Case report: Atypical teratoid/rhabdoid tumor of the lateral ventricle in a male adolescent (case-based review and diagnostic challenges in developing countries).
Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and highly malignant central nervous system (CNS) embryonal neoplasm: it accounts for <2% of all pediatric CNS tumors and occurs mainly in infants and young children. The primary site of this tumor is usually the posterior cranial fossa. Supratentorial and, in detail, latero-ventricular location is extremely uncommon, especially in adolescents. This tumor is characterized by rapid growth and spread in cerebrospinal fluid and, therefore, it is characterized by a poor prognosis. Neurological signs and symptoms are related the location of the tumor. The radiological features of AT/RT are nonspecific. Immunohistochemical staining for loss of nuclear integrase interactor 1 (INI1) expression is considered a reliable criterion for the diagnosis of this type of tumor. AT/RT has been linked to mutations of SMARCB1 or, rarely, SMARCA4 genes, which function as tumor suppressor genes. Currently, there is no validated protocol of treatment for children with AT/RT, and multimodality treatment (consisting of surgery, chemotherapy, and radiation therapy) is considered. In this case report, we describe a 15-year-old adolescent with an AT/RT of the left lateral ventricle. Despite the late diagnosis, the multimodal therapeutic approach provided a good outcome for our patient at 21 months' follow-up. Based on our case-based review, early diagnosis and a multimodal approach to treatment play a key role in improving the survival of patients with this diagnosis. Implementing a system supporting pathological and molecular analyses for developing countries and, in general, for non-academic centers is of primary importance to timely diagnose and treat rare tumors, such as AT/RT.


The effect of dietary vitamin E level on selenium status in rats.
The effect of varying levels of dietary vitamin E on selenium status was determined using 40 Wistar rats with similar initial body weight. The rats were equally divided into four groups and fed the following dietary treatments (mg vitamin E/kg DM): 18 (control; C-diet), 0 (0E-diet), 9 (0.5E-diet) and 36 (2E-diet) for either 4-week (Phase 1) or 8-week (Phase 2) period. At the end of experiment, animals were slaughtered to measure vitamin E and selenium levels in the brain, liver, spleen, kidney, muscles and blood tissues. Dietary vitamin E levels did not affect feed and water intake and body weight. But whole-blood selenium concentration in rats fed 0E-diet was higher than in rats fed 2E-diet after 4 weeks. Selenium level in muscle, spleen and brain was also higher (p < 0.05) in rats fed the 0E-diet than in rats fed C-diet after 4 weeks of feeding. On the other hand, selenium level in the muscle was lower (p < 0.05) in rats fed 0.5E-diet than in those fed 0E-diet after 4 weeks of feeding, but not after 8 weeks of feeding. Increasing dietary vitamin E level directly influenced selenium content of the spleen and brain after 8 weeks of feeding 2E-diet. Moreover, the twofold increase in vitamin E intake resulted in a tendency to reduce whole-blood selenium level and total selenium in the liver and kidney after 4 and 8 weeks. The results showed that the increasing dietary vitamin E level resulted in a tendency to reduce Se contents in some vital organs of the body such as the liver and kidney, suggesting their close compensatory interrelationship. Therefore, dietary vitamin E level directly influenced selenium metabolism in the animal body.


Study of 30 DNA markers in three southern African populations.
Thirty anonymous DNA markers were investigated in Southern African Caucasoid, Negroid and San populations. Sixteen of these are new markers that were developed in our laboratory; the remainder are closely linked to the cystic fibrosis locus on chromosome 7. Average heterozygosity in the Caucasoid and Negroid populations was calculated at the loci identified by each of the anonymous probes, using two approaches, and was found to be .0020 and .0030 for the Caucasoid population and .0023 and .0025 for the Negroid population. Variation between populations (measured by FST) and between markers was calculated from allele frequency data gathered for all markers in the three populations. Significant differences in allele frequency between the populations were observed for the cystic fibrosis markers MET D, MET H and 7C22, with little or no variation observed in the Negroid and San populations. Mean heterozygosity (D) was found to be considerably lower in San (.250) than in Caucasoid (.373) and Negroid populations (.0320) and possible explanations for this are provided. The smallest genetic distance (60 x 10(-3)) was found between the Negroid and San populations, and the greatest distance between the Caucasoid and San populations (167 x 10(-3)).


The impact of mild renal dysfunction on postoperative mortality in the surgical intensive care unit.
The negative impact of mild to moderate renal dysfunction on patient outcome is often under-estimated. Any amount of renal dysfunction is deleterious in the surgical intensive care unit (SICU). We evaluated all surgery patients admitted to our SICU. We identified two groups of patients: no renal failure and acute renal failure. A total of 5152 patients were included in this study. There were 1259 patients in the acute renal failure group. The average number of ventilator days increased by 2.2 for every increase of creatinine by 1.0. Patients who required dialysis stayed an average of 11 days longer than patients who did not have any renal failure. For every increase of creatinine by 1.0, average cost increased by $23,048. Only 7 per cent of the patients with acute renal failure required dialysis (n = 85). The odds ratio for mortality compared with those patients without renal failure was 7.06 (confidence interval, 3.91-12.76) regardless of the definition of renal failure. This study demonstrates that even mild to moderate renal failure increases mortality. Moreover, we demonstrated that even a mild decline in renal function increases length of stay, ventilator days, and cost in patients in the SICU. Aggressive vigilance in the prevention of any loss of renal function is warranted in the SICU.


Prevalence of beta lactamase producing species of pseudomonas and acinetobacter in pediatric burn patients.
Burn wound infection is a major cause of morbidity and mortality in burn victims. Pseudomonas and Acinetobacter species are among the most common organisms complicating burn wounds. Presence of extended spectrum ß-lactamase (ESBL) and metallo-ß-lactamase (MBL) genes plays an important role in spreading ß-lactam resistant strains of these organisms and is a serious condition in the treatment of the affected patients. As a result, we aimed to determine the prevalence of SHV, TEM, PER and VIM ß-lactamases in Pseudomonas and Acinetobacter species isolates from burn wound swabs of children with burn injury. In this descriptive observational study, 107 Pseudomonas and Acinetobacter isolates collected from burn patients were subjected to PCR assay. Using PCR method and DNA sequencing, the existence of SHV-, TEM-, PER- and VIM-type ß-lactamase encoding genes were determined. Out of the 107 Pseudomonas and Acinetobacter isolates, 66 (77.6%) were ESBL positive, 26.2% were positive for SHV gene, 37.4% were positive for TEM gene, 14% were positive for PER gene and 15.9% of them harbored VIM gene. More than half of the Pseudomonas and Acinetobacter strains in our pediatric burn unit harbor ß-lactamase encoding genes that make them resistant to a wide range of ß-lactam antibiotics. Consequently, it is suggested to choose an appropriate antibiotic regimen based on the antibiogram pattern of the strains.


The benefit of arthroscopy for symptomatic total knee arthroplasty.
Thirty-one knees with symptomatic total knee arthroplasty were diagnosed and treated arthroscopically. There were 18 knees with soft tissue impingement and 13 knees without. There were 16 knees with painful arthroplasty and range of motion (ROM) greater than 90 degrees. Hypertrophied synovitis with or without impingement was more easily found by arthroscopy in this group than in the other 15 knees with the chief complaint of limited ROM, where more remarkable fibrotic tissue with intra-articular adhesion was found. Overall, the average improvement in ROM was 43.1 degrees immediately after arthroscopy, and 20 degrees at the final follow-up. Symptoms improved in 90.3% of patients, and 58.1% were satisfied with the outcome of their surgery. Arthroscopy is helpful for intra-articular diagnosis, obtaining a specimen for histopathologic analysis, culture for subclinical infection, and better improvement in ROM. In our experience, arthroscopy for symptomatic knee arthroplasty is reliable, safe and effective.


[Organization of diagnosis, treatment, and further measures for patients with gastrointestinal cancer (author's transl)].
One third of the total surgical care at the Department of Surgery, University of Lund, Sweden, is for cancer patients. Gastrointestinal cancer occupies 9,000 of a total of 12,000 bed-days and this disease is usually handled by the team who cares for the specific organ in which the cancer is localized. A particularly important part of gastrointestinal care is endoscopy (gastroscopy and colo-sigmoideo-rectoscopy). These diagnostic procedures can sometimes be curative. The value of preoperative liver tests for diagnosing liver metastases in colorectal cancer is very low because of the low prevalence of liver metastases in this population. Palliative therapeutical procedures, such as Celestin-tubes for esophageal or cardia carcinoma and transhepatic endoprostheses for bile duct occlusive cancer, have been tested. Palliative cytostatic therapy is partly established, i.e., intraarterial infusion of 5-FU for recurrent rectal carcinoma in the lower pelvis. This type of treatment has a very good pain relief effect. Cytostatic therapy for tumour control in patients without symptoms e.g. primary or secondary liver carcinomas, has not yet been established. Most of the patients with cytostatic therapy are treated on an outpatient basis. The cytostatic therapist must always be properly protected when working with cytostatic drugs. It is very important that the patient who gets cytostatic therapy is followed in order to see if the drug has any growth-controlling effect. A cost-benefit analysis of the therapy should also be made.


Systematic prediction of kinetically limited crystal growth morphologies.
We develop a new, combined experimental and theoretical approach to make reliable predictions for the limiting case of surface reaction kinetics controlled growth. We solve the inverse problem of determining the growth velocity from observations of the evolution of the morphology of GaN islands grown by metalorganic chemical vapor deposition and make use of crystal symmetry and established theorems. We are able to predict the growth for both convex and concave surfaces, with faceted and curved features. We also give a general guideline for deducing growth velocities from experimental observations.


RutR is the uracil/thymine-sensing master regulator of a set of genes for synthesis and degradation of pyrimidines.
Using the genomic SELEX, a total of six Escherichia coli DNA fragments have been identified, which formed complexes with transcription factor RutR. The RutR regulon was found to include a large number of genes encoding components for not only degradation of pyrimidines but also transport of glutamate, synthesis of glutamine, synthesis of pyrimidine nucleotides and arginine, and degradation of purines. DNase I footprinting indicated that RutR recognizes a palindromic sequence of TTGACCAnnTGGTCAA. The RutR box in P1 promoter of carAB encoding carbamoyl phosphate synthetase, a key enzyme of pyrimidine synthesis, overlaps with the PepA (CarP) repressor binding site, implying competition between RutR and PepA. Adding either uracil or thymine abolished RutR binding in vitro to the carAB P1 promoter. Accordingly, in the rutR-deletion mutant or in the presence of uracil, the activation in vivo of carAB P1 promoter was markedly reduced. Northern blot analysis of the RutR target genes indicated that RutR represses the Gad system genes involved in glutamate-dependent acid resistance and allantoin degradation. Altogether we propose that RutR is the pyrimidine sensor and the master regulator for a large set of the genes involved in the synthesis and degradation of pyrimidines.


Seizures in horses: diagnosis and classification.
Seizures are a diverse and very common set of chronic neurologic disorders in humans and dogs but are less common in horses. Seizures refer to a specific clinical event (described as sudden and severe) regardless of the etiology, which includes both intracranial and extracranial causes. Therefore, after briefly reviewing some definitions, this article aims to describe the use of a standardized classification, which could facilitate a logical approach for the clinician to establish a diagnosis, as well as to use a consistent mode of communication. For instance, seizures can be classified by type (ie, focal vs generalized) or etiology (ie, reactive, symptomatic, cryptogenic, idiopathic). In particular, epilepsy, a brain disorder characterized by recurrent seizures can be classified as primary (ie, genetic origin) or secondary (ie, acquired). This review further discusses the limitations associated with the clinical workup of horses with seizures. This is germane to the fact that the identification of the underlying cause remains challenging due to the technical limitations of imaging the equine adult brain. Indeed, as in man and dogs, epilepsies of unknown cause (ie, cryptogenic) account for the majority of all epilepsies. Therefore, although electroencephalography and advanced brain imaging techniques (eg, computed tomography and magnetic resonance imaging) are becoming increasingly available, information obtained from the history, physical, and neurologic examinations and progression of clinical signs and response to treatment remain essential in the workup of horses with seizures.


Transcriptional regulation of matrix metalloprotease gene expression in health and disease.
The mammalian extracellular matrix (ECM) is a complex network of collagens, proteoglycans, glycoproteins, polysaccharides and other secreted proteins that plays fundamental structural and functional roles. In addition to its key function as an extracellular space-filling scaffold, the ECM is also implicated in the formation of important cell-cell and cell-ECM (i.e. juxtacrine) interactions that subsequently provide key regulatory signals that influence cellular proliferation and viability, differentiation, specialization and gene expression. Regulated turnover of the ECM, a process largely mediated by the tightly controlled matrix metalloprotease (MMP) enzyme family, is critical to a number of physiological processes involved in growth and development while aberrant turnover of matrix components is associated with congenital and metabolic diseases. The following review will focus on the transcriptional aspects of MMP gene expression, particularly in diseased states.


Preliminary pharmacological evaluation of enantiomeric morphinans.
A series of levo- and dextromorphinan pairs have been synthesized and evaluated for their affinities to the mu, kappa, and delta opioid receptors, the N-methyl-D-aspartate (NMDA) channel, and sigma 1 and 2 receptors. It was found that levo isomers tended to have higher affinities at the opioid receptors and moderate to high affinities to the NMDA and sigma receptors, while dextro isomers tended to have lower affinities to the opioid receptors but comparatively higher affinities to the NMDA and sigma receptors. This series of compounds have interesting and complex pharmacological profiles, and merit further investigation as potential therapies for drug abuse treatment.


The dizziness handicap inventory and its relationship with functional balance performance.
The purpose of this study was to describe the relation between the Dizziness Handicap Inventory (DHI) and balance performance measures. Retrospective case series. Outpatient balance clinic in a tertiary referral center. Patients referred with dizziness or imbalance of vestibular and nonvestibular origin. DHI, Romberg with Jendrassik maneuver, standing on foam, tandem Romberg, single-leg stance, the timed up and go test, the Dynamic Gait Index (DGI), tandem gait, and the 10-m walking test. The mean age of participants (n = 214) was 53.9 years. The mean DHI total score was 35.1, ranging from 0 to 96. Spearman rank correlation coefficients (rS) between DHI and the static balance tests were fair and ranged between -0.42 (p < 0.01) for single-leg stance with eyes closed and -0.51 (p < 0.01) for single-leg stance with eyes open. Only the Romberg test with Jendrassik maneuver correlated weakly (rS = -0.25; p < 0.01) with the DHI. Correlations with the walking tests were moderate, the connection with the DGI being the strongest one (rS = -0.69; p < 0.01). Forty-two percent of the variance in DHI scores in our patients was accounted for by the DGI score (r = 0.417). Functional balance tests involving locomotion correlate better with DHI scores when compared with static balance measures. The DGI explains a large component of handicap in dizzy and unsteady patients, which advocates its use in these patients.


[Selection and interaction of Ni2+ metal-binding peptides].
Ni2+ binding peptides were selected from phage random dodecapeptide library by metal affinity chromatography. After four rounds of biopanning, phage amplification and DNA sequencing, a group of peptide sequences were obtained. GenBank blast found no homogenous sequences, Clustal W analysis showed no motifs but they were really riched in histidines and contained di- or more histidines(his). Affinity assays of selected metal-binding phages for various metal-charged NTA resins and the experiments of E. coli suppression and detoxification gave positive results for Ni2+ binding peptides: strong affinities for Ni2+ were found for Ni2+ binding peptide displayed phages, as well as for other metals (Cu2+, Co2+, Zn2+, Cr2+, Cd2+); affinities of the binding peptides for Cu2+, Ni2+, Co2+ and Zn2+ were much higher than that of Cd2+ and Cr2+; in addition, Ni2+ binding peptides displayed phages had effects on E. coli as to enhance the tolerance and detoxification of E. coli for heavy metals when exposed to Ni2+ and Cd2+. The interactions of meal binding peptides for heavy metals were also disclosed by microscopic observation. The research offered great values for the study of the interaction between metals and peptides, as well as in other areas such as heavy metal bioremediation.


PSS resin-fortified polythiophene nanoparticles for highly transparent conducting films.
Polythiophene/poly(sodium 4-styrene sulfonate) (PT/PSS) composite nanoparticles having different particle size were prepared by Fe(3+)-catalyzed oxidative polymerization in aqueous medium. This facile method includes a FeCl3/H2O2 (catalyst/oxidant) combination system, which guarantees a high conversion (more than 95%) of thiophene monomers in various concentration of poly(styrene sulfonate) (PSS) with only a trace of FeCl3. Particle size of PT/PSS composite nanoparticles decreased from 134 nm to 26 nm as the concentration of PSS and H2O2 increased, and which was confirmed by SEM and CHDF analyses. The poly(ethylene terephthalate) (PET) film coated with PT/PSS was transparent and showed a high conductivity in a dried state. The sheet resistivity decreased as the ratio of PT to PSS increased. Photoluminescence property of the PT/PSS composite nanoparticles was also investigated.


Effects of a kappa-opioid agonist on adrenocorticotropic and diuretic function in man.
Although kappa-opiate receptors represent an important fraction of the total opiate receptor capacity in human brain their endocrine function is unknown. We determined the effects of a kappa-opiate receptor agonist on the secretion of vasopressin, ACTH and cortisol and on diuresis. The racemic benzomorphan kappa agonist MR 2033 or its opiate active (-)-isomer, MR 2034, inhibited the release of cortisol and ACTH in 12 trials in a naloxone reversible manner; plasma levels of vasopressin were not altered. The (+)-isomer, MR 2035, did not affect the secretion of cortisol or ACTH. Surprisingly, in five other subjects large increases were observed in vasopressin, ACTH and cortisol following the kappa-agonist, which were probably elicited indirectly by aversive effects of the opioid. The subjects in whom vasopressin release was not altered by MR 2033 and MR 2034 displayed large decreases in urine osmolality which were not antagonized by naloxone. The opiate inactive (+)-isomer, MR 2035, caused no diuretic response. Subjects in whom vasopressin release was stimulated did not show decreases in urine osmolality indicating that vasopressin is capable of antagonizing the diuretic action of the kappa-agonist. Our data show that a kappa-agonist inhibits secretion of cortisol and ACTH by acting at stereospecific opiate receptors and elicits diuresis by acting at stereospecific, but naloxone-insensitive non-classical opioid receptors. These data support the concept that different types of kappa-receptors can be distinguished in man.


[The effect of folic acid fortification on the reduction of neural tube defects].
Neural tube defects are congenital malformations that occur during initial fetal development, leading to anencephaly and spina bifida; folic acid deficiency is the most important risk factor identified to date. Brazil has one of the world's highest neural tube defect rates. Food consumption surveys among pregnant Brazilian women showed a high rate of inadequate folic acid intake (< 0.6 mg/day). In 2004, the National Health Surveillance Agency (ANVISA) mandated the fortification of corn meal and wheat flour with folic acid (0.15 mg/100g). The National Family Budget Survey estimated the average amount of bread/flour products available in households as 106.1g/day (contributing with 0.16 mg folic acid/day). However, while in the South of the country the supply was 144 g/day, in the North and Central West it barely reached 70 g/day. Folic acid food fortification is mandatory in some 40 countries, but only four have assessed this strategy. The existing studies have all shown a significant impact, ranging from 19 to 78%. Folic acid fortification is an undeniably important intervention for primary prevention, and neural tube defects can now be considered a preventable epidemic.


[Not Available].
I discuss here the therapy of three borderline cases and one neurotic patient. I aproach this from the point of view of Hermann's (1984) theory of clinging. I observe two patterns of clinging in the transference. The typical sequence exhibited by a homosexual borderline patient and by a strongly regressed neurotic one was the following: first the idealizing transference together wtih the intensification of the desire to cling appeared, followed by the negative phase of angry disappointment, aggression and autoaggression. I assume that this latter phase was primarily a reaction to the unsatisfiability of the desire to cling. In the case of two other female borderline patients the frustration of the desire to cling manifested itself in a form of mental and bodily paralysis, rigidity and inhibition. This repeated a feeling that originally arose in connection with, and typically in the physical presence of the mother.


Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self.
The intestinal epithelium functions to absorb nutrients and to protect the organism against microbes. To prevent autoimmune attack on this vital tissue, T cell tolerance to intestinal self-antigens must be established. Central tolerance mechanisms involve medullary thymic epithelial cells (mTECs), which use endogenously expressed peripheral-tissue antigens (PTAs) to delete self-reactive thymocytes. The prevailing model for the induction of peripheral tolerance involves cross-presentation of tissue antigens by quiescent dendritic cells. Here we show that lymph node stromal cells present endogenously expressed PTAs to T cells. Moreover, antigen presentation by lymph node stroma is sufficient to induce primary activation and subsequent tolerance among CD8(+) T cells. Thus, lymph node stromal cells are functionally akin to mTECs and provide a direct strategy for purging the peripheral repertoire of self-reactive T cells.


Accuracy of Sequential Organ Failure Assessment (SOFA) scoring in clinical practice.
The Sequential Organ Failure Assessment (SOFA) score is used to quantify the severity of illness daily during intensive care. Our aim was to evaluate how accurately SOFA is recorded in clinical practice, and whether this can be improved by a refresher course in scoring rules. The scores recorded by physicians in a university hospital intensive care unit (ICU) were compared with the gold standard determined by two expert assessors. Data concerning all consecutive patients during two 6-week-long observation periods (baseline and after the refresher course) were compared. SOFA was accurate on 75/158 (48%) patient days at baseline. The cardiovascular, coagulation, liver, and renal component scores showed excellent accuracy (>or=82%, weighted kappa >or=0.92), while the neurological score showed only moderate (70%, weighted kappa 0.51) and the respiration score showed good accuracy (75%, weighted kappa 0.79). After the refresher course, the number of >or=2 point errors decreased (P<0.01). Sedation precluded neurological evaluation on 135/311 (43%) days. The accuracy of the assumed neurological scores was lower than those based on timely data: 89/135 (66%, weighted kappa 0.55) vs. 125/176 (71%, weighted kappa 0.81) (P<0.01). Only half of the SOFA scores were accurate. In most cases, they were accurate enough to allow the recognition of organ failure and detection of change. The component scores showed good to excellent accuracy, except the neurological score. After the refresher course, the results improved slightly. The moderate accuracy of the neurological score was not amended. A simpler neurological classification tool than the Glasgow Coma Scale is needed in the ICU.


Measuring cannabis-related knowledge, attitudes, perceptions, motivations, and influences among women of reproductive age: a scoping review.
Cannabis use among women of reproductive age has increased substantially in recent decades. Understanding reasons for cannabis use in this population is critical for cannabis use prevention efforts. Thus, this scoping review aimed to identify and synthesize current measures on reasons for cannabis use in women of reproductive age. We searched PubMed, PyschINFO, CINAHL, and Google Scholar for relevant studies published in English between January 2010 and April 2021. Peer-reviewed, quantitative studies reporting on measures of cannabis-related knowledge, attitudes, perceptions, motivations, and influences among women of reproductive age were eligible for inclusion. We excluded studies not focused on women of reproductive age and studies reporting cannabis use prevalence data only. We included 11 studies (10 primary studies and 1 review) with varying subpopulation samples of women, including non-pregnant women (n = 2), women experiencing infertility (n = 1), pregnant women (n = 4), postpartum women (n = 3), and women in the perinatal period (n = 1). Measurement topic areas included information received from health care professionals, attitudes, perceptions and experiences about cannabis use, knowledge of potential harms, and motivations for cannabis use. Most studies including measures of risk perceptions were conducted among pregnant or postpartum women (n = 4). A single study measured influences of cannabis use; no studies measured social or peer influences of use. Most studies (n = 7) created their own measures, with 2 studies using secondary data via measures from population-based surveillance systems in the United States, and one using a previously validated instrument. Recommendations for future research were centered around addressing knowledge gaps of health effects of cannabis use across different time periods, and etiology of cannabis use. We found vast measurement gaps in current measures of antecedents of cannabis use among women of reproductive age, providing clear direction for future research in this area. Findings necessitate psychometric evaluation of existing measures to ascertain validity and reliability, as well as development of additional measures of women's cannabis-related attitudes, perceptions, motivations, and influences. This work is critical to guide not only epidemiologic studies, but cannabis-related prevention work as well.


Germline mutations of hMLH1 and hMSH2 genes in patients with suspected hereditary nonpolyposis colorectal cancer and sporadic early-onset colorectal cancer.
The present study was designed to determine the frequency of germline mutations in the hMLH1 and hMSH2 genes in 31 families suspected of having hereditary nonpolyposis colorectal cancer who do not fulfill the criteria of the International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer but in whom a genetic basis for colon cancer is strongly suspected and 45 patients with sporadic early-onset colorectal cancer who developed colorectal cancer before the age of 40 years without any family history of colorectal cancer. Genomic DNAs were prepared from peripheral blood samples of patients who were tested. All coding exons and exon-intron borders of these two genes were screened, first with the polymerase chain reaction-single-strand conformation polymorphism method, followed by sequencing of the DNA fragments displaying an abnormal single-strand conformation polymorphism pattern. In 31 families with suspected hereditary nonpolyposis colorectal cancer, we found six different germline mutations in seven unrelated families, including one missense mutation and three frame-shift mutations in the hMLH1 gene and one missense mutation and one frame-shift mutation in the hMSH2 gene. Totally, frequency of mutation was 23 percent, 16 percent and 7 percent in the hMLH1 and hMSH2, respectively. Only one missense mutation of the hMSH2 gene was identified in 45 patients (2 percent) with sporadic early-onset colorectal cancer. The mutation detection rate in families with suspected hereditary nonpolyposis colorectal cancer was significantly higher than that of patients with sporadic early-onset colorectal cancer (P < 0.05). Our definition of suspected hereditary nonpolyposis colorectal cancer is useful in the diagnosis of hereditary nonpolyposis colorectal cancer and for identifying those families who need genetic presymptomatic diagnosis. Our results indicate that it may be important to perform DNA testing in families suspected of having hereditary nonpolyposis colorectal cancer. On the other hand, we only detected a low mutation rate (2 percent) in 45 patients with sporadic early-onset colorectal cancer.


Drift velocity saturation in field-effect transistors based on single CdSe nanowires.
Field-effect transistors (FETs) based on semiconductor nanowires (NWs) have been extensively investigated and used for constructing novel nanoelectronic and optoelectronic devices in the past two decades. High electric field transport characteristics in FETs are of significance in both physics and applications. However, some specific physics phenomena at high electric field, such as drift velocity saturation, have rarely been reported in semiconductor NW FETs. In this work, the high electric field transport characteristics in FETs based on CdSe NWs were investigated. In the output characteristic curves, the current saturation phenomenon at high electric field caused by drift velocity saturation was observed. Typical values of saturation drift velocity and low electric field mobility in CdSe NW FETs were obtained. The low electric field mobility is in the range of 265.2 to 388.0 cm2 V-1 s-1. The saturation drift velocity is in the range of 5.1 × 105 to 7.0 × 105 cm s-1 and decreases monotonically with the increase of charge density, indicating that the electron-phonon scattering mechanism dominates at high electric field. Saturation drift velocity is an important figure-of-merit which characterizes the high electric field transport performance in FETs. As far as we know, this is the first experimental report on saturation drift velocity in CdSe NW FETs, which may provide valuable guidance for the design of nanoelectronic and optoelectronic devices based on CdSe NWs in the future.


Reduced trolling on Russian holidays and daily US Presidential election odds.
Russian trolls generally supported the Trump campaign and were particularly active on Twitter 2015-2017. We find that trolling fell 35% on Russian holidays and to a lesser extent, when temperatures were cold in St. Petersburg. Exogenous variation in trolling by day allows us to consider indirectly-affected political behaviors in the US-outcomes that are less traceable via tweet sharing but potentially more important to policymakers than the direct dissemination previously studied. As a case in point, we describe reduced form evidence that Russian holidays affected daily trading prices in 2016 election betting markets. This response is consistent with successful Russian interference in support of Trump.


Directed Self-Assembly and Pattern Transfer of Five Nanometer Block Copolymer Lamellae.
The directed self-assembly (DSA) and pattern transfer of poly(5-vinyl-1,3-benzodioxole-block-pentamethyldisilylstyrene) (PVBD-b-PDSS) is reported. Lamellae-forming PVBD-b-PDSS can form well resolved 5 nm (half-pitch) features in thin films with high etch selectivity. Reactive ion etching was used to selectively remove the PVBD block, and fingerprint patterns were subsequently transferred into an underlying chromium hard mask and carbon layer. DSA of the block copolymer (BCP) features resulted from orienting PVBD-b-PDSS on guidelines patterned by nanoimprint lithography. A density multiplication factor of 4× was achieved through a hybrid chemo-/grapho-epitaxy process. Cross-sectional scanning tunneling electron microscopy/electron energy loss spectroscopy (STEM/EELS) was used to analyze the BCP profile in the DSA samples. Wetting layers of parallel orientation were observed to form unless the bottom and top surface were neutralized with a surface treatment and top coat, respectively.


Treatment of advanced malignant melanoma with vinblastine, bleomycin, and cisplatin.
Thirty-two consecutive patients with metastatic malignant melanoma were treated with vinblastine, bleomycin, and cisplatin (VBD) chemotherapy. There were 29 evaluable patients; complete remission was observed in three and partial remission in five. No patient with visceral metastasis showed objective response. The 10-month survival rate of responders was significantly higher than that of nonresponders (57.1% vs 18.2%, P = 0.01); however, present results do not confirm that VBD is superior to other drug combinations for malignant melanoma.


Gonioscopy-assisted Transluminal Trabeculotomy (GATT) is An Effective Procedure for Steroid-induced Glaucoma.
Gonioscopy-assisted transluminal trabeculotomy (GATT) is a novel technique that lowers intraocular pressure (IOP) by fracturing the trabecular meshwork. In this retrospective chart review, GATT was found to be effective at lowering the intraocular pressure for steroid-induced glaucoma (SIG). GATT is a novel microinvasive glaucoma surgery that builds on traditional trabeculotomy techniques to decrease the proximal resistance of conventional outflow, and it is proposed to be an effective surgical treatment for SIG. The purpose of this study is to evaluate the efficacy of GATT for lowering the IOP in SIG. A retrospective chart review was performed of all GATT procedures performed on patients with a predominant diagnosis of steroid-induced glaucoma between March 1, 2016 and March 30,2018 at the University of Michigan. Primary outcome measures include IOP, the number of IOP-lowering medications prescribed, and the topical steroid dosing over the duration of follow-up. A total of 13 patients with steroid-induced glaucoma underwent the GATT procedure. There was a significant reduction in the mean IOP at all postoperative visits. The average IOP decreased by 16.4 (55%) to 19.5 mm Hg (63%) between 3 and 24 months postoperatively. By 24 months, all patients had a reduction in IOP of >20%. The number of glaucoma medications also decreased significantly from an average of 3.1 medications preoperatively to an average of 0.8 medications at last follow-up. The majority of patients (>67%) required continued use of steroids at all postoperative visits. The most common postoperative complication was a transient hyphema (38%). No patients required a repeat glaucoma surgery or anterior chamber washout. This small case series suggests that GATT is an effective and safe surgical technique to decrease IOP and decrease medication burden in patients with predominantly steroid-induced glaucoma. To our knowledge, this is the first study looking specifically at the efficacy of GATT for predominantly SIG.


Electrocatalytic Mechanisms for an Oxygen Evolution Reaction at a Rhombohedral Boron Monosulfide Electrode/Alkaline Medium Interface.
Rhombohedral boron monosulfide (r-BS) with a layer stacking structure is a promising electrocatalyst for an oxygen evolution reaction (OER) within an alkaline solution. We investigated the catalytic mechanisms at the r-BS electrode/alkaline medium interface for an OER using hybrid solvation theory based on the first-principles method combined with classical solution theory. In this study, we elucidate the activities of the OER at the outermost r-BS sheet with and without various surface defects. The Gibbs free energies along the OER path indicate that the boron vacancies at the first and second layers of the r-BS surface (VB1 and VB2) can promote the OER. However, we found that the VB1 is easily occupied by the oxygen atom during the OER, degrading its electrocatalytic performance. In contrast, VB2 is suitable for the active site of the OER due to its structure stability. Next, we applied a bias voltage with the OER potential to the r-BS electrode. The bias voltage incorporates the positive excess surface charge into pristine r-BS and VB2, which can be understood by the relationship between the OER potential and potentials of zero charge at the r-BS electrode. Because the OH- ions are the starting point of the OER, the positively charged surface is kinetically favorable for the electrocatalyst owing to the attractive interaction with the OH- ions. Finally, we qualitatively discuss the flat-band potential at a semiconductor/alkaline solution interface. It suggests that p-type carrier doping could promote the catalytic performance of r-BS. These results explain the previous measurement of the OER performance with the r-BS-based electrode and provide valuable insights into developing a semiconductor electrode/water interface.


Folded free vascularized fibular grafts for the treatment of subtrochanteric fractures complicated with segmental bone defects.
Subtrochanteric fractures of the femur complicated with segmental bone defects are uncommon injuries and challenging to manage. We evaluated the effect of reconstructing extensive bone defect in the subtrochanteric area (mean, 6.9 cm) with folded free vascularized fibular graft (FVFG). Between 2001 and 2007, 14 cases of subtrochanteric fractures complicated with huge bone defects treated by folded FVFG transfer in our hospital were retrospectively reviewed. The defect was reconstructed by folded FVFG transfer and locking plate stabilization in 10 patients with no sign of infection at admission (group 1). In the other four patients presented with infections (group 2), the defect was reconstructed by folded FVFG transfer and external fixator fixation. The average follow-up period was 67.4 months. Bone union was achieved in all of the cases at an average of 5.4 months (range, 4-6 months). Primarily, bone union was achieved in all of the cases in group 1, but one stress fracture occurred in group 2. The full weight bearing time was 5.4 months (range, 5-6 months) in group 1 and 8.5 months (range, 8-9 months) in group 2. Seven patients in group 1 had the locking plate removed in an average of 27 months (range, 18-38 months). In group 2, the external fixator removal time was 13 months (range, 10-18 months). There was no varus deformity at the final follow-up in group 1. The neck-shaft angle measured during the postoperative period and at final follow-up was 129.6 degrees and 129.4 degrees, respectively. In group 2, the neck-shaft angle at the final follow-up was significantly less than the angle measured at the postoperative period (115.5 vs. 129.5 degree, p = 0.021). The range of motion of the hip and knee joint (extend and flex) was 100 degrees or more in all patients at the final follow-up. The results of this study showed that huge subtrochanteric bone defects reconstructed by folded FVFG and locking plate were highly successful in achieving bone union, reducing risks of postoperative stress fracture and preventing malunion. When huge bone defects in the subtrochanteric area complicated with acute or chronic infections, the technique of external fixator offers an alternative to reconstruct the stability of the proximal femur after folded FVFG. However, because of the inadequate stabilization, the risks of varus malunion and postoperative stress fracture could be increased after external fixator fixation. V, therapeutic study.


Prediction of protein interactions is essential for studying biomolecular mechanisms.
Structural characterization of protein interactions is essential for our ability to understand and modulate physiological processes. Computational approaches to modeling of protein complexes provide structural information that far exceeds capabilities of the existing experimental techniques. Protein structure prediction in general, and prediction of protein interactions in particular, has been revolutionized by the rapid progress in Deep Learning techniques. The work of Schweke et al. (Proteomics 2023, 23, 2200323) presents a community-wide study of an important problem of distinguishing physiological protein-protein complexes/interfaces (experimentally determined or modeled) from non-physiological ones. The authors designed and generated a large benchmark set of physiological and non-physiological homodimeric complexes, and evaluated a large set of scoring functions, as well as AlphaFold predictions, on their ability to discriminate the non-physiological interfaces. The problem of separating physiological interfaces from non-physiological ones is very difficult, largely due to the lack of a clear distinction between the two categories in a crowded environment inside a living cell. Still, the ability to identify key physiologically significant interfaces in the variety of possible configurations of a protein-protein complex is important. The study presents a major data resource and methodological development in this important direction for molecular and cellular biology.


The Radiographic Prepatellar Fat Thickness Ratio Correlates With Infection Risk After Total Knee Arthroplasty.
Obesity has been associated with complications after a total knee arthroplasty (TKA). Surgical site infection (SSI) after TKA is one of the feared complications as it increases revision rates, costs, and stress to the patient. There is conflicting evidence in the literature regarding body mass index (BMI) and risk of infection after TKA, and some studies have suggested that site-specific fat distribution may be a better metric for determining risk of postoperative infections. Here, we investigate the correlation of soft tissue distribution about the knee to SSI after TKA. We retrospectively review 572 patients who underwent primary TKA at a single institution from 2006 to 2010. We introduce the prepatellar fat thickness ratio (PFTR) as a radiographic means to quantitatively assess fat distribution about the knee and evaluate this measurement's ability to assess the risk of developing an SSI after TKA. The PFTR was shown to be a better predictor of SSI than BMI in both the univariate (P = .05) and multivariate (P = .01) analyses. Although BMI cannot fully account for variations in adipose distribution, the PFTR may account for this variability and may be a helpful tool for assessing a patient's preoperative risk of SSI after TKA.


Delayed posttraumatic vertebral collapse with intravertebral vacuum cleft.
To discuss the case of a 79-year-old man who had a delayed posttraumatic vertebral collapse and an intravertebral vacuum cleft. The patient had been on long-term corticosteroid therapy. A discussion of Kummell's disease and the controversy surrounding the etiology of the condition is also presented. Six weeks before coming to the clinic, the patient remembered twisting, hearing a pop, and having severe low back pain. Two weeks after the incident, while hospitalized for bacterial cellulitis, he underwent lumbar spine radiography. The radiographs showed degenerative changes and remote (healed) compression fractures but did not demonstrate any deformity of L2. Four weeks later, he sought care for persistent low back pain. Radiographs revealed marked compression of the L2 vertebral body with an intravertebral vacuum phenomenon. The patient was referred to his geriatrician for evaluation as a candidate for vertebroplasty or other stabilization procedures. He required a moderately high dose (60 mg) of prednisone daily to combat the symptoms of myasthenia gravis; therefore, the prognosis appears unfavorable for this patient. Clinical research is needed to determine the definitive etiology and pathophysiology of Kummell's disease. This case demonstrates that the intravertebral vacuum is a dynamic entity, subject to changes in size and shape. Previous case reports have suggested that Kummell's disease only presents as a linear, horizontal cleft. This disease needs further investigation to determine the true correlation between radiographic signs and the underlying pathophysiology.


Preliminary study of IVIM-DWI and DCE-MRI in early diagnosis of esophageal cancer.
To investigate the application value of double exponential model diffusion weighted imaging (IVIM-DWI) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in the diagnosis of early esophageal cancer. 30 cases of patients with early esophageal cancer confirmed by pathology were collected. They were performed MRI plain scan, IVIM-DWI and DCE-MRI scan. The normal esophageal tissue, SlowADC value in tumor focus, FastADC value, F value, Ktrans, Kep and Ve values were measured. The difference between cancer tissue and normal tissue was compared using two independent sample t test. The prediction parameters and diagnostic threshold were compared by drawing receiver operating characteristic curve (ROC). The average F, Ktrans and Kep values in esophageal cancer and normal esophageal tissue were: (0.48 ± 0.19), (0.64 ± 0.08); (0.45 ± 0.19)/min, (0.14 ± 0.04)/min and (1.14 ± 0.42)/min, (0.56 ± 0.25)/min respectively. Compared with normal esophageal tissue, esophageal cancer F value decreased, Ktrans value increased, Kep value increased, and the difference was statistically significant (p < 0.05); There was no difference in SlowADC, FastADC, Ve values of esophageal cancer and those in normal esophageal tissues (p > 0.05). The areas under ROC curve F, Ktrans and Kep values were 0.90, 0.98 and 0.92 respectively. They had the higher diagnostic efficiency. IVIM-DWI and DCE-MRI can be used as the imaging method to diagnose esophageal malignant tumor, which has the higher diagnostic value.


Age determination and longevity in fishes.
It is possible to determine the age of fishes with reasonable accuracy by reading the 'growth rings' (annuli) in hard parts (scale, otolith, opercular bone, vertebra and cross-section of dorsal or pectoral spine and fin rays). Primary growth increments in 'otoliths' can also be used as an alternative method of age determination. The traditional methods could be supplemented with more reliable fluorochrome and microradiographic techniques. The suitability of the use of hard parts and the techniques may vary among the species. It is essential that the 'true rings' be distinguished from other types of rings, such as false rings, larval rings and spawning rings through repeated examination of samples to avoid confusion and inaccuracy in age determination. The causes and the periodicity of ring formation may vary from species to species. The growth history of fishes could be traced by back calculation of length attained at different ages. Among the different types of growth equations, the Von Bertalanffy's model appears to be the most suitable for fishes of both temperate and tropical regions. With slight modification, the same model may also serve to estimate the maximum theoretical calculated age (longevity) of fishes. The longevity of fishes show wide variations. The life-span may be short, intermediate and long. Whereas the lowest range of life-span (1-2 years) is exhibited by some species of lampreys and teleosts, there are species of dogfishes, sturgeons, paddlefishes, rockfishes and eels which have the life-span (70-152 years) in the highest range. A number of factors (size, sex, temperature, diet, reproduction, age at maturity and genetic composition) are believed to influence the longevity of fishes.


Molecular Properties and New Potentials of Plant Nepenthesins.
Nepenthesins are aspartic proteases (APs) categorized under the A1B subfamily. Due to nepenthesin-specific sequence features, the A1B subfamily is also named nepenthesin-type aspartic proteases (NEPs). Nepenthesins are mostly known from the pitcher fluid of the carnivorous plant Nepenthes, where they are availed for the hydrolyzation of insect protein required for the assimilation of insect nitrogen resources. However, nepenthesins are widely distributed within the plant kingdom and play significant roles in plant species other than Nepenthes. Although they have received limited attention when compared to other members of the subfamily, current data indicates that they have exceptional molecular and biochemical properties and new potentials as fungal-resistance genes. In the current review, we provide insights into the current knowledge on the molecular and biochemical properties of plant nepenthesins and highlights that future focus on them may have strong potentials for industrial applications and crop trait improvement.


IL-6 is constitutively expressed during lung morphogenesis and enhances fetal lung explant branching.
Previous studies have shown that chorioamnionitis, with increased IL-6, promotes fetal lung maturation and decreases the incidence of respiratory distress syndrome in premature neonates. However, the expression pattern and the effects of IL-6 on fetal lung growth mechanisms remain unknown. IL-6 expression was assessed by in situ hybridization and by real-time PCR between 14.5 and 21.5 d postconception. Normal and nitrofen-induced hypoplastic lung explants were cultured with increasing IL-6 doses or IL-6 neutralizing antibodies. Branching, cellular proliferation (Ki-67) and MAPK phosphorylation in fetal lung explants were analyzed. Pulmonary primitive epithelium expressed IL-6 constitutively throughout all gestational ages, displaying highest levels during earliest stages. In normal and hypoplastic lung explants, IL-6 neutralizing antibodies significantly reduced, whereas IL-6 supplementation induced a biphasic effect (lower doses increased, while the highest dose did not accomplish additional effect) on branching and cellular proliferation. IL-6 enhanced p38-MAPK phosphorylation without changing MEK1/2 and JNK pathways. The present study suggests a physiological role for IL-6 on pulmonary branching mechanisms most likely involving p38-MAPK intracellular signalling pathway.


Further approaches to the quaternary structure of octopus hemocyanin: a model based on immunoelectron microscopy and image processing.
The direction of the polypeptide chains and the location of the functional units in Octopus vulgaris hemocyanin were studied by various methods. Monoclonal antibodies specific for the Ovc (clone Ov409) and Ovg (clone Ov315) functional units produced immunocomplex strings which were examined in the electron microscope. In both cases the immunocomplexes contained more than two hemocyanin molecules in their side view, demonstrating that in the whole hemocyanin neighboring polypeptide chains run in antiparallel directions. The interhemocyanin distances in the immunocomplexes also indicated that Ovg is located inside the cylinder, while Ovc is located in the external layers of functional units. In addition, the fact that the binding point of the Fab arm to the hemocyanin molecule was occasionally visible confirmed the external location of functional unit Ovc. Image processing of the whole hemocyanin cross-linked with dimethyl suberimidate showed that the end-on view is not a perfect cylinder but a regular pentahedron and that the five-arch collar is probably composed of five pairs of functional unit Ovg located inside the cylinder. The accessibility of cross-linked hemocyanin to functional unit-specific polyclonal antibodies, studied in immunoelectrophoresis, showed that Ovb and Ove are highly accessible, while Ovd, Ovf, and Ovg are not. The low accessibility of Ovd may be at least partially explained by its high sugar content which could hamper the accessibility of the antibody to the antigen.


Acupuncture Attenuates Renal Sympathetic Activity and Blood Pressure via Beta-Adrenergic Receptors in Spontaneously Hypertensive Rats.
The sympathetic nervous system, via epinephrine and norepinephrine, regulates β-adrenergic receptor (β-AR) expression, and renal sympathetic activation causes sustained increases in blood pressure by enhanced renin release. In this study, we aim to investigate the effect and underlying mechanism of acupuncture at Taichong (LR3) on renal sympathetic activity in spontaneously hypertensive rats. Unanesthetized rats were subject to daily acupuncture for 2 weeks. Mean blood pressure (MBP) and heart rate variability (HRV) were monitored at days 0, 7, and 14 by radiotelemetry. After euthanasia on the 14th day, blood and the kidneys were collected and subject to the following analyses. Epinephrine and norepinephrine were detected by ELISA. The expression of β-ARs was studied by western blotting and PCR. The renin content was analyzed by radioimmunoassay. 14-day acupuncture significantly attenuates the increase of MBP. The HRV indices, the standard deviation of all normal NN intervals (SDNN), and the ratio of the low-frequency component to the high-frequency component (LF/HF) were improved following acupuncture. Renal sympathetic activation induced upregulation of epinephrine, norepinephrine, and renin content were attenuated by acupuncture. In addition, acupuncture decreased β1-AR expression and improved β2-AR expression. These results indicated that acupuncture relieves the increased MBP via the regulation of renal sympathetic activity and β-ARs.


Differences in Affective Temperaments in Anxiety Disorders: Comparison of Panic Disorder and Obsessive Compulsive Disorder.
In this study, probable differences in affective temperament among anxiety disorders were investigated via a comparison of panic disorder (PD) and obsessive-compulsive disorder (OCD). 44 patients with OCD and 42 patients with PD, who were admitted to Bakirkoy Prof. Dr. Mazhar Osman Research and Training Hospital for Psychiatry, Neurology and Neurosurgery outpatient clinics with complaints of OCD and PD and were diagnosed according to DSM IV criteria, were consecutively included in the study after informed consent was taken. A sociodemographic form, the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID I), Hamilton Depression Rating Scale (HAM-D), Beck Anxiety Inventory, Panic and Agoraphobia Scale, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the temperament evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A) were given to the patients. PD and OCD patients were compared in terms of affective temperament characteristics. Mean age, educational status and gender distribution of OCD and PD patients were similar (p>0.05). Dominant depressive temperament was more prominent in OCD group than in PD group (p=0.021). Hyperthymic temperament scores were higher in PD group than in OCD group (p=0.002). Dominant hyperthymic temperament was not encountered in either group. Dominant depressive temperament was more prominent in OCD group whereas hyperthymic temperament scores were higher in PD group. These findings should be evaluated in studies with larger sample sizes.


Risk factors for the transmission of foot-and-mouth disease during the 2010 outbreak in Japan: a case-control study.
In 2010, foot-and-mouth disease (FMD) occurred for the first time in a decade in Japan. Movement or shipment of people and animals around infected farms was restricted; however these contingency measures proved insufficient to prevent FMD spread. Consequently, a total of 292 farms were confirmed as infected during this outbreak. We conducted a case-control study to identify the risk factors associated with FMD transmission between farms during these restrictions. As there was discordance in the control measures taken, risk factors were examined separately for two areas. Analyses were also performed separately for cattle and pig farms given their different infectivity and susceptibility. For cattle farms in the movement restriction area, the odds of having the factor 'farm equipment was shared with other farms' was significantly higher for case farms than for control farms. For cattle farms in the shipment restriction area, the odds of having the factors 'feed transport vehicles visited the farm' and 'staff of livestock-related companies visited the farm' were significantly higher on case farms than control farms. In pig farms in the movement restriction area, the odds of having factor 'farm staff commuted from outside' was 20 times higher for case farms than control farms. In addition, case farms were less likely to have the factors 'fattening farm' and 'barn has physical barriers' compared with control farms. In the movement restriction area, the disease was likely to spread regardless of the movement of people and vehicles, and physical barriers were found to be a protective factor. Therefore, physical barriers from the surrounding environments seemed to prevent farms from being infected. Conversely, in the shipment restriction area, movement of people and vehicles was strongly associated with disease spread. These results allow a better understanding of the risk factors associated with FMD transmission and are useful to enhance future preventive measures against transmission during FMD outbreaks.


Spontaneous Bilateral Carotid-Cavernous Fistulas Secondary to Cavernous Sinus Thrombosis.
Bilateral carotid cavernous fistulas are rare entities that can cause debilitating symptoms and can lead to more severe consequences if left untreated. Therefore, the recognition and adequate treatment of these pathologies is very important. We present 2 cases of bilateral carotid cavernous fistulas that arose as a result of cavernous sinus thrombosis. We review the literature and discuss the pathophysiology, symptomatology, management, and treatment of bilateral carotid cavernous fistulas. Within our own cases, treatment of the patients was varied. The patient in case 1 was successfully treated with endovascular therapy after a failed trial of anticoagulation. The patient in case 2 demonstrated resolution of bilateral carotid cavernous fistulas after anticoagulation therapy. Case 2 highlights the fact that certain cases of bilateral carotid cavernous fistulas due to cavernous sinus thrombosis may benefit from extensive anticoagulation therapy. If anticoagulation therapy is unsuccessful, endovascular therapy may prove beneficial in resolving the fistulous shunt.


Pulmonary parenchymal abnormalities of vascular origin: high-resolution CT findings.
High-resolution computed tomography (HRCT) is a proved imaging modality for use in assessment of infiltrative lung disease. Findings suggestive of infiltrative lung disease on HRCT scans include ground-glass attenuation, consolidation, nodules, and interlobular septal thickening. Similar patterns, however, may be caused by various vascular abnormalities including regional or diffuse increase in blood flow, pulmonary edema, pulmonary hypertension, and thromboembolism. A correct diagnosis can usually be made by careful analysis of the pulmonary vasculature. Parenchymal abnormalities of vascular origin are associated with increased or decreased vessel diameter, vascular compression, or intraluminal filling defect.


Identifying source proteins for MHC class I-presented peptides.
Identification of antigenic peptides recognized by cytolytic T lymphocytes (CTL) is a prerequisite for the development of targeted cancer immunotherapy approaches. This chapter provides a global approach for the identification of peptides recognized by CTL. It implies the identification of the HLA molecule presenting the peptide as well as the design and screening of a cDNA library derived from the tumor cells.


Human diseases caused by foodborne pathogens of animal origin.
Many lines of evidence link antimicrobial-resistant human infections to foodborne pathogens of animal origin. Types of evidence reviewed include: (1) direct epidemiologic studies; (2) temporal evidence; (3) additional circumstantial evidence; (4) trends in antimicrobial resistance among Salmonella isolates; and (5) trends in antimicrobial resistance among other pathogens, such as Campylobacter jejuni. Commensal microorganisms in animals and humans may contribute to antimicrobial resistance among pathogens that cause disease among humans. For instance, enterococci of food-animal origin, particularly strains that are vancomycin resistant, have been linked to strains found in the human gastrointestinal tract. The latent period between the introduction of a given antimicrobial and emergence of resistance varies considerably, but once the prevalence in a population reaches a certain level, control becomes extremely difficult.


Incident cases of vision impairment and blindness among adult foreign-born and Swedish-born individuals: A national Swedish study.
To analyse risk of vision impairment (VI) and blindness in adult foreign-born individuals and Swedish-born individuals. A nationwide study of individuals 18 years of age and older (N = 6,042,891; 2,902,918 men and 3,139,973 women) in Sweden. VI (in general) and blindness was defined as at least one registered diagnosis in the National Patient Register between January 1, 1998 and December 31, 2015. Cox regression analysis was used to estimate the relative risk (hazard ratios (HR) with 95% confidence intervals (CI)) of incident VI in foreign-born compared to Swedish-born individuals. The Cox regression models were stratified by sex and adjusted for age, co-morbidities, and for sociodemographic status. A total of 14,597 cases (6433 men and 8164 women) of VI were registered, with an age-standardized incidence per 100,000 person-years of 10.37 in men and 11.03 in women. VI (in general) was more common in immigrants, fully adjusted HRs (95% CI) were for immigrant men 1.38 (95% CI, 1.29-1.48) and women 1.24 (95% CI, 1.16-1.32), with significantly higher HRs among men and women from Eastern Europe, Africa, Latin America and Asia. Higher risks of blindness were also seen for immigrant men, HR 1.75 (95% CI 1.36-2.25), as well as for the other degrees of VI among immigrant men, HR 1.36 (95% CI 1.26-1.47), and immigrant women, HR 1.26 (95% CI 1.18-1.35). We observed a generally higher risk of VI among foreign-born men and women, especially from some regions.


Performance of the 2016 ACR-EULAR Myositis Response Criteria in adult dermatomyositis/polymyositis therapeutic trials and consensus profiles.
The ACR-EULAR Myositis Response Criteria (MRC) were developed as a composite measure using absolute percentage change in six core set measures (CSMs). We aimed to further validate the MRC by assessing the contribution of each CSM, frequency of strength vs extramuscular activity improvement, representation of patient-reported outcome measures (PROM), and frequency of CSM worsening. Data from adult dermatomyositis/polymyositis patients in the rituximab (n = 147), etanercept (n = 14), and abatacept (n = 19) trials, and consensus patient profiles (n = 232) were evaluated. The Total Improvement Score (TIS), number of improving vs worsening CSMs, frequency of improvement with and without muscle-related CSMs, and contribution of PROM were evaluated by MRC category. Regression analysis was performed to assess contribution of each CSM to the MRC. Of 412 adults with dermatomyositis/polymyositis, there were 37%, 24%, 25%, and 14% with no, minimal, moderate, and major MRC improvement, respectively. The number of improving CSMs and absolute percentage change in all CSMs increased by improvement category. In minimal-moderate improvement, only physician-reported disease activity contributed significantly more than expected by MRC. Of patients with at least minimal improvement, 95% had improvement in muscle-related measures and a majority (84%) had improvement in PROM. Patients with minimal improvement had worsening in a median of 1 CSM, and most patients with moderate-major improvement had no worsening CSMs. Physician assessment of change generally agreed with MRC improvement categories. The ACR-EULAR MRC performs consistently across multiple studies, further supporting its use as an efficacy end point in future myositis therapeutic trials.


Pregnant women's views on the acceptability, enablers, and barriers of participation in a randomized controlled trial of maternal posture for fetal malposition in labor.
Fetal malposition in labor results in adverse maternal and infant health. Whilst evidence for effective interventions is inconclusive, based on the hypothesis that gravity corrects malposition, the feasibility and design of a randomized controlled trial (RCT) to improve maternal and infant health outcomes should be considered. The aim was to assess pregnant women's views on the acceptability, enablers, and barriers of participation in an RCT of maternal posture for fetal malposition in labor. A web-based anonymous survey of pregnant women was conducted in Auckland during 2020. Quantitative data were summarized descriptively using a chi-squared test to assess differences in proportions. Maternal characteristics influence on women's responses was assessed using cross-tabulation. A thematic content analysis of free text responses was undertaken. Most of the 206 respondents were aged 26-35 years (75%), 29-38 weeks pregnant (71%), of European (40%) or Asian (36%) ethnicity, and similarly nulliparous or multiparous. Most women (76%) knew of fetal malposition in labor; however, only 28% were aware of maternal posture to correct this. Most women (86%) were interested in labor research and although 37% would participate in an RCT, almost half (47%) were unsure and a 15% would not participate. Concerns mostly related to comfort (22%). Nearly half of women (49%) would need to consult their partner regarding participation in an RCT. Enablers for participation in a posture trial in labor include measures to enhance maternal comfort, increasing awareness of malposition and the role of posture, and involving partners in pre-trial counselling and recruitment.


Antibacterial and Pharmacological Evaluation of Fluoroquinolones: A Chemoinformatics Approach.
Fluoroquinolone (FQ) antibiotics are an important class of synthetic antibacterial agents. These are the most extensively used drugs for treating bacterial infections in the field of both human and veterinary medicine. Herein, the antibacterial and pharmacological properties of four fluoroquinolones: lomefloxacin, norfloxacin, ciprofloxacin, and ofloxacin have been studied. The objective of this study was to analyze the antibacterial characteristics of the different fluoroquinolones. Also, the pharmacological properties of the compounds including the Lipinski rule of five, absorption, distribution, metabolism, and excretion, LD50, drug likeliness, and toxicity were evaluated. We found that among all four FQ molecules, ofloxacin showed the highest antibacterial activity through in silico assays with a strong interaction (‒38.52 kJ/mol) with the antibacterial target protein (topoisomerase-II DNA gyrase enzyme). The pharmacological and pharmacokinetic analysis also showed that the compounds ciprofloxacin, ofloxacin, lomefloxacin and norfloxacin have good pharmacological properties. Notably, ofloxacin was found to possess an IGC50 (concentration needed to inhibit 50% growth) value of 0.286 μg/L against the Tetrahymena pyriformis protozoa. It also tested negative for the Ames toxicity test, showing its non-carcinogenic character.


Visual and somatosensory information about object shape control manipulative fingertip forces.
We investigated the importance of visual versus somatosensory information for the adaptation of the fingertip forces to object shape when humans used the tips of the right index finger and thumb to lift a test object. The angle of the two flat grip surfaces in relation to the vertical plane was changed between trials from -40 to 30 degrees. At 0 degrees the two surfaces were parallel, and at positive and negative angles the object tapered upward and downward, respectively. Subjects automatically adapted the balance between the horizontal grip force and the vertical lift force to the object shape and thereby maintained a rather constant safety margin against frictional slips, despite the huge variation in finger force requirements. Subjects used visual cues to adapt force to object shape parametrically in anticipation of the force requirements imposed once the object was contacted. In the absence of somatosensory information from the digits, sighted subjects still adapted the force coordination to object shape, but without vision and somatosensory inputs the performance was severely impaired. With normal digital sensibility, subjects adapted the force coordination to object shape even without vision. Shape cues obtained by somatosensory mechanisms were expressed in the motor output about 0. 1 sec after contact. Before this point in time, memory of force coordination used in the previous trial controlled the force output. We conclude that both visual and somatosensory inputs can be used in conjunction with sensorimotor memories to adapt the force output to object shape automatically for grasp stability.


Alpinia oxyphylla Miq. extract changes miRNA expression profiles in db-/db- mouse kidney.
A number of dysregulated miRNAs have been identified and are proposed to have significant roles in the pathogenesis of type 2 diabetes mellitus or renal pathology. Alpinia oxyphylla has shown significant anti-inflammatory properties and play an anti-diabetes role. The objective of this study was to detect the alteration of miRNAs underlying the anti-diabetes effects of A. oxyphylla extract (AOE) in a type II diabetic animal model (C57BIKsj db-/db-). Treatment with AOE for 8 weeks led to lower concentrations of blood glucose, urine albumin, and urine creatinine. 17 and 13 miRNAs were statistically identified as differentially regulated in the DB/DB and db-/db- AOE mice, respectively, compared to the untreated db-/db- mice. Of these, 7 miRNAs were identified in both comparison groups, and these 7 miRNAs were verified by quantitative real-time PCR. Functional bioinformatics showed that the putative target genes of 7 miRNAs were associated with several diabetes effects and signaling pathways. These founding suggest that the potential of AOE as a medicinal anti-diabetes treatment through changes in the expressions of specific miRNAs. The results provide a useful resource for future investigation of the role of AOE-regulated miRNAs in diabetes mellitus.


Organizational Context and Female Faculty's Perception of the Climate for Women in Academic Medicine.
Gender inequalities in the careers of faculty in academic medicine could partially be attributed to an organizational climate that can exclude or be nonsupportive of women faculty. This study explores the climate for women faculty from a systems perspective at the organizational and individual levels based on the perceptions of women faculty. Race differences were also investigated. Cross-sectional survey data from women faculty (N = 3127) at 13 purposively sampled medical schools and an institutional assessment of organizational characteristics were used. Organizational factors related to the climate for women were identified using bivariate statistics. The association between perceived climate for women and organizational characteristics, individual perceptions of the work environment and individual career, and personal characteristics with control variables were investigated using hierarchical linear regression models. Organizational effects by race/ethnicity were estimated using interaction terms. The climate for women faculty varied across institutions and by classification as minority-serving institutions (MSIs). Respondent's report of existence of an office for women's affairs, trust in leadership, and satisfaction with mentoring were positively associated with the climate for women. Perceived workplace discrimination and work-family conflict were inversely associated with a positive climate. No race/ethnicity differences were observed in the multivariable analysis. The climate for women faculty in academic medicine should not be regarded constant across organizations, specifically between MSIs and non-MSIs. Efforts to advance a positive climate for women could focus on improving trust in leadership, increasing support for structures/offices for women, and mitigating perceived discrimination and work-family conflict.


Identification of co-expressed genes associated with MLL rearrangement in pediatric acute lymphoblastic leukemia.
Rearrangements involving the mixed lineage leukemia (MLL) gene are common adverse prognostic factors of pediatric acute lymphoblastic leukemia (ALL). Even allogeneic hematopoietic stem cell transplantation does not improve the outcome of ALL cases with some types of MLL rearrangements. The aim of the present study was to identify the co-expressed genes that related to MLL rearrangement (MLL-r) and elucidate the potential mechanisms of how MLL-r and their partner genes lead to leukemogenesis. Gene co-expression networks were constructed using the gene expression data and sample traits of 204 pretreated pediatric ALL patients, and co-expression modules significantly related to the MLL-r were screened out. Gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis of the module genes were performed. Hub genes were identified and their expression levels were analyzed in samples with or without MLL-r and the results were validated by an independent investigation. Furthermore, the relationships between the hub genes and sample traits were analyzed. In total, 21 co-expression modules were identified. The green module was positively correlated with MLL-r. PROM1, LGALS1, CD44, FUT4 and HOXA10 were identified as hub genes, which were involved in focal adhesion, calcium-dependent phospholipid binding, connective tissue development and transcriptional misregulation in cancer. The expression levels of the five hub genes were significantly increased in MLL-r samples, and the results were further validated. PROM1, LGALS1, CD44 and HOXA10 were positively related to the leukocyte count. These findings might provide novel insight regarding the mechanisms and potential therapeutic targets for pediatric ALL with MLL-r.


YAP promotes myogenic differentiation via the MEK5-ERK5 pathway.
Yes-associated protein (YAP) is a transcriptional coactivator in the Hippo pathway that regulates cell proliferation, differentiation, and apoptosis. The MEK5/ERK5 MAPK cascade is essential for the early step of myogenesis. In this study, we generated C2C12 stable cell lines that expressed YAP (C2C12-YAP cells) and found that ERK5 and MEK5 were activated in C2C12-YAP cells compared with control C2C12 (C2C12-vector) cells. C2C12-YAP stable cells also differentiated into myotubes better than C2C12-vector cells, and expressed elevated levels of myogenin, a transcription factor that regulates myogenesis, as well as elevated levels of myosin heavy chain, a skeletal muscle marker. Western blot analysis revealed that Src and c-Abl (Abelson murine leukemia viral oncogene homolog 1) activation were enhanced in C2C12-YAP cells. Conversely, treatment of inhibitors of c-Abl, Src, or MEK5 inhibited activation of MEK5 and ERK5 and myogenesis of C2C12 myoblasts. Specific interactions between YAP and proteins in the ERK5 pathway, such as MEK kinase 3 (MEKK3) and ERK5, were illustrated by coimmunoprecipitation experiments. MEKK3 contains the PPGY motif (aa 178-181), which may interact with YAP. Site-directed mutagenesis experiments revealed that expression of MEKK3 Y181F mutant inhibited MEK5/ERK5 activation and myogenic differentiation. These results suggest that YAP promotes muscle differentiation by activating the Abl/Src/MEKK3/MEK5/ERK5 kinase cascade.-Chen, T.-H., Chen, C.-Y., Wen, H.-C., Chang, C.-C., Wang, H.-D., Chuu, C.-P., Chang, C.-H. YAP promotes myogenic differentiation via the MEK5-ERK5 pathway.


Assessment of panoramic radiomorphometric indices in Turkish patients of different age groups, gender and dental status.
The aim of the study was to determine the distribution of the appearance of the inferior mandibular cortex (Mandibular Cortical Index (MCI)) in a large Turkish population group and to assess a range of values for cortical width at the mental foramen region (Mental Index (MI)) and the ratio of the thickness of the mandibular cortex to the distance between the inferior margin of the mental foramen and the inferior mandibular cortex (Panoramic Mandibular Index (PMI)) according to the MCI. In addition, we assess how age, sex and dental status affected the MCI. Panoramic radiographs of 1,863 patients, 698 (37.5%) men and 1,165 (62.5%) women over 20 years old, were assessed during 2005-2006 from the files of Baskent University. Gender, age and dental status were recorded for each patient. MCI classifications, MI and PMI values in the MCI groups were evaluated and comparisons were made using logistic regression analysis. Compared with patients aged 20-49 years, the likelihood of MCI C3 category in patients over 70 years of age and in patients aged 50-69 years of age was 79.14 and 9.17 times higher. The likelihood of the C3 category in edentulous and partially dentate patients was 27.30 and 2.68 times higher than in fully dentate patients, respectively. The likelihood of C3 category in patients with MI <3 mm was 14.86 times higher than in patients with MI >or=3 mm; also, in patients with a PMI of <0.30 this likelihood was 9.78 times higher than in patients with a PMI of >or=0.30. Without respect to gender, edentulous patients with C3 category, MI <3 mm and PMI <0.30 may be seen as high-risk patients for osteoporosis and therefore should be referred for further osteoporosis investigation.


[Photochemiluminescence arising during sensitized photooxidation of trypsin solutions].
Kinetic study of eosin-sensitized photochemoluminescence (PCL) in tripsin solutions was carried out. Kinetics of luminescence increase and decrease, connection between sensitized PCL with triptophane photodissociation in protein were investigated. Effect of the concentrations of protein and oxygen in solution on the parameters of eosin-sensitized PCL was studied in order to establish the succession of processes resulting in the formation of free radicals. The experimental data made it possible to propose a scheme of primary processes responsible for PCL, which shows that the formation of protein radicals proceeded in the reactions between the triplet excited states of dye and singlet oxygen and protein triptophyle residues. It was found that during the formation of radicals in the air at small concentrations of proteins singlet oxygen played a major role in the sensitized photooxidation of protein. It was shown that the mechanism of processes responsible for sensitized PCL, determining postluminescence is similar to tripsin chemoluminescence under UV-illumination. Some kinetic parameters of the processes proceeding during sensitized photooxidation were determined and estimated.


Combined radiotherapy and bleomycin for advanced head and neck cancers: results of a phase I pilot study.
Forty-two patients with inoperable stage III or IV head and neck epithelial tumors were entered in a phase I pilot study to evaluate the toxicity and efficacy of combined radiotherapy and bleomycin for advanced head and neck cancers. Twenty-three patients (52%) achieved complete remissions and 18 patients (42%) had greater than 50% regression. Most patients tolerated bleomycin at a dose of 5 units twice a week, with a full course of radiotherapy delivered at 1809 rads/day, 5 days/week. Although the complete remission rate appears to be higher than with radiotherapy alone and 13 of the 23 complete remissions (57%) lasted greater than 1 year, methods of prolonging the duration of remission need to be developed.


Analysis of a Resident Aesthetic Clinic: Process for Rhinoplasty, Resident Experience, and Patient Satisfaction.
Plastic surgery residents often desire additional training in rhinoplasty than what is provided by their residency program. The goal of this study was to define and evaluate a specific process used to structure preoperative, intraoperative, and postoperative protocols for rhinoplasty patients in the resident aesthetic clinic (RAC) to enhance qualitative and quantitative experience. Complication rates and patient/resident satisfaction scores were also examined. Resident clinic rhinoplasty patients underwent a well-defined and established process that included patient education and informed consent, preoperative planning in a conference-based session, specific adherence to established surgical techniques, and structured postoperative management and follow-up. This process also included supervision criteria for residents in the operating room and clinical setting. Patient and resident satisfaction at the RAC was evaluated by a Web-based survey. A database of procedural complications and methods was compiled and evaluated. Between June 2012 and June 2015, 146 aesthetic resident cases were completed through the University of California, San Diego Residency Aesthetic Surgery Program. Of these cases, 34 (17%) were rhinoplasty procedures. Residents at our institution assisted on an average of 55 rhinoplasty procedures with the faculty and performed an average of 12 rhinoplasty procedures as primary surgeons. The residents surveyed felt that they had a good autonomous experience (P < 0.001), and 90% reported confidence with rhinoplasty. Postoperative complications were recorded and included asymmetry (n = 4, 10.5%), septal perforation (n = 1, 2.6%), and difficulty in breathing (n = 6, 15.8%). There were no patients who experienced infections, and the complication rate requiring revision in the operating room was 0%. Optimizing protocols in rhinoplasty in an RAC has allowed for the RAC to flourish in the breadth and complexity of rhinoplasty operations. This has enabled residents to gain a structured and autonomous exposure to rhinoplasty cases. Cases were done with an acceptable complication rate and with good patient and resident satisfaction. This is a unique report in that it provides a structured process for preoperative, intraoperative, and postoperative care in rhinoplasty operations.


[Interactions of oral anti-diabetic agents and non-steroid anti-rheumatic agents].
Due to the relative increase of age-diabetes and to the different forms of rheumatic diseases, long-term medicament therapy and the question of possible interactions between oral antidiabetic drugs ( OAD ) and nonsteroidal anti-inflammatory drugs (NSAID) become more important. Unfortunately there exist studies on most of the well-known NSAID, but carried out on different conditions. The present study is intended to summarize the results at hand and to evaluate them in a certain sense. From almost all the NSAID, except from the salicylates and those connected with, as well as the pyrazolones, one may say, based on published data and long-term experience, that interactions with the OAD in use nowadays are not to be expected unless without clinical relevance.


Generalized Haus master equation model for mode-locked class-B lasers.
Using an asymptotic technique, we develop a generalized version of the class-B Haus partial differential equation mode-locking model that accounts for both the slow gain response to the averaged value of the field intensity and the fast gain dynamics on the scale comparable to the pulse duration. We show that unlike the conventional class-B Haus mode-locked model, our model is able to describe not only Q-switched instability of the fundamental mode-locked regime but also the leading edge instability leading to harmonic mode-locked regimes with the increase of the pump power.


Predicting the recurrence/metastasis of stage II and III breast cancer with lymph node metastasis.
This study compared prediction of the recurrence of breast cancer by detection of occult neoplastic cells (ONCs) in lymph nodes or by using the criteria for a high risk of recurrence and metastasis of gastric/large bowel cancer. The subjects were 45 patients with stage II and III node-positive breast cancer. Prediction of recurrence by detection of ONCs showed a sensitivity of 78.6% (11/14), a false-negative rate of 21.4% (3/14), a specificity of 96.4% (30/31), a false-positive rate of 3.2% (1/31), and an accuracy of 87.7% in patients with stage II and III node-positive cancer. Prediction of recurrence based on positivity for at least 2 of the high-risk criteria showed a sensitivity of 92.9% (13/14), a false-negative rate of 7.1% (1/14), a specificity of 87.1% (27/31), a false-positive rate of 12.9% (4/31), and an accuracy of 90.0% in patients with stage II and III node-positive cancer. These results suggest that ONCs plus the high-risk criteria are useful for predicting recurrence/metastasis of stage II and III node-positive breast cancer during the early postoperative period with a high sensitivity and accuracy.


Structural asymmetry and half-site reactivity in the T to R allosteric transition of the insulin hexamer.
The zinc-insulin hexamer, the storage form of insulin in the pancreas, is an allosteric protein capable of undergoing transitions between three distinct conformational states, designated T6, T3R3, and R6, on the basis of their ligand binding properties, allosteric behavior, and pseudo point symmetries [Kaarsholm, N. C., Ko, H.-C., & Dunn, M. F. (1989) Biochemistry 28, 4427-4435]. The transition from the T-state to the R-state involves a coil-to-helix transition in residues 1-8 of the B-chain wherein the ring of PheB1 is displaced by approximately 30 A. This motion also is accompanied by small changes in the positions of A-chain residues and other B-chain residues. In this paper, one- and two-dimensional (COSY and NOESY) 1H NMR are used to characterize the ligand-induced T to R transitions of wild-type and EB13Q mutant human zinc-insulin hexamers and to make sequence-specific assignments of all resonances in the aromatic region of the R6 complex with resorcinol. The changes in the 1H NMR spectrum (at 500 and 600 MHz) that occur during the T to R transition provide specific signatures of the conformation change. Analysis of the dependence of these spectral changes for the phenol-induced transition as a function of the concentration of phenol establish (1) that the interconversion of T6 and R6 occurs via a third species assigned as T3R3 and (2) that the system shows both negative and positive cooperative allosteric behavior. One- and two-dimensional COSY and NOESY studies show that, in the absence of phenolic compounds, anions act as heterotropic effectors that shift the distribution of hexamer conformations in favor of the R-state with the order of effectiveness, SCN- > N3- >> I- >> Cl-. Analysis of one- and two-dimensional spectra indicate that with wild-type insulin, SCN- and N3- give T3R3 species, whereas the EB13Q mutant gives an R6 species. An allosteric model for the insulin T to R transition based on the structural asymmetry model [Seydoux, F., Malhotra, O. P., & Bernhard, S. A. (1974) CRC Crit. Rev. Biochem. 2, 227-257] is proposed that explains the negative and positive allosteric properties of the system, including the role of T3R3 and the action of homotropic and heterotropic effectors.


Day length constrains the time budget of aphid predators.
Phenology shifts and range expansions cause organisms to experience novel day length - temperature correlations. Depending on the temporal niche, organisms may benefit or suffer from changes in day length, thus potentially affecting phenological adaptation. We assessed the impact of day length changes on larvae of Chrysoperla carnea (Stephens) and Episyrphus balteatus (De Geer), both of which prey on aphids. Larvae of E. balteatus are night-active, whereas those of C. carnea appear to be crepuscular. We subjected both species in climate chambers to day lengths of 16 : 8 L : D and, to circumvent diapause responses, 20 : 4 L : D. We recorded development times and predation rates of both species. E. balteatus grew 13% faster in the 16 : 8 L : D treatment and preyed on significantly more aphids. In contrast, C. carnea grew 13% faster in the 20 : 4 L : D treatment and higher predation rates in 20 : 4 L : D were marginally significant. Our results show that day length affects development and predation, but that the direction depends on species. Such differences in the use of day length may alter the efficiency of biocontrol agents in a changing climate.


The Oral Transglutaminase 2 Inhibitor ZED1227 Accumulates in the Villous Enterocytes in Celiac Disease Patients during Gluten Challenge and Drug Treatment.
The enzyme transglutaminase 2 (TG2) plays a key role in celiac disease (CeD) pathogenesis. Active TG2 is located mainly extracellularly in the lamina propria but also in the villous enterocytes of the duodenum. The TG2 inhibitor ZED1227 is a promising drug candidate for treating CeD and is designed to block the TG2-catalyzed deamidation and crosslinking of gliadin peptides. Our aim was to study the accumulation of ZED1227 after oral administration of the drug. We studied duodenal biopsies derived from a phase 2a clinical drug trial using an antibody that detects ZED1227 when bound to the catalytic center of TG2. Human epithelial organoids were studied in vitro for the effect of ZED1227 on the activity of TG2 using the 5-biotin-pentylamine assay. The ZED1227-TG2 complex was found mainly in the villous enterocytes in post-treatment biopsies. The signal of ZED1227-TG2 was strongest in the luminal epithelial brush border, while the intensity of the signal in the lamina propria was only ~20% of that in the villous enterocytes. No signal specific to ZED1227 could be detected in pretreatment biopsies or in biopsies from patients randomized to the placebo treatment arm. ZED1227-TG2 staining co-localized with total TG2 and native and deamidated gliadin peptides on the enterocyte luminal surface. Inhibition of TG2 activity by ZED1227 was demonstrated in epithelial organoids. Our findings suggest that active TG2 is present at the luminal side of the villous epithelium and that inhibition of TG2 activity by ZED1227 occurs already there before gliadin peptides enter the lamina propria.


[Standardization and issues of rheumatoid factor measurement].
To disclose the current situation of rheumatoid factor (RF) measurement in Japan. A small-scale survey was performed among members of the committee for the improvement of RF measurement in 2003 using manufacturers' RF reference materials valued based on WHO RF reference and pooled sera. A nationwide questionnaire survey was also performed. Questionnaires were sent to 356 educational institutes certified by the Japan College of Rheumatology in December 2004. The small-scale survey showed inter-laboratory differences of measured RF values, especially using RF references, and less in pooled sera. In the questionnaire survey (187 responses, recovery, 53%), qualitative or semi-quantitative RF measurement methods were used in a small number of institutes and quantitative methods were used in large numbers of institutes, the latex immunoassay (turbidimetric or nepherometric) was predominantly employed. The measuring instruments were various. The upper limit of the reference interval was distributed widely from 5 IU/ml to 40 IU/ml, indicating obvious inter-laboratory differences in RF measurement. Many institutes used the reference intervals recommended by the manufacturers. There are remarkable inter-laboratory differences in RF measurement. Clearly, one of the major issues is the lack of reference materials. We therefore need to establish a reference material of RF, even if it is a temporary one. Scientific societies (Japan College of Rheumatology and Japanese Society of Laboratory Medicine) and manufacturers providing RF measurement reagents should work together for the improvement of RF measurement.


Upcycling of black currant pomace for the production of a fermented beverage with Wolfiporia cocos.
Pomace as a side stream from black currant juice production is mostly discarded, even though it is rich in nutrients like protein, fiber, sugars, anthocyanins, polyphenols, and other secondary metabolites. Fungi from the division of Basidiomycota have a great enzymatic toolbox to recycle these complex mixtures of nutrients. In particular, the edible medicinal fungus Wolfiporia cocos has been described as a suitable biocatalyst to form pleasant aroma compounds in fermentation processes. Therefore, medium optimization, upscaling, and filtration were performed to produce a beverage based on black currant pomace fermented with W. cocos. A trained panel described the beverage as highly pleasant, reminiscent of honey, flowers and berries with a well-balanced sour and sweet taste. The flavor compounds linalool (citrus), geraniol (flowery), phenylacetic acid (honey), methyl phenylacetate (honey), eugenol (clove), and 2-phenylethanol (rose) were produced during fermentation and the concentrations exceeded their respective odor thresholds. The produced beverage was evaluated with 8.0 ± 1.4 from 10 for the question of whether panelists would buy the product. Fungal fermentation with the edible fungus W. cocos enabled the production of a highly pleasant beverage and additionally may reduce waste by using pomace and table sugar as sole ingredients. The online version contains supplementary material available at 10.1007/s13197-023-05677-4.


Excitation wavelength dependent fluorescence anisotropy of eosin-myosin adducts. Evidence for anisotropic rotations.
Steady-state and time-resolved fluorescence anisotropy measurements of eosin in solution and eosin-5-maleimide bound to purified myosin were made to study localized motions of the "head region" of this protein. The lifetime and apparent Debye rotational relaxation times of eosin in aqueous solution are essentially invariant with changes in excitation wavelength. In more viscous solvents, such as propylene glycol/water mixtures, the apparent Debye rotational relaxation times of eosin differ upon excitation in the regions of positive and negative anisotropy. Using eosin attached to the SH-1 thiol of the myosin head differing rotational modes of the bound probe were detected, dependent upon excitation wavelength. The main features of the anisotropy data for eosin-myosin are consistent with the existence of a 'crevice' or 'pocket' in the myosin head. A model is presented which allows estimation of the ratio of distinct rotational diffusion terms (selected by different excitation wavelengths) that produce both the observed steady-state anisotropy and differential phase results.


Applications of Chromatographic Techniques for Fingerprinting of Toxic and Non-toxic Euphorbia Species.
Euphorbia species have historically been used as medicinal plants to treat different ailments. However, some species have been reported to exhibit various degrees of toxicity. It becomes critical to distinguish toxic species from those that are non-toxic, for a particular application. The aim of the study was to determine the method for fingerprinting the chemical constituents of the selected toxic and non-toxic Euphorbia species to identify markers of toxicity. Hexane, DCM, methanol, ethyl acetate and water plant extracts of Euphorbia ammak, clavarioides, caerulescens, polygona and trigona were investigated for their cytotoxic activities towards the mammalian Vero cell line using MTT cell viability test assay. The presence of secondary metabolites and proteins were assessed in the plant extracts. Moreover, the study used chromatographic methods to fingerprint the plant extracts to identify toxicity markers. The DCM extract of E. ammak exhibited the highest cell growth inhibition at all concentrations tested. The non-polar extracts of E. clavarioides exhibited the highest cell growth inhibition activity with hexane extract reaching IC50 at 1 μg mL-1. The DCM extract of E. caerulescens reached IC50 at a concentration of 10 μg mL-1, while other extracts didn't show any activity. The hexane and DCM extracts of E. polygona exhibited the highest cell growth inhibition activity, reaching IC50 at a concentration of 10 μg mL-1. All 4 extracts of E. trigona didn't show cell growth inhibition. All Euphorbia species showed the presence of secondary metabolites. The biuret and xanthoprotein methods indicated that there were no proteins detected in all 5 Euphorbia species. TLC profiles of toxic extracts revealed additional bands which were absent in non-toxic species. It is concluded that the TLC method developed in this study can be used as a quick screen method to possibly distinguish toxic from non-toxic species, as well as in identifying the studied species.


Adenocarcinoid tumor of the ampulla of Vater.
We report a rare case of adenocarcinoid tumor of the ampulla of Vater. The tumor contained an intermixture of adenocarcinoma and carcinoid tumor and was removed successfully by pancreaticoduodenectomy. The characteristics of these rare tumors are reviewed.