, differentiation, field size, total dose, total treatment time, and fraction size. Overall local control was 87% with a median follow-up of 63 months. The only factor that influenced local control was fraction size. Of 28 patients treated with 180 cGy fractions, seven (25%) had a local recurrence within 3 years. Twenty-eight patients treated with 200 cGy or greater fractions have had no failures to date. The difference in control rate when comparing the two treatment schema was significant (p less than 0.01). The median dose in the controlled 180 cGy group was 6660 cGy (range, 6300-7020 cGy). In the patients who failed in the 180 cGy group the median dose was 6660 cGy (range, 6480-6840 cGy). The patients receiving 200 cGy fractions or greater had a median dose of 6600 cGy (range, 6000-6950 cGy) and an average dose of 6507 cGy. The mean NSD in the 180 cGy group failing was 1787 RET (range, 1735-1843 RET). Patients who were controlled and received 180 cGy fractions had a median NSD of 1796 RET (range, 1743-1868). The mean NSD in the 200 cGy group was 1847 RET. The median TDF in the 180 cGy group of patients controlled was 102. Those failing also had a TDF of 102 (range, 101-105). Patients receiving 200 cGy fractions or greater had a median TDF of 109. It appears from this data that fraction size is a highly significant factor in our ability to control glottic laryngeal cancer.


Taohong siwu decoction ameliorates cognitive dysfunction through SIRT6/ER stress pathway in Alzheimer's disease.
A growing number of people suffer from Alzheimer's disease (AD), but there is currently no effective treatment yet. Taohong Siwu Decoction (TSD) has been proved to take strong neuropharmacological activity on dementia, but the effect and mechanism of TSD against AD are still elusive. To investigate whether TSD could be effective in ameliorating cognitive deficits through SIRT6/ER stress pathway. Herein, the APP/PS1 mice, an AD model, and HT-22 cell lines were utilized. Different dosages of TSD (4.25, 8.50 and 17.00 g/kg/d) were administered to the mice for 10 weeks by gavage. Following the behavioral tests, oxidative stress levels were measured using malondialdehyde (MDA) and superoxide dismutase (SOD) kits. Nissl staining and Western blot analyses were used to detect the neuronal function. Then, immunofluorescence and Western blot analysis were applied to evaluate silent information regulator 6 (SIRT6) and ER Stress related protein levels in APP/PS1 mice and HT-22 cells. Behavioral tests revealed that APP/PS1 mice administered with TSD orally took more time in the target quadrant, crossed more times in the target quadrant, had a higher recognition coefficient, and spent more time in the central region. In addition, TSD could ameliorate oxidative stress and inhibit neuronal apoptosis in APP/PS1 mice. Furthermore, TSD could up-regulate the SIRT6 protein expression and inhibit ER sensing proteins expressions, such as p-PERK and ATF6, in APP/PS1 mice and Aβ1-42-treated HT22 cells. According to the abovementioned findings, TSD could alleviate cognitive dysfunction in AD by modulating the SIRT6/ER stress pathway.


How I approach B-lymphoblastic lymphoma in children.
There are limited data pertaining to the prognostic features and optimal therapeutic approach for the 20%-25% of children with lymphoblastic lymphoma (LLy) who have the B-lymphoblastic subtype. Outcomes are favorable following treatment modeled after acute lymphoblastic leukemia (ALL) regimens, but prognosis is dismal after relapse, and there are no established features for predicting therapy response. Ongoing US and international trials will include the largest cohort of uniformly treated patients with B-LLy to date, providing an opportunity to define clinical and molecular predictors of relapse and to establish a standard of care for treatment to improve outcomes for this rare pediatric cancer.


Genetic diversity study on 12 X-STR loci of investigator® Argus X STR kit in Bangladeshi population.
The X-chromosome short tandem repeat (STR) loci are of particular interest for solving complex kinship and paternity cases. Here, we report the genetic data from 209 unrelated Bangladeshi individuals (102 males and 107 females) that were genotyped using the 12 X-chromosomal STR markers included in the Investigator® Argus X-12 kit (Qiagen). The 12 X-STR markers are located in four linkage groups (linkage group I: DXS10135, DXS10148, and DXS8378; linkage group II: DXS7132, DXS10079, and DXS10074; linkage group III: DXS10103, HPRTB, and DXS10101; and linkage group IV: DXS10146, DXS10134, and DXS7423). Allelic frequencies of the 12 X-STR loci and haplotype frequencies of the four linkage groups were investigated. No significant difference was observed in the allele frequencies of males and females. Distributions of heterozygosity were observed from 64.5 to 92.5% among the studied 12 X STR loci. DXS10135 and DXS10101 loci were found to be most polymorphic. For all the four linkage groups, the haplotype diversity was found to be greater than 0.986. A total of 95, 73, 66, and 74 haplotypes were observed in linkage groups I, II, III, and IV, respectively. Hardy-Weinberg equilibrium tests showed no significant deviation from expected values for all 12 loci (p > 0.05). The exact test for pairwise linkage disequilibrium for the 12 loci in the male samples did not show any significant linkage disequilibrium except the DXS10103 and DXS10101 loci after the p values were corrected by Bonferroni's correction for multiple testing (p > 0.05/66). A combined power of discrimination in male and female individuals were 0.999999998159791 and 0.999999999999993, respectively. The combined mean exclusion chance were 0.999997635 in deficiency cases, 0.999999996 in normal trio cases, and 0.999999178 in duo cases. The currently investigated Bangladeshi population showed significant differences when compared with previously reported X-STR data from other 12 populations. The results of the data analysis indicated that all the loci in the Investigator® Argus X 12 kit were fairly informative and might be useful in forensic application and kinship analysis in Bangladeshi population.


Stent reconstruction of an injured parotid duct in a thoroughbred colt.
To report successful use of stent repair for a chronically injured parotid duct in a thoroughbred colt. Clinical report. A 2-year-old thoroughbred colt. Chronic injury to the parotid duct was identified 4-cm caudal to the facial vessel notch on the ventral border of the right mandible. After careful surgical dissection of the surrounding firm fibrous tissue, the defect was temporarily stented using an 8-Fr human ureteral catheter (223600 ERU(®) SOFT URETERAL(®) , Laboratoires pharmaceutique, Betschdorf, France) to bridge the tissue loss. The rostral end of the catheter exited the oral cavity through a buccotomy stab incision at the level of the second premolar tooth of the maxilla. Primary wound healing occurred and the stent was maintained for 5 weeks with saliva drainage visible when the colt was fed. After stent removal, function was restored with good cosmesis. A tissue defect in the parotid duct can be repaired successfully by temporary use of a stent until wound healing occurs.


Mutation analysis of the MYO7A and CDH23 genes in Japanese patients with Usher syndrome type 1.
Usher syndrome (USH) is an autosomal recessive disorder characterized by retinitis pigmentosa and hearing loss. USH type 1 (USH1), the second common type of USH, is frequently caused by MYO7A and CDH23 mutations, accounting for 70-80% of the cases among various ethnicities, including Caucasians, Africans and Asians. However, there have been no reports of mutation analysis for any responsible genes for USH1 in Japanese patients. This study describes the first mutation analysis of MYO7A and CDH23 in Japanese USH1 patients. Five mutations (three in MYO7A and two in CDH23) were identified in four of five unrelated patients. Of these mutations, two were novel. One of them, p.Tyr1942SerfsX23 in CDH23, was a large deletion causing the loss of 3 exons. This is the first large deletion to be found in CDH23. The incidence of the MYO7A and CDH23 mutations in the study population was 80%, which is consistent with previous findings. Therefore, mutation screening for these genes is expected to be a highly sensitive method for diagnosing USH1 among the Japanese.


Trisomy 16p in a liveborn infant and a review of partial and full trisomy 16.
An abnormal female infant, who survived for 10 months with almost complete trisomy 16p and monosomy of sub-band 21q22.3, is described. The chromosome anomaly was the result of an unbalanced segregation of a maternal balanced translocation t(16;21)(p11;q22.3). The partial monosomy was considered to have had little or no adverse phenotypic effect. Cases with trisomy of chromosome 16 material are reviewed. It appears that while full trisomy 16 always results in early spontaneous abortion, trisomy 16p or 16q may be compatible with limited postnatal survival.


[Experience in use of amoxicillin tablets for treatment of cases mostly of acute tympanitis (author's transl)].
Amoxicillin tablets (50 mg (potency)/tablet) were administered to 14 cases of acute tympanitis and one case of acute tonsillitis, and the following results were obtained. (1) Of 15 cases in total, 3 cases were remarkably improved, 11 improved, and one not improved; that is, the effective rate was 93%. (2) Acute simple tympanitis: 6 cases, effective rate 100%. Acute suppurative tympanitis: 8 cases, effective rate 88%. Acute tonsillitis: 1 case, improved. (3) There was one case of diarrhea which appeared to be a side effect of this drug.


Cell cycle dependent telomere regulation by telomerase in human bone marrow mesenchymal stem cells.
Human bone marrow mesenchymal stem cells (hMSCs) are a promising source for clinical stem cell transplantation. However, telomere regulation mechanisms, as one of the possible major mechanisms by which hMSCs sustain their stem cell characteristics, remain unknown. We isolated hMSCs by plastic adhesion and characterized these cells by morphology, immune phenotype and differentiation capacity. Telomerase was found negative in hMSCs, but slightly up-regulated in hMSC-derived adipocytes by the Telomeric Repeat Amplification Protocol (TRAP) assay. Moreover, hMSCs lack the alternative lengthening of telomeres (ALT) mechanism, because the hallmarks of ALT, such as very long and heterogeneous telomeres, extra-chromosome telomere repeat DNA (ECTR), and ALT-associated promyelocytic leukemia bodies (APBs), were not evident. However, when hMSCs were arrested in S phase with a combination of serum deprivation and aphidicolin, previously undetectable telomerase activity became predominantly positive. Meanwhile, the expression level of hTERT protein and mRNA increased, paralleled with the appearance of a large cohort of synchronized hMSCs at S phase. These findings provide a profile of telomere regulation by cell cycle dependent expression of telomerase in hMSCs and may lead to a better understanding of the stem cell nature of these cells.


Myocardial ischemia and reperfusion injury in rats: lysosomal hydrolases and matrix metalloproteinases mediated cellular damage.
The aim of this study was to evaluate the time course events of cellular damage during myocardial ischemia and reperfusion injury in rats and to find out a correlation between the structural alterations with respect to the biochemical changes. Cardiac biomarkers and lysosomal enzymes viz. cathepsin D, acid phosphatase and beta-glucuronidase and matrix metalloproteinases (MMPs) were evaluated at different time points, in response to ischemia-reperfusion induced oxidative stress in an isolated rat heart model perfused in Langendorff mode. Microscopically, changes in myocardial architecture, myofibrillar degradation, and collagen (COL) integrity were studied using hematoxylin-eosin, Masson's trichrome and toluidine blue staining techniques. A three-fold increase in the level of myoglobin was observed after 30 min of ischemia followed by 120 min of reperfusion as compared to 15 min ischemia, 120 min reperfusion. Similarly, a significant increase (P<0.05) in the levels of lipid peroxides and superoxide anion coupled with a decrease in enzymatic and nonenzymatic antioxidant levels were observed. A concomitant increase in the activity of cathepsin D (24.07+/-0.95) and a higher expression of MMPs after 120 min of reperfusion following 30 min ischemia were shown to correlate with the myocardial damage as shown by histopathology, suggesting that free radical induced activation of cathepsin D and MMPs could mediate early damage during myocardial ischemia and reperfusion.


Role of radiofrequency ablation and cement injection for pain control in patients with spinal metastasis.
The study aimed to investigate the effects and reliability of simultaneous vertebroplasty and radiofrequency ablation or radiofrequency ablation applied alone for pain control in patients with painful spine metastasis, and to investigate the effect of preventing tumor spread in long-term follow-up. Patients with painful vertebrae metastasis in the Afyonkarahisar Health Sciences University, Medical Faculty, Hospital Neurosurgery Clinic between 01.01.2015 and 01.06.2020 were recruited. They were divided into groups according to the surgical procedures applied. Group 1 included 26 patients who underwent radiofrequency ablation only, and group 2 included 40 patients who underwent vertebroplasty with radiofrequency ablation. Computed tomography and magnetic resonance imaging were performed in all patients pre-operation. The patients were followed for at least 6 months. Magnetic resonance imaging was performed at the end of the 6th month in neurologically stable patients. The metastatic lesion, pain, and quality of life were evaluated with Visual Analog Scale and Oswestry Disability Survey before and after the procedure. The mean VAS score before the procedure was 8.3 ± 1.07 in the RFA group, and a statistically significant difference was observed in VAS scores at all post-procedural measurement time-points (p < 0.001). The pain scores decreased at a rate of 58.8 and 69.6% of patients showed significant improvements in the QoL in the RFA-only group. The mean VAS score was 7.44 ± 1.06 in group RFA + VP before the procedure; the difference in the mean VAS scores was statistically significant at all measurement time-points after the procedure (p < 0.001). The mean pre-treatment Oswestry Index (to assess the QoL) was 78.50% in the RFA + VP group, which improved to 14.2% after treatment. Ablation + vertebroplasty performed to control palliative pain and prevent tumor spread in patients with painful vertebral metastasis is more successful than vertebroplasty performed alone.


Chylothorax after spinal fusion surgery: A case report and literature review.
Chylothorax is reported as a postoperative complication, mainly in the field of thoracic surgery, but there are only 14 reports in the field of spinal surgery. A 64-year-old woman underwent spinal fusion surgery by the anterior and posterior approach for her scoliosis. She developed leg edema and right pleural effusion 2 months after the surgery. Laboratory findings showed decreased total protein and albumin levels in serum. The color of the thoracentesis sample was pinkish white, and the Triglyceride level in the pleural effusion was high. So, her leg edema was found to be associated with malnutrition and the pleural effusion was caused by chylothorax. The point of leakage from the lymph duct was confirmed in the right thoracic cavity of the slice that corresponded to that with the screw at Th11 by lymphatic scintigraphy. Her symptoms did not improve by diet restriction and lipidol lymphography, but her pleural effusion and albumin levels improved by the administration of octreotide. In the clinical course, serum albumin levels appeared to show an inverse correlation with the amount of pleural effusion, so it was thought that her serum albumin level decreased owing to leakage of protein, including albumin, into the thoracic cavity via the injured thoracic duct. We concluded that the chylothorax was owing to complications of the surgery. Although reports of chylothorax occurring as a complication of spinal fusion surgery are rare, when prolonged hypoalbuminemia or unilateral pleural effusion is observed, chylothorax should be considered as a differential diagnosis.


Plasma MIP-1beta levels and skin toxicity in Japanese non-small cell lung cancer patients treated with the EGFR-targeted tyrosine kinase inhibitor, gefitinib.
Gefitinib (Iressa() is an orally active, selective EGFR tyrosine kinase inhibitor that blocks signal transduction pathways. Skin toxicity has been reported to be the major toxicity observed in patients treated with the EGFR-targeted tyrosine kinase inhibitors, such as gefitinib and erlotinib. Although the mechanisms underlying the development of the skin toxicity remain to be precisely clarified, immunological mechanisms are considered to be involved. We examined the correlations between the plasma levels of several cytokines and the risk of development of adverse events, especially skin toxicity, induced by the administration of gefitinib as first-line monotherapy in non-small cell lung cancer (NSCLC) patients. Paired plasma samples were obtained from a total 28 patients of non-small cell lung cancer; the first before the initiation of gefitinib administration (250 mg/day) (24 patients) and the second 2 or 4 weeks after the initiation of treatment (23 patients). The plasma concentrations of 17 major cytokines were measured using a bead-based multiplex assay. The median concentrations of eight of these cytokines before the start of treatment ranged from 0.06 (IL-5) to 58.26 (MIP-1beta) (microg/ml). The concentrations of the remaining nine cytokines were under the detectable limit (<0.01 microg/ml) in more than 50% of the samples. Comparisons of the levels before and after treatment showed no significant differences for any of the cytokines measured. The MIP-1beta levels were significantly lower in the patients with skin toxicity (16/24) as compared with those in the patients not showing any skin toxicity (59.1+/-10.5 versus 119.0+/-36.8; p=0.042 by the two-sample t-test). The K-Nearest Neighbor Prediction (K=3) showed the classification rate to be 75% for the prediction sets containing MIP-1beta, IL-4 and IL-8. There were no significant associations between the levels of any of the cytokines measured and any other parameters, including the tumor response to the drug. In conclusion, the plasma MIP-1beta level may be a useful predictor of the development of skin toxicity in patients receiving gefitinib treatment.


What I want fellows to do: change the world!
Maternal-fetal medicine fellows and trainees in general should be inspired by their mentors to help improve clinical practice, so that pregnant individuals and their babies have better outcomes, by contributing research data in peer-reviewed manuscripts that get incorporated in national and international guidelines, and so 'change the world.'


Group IIA phospholipase A(2) concentration of tears in patients with ocular rosacea.
To determine the concentration of group IIA phospholipase A(2) (GIIAPLA(2)) in tears of patients with ocular rosacea, and to compare it with GIIAPLA(2) concentration in tears of age-matched healthy controls. The GIIAPLA(2) concentration in tears was measured with a time-resolved fluoroimmunoassay in 21 patients with ocular rosacea (mean age 55.6+/-9.2 years) and in 21 normal subjects (mean age 53.4+/-8.2 years). Conjunctival brush cytology was carried out and eosinophils, neutrophils, lymphocytes, squamous epithelial cells, columnar epithelial cells, metaplastic changes and goblet cells were calculated separately. The GIIAPLA (2) concentration in tears was statistically significantly lower in patients with ocular rosacea (31.0+/-18.4 microg/ml, p=0.0099) and, more specifically, in patients who had dry eye (25.8+/-15.1 microg/ml, p=0.0034), compared to that in normal controls. There was no correlation between the GIIAPLA (2) content of tears and the conjunctival cells collected by the brush cytology. The tears of patients with dry eye symptoms due to ocular rosacea have decreased GIIAPLA (2) content. The pathogenic importance of this finding is discussed.


Comparative efficacy and tolerability of sarilumab 150 and 200 mg in patients with active rheumatoid arthritis : A Bayesian network meta-analysis of randomized controlled trials.
This study aimed to assess the relative efficacy and tolerability of every other week (q2w) dosing of sarilumab 150 and 200 mg in patients with active rheumatoid arthritis (RA). In this network meta-analysis, randomized controlled trials (RCTs) examining the efficacy and tolerability of sarilumab in patients with active RA were included. A Bayesian network meta-analysis was conducted to combine the direct and indirect evidence from the RCTs. Four RCTs, involving 2667 patients, met the inclusion criteria. The American College of Rheumatology (ACR)50 response rate was significantly higher in the sarilumab 200 mg and sarilumab 200 mg + methotrexate (MTX) groups than in the placebo + MTX group (odds ratio, OR, of 4.05, 95% credible interval, CrI, of 2.04-8.33 and OR of 3.75, 95% CrI of 2.37-5.72, respectively). Compared to the placebo + MTX group, the sarilumab 150 mg + MTX and adalimumab 40 mg groups showed a significantly higher ACR50 response rate. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that sarilumab 200 mg was likely to achieve the best ACR50 response rate (SUCRA = 0.8518), followed by sarilumab 200 mg + MTX (SUCRA = 0.8225), sarilumab 150 mg + MTX (SUCRA = 0.5112), adalimumab 40 mg (SUCRA = 0.3072), and placebo + MTX (SUCRA = 0.0072). The ACR50 and ACR70 response rate distributions were comparable, except that sarilumab 200 mg + MTX was likely to achieve the best ACR70 response rate. The tolerability based on the number of patient withdrawals due to adverse events (AEs) did not differ significantly between the treatments, except that placebo + MTX was likely to be the best tolerated. Sarilumab 150 and 200 mg are efficacious treatments for active RA and are well tolerated.


Rbm19 is a nucleolar protein expressed in crypt/progenitor cells of the intestinal epithelium.
Intestinal development and homeostasis rely on the coordination of proliferation and differentiation of the epithelium. To better understand this process, we are studying Rbm19, a gene expressed in the gut epithelium that is essential for intestinal morphogenesis and differentiation in the zebrafish (Development 130, 3917). Here we analyzed the expression of Rbm19 in several biological contexts that feature proliferation/differentiation cell fate decisions. In the undifferentiated embryonic gut tube, Rbm19 is expressed throughout the epithelium, but then becomes localized to the crypts of Lieberkühn of the adult intestine. Consistent with its expression in adult crypt/progenitor cells, expression is widespread in human colorectal carcinomas and dividing Caco-2 cells. Its expression in Caco-2 cells recapitulates the in vivo pattern, declining when the cells undergo confluence-induced arrest and differentiation. Rbm19 protein localizes to the nucleolus during interphase and to the perichromosomal sheath during mitosis, in accordance with the pattern described for other nucleolar proteins implicated in ribosome biogenesis. Interestingly, the loss of nucleolar rbm19, nucleolin/C23, and nucleophosmin/B23 in confluent Caco-2 cells did not signify loss of nucleoli as detected by electron microscopy. Taken together, these data point to the nucleolus as a possible locus for regulating the proliferation/differentiation cell fate decision in the intestinal epithelium.


Unexpected Cu and Zn speciation patterns in the broiler feed-animal-excreta system revealed by XAS spectroscopy.
Trace minerals such as copper (Cu) and zinc (Zn) are animal nutrition supplements necessary for livestock health and breeding performance, yet they also have environmental impacts via animal excretion. Here we investigated changes in Cu and Zn speciation from the feed additive to the broiler excreta stages. The aim of this study was to assess whether different Cu and Zn feed additives induce different Cu and Zn speciation patterns, and to determine the extent to which this speciation is preserved throughout the feed-animal-excreta system. Synchrotron-based X-ray absorption spectroscopy (XAS) was used for this investigation. The principal findings were: (i) in feed, Cu and Zn speciation changed rapidly from the feed additive signature (Cu and Zn oxides or Cu and Zn sulfates) to Cu and Zn organic complexes (Cu phytate and Zn phytate). (ii) in the digestive tract, we showed that Cu and Zn phytate were major Cu and Zn species; Cu sulfide and Zn amorphous phosphate species were detected but remained minor species. (iii) in fresh excreta, Cu sulfide and Zn amorphous phosphate were major species. These results should help to: (i) enhance the design of future research studies comparing different feed additive performances; (ii) assess Cu and Zn bioavailability in the digestive tract; (iii) gain further insight into the fate of Cu and Zn in cultivated soils when poultry manure is used as fertilizer.


Teaching pigeons an abstract relational rule: insideness.
In 49 sessions, pigeons failed to learn to sort a collection of 80 stimuli composed of a closed curve and a dot, divided into two categories, according to whether the dot was or was not inside the curve. Next, the pigeons were successfully trained, first with the insides of the curves shown in bright red, then with a darker red, and finally with a black matching the background outside the curve. After this stepwise procedure, the pigeons displayed a limited ability to sort novel curves and dot locations according to whether the dot was or was not inside the curve.


Free fibosomes and growth stimulation in human peripheral lymphocytes: activation of free ribisomes as an essential event in growth induction.
During the initial ten hours of growth in lymphocytes stimulated by phytohemagglutinin, the cells are converted from a state in which over 70% of all ribosomes are inactive free ribosomes, to one in which over 80% of ribosomes are in polysomes or in native ribosomal subunits. In this initial period, there was a neglible increase in total ribosomal RNA due to increased RNA synthesis, and abolition of ribosomal RNA synthesis with low concentrations of actinomycin D did not interfere with polysome formation. Therefore, the conversion is accomplished by the activation of existing free ribosomes rather than by accumulation of newly synthesized particles. The large free ribosome pool of resting lymphocytes is thus an essential source of components for accelerated protein synthesis early in lymphocyte activation, before increased synthesis can provide a sufficient number of new ribosomes. Free ribosomes accumulate once more after 24 to 48 hours of growth, when RNA and DNA synthetic activity are maximal. This reaccumulation of inactive ribosomes at the peak of growth activity may represent preparation for a return to the resting state where cells are again susceptible to stimulation. Activation of free ribosomes to form polysomes appears to involve modification of at least two steps: (a) dissociation of free ribosomes with stabilization as native subunits, and (b) adjustment of a rate-limiting step at initiation.


The nutritive value of rumen micro-organisms in ruminants. 3. The digestion of microbial amino and nucleic acids in, and losses of endogenous nitrogen from, the small intestine of sheep.
An experiment was conducted with three sheep maintained entirely by intragastric nutrition to estimate the digestibility of isolated individual constituents and amino acids (AA) of rumen micro-organisms (RMO) in the small intestine. Five levels of RMO were infused into the abomasum. The apparent and true disappearance of the individual components were measured by regression of abomasal input on the passage at the ileum. The true digestibility values of N, AA-N, DNA and RNA were 0.82, 0.85, 0.81 and 0.87, respectively. The digestibility of individual AA varied between 0.80 and 0.88, the only exceptions being diaminopimelic acid (0.37), histidine (0.68) and cystine (0.73), which were significantly lower than the average (0.847). The endogenous components in the ileal fluid in sheep given protein-free infusions, expressed in mg/kg live weight0.75 per d, were total N 42 and AA-N 20.


PTEN Hamartoma Tumor Syndrome: A Case of Renal Cell Carcinoma in a Young Female.
PTEN Hamartoma-Tumor-Syndrome (PHTS) describes a series of conditions characterized by germline-mutation of the PTEN tumor-suppressor gene. PHTS patients have an increased lifetime risk of multiple malignancies, including thyroid, breast, and endometrial cancers. PHTS patients also have 20-30 fold increased risk of renal cell carcinoma (RCC) compared to age-matched controls. As with many hereditary RCC syndromes, tumors present early and multifocally. We present a case of one of the youngest patients diagnosed with RCC in PHTS and review the urologic implications of this syndrome.


Safe management of anastomotic leakage after gastric cancer surgery with enteral nutrition via a nasointestinal tube.
Anastomotic leakage is a serious complication after gastric cancer surgery. Despite the superiority of enteral nutrition (EN), total parenteral nutrition (PN) remains the standard therapy for anastomotic leakage. After introduction of EN via a nasointestinal tube for patients with anastomotic leakage in our institution in 2006, standard nutritional therapy was shifted gradually from PN to EN. The present preliminary study evaluates the safety and feasibility of EN via a nasointestinal tube for anastomotic leakage after gastric cancer surgery. Retrospective review of all gastric cancer surgeries from 2005 to 2009 (n = 2,588) revealed 53 patients (2.0%) who developed anastomotic leakage and were treated conservatively. EN was performed via a nasointestinal tube inserted using a guidewire under X-ray fluoroscopy. Clinical outcomes and complications following EN were compared with those in patients treated with PN (historical control group). The severity of complications was evaluated according to the Clavien-Dindo classification. Fifty patients were included in the final analysis (three patients died): 29 patients managed by EN and 21 managed by PN. There were no significant differences in clinical outcomes and the frequency of total complications between the two groups; however, there were fewer tube/catheter-related complications in the EN compared with the PN group (1 vs. 7, respectively; P < 0.01). There was one epistaxis (3.4%; grade I) in the EN group and seven catheter infections (33.3%; grade II) in the PN group. The risk of grade II or higher complications was greater in the PN than the EN group (11 vs. 4, respectively; P < 0.01), with the greatest difference seen in the incidence of catheter infections. On days 7, 10, and 15 after diagnosis of leakage, the white blood cell count and C-reactive protein levels were higher in the PN than in the EN group. The PN group required prolonged intravenous antibiotic infusion (P < 0.01). Nasointestinal tube insertion with EN can be performed safely for patients with anastomotic leakage. A major advantage of EN is fewer infectious complications. Because EN was not inferior to PN in terms of clinical outcome, we recommended that it is used in patients with anastomotic leakage after gastric cancer surgery.


Bilateral choanal atresia; evaluation with scintigraphy: case report.
Bilateral choanal atresia is a rare congenital anomaly that may cause severe neonatal respiratory distress. The clinical presentation varies from immediate postnatal cyanosis and respiratory distress to nasal obstruction with an associated persistent mucoid discharge. The aim of this study was to evaluate the effect of bilateral choanal atresia preoperatively and postoperatively on nasal mucociliary clearance with the radioisotope method (using technetium-99m macroaggregated albumin). We present a 17-year-old girl with bilateral choanal atresia treated by transnasal endoscopic surgery. The patient was free of symptoms for three years postoperatively. Mucociliary activity was returned to normal images.


Optimization of stabilized leachate treatment using ozone/persulfate in the advanced oxidation process.
The objective of this study was to investigate the performance of employing persulfate reagent in the advanced oxidation of ozone to treat stabilized landfill leachate in an ozone reactor. A central composite design (CCD) with response surface methodology (RSM) was applied to evaluate the relationships between operating variables, such as ozone and persulfate dosages, pH, and reaction time, to identify the optimum operating conditions. Quadratic models for the following four responses proved to be significant with very low probabilities (<0.0001): COD, color, NH3-N, and ozone consumption (OC). The obtained optimum conditions included a reaction time of 210 min, 30 g/m(3) ozone, 1g/1g COD0/S2O8(2-) ratio, and pH 10. The experimental results were corresponded well with predicted models (COD, color, and NH3-N removal rates of 72%, 96%, and 76%, respectively, and 0.60 (kg O3/kg COD OC). The results obtained in the stabilized leachate treatment were compared with those from other treatment processes, such as ozone only and persulfate S2O8(2-) only, to evaluate its effectiveness. The combined method (i.e., O3/S2O8(2-)) achieved higher removal efficiencies for COD, color, and NH3-N compared with other studied applications. Furthermore, the new method is more efficient than ozone/Fenton in advanced oxidation process in the treatment of the same studied leachate.


Loxapine succinate as a neuroleptic agent: evaluation in two populations of elderly psychiatric patients.
Loxapine succinate, a newly developed neuroleptic drug, was administered to two groups of geropsychiatric patients: (a) 12 with psychosis and organic brain syndrome, and (b) 14 with chronic schizophrenia. After a two-week baseline period, loxapine was given for 12 weeks. The moderate therapeutic effect of loxapine in the "responders" was similar to that of other neuroleptic drugs. The therapeutic dosage range was found to be from 10 to 80 mg daily--about half that used for younger patients. The chief side effects were drowsiness, mild extrapyramidal symptoms, and a slight increase in blood pressure.


Effects of ionization on stability of 1-methylcytosine - DFT and PCM studies.
Consequences of ionization were studied by quantum-chemical methods (DFT and PCM) for 1-methylcytosine (MC)-a model of the nucleobase cytosine (C) connected with sugar in DNA. For calculations, three prototropic tautomers (one amino and two imino forms) and two imino zwitterions were considered, including conformational or configurational isomerism of exo heterogroups. Ionization and interactions between neighboring groups affect intramolecular proton-transfers, geometric and thermodynamic parameters, and electron delocalization for individual isomers. We discovered that an imino isomer is present in the isomeric mixture in the highest amount for positively ionized MC. Its contribution in neutral and negatively ionized MC is considerably smaller. Acid-base parameters for selected radical ions were estimated in the gas phase and compared to those of neutral MC. Gas-phase acidity of radical cations is close to that of the conjugate acid of MC, and gas-phase basicity of radical anions is close to that of the conjugate base of MC. Various routes of amino-imino conversion between neutral and ionized isomers were considered. Energetic-barrier for intramolecular proton-transfer in MC is close to that in the parent system-formamidine.


Application of numerical simulation to solid phase-microextraction for decreasing of extraction time of pyrene and phthalate esters on solid coatings.
Reynolds-Averaged Navier-Stokes (RANS) approach with the k-ε closure model is employed for the first time to simulate direct Solid-Phase Micro-Extraction (SPME) computationally. Simulations are performed by using COMSOL Multiphysics in order to examine methods to decrease the extraction time. Experiments are also conducted to support data obtained from the numerical framework. Di-n-Butyl Phthalate (DNBP) and etched steel wire are chosen as the analyte and the adsorbent, respectively. Stirring rate, fiber's location, stirrer magnet's size, and the method of sample rotation are examined to decrease the extraction time. In addition, the effects of adding a baffle to the vial and implementing a periodic function for stirring the sample are studied. Increasing the stirring rate from 700 to 3000 rpm reduces the extraction time from 50 to 36 minutes. Present results suggest that changing the fiber's location and implementing a periodic stirring pattern significantly decrease the extraction time of SPME. The optimum fiber's location is found at 7.5 mm far from the vial's center, which leads to a 51% decrease in the extraction time. Furthermore, using a periodic stirring pattern results in a 60% decrease in the extraction time compared to the traditional uniform stirring pattern. To examine the robustness and reliability of the presented framework, two additional analytes, namely pyrene and Dioctyl phthalate (DOP), are chosen with one additional fiber, Al2O3. In this regard, the additional materials are used in the framework to investigate the effects of fiber's location and stirring pattern. By optimizing the fiber's location, the extraction time is reduced by 36% and 40% for SPME of pyrene and DOP, respectively. On the other hand, by using a periodic stirring pattern, the extraction time is reduced by 42% and 46% for SPME of pyrene and DOP, respectively.


CircETFA upregulates CCL5 by sponging miR-612 and recruiting EIF4A3 to promote hepatocellular carcinoma.
As a kind of malignant tumors, hepatocellular carcinoma (HCC) has been studied continuously, but the mechanisms are not well understood. Circular RNAs (circRNAs) are widespread in eukaryotes and play an important role in the growth of organisms and in the occurrence of diseases. The role of circRNAs in HCC remains to be further explored. In this study, CircRNA microarray analysis was used to assess the plasma from HCC patients and healthy controls and to identify circRNAs involved in HCC tumorigenesis. CircETFA was overexpressed in HCC tissues, plasma, and cells. Clinicopathological data revealed that abnormally high circETFA expression was associated with a poor prognosis. In function, circETFA promotes the malignant phenotype of HCC cells in vivo and in vitro, inhibits cycle arrest, and decreases the proportion of apoptotic cells. In mechanism, it can upregulate C-C motif chemokine ligand 5 (CCL5) in HCC cells, thereby regulating the phosphoinositide 3-kinase (PI3K)/Akt pathway and other key downstream effectors (e.g., FoxO6). Furthermore, circETFA prolonged the half-life of CCL5 mRNA by recruiting the eukaryotic initiation factor 4A3 (EIF4A3) and acted as a sponge of hsa-miR-612 to suppress the silencing effect of hsa-miR-612 on CCL5. In conclusion, CircETFA can increase the expression of CCL5 to promote the progression of HCC by sponging hsa-mir-612 and recruiting EIF4A3, and is promising as a novel biomarker and therapeutic target.


Shoshin beriberi mimicking a high-risk non-ST-segment elevation acute coronary syndrome with cardiogenic shock: when the arteries are not guilty.
Cardiac acute beriberi (Shoshin syndrome) is a rare disease that may lead to a fatal outcome if not treated specifically. We report a case of Shoshin syndrome with an unusual presentation of cardiogenic shock and an electrocardiographic pattern of severe myocardial ischemia suggesting left main coronary artery obstruction. A 35-year-old man presented with chest discomfort, diffuse ST-segment depression in the 12-lead electrocardiogram (ECG) with ST-segment elevation in aVR, and rapidly evolving congestive heart failure leading to cardiogenic shock. Intensive support was required, including mechanical ventilation, high doses of inotropics and vasopressors, intra-aortic balloon counterpulsation, and continuous renal replacement therapy. An emergency coronary angiogram was performed that showed normal coronary arteries. Right heart catheterization showed a high-output state with elevated filling pressures suggesting high-output heart failure. The echocardiography confirmed normal left and right ventricular contraction. Thiamine deficiency was suspected as the cause of the high-output heart failure. After a single dose of intravenous thiamine (100 mg), the patient's hemodynamic status improved dramatically within minutes, allowing a rapid discontinuation of hemodynamic support. Subsequent ECGs showed complete resolution of ST-segment abnormalities. Serial lactate measurements, red blood cell transketolase activity, and the thiamine pyrophosphate response test were concordant with a thiamine deficiency state. Shoshin syndrome may present as cardiogenic shock with an ECG mimicking severe myocardial ischemia, and if suspected, can be rapidly and effectively treated.


Betaine as an alternative feed additive to choline and its effect on performance, blood parameters, and egg quality in laying hens rations.
This research aimed to evaluate how using betaine levels as a choline substitute affects productive performance, egg quality parameters, fatty acids profile, and antioxidant status in laying hens. One hundred and forty brown chickens, 45 wk old, were divided into 4 groups, each group of 7 replicates with 5 chickens per replicate. The first group of diets with choline has control (A) 100% choline, the second group (B) 75% choline + 25% betaine, the third group (C) 50% choline + 50% betaine, and the fourth group (D) received 100% betaine. No significant effects were observed in final body weight (BW), body weight gain (BWG), egg production (EW), and feed intake (FI) for laying hens. In the diet in which betaine was replaced choline, egg mass (EM) and egg weight (EW) increased compared to the control group (P < 0.05). Also, after 12 wk of feeding, the egg quality parameters were not influenced; however, yolk color was increased significantly compared with the control group. Serum total cholesterol, LDL-lipoprotein, HDL-lipoprotein, triglyceride, glucose, aspartate transaminase (AST), and alanine transaminase (ALT) were not affected by replacing choline with betaine. Furthermore, liver malondialdehyde (MDA) content, yolk vitamin E, and fatty acid levels were not significantly affected by replacing choline with betaine. Moreover, hens fed betaine displayed an increased antibody titer of the Newcastle disease (ND) virus. EW and EM were increased by 3.50% and 5.43% in 100% betaine group (D) when compared to the control group. Isthmus weight was decreased by 48.28 % in 50% choline + 50% betaine group (C) when compared to the control group. ND was increased by 26.24% in 100% betaine group when compared to the control group. In conclusion, betaine supplementation positively affected productive performance, egg quality measurements, and immunity response in Bovans brown laying hens.


Bidirectional regulation between 1st trimester HTR8/SVneo trophoblast cells and in vitro differentiated Th17/Treg cells suggest a fetal-maternal regulatory loop in human pregnancy.
During normal pregnancy, delicate crosstalk is established between fetus-derived trophoblasts and maternal immune cells to ensure maternal-fetal tolerance and successful placentation. Dysfunction in these interactions has been highly linked to certain pregnancy complications. Naïve CD4+ T cells were cultivated with or without 1st trimester derived trophoblast cell line HTR8/SVneo cells in the absence or presence of T helper 17 (Th17) or regulatory (Treg)cell-inducing differentiation conditions. After 5 days of co-culture, HTR8/SVneo cells and CD4+ T cells were harvested and analyzed using flow cytometry. CD4+ T cells exposed to HTR8/SVneo cells showed enhanced induction of CD4+ Foxp3+ Treg cells with strong expression of TGF-β1 and inhibitory molecules (cytotoxic T lymphocyte-associated protein-4 [CTLA-4], T-cell immunoglobulin mucin-3 [Tim-3], and programmed cell death-1 [PD-1]). Though not effecting Th17 differentiation, exposure to HTR8/SVneo cells promoted increased expression of proliferative and apoptotic markers on Th17 cells. Co-culture with Th0 cells, or differentiated Th17 or Treg cells, down-regulated Caspase-3 and MMP-9 (but not MMP-2) expression in HTR8/SVneo cells, while promoting Ki67 expression. HTR8/SVneo cells regulated maternal CD4+ T-cell differentiation, resulting in the expansion of immunosuppressive Treg cells, while CD4+ T cells might promote the growth, and control the invasiveness of HTR8/SVneo cells. Thus, a bidirectional regulatory loop might exist between trophoblasts and maternal immune cell subsets, thereby promoting harmonious maternal-fetal crosstalk.


Dwyer-Hartshill transpedicular fixation for spinal fusion.
We report the technique and early results of the Dwyer-Hartshill method for segmental fixation of the spine. This uses pedicular screws wired to a rectangular frame and is indicated after laminectomy.


Direct determination of arsenic and antimony in naphtha by electrothermal atomic absorption spectrometry with microemulsion sample introduction and iridium permanent modifier.
This paper reports the determination of arsenic and antimony in naphtha by employing electrothermal atomic absorption spectrometry (ETAAS) as the analytical technique. In order to promote the direct determination of the analytes in the very volatile naphtha, the formation of a microemulsion with different surfactants (Triton X-100 and Brij-35) and different chemical modification strategies were tested. The results indicated that Triton X-100 is the best emulsification agent for naphtha in both As and Sb determination when it is employed at a concentration of 1% w/v in the microemulsion. Under these conditions, the microemulsion was stabile for at least 2 h. By using Brij-35 it was possible to achieve good stability only in the first 15 min. Among all chemical modification approaches investigated (Ir permanent modifier, W-Ir permanent modifier, and Pd modifier), the Ir permanent modifier provided better sensitivity for both analytes and allowed a higher pyrolysis temperature, which decreased the background signals at lower levels. Under the best conditions established in this work, an RSD of 4.6% (20 microg L(-1)) and a detection limit of 2.7 microg L(-1) were observed for arsenic. For antimony, an RSD of 4.0% (20 microg L(-1)) and a detection limit of 2.5 microg L(-1) were obtained. The accuracy of the procedure was assessed by analyzing spiked samples of naphtha from different origins.


Lymphoepithelioma-like carcinoma of the stomach associated with adenosquamous carcinoma.
Lymphoepithelioma-like carcinoma and adenosquamous carcinoma of the stomach are relatively rare tumors. To date, there are no reports on lymphoepithelioma-like carcinoma of the stomach associated with adenosquamous carcinoma. We report herein the first case of such a tumor. A 67-year-old Japanese man presented with dull epigastralgia. The gastric endoscopy revealed an ulcerative cancerous lesion of the upper portion. Histological examination of the gastric tumor showed the coexistence of lymphoepithelioma-like carcinoma and adenosquamous carcinoma. The former showed a positive reaction for Epstein-Barr virus-encoded RNA (EBER). Neoplastic cells of the latter were immunoreactive for p63 and keratin 903, and Alcian blue stain detected acid mucin in glandular lumens. This pattern resembled mucoepidermoid carcinoma in the salivary gland. Finally, this is the first case of gastric lymphoepithelioma-like carcinoma associated with adenosquamous carcinoma, and clinicians and pathologists should recognize the presence of such a tumor.


Development of gold-silica composite nanoparticle substrates for perchlorate detection by surface-enhanced Raman spectroscopy.
Surface-enhanced Raman spectroscopy (SERS) holds promise for rapid, in situ detection of perchlorate (ClO4-) in the environment if sensitive and reproducible SERS substrates can be developed. In this study, new, functionalized gold-silica (Au-SiO2) composite nanoparticles were synthesized and used as SERS substrates for ClO4- detection. These nanoparticles were composed of a silica core with Au nanoparticles grafted onto the SiO2 spheres by in situ chemical reduction of AuCl4- or physisorption of Au colloids. Chemical coupling agents with such functional groups as -N+(CH3)3 and -NH3+/-NH2 were used to enhance perchlorate sorption onto the substrate and therefore the detection of ClO4-. These new substrates were found to be optically stable and provide a greatly enhanced surface plasmon or SERS, resulting in a detection limit as low as 10(-6) M ClO4- (0.1 mg/L) in water.


Sanitary Emergencies at the Wild/Domestic Caprines Interface in Europe.
Population density and distribution of the four native European wild Caprines (Rupicapra rupicapra, Rupicapra pyrenaica, Capra ibex, Capra pyrenaica) have increased in recent decades. The improved conservation status of this valuable wildlife, while a welcome event in general terms, is at the same time a matter of concern since, intuitively, frequent and tighter contacts with sympatric livestock imply a greater risk of cross-transmission of emerging and re-emerging pathogens, and offer unexpected opportunities for pathogens to spread, persist and evolve. This article recalls the transmissible diseases that are perceived in Europe to be of major significance from a conservation perspective, namely brucellosis (BRC) by Brucella melitensis, infectious kerato-conjunctivitis (IKC) by Mycoplasma conjunctivae, pestivirosis (PV) by the border disease virus strain 4 and mange by Sarcoptes scabiei. Special emphasis has been put on the epidemiological role played by small domestic ruminants, and on key knowledge needed to implement evidence-based prevention and control strategies. Remarkably, scientific evidence demonstrates that major demographic downturns in affected wild Caprinae populations in recent decades have often been triggered by pathogens cross-transmitted at the livestock/wildlife interface.


Immunoproteomic analysis of the sporozoite antigens of Eimeria necatrix.
Eimeria necatrix, an apicomplexan protozoa of the genus Eimeria, causes intestinal coccidiosis that can reduce growth performance of poultry and result in high mortality in older chickens. In this report, the whole sporozoite proteins of E.necatrix were studied by two-dimensional electrophoresis (2-DE) and Western blotting using hyper-immune chicken serum containing E.necatrix-specific antibodies. Approximately 680 protein spots for E.necatrix sporozoite were detected by 2-DE with silver staining, where 98 spots were cross-reacted with the E. necatrix-specific immune sera. Out of the 56 spots that were selected for MALDI-TOF-MS/MS analysis, 50 unique proteins were identified using the MASCOT software, 8 proteins were identified as known E.necatrix proteins and the rest were all putative proteins. These proteins have a wide range of known or predicted structures, cellular locations and functions, including proteins in category nuclear location & function, multifunctional- or multifunctional motifs-containing proteins, cellular transport and structure-related proteins, proteins of enzymatic activities, motor proteins-related, cell surface and organelle-related proteins. These new findings will enhance our understandings of parasite immunogenicity and immune evasion mechanisms of E. necatrix and facilitate the discovery phase of highly effective vaccine candidates.


Big brown bats (Eptesicus fuscus) successfully navigate through clutter after exposure to intense band-limited sound.
Echolocating big brown bats fly, orient, forage, and roost in cluttered acoustic environments in which aggregate sound pressure levels can be as intense as 100 to 140 dB SPL, levels that would impair auditory perception in other terrestrial mammals. We showed previously that bats exposed to intense wide-band sound (116 dB SPL) can navigate successfully through dense acoustic clutter. Here, we extend these results by quantifying performance of bats navigating through a cluttered scene after exposure to intense band-limited sounds (bandwidths 5-25 kHz, 123 dB SPL). Behavioral performance was not significantly affected by prior sound exposure, with the exception of one bat after exposure to one sound. Even in this outlying case, performance recovered rapidly, by 10 min post-exposure. Temporal patterning of biosonar emissions during successful flights showed that bats maintained their individual strategies for navigating through the cluttered scene before and after exposures. In unsuccessful flights, interpulse intervals were skewed towards shorter values, suggesting a shift in strategy for solving the task rather than a hearing impairment. Results confirm previous findings that big brown bats are not as susceptible to noise-induced perceptual impairments as are other terrestrial mammals exposed to sounds of similar intensity and bandwidth.


Intraoperative Three-dimensional Virtual Reality and Computed Tomographic Guidance in Temporomandibular Joint Arthroplasty of Syndromic Craniofacial Dysostoses.
Bony ankylosis of the temporomandibular joints (TMJ) occurs in up to 28% of patients with syndromic mandibular dysostoses. Release of complete osseous ankylosis is particularly challenging due to the lack of tissue planes separating the mandible from the skull base and the presence of congenital skeletal abnormalities. One recent advance in surgical imaging technology is three-dimensional virtual reality (3D VR), now in common use in neurosurgical resections. In this study, we describe the usage of 3D VR in TMJ arthroplasty and compare 3D VR to traditional computed tomographic (CT) guidance. Pediatric patients with syndromic mandibular micrognathia including Treacher Collins, Nager, and cerebrocostomandibular syndrome were retrospectively evaluated between 2008 and 2016. Patient characteristics, complications, inpatient times, and operative times were recorded. Of the 29 children with syndromic mandibular micrognathia treated between 2008 and 2016, 7 were diagnosed with TMJ ankyloses. Four consecutive pediatric patients (mean 8.7 years) undergoing interpositional TMJ arthroplasty with Matthews device placement were retrospectively evaluated. Two patients underwent traditional CT-guided versus 3D VR-guided temporomandibular joint arthroplasty (TMJA). No statistically significant differences were found among the age, complications, or inpatient hospitalization times. The average operative time in the traditional CT guidance group was 300 minute versus 134 minutes in the 3D VR group. Three-dimensional VR is a useful preoperative planning and intraoperative guidance tool. The major difference between VR and older technologies is the improved imaging in 3 dimensions for guidance, thereby potentially decreasing operative times.


Reversing abnormal hole localization in high-Al-content AlGaN quantum well to enhance deep ultraviolet emission by regulating the orbital state coupling.
AlGaN has attracted considerable interest for ultraviolet (UV) applications. With the development of UV optoelectronic devices, abnormal carrier confinement behaviour has been observed for c-plane-oriented AlGaN quantum wells (QWs) with high Al content. Because of the dispersive crystal field split-off hole band (CH band) composed of p z orbitals, the abnormal confinement becomes the limiting factor for efficient UV light emission. This observation differs from the widely accepted concept that confinement of carriers at the lowest quantum level is more pronounced than that at higher quantum levels, which has been an established conclusion for conventional continuous potential wells. In particular, orientational p z orbitals are sensitive to the confinement direction in line with the conducting direction, which affects the orbital intercoupling. In this work, models of Al0.75Ga0.25N/AlN QWs constructed with variable lattice orientations were used to investigate the orbital intercoupling among atoms between the well and barrier regions. Orbital engineering of QWs was implemented by changing the orbital state confinement, with the well plane inclined from 0° to 90° at a step of 30° (referred to the c plane). The barrier potential and transition rate at the band edge were enhanced through this orbital engineering. The concept of orbital engineering was also demonstrated through the construction of inclined QW planes on semi- and nonpolar planes implemented in microrods with pyramid-shaped tops. The higher emission intensity from the QWs on the nonpolar plane compared with those on the polar plane was confirmed via localized cathodoluminescence (CL) maps.