Using genetic variation to optimize cancer chemotherapy.
The high level of interpatient variation in response to chemotherapy and the lack of objective tools to select chemotherapy regimens for a given tumor type have created a clinical problem. A possible solution may be pharmacogenetics: the study of inherited DNA polymorphisms that influence drug disposition and effects in order to individualize drug treatment. Because unpredictable efficacy and high levels of systemic toxicity are common in cancer chemotherapy, pharmacogenetics is particularly appealing to oncologists. Polymorphisms in drug metabolism, drug transport, drug target, and DNA repair genes have been implicated interpatient variability in response to many chemotherapy agents. This review will discuss recent clinically relevant examples of cancer pharmacogenetics and how genetic differences are helping to shape the future of individualized cancer chemotherapy.


[Evaluation of in vitro drug sensitivity of antimalarials for Plasmodium falciparum using a colorimetric assay (DELI-microtest)].
The DELI-microtest (Double-Site Enzyme Linked LDH Immunodetection) is a colorimetric method for determination of Plasmodium falciparum in vitro sensitivity to antimalarial drugs. This method is based on the capture of the specific lactate deshydrogenase of Plasmodium falciparum (pLDH) using 2 monoclonal antibodies which recognize 2 different sites of the enzyme. The second monoclonal antibody is biotinylated and may catch a peroxidase-labelled streptavidine and develop a colorimetric reaction in the presence of peroxidase substrate. The level of pLDH released by parasite growth is determined by the measure of optical densities. An excellent correlation has been observed between the IC50's obtained using the DELI-microtest and the classical isotopic microtest, and the high sensitivity of the DELI-microtest can be used to measure the IC50's for isolates with parasitemia as low as 0.005%. It is easier and faster to process than isotopic microtest in field conditions. In addition, due to high sensitivity of the DELI-microtest, isolates with a low parasitemia may be included in the studies.


Enhancing self-esteem among cardiac patients.
This study examined the development, implementation, and evaluation of a module to enhance self-esteem among patients in an outpatient cardiac clinic. Eighty percent of the subjects reported that activities such as exercise and social functions helped them feel better about themselves. This data supported the use of spirituality, interpersonal relationships, self-care activities, and self-preservation concepts to enhance self-esteem in cardiac patients.


Narcolepsy and idiopathic hypersomnolence.
Narcolepsy is among the leading causes of excessive daytime sleepiness. Its classic form associates daytime sleepiness with cataplexy, sleep paralysis, hypnopompic hallucinations, and nocturnal disrupted sleep. This form is associated with HLA DQ betal-0602 in about 85% to 90% of affected subjects, independently of their ethnicity. But the definition of the variants of narcolepsy remains controversial, despite the fact that, in some cases, narcolepsy may be limited to daytime sleepiness. In its classic form, it is associated with two or more sleep onset rapid eye movement periods at the Multiple Sleep Latency Test. This test, performed after nocturnal polysomnography, can be helpful in diagnosing narcolepsy, in the absence of a convincing history of partial or complete attacks of cataplexy--a pathognomonic symptom. Investigation of narcoleptic Dobermans has indicated that a muscarinic cholinergic hypersensitivity exists in the brain of affected animals and abnormalities involve also the dopaminergic system. Despite its prevalence of 0.03% to 0.05%, it is still a neurologic entity often missed. Investigations of families of narcoleptics, including monozygotic twins, indicate that this syndrome is polygenic in nature with association of environmental factors. As the peak of onset of disabling symptoms occurs between 15 and 25 years of age, it is important to improve the treatment of this lifelong, disabling illness. Stimulants medications, independently of their mode of action, are prescribed to help daytime sleepiness, and tricyclic antidepressant drugs or serotonergic reuptake blockers are used on the other symptoms. But these medications have a limited efficacy. Short naps at regular intervals during the day are a strong therapeutic adjuvent.


3D-Printed Polylactic Acid/Lignin Films with Great Mechanical Properties and Tunable Functionalities towards Superior UV-Shielding, Haze, and Antioxidant Properties.
Three-dimensional (3D) printing is regarded as a novel technique to realize the customized production of films. However, the relative lack of printable materials with excellent mechanical properties and tailored functionalities seriously restricts its wide application. Herein, a promising multifunctional 3D printing filament was fabricated by incorporating lignin into the polylactic acid (PLA) matrix and firstly applied to film production. The results indicate that lignin was an excellent mechanical reinforcement of the PLA matrix, especially for toughening. Only 0.5% lignin doping improved the toughness by 81.8%. Additionally, 3D-printed films with 0.5-5% lignin exhibited excellent ultraviolet (UV)-blocking capability of 87.4-99.9% for UVB and 65.6-99.8% for UVA, as well as remarkable antioxidant properties, ranging from 24.0% to 79.0%, and high levels of haze, ranging from 63.5% to 92.5%. Moreover, the prepared PLA/lignin (P/L) films based on 3D printing achieved the customization of film production and have potential applications in the fields of packaging, electronic products, medical care, and so forth. Overall, this work not only enriches the 3D printing composites with tailored multifunctionality but also brings the promising potential for the production of customized films.


Hydrogen bond induced enhancement of Fermi resonances in N-HN hydrogen bonded complexes of anilines.
The hydrogen-bonded complexes of aniline, 4-fluoroaniline and 4-ethynylaniline with ammonia, methylamine, dimethylamine, trimethylamine and triethylamine, were investigated using IR-UV double resonance spectroscopy. The formation of N-HN hydrogen bonded complexes with anilines as donors and alkylamines as acceptors was inferred from the appearance of the spectra. Two bands appearing in the 3100-3400 cm-1 region were found to be originating from the Fermi resonance coupling between the hydrogen-bonded NH2 stretching and NH2 bend-overtone vibrations. A two-state de-perturbation analysis yields the zero-order (unperturbed) vibrational states and the coupling constant. An inverse correlation between the zero-order hydrogen-bonded NH2 stretching and NH2 bend-overtone was observed due to a switch in the relative contributions of hydrogen-bonded NH2 stretching and NH2 bend-overtone vibrations to the Fermi resonance bands. These results lead to the reassignment of the hydrogen-bonded N-H stretching frequencies of aniline complexes reported earlier. Furthermore, the stretch-bend Fermi-resonance coupling constant for the NH2 group is around 50 cm-1, which is independent of the nature of the parent donor molecule and the acceptor, and is intrinsic to the NH2 group.


Wet-Spun Superelastic Graphene Aerogel Millispheres with Group Effect.
Graphene aerogel has attracted great attention due to its unique properties, such as ultralow density, superelasticity, and high specific surface area. It shows huge potential in energy devices, high-performance pressure sensors, contaminates adsorbents, and electromagnetic wave absorbing materials. However, there still remain some challenges to further promote the development and real application of graphene aerogel including cost-effective scalable fabrication and miniaturization with group effect. This study shows millimeter-scale superelastic graphene aerogel spheres (GSs) with group effect and multifunctionality. The GSs are continuously fabricated on a large scale by wet spinning of graphene oxide liquid crystals followed by facile drying and thermal annealing. Such GS has an unusual core-shell structure with excellent elasticity and specific strength. Significantly, both horizontally and vertically grouped spheres exhibit superelasticity comparable to individual spheres, enabling it to fully recover at 95% strain, and even after 1000 compressive cycles at 70% strain, paving the way to wide applications such as pressure-elastic and adsorbing materials. The GS shows a press-fly behavior with an extremely high jump velocity up to 1.2 m s-1 . For the first time, both free and oil-adsorbed GSs are remotely manipulated on water by electrostatic charge due to their ultralow density and hydrophobic properties.


[Incidence of HBsAG in symptom-free pregnant women. Results of screening at the University of Zurich Gynecology Clinic].
Passive and active immunization prevent materno-fetal and postnatal hepatitis B-virus infection. Precondition for interruption of perinatal transmission is knowledge of the mothers' hepatitis B markers before delivery. In switzerland the prevalence of chronic asymptomatic pregnant HBsAG carriers is not known. From February to December 1983 all pregnant women at the Obstetric Clinic, University Hospital of Zurich were screened for HBsAG. 30 out of 2550 women were HBsAG positive (1.2%); the prevalence among Swiss women is 0.5%, and among immigrants 1.9%. It is suggested that screening for HBsAG be confined to pregnant women who belong to a risk group and to immigrants, and that all children born of HBsAG positive mothers be immunized actively and passively regardless of the presence of HBeAG and/or anti-HBe.


Somatization: the concept and its clinical application.
Somatization, a tendency to experience and communicate somatic distress in response to psychosocial stress and to seek medical help for it, poses a major medical, social, and economic problem. It is most often associated with depressive and anxiety disorders and constitutes the core of somatoform disorders. Its persistent form is especially costly and difficult to prevent and manage. The author discusses the prevalence, clinical manifestations, etiology, and treatment of somatization and presents a critical review of somatoform disorders.


A case of biliary cystadenocarcinoma.
Biliary cystadenocarcinoma is a very rare cystic tumor that arises in the liver or, less frequently, in the extrahepatic biliary system. It has been shown to arise in congenital liver cysts, bile ducts, biliary cystadenoma, in the context of fibropolycystic disease and in the hepatoduodenal ligament. Common presenting symptoms include an abdominal mass, local pain, nausea, jaundice, fever or occasional ascites. Some patients are asymptomatic, the lesion being an incidental finding at autopsy or surgery. Approximately 50 cases have been reported in the literature. We report a case of biliary cystadenocarcinoma in a 63-year-old man with a review of the literature.


Computational modeling of di-transition-metal-substituted gamma-keggin polyoxometalate anions. Structural refinement of the protonated divacant lacunary silicodecatungstate.
The B3LYP density functional method has been validated for the di-Mn-substituted gamma-Keggin polyoxometalate (POM) anion, [(SiO4)MnIII2(OH)2W10O32]4-, and for the divacant lacunary silicodecatungastate, gamma-[(SiO4)W10O32]8-. This approach was shown to adequately describe the geometries of [(SiO4)MnIII2(OH)2W10O32]4- and gamma-[(SiO4)W10O32]8. Three different geometrical models, "full", "medium", and "small", for Mn2-gamma-Keggin have also been validated. It was shown that the medium [(SiO4)MnIII2(OH)2W6O24H8]4- model, as well as small [(SiO4)MnIII2(OH)2W4O18H10]2- model, preserves structural features of the full system, [(SiO4)MnIII2(OH)2W10O32]4-. However, the small model distorts the charge distribution at the "active site" of the system and should be used with caution. The same computational approach was employed to elucidate the structure of the di-Fe-substituted gamma-Keggin POM. The structure of the acidic (tetra-protonated form) of lacunary POM, gamma-[(SiO4)W10O32H4]4-, was shown to be gamma-[(SiO4)W10O28(OH)4]4- with four terminal hydroxo ligands, rather than gamma-[(SiO4)W10O30(H2O)2]4- with two aqua and two oxo(terminal) ligands as reported by Mizuno and co-workers (Science 2003, 300, 964). The observed and calculated asymmetry in the W-O(terminal) bond distances of gamma-[(SiO4)W10O32H4]4- is explained in terms of the existence of O1H1...O2H2 and O4H4...O3H3 hydrogen-bonding patterns in the gamma-[(SiO4)W10O28(OH)4]4- structure.


A simple operation for bilateral vocal cord paralysis.
To reduce the laryngeal obstruction in bilateral vocal cord paralysis, a new method of laterofixation was developed. The method is technically simple and less traumatic than previously published methods. No peroperative tracheostomy is needed. During surgery two needles are inserted through the thyroid cartilage. A nylon thread is passed through the needles and the needles are then withdrawn. The thread thus forms a permanent loop around the vocal cord. The effects of the laterofixation on breathing and on the voice are documented by assessment of upper airway resistance and by two listening panels respectively. Thirteen patients have been operated upon so far. In most cases the breathing was improved and the influence on the voice was moderate and adjustable. If needed the possibility to perform a more extensive surgical procedure still remains. We suggest our method of laterofixation to be the first treatment of choice in patients suffering from bilateral vocal cord paralysis.


How does the brain age in individuals with multiple sclerosis? A systematic review.
Multiple Sclerosis (MS) is a complex neurological disorder that involves demyelination, lesions and atrophy in both white and gray matter. Such changes in the central nervous system are diagnostic in MS and has a strong relationship with both physical and cognitive symptoms. As a result, magnetic resonance imaging (MRI) scans as a metric of brain atrophy have emerged as an important outcome measure in MS studies. Recently, research has begun to focus on the contribution of aging to the structural changes in the brain associated with MS; prompting questions about whether there is an amplifying effect of aging superimposed on MS-related brain atrophy. To examine current evidence of how the brain ages in individuals with MS, a systematic review of the literature was performed. Specific questions were focused on how aging affects gray and white matter structure, whether patterns of brain atrophy differ in younger and older cohorts and if there are structural differences in the brain as a function of sex in aging people with MS. This review considered studies that used MRI to examine the effects of aging in adults with MS. Twenty-one studies met eligibility criteria. Findings across these studies revealed that gray matter atrophy was more pronounced in older adults with MS, particularly in subcortical regions such as the thalamus; that the rates of atrophy were similar but varied by region for younger and older cohorts; and that males may experience more brain atrophy than females. Further studies that use multimodal MRI acquisition methods are needed to capture changes in both males and females over time, particularly in middle to older adulthood.


Multicentric human papillomavirus infections of the female genital tract: correlation of viral types with abnormal mitotic figures, colposcopic presentation, and location.
Human papillomavirus deoxyribonucleic acid (DNA) was identified by Southern blot hybridization in 21 of 24 patients with multicentric anogenital lesions and in 46 of 61 individual lesions. Type 6/11 was present in nine patients, type 16 in one, an undetermined type in one, and more than one type in ten patients. Mixed types were present in eight of 46 virus-positive individual lesions. Abnormal mitotic figures were found in 16, 87, and 75% of lesions associated with type 6/11, type 16, and mixed types, respectively. Colposcopic presentation or location of lesions was not predictive of viral types. The relatively high rate of mixed human papillomavirus types in multicentric lesions and in single lesions, and the lack of absolute correlation between viral types and abnormal mitotic figures, suggest that lesions should be removed to prevent viral transmission and possible progression to carcinoma.


Simultaneous spectrophotometric determination of cobalt and nickel by partial least square regression in micellar media.
Diphenycarbazone has been used for the simultaneous determination of cobalt and nickel by partial least square regression method. DPC complexes of cobalt and nickel at pH 7-10 are of pink color, which are soluble in TX-100 micellar media. A partial least square multivariate calibration method for the analysis of binary mixtures of cobalt and nickel was developed. The total relative standard error for applying the PLS method was calculated. The accuracy and reproducibility of the determination method for various known amounts of Co(II) and Ni(II) in their binary mixtures were tested. The effects of diverse ions on the determination of cobalt and nickel to investigate the selectivity of the method were also studied. The proposed method was applied to the synthetic binary mixtures, alloys and pharmaceutical samples.


Neurologic decompression sickness following cabin pressure fluctuations at high altitude.
Decompression sickness (DCS) occurs in diving, altitude chamber exposures, and unpressurized or depressurized high-altitude flights. Because DCS takes many forms, in-flight cases may be misinterpreted as hypoxia, hyperventilation, or viral illness, with resulting failure to respond appropriately. In this case, a 28-yr-old male pilot of a single-seat, tactical aircraft experienced 12 rapid pressure fluctuations while flying at 43,000 ft above sea level. He had no symptoms and decided to complete the flight, which required an additional 2 h in the air. Approximately 1 h later he began to experience fatigue, lightheadedness, and confusion, which he interpreted as onset of a viral illness. However, symptoms progressed to visual, cognitive, motor, and sensory degradations and it was with some difficulty that he landed safely at his destination. Neurologic DCS was suspected on initial evaluation by flight line medical personnel because of the delayed onset and symptom progression. He was transferred to a local Emergency Department and noted to have altered mental status, asymmetric motor deficits, and non-dermatomal paresthesias of the upper and lower extremities. Approximately 3.5 h after the incident and 2.5 h after the onset of symptoms he began hyperbaric oxygen therapy. He received partial relief at 30 min of the Navy DiveTable 6 and full resolution at 90 min; there were no recurrent symptoms at a 1-yr follow-up. This case highlights the importance of early recognition of in-flight DCS symptoms and landing as soon as possible rather than as soon as practical in all likely scenarios.


Japanese encephalitis virus activates autophagy through XBP1 and ATF6 ER stress sensors in neuronal cells.
Endoplasmic reticulum (ER) stress and autophagy are key cellular responses to RNA virus infection. Recent studies have shown that Japanese encephalitis virus (JEV)-induced autophagy negatively influences virus replication in mouse neuronal cells and embryonic fibroblasts, and delays virus-induced cell death. Here, we evaluated the role of ER stress pathways in inducing autophagy during JEV infection. We observed that JEV infection of neuronal cells led to activation of all three sensors of ER stress mediated by eIF2α/PERK, IRE1/XBP1 and ATF6. The kinetics of autophagy induction as monitored by levels of SQSTM1 and LC3-II paralleled activation of ER stress. Inhibition of the eIF2α/PERK pathway by siRNA-mediated depletion of proteins and by the PERK inhibitor had no effect on autophagy and JEV replication. However, depletion of XBP1 and ATF6, alone or in combination, prevented autophagy induction and significantly enhanced JEV-induced cell death. JEV-infected cells depleted of XBP1 or ATF6 showed reduced transcription of ER chaperones, ERAD components and autophagy genes, resulting in reduced protein levels of the crucial autophagy effectors ATG3 and BECLIN-1. Conversely, pharmacological induction of ER stress in JEV-infected cells further enhanced autophagy and reduced virus titres. Our study thus demonstrates that a crucial link exists between the ER stress pathways and autophagy in virus-infected cells, and that these processes are highly regulated during virus infection.


Ultrastructural changes of mitochondria in the skeletal muscle of patients with amyotrophic lateral sclerosis.
Functional defects and morphological changes of mitochondria have been reported to be in the skeletal muscle of patients with amyotrophic lateral sclerosis (ALS). Recent studies suggested that mitochondrial abnormalities are related to the pathogenesis of ALS. The purpose of this study is to evaluate the ultrastructural changes of muscle mitochondria in ALS patients. The authors examined 49 cases of diagnostic muscle biopsy samples with definite or probable ALS by electron microscopy. Of the 49 cases, 5 (10%) had ultrastructural abnormalities of muscle mitochondria, including giant mitochondria, paracrystalline inclusions, and abnormal cristae. These abnormal mitochondria were mainly observed among subsarcolemmal mitochondrial aggregates.


Two-stage hip revision arthroplasty with a hexagonal modular cementless stem in cases of periprosthetic infection.
Two-stage revision arthroplasty is today regarded as the gold standard treatment method for deep prosthetic joint infection. The aim of the present study was to evaluate clinical and functional outcomes with the Modular Universal Tumor And Revision System (MUTARS) RS stem in patients undergoing two-stage revisions. The functional and clinical outcomes for 43 patients who had undergone two-stage revision procedures for PJI were analyzed in a retrospective study. The minimum follow-up period was 24 months. Shorter follow-up periods were only observed when there were complications such as loosening or recurrent infection. The mean follow-up period was 3.86 years (range 7 months to 11.6 years). The success rate with infection control for PJI was 93%. Reinfection occurred in four cases (7%). The risk of reinfection after MRSA infection was 20.5 times greater (P >0.01) than with sensitive or unknown bacteria. Two aseptic loosening occurred after 7 and 20 months. The average Harris Hip Score was 80 (range 62-93). This retrospective study showed a 93% rate of eradication using specific antibiotic therapy. With the modular MUTARS RS stem, there was a low rate of aseptic loosening of 4.6%. MRSA infection was identified as a risk factor for reinfection. The two-stage procedure with modular cementless implants used is therefore appropriate for treating periprosthetic infections associated with hip endoprostheses.


Impact of Inadequate Bowel Cleansing on Colonoscopic Findings in Routine Screening Practice.
Colonoscopy is an imperfect gold standard for detecting colorectal neoplasms because some proportion of adenomas may be missed, mainly small lesions. This proportion is expected to be higher in case of inadequate bowel cleansing, which is frequently seen in routine practice. We estimated the proportions of neoplasms that are in principle detectable by colonoscopy but might be missed in case of incomplete bowel preparation. For 8,193 participants of screening colonoscopy in South-Western Germany, recruited between 2005 and 2016, the prevalence and numbers of different findings were extracted from colonoscopy reports and compared according to the reported bowel preparation quality. Bowel preparation quality was reported as good, poor, or was unspecified in 30.3%, 11.1%, and 58.6% of colonoscopy records. Reported prevalences of nonadvanced adenomas (NAAs) were similar among participants with poor and unspecified bowel preparation quality but substantially lower than among participants with good bowel preparation (adjusted prevalence rate ratio [RR] 0.86, 95% confidence interval [CI]: 0.77-0.96). The differences were observed for proximal but not for distal NAAs (RRs 0.82, 95% CI: 0.71-0.95 and 0.95, 95% CI: 0.82-1.10). Our study suggests that a significant proportion of NAAs located in the proximal colon might be missed during colonoscopy if bowel cleansing is not adequate. Major efforts should be made to further facilitate and enhance high-quality bowel preparation in routine screening practice.


Post-synthesis DNA modifications using a trans-cyclooctene click handle.
Post-synthesis DNA modification is a very useful method for DNA functionalization. This is achieved by using a modified NTP, which has a handle for further modifications, replacing the corresponding natural NTP in polymerase-catalyzed DNA synthesis. Subsequently, the handle can be used for further functionalization after PCR, preferably through a very fast reaction. Herein we describe polymerase-mediated incorporation of trans-cyclooctene modified thymidine triphosphate (TCO-TTP). Subsequently, the trans-cyclooctene group was reacted with a tetrazine tethered to other functional groups through a very fast click reaction. The utility of this DNA functionalization method was demonstrated with the incorporation of a boronic acid group and a fluorophore. The same approach was also successfully used in modifying a known aptamer for fluorescent labelling applications.


[Mechanism of Danzhi Jiangtang Capsules on improving liver injury in hyperlipidemia rats based on MAPK pathway].
This study aimed to investigate the protective effect and preliminary mechanism of Danzhi Jiangtang Capsules( DJC) on liver of hyperlipidemic rats. The hyperlipidemia models were successfully made by high-fat diet for 12 weeks in male SD rats,and then divided into model control group and DJC treatment groups( 500 and 1 000 mg·kg~(-1)·d-1) via gavage administration for additional 8 weeks.The levels of serum lipid and liver metabolism indices were detected; HE and oil red O staining were used to observe the pathological changes of liver. Expression levels of extracellular regulated protein kinase 1/2( ERK1/2),c-Jun N-terminal kinase( JNK),and p38 mitogen-activated protein kinase( p38 MAPK) were detected by real-time polymerase chain reaction( RT-PCR). Expression of MCP-1,phosphorylated ERK( p-ERK),phosphorylated JNK( p-JNK),and phosphorylated p38 MAPK( p-p38) were analyzed by immunohistochemistry and Western blot. The results showed that DJC decreased body weight and serum levels of total cholesterol( TC),triglyceride( TG),alanine aminotransferase( ALT),aspartate aminotransferase( AST),increased serum high-density lipoprotein cholesterol( HDL-C) level,ameliorate injury and lipid deposition in the liver induced by the high-fat diet,decreased mRNA expression of ERK1/2,JNK and p-38 MAPK as well as protein expression of p-ERK,p-JNK,p-p38,and MCP-1,somewhat showing a dose-dependent effect. Therefore,DJC has an obvious protective effect on liver of hyperlipidemic rats with certain dose-dependent effect,and the mechanism may be related with inhibiting MAPK pathways and inflammation.


Obsessive compulsive disorder: report of six cases.
Obsessive-compulsive disorder (OCD) refers to interloping and interative thoughts, ideas, images, fantasies, impulses and actions accompanied by feelings of distress and declarations of resistance. It is assumed that OCD is rare among black Africans. This paper reports six cases from Uganda. The report indicates that OCD exists among black Africans and that those affected experience considerable amounts of emotional, social and occupational distress. It is suggested that OCD should be taught adequately to medical students to enable future general-duty medical officers to recognise and manage it appropriately. The names that appear in the text are pseudonyms.


Complexity of Advanced Glycation End Products in Foods: Where Are We Now?
Recent clinical trials indicate that consumption of dietary advanced glycation end products (AGEs) may promote the development of major chronic diseases. However, the outcomes of human studies have proven inconclusive as a result of estimates of the total AGE intake being taken with a single AGE in most of the studies. In this perspective, we summarized the major types of AGEs derived from proteins, nucleic acids, and phospholipids during food processing and suggested a panel of AGEs as markers to better measure the intake of total dietary AGEs in human studies.


History and Highlights of Cardiothoracic Surgery at Baylor College of Medicine.
The history of cardiothoracic surgery at Baylor College of Medicine begins in 1948, when Michael E. DeBakey was recruited as chair of the Department of Surgery. With the addition of Denton A. Cooley, E. Stanley Crawford, and other surgical legends, Baylor College of Medicine quickly rose to the forefront of cardiothoracic surgery. Highlights in its history include treatment of aortic aneurysm and dissection, development of synthetic aortic substitutes, early experience with cardiac replacement valves, the first successful use of coronary artery bypass grafts to revascularize the heart, and the cardiac transplantation and total artificial heart program, which led to the creation of the left ventricular assist device. Baylor's Division of Cardiothoracic Surgery continues to build on its history and legacy to remain a vital contributor to the specialty in the 21st century.


In-vitro fertilization of hamster eggs in different media and the stimulating effect of heterologous and homologous spermatozoa.
Hamster eggs with follicular cells were fertilized by epididymal spermatozoa in two chemically defined media. The proportion of penetrated eggs was significantly higher in a medium for rabbit (16%) than in a medium for rat eggs (6%), but much lower than in Tyrode's solution containing follicular fluid or blood serum as reported by others. The optimal sperm concentration for sperm penetration ranged from 0.5 to 5 X 10(6)/ml but penetration of denuded eggs failed in these media. When exposed to hamster spermatozoa in the rabbit medium containing living or dead spermatozoa of guinea-pig, rat, mouse or hamster, high proportions of denuded eggs (24-96%) and eggs with follicular cells (93%) were penetrated. By exposure of denuded hamster eggs to hamster spermatozoa in supernatant fluid of frozen-thawed guinea-pig spermatozoa, 97% of eggs were penetrated in 8 hr compared to 0% in the control group. Sperm capacitation was also efficiently induced by preincubation of hamster spermatozoa in the supernatant fluid. The fertilizing capacity of hamster spermatozoa was maintained for 12 hr during incubation with frozen-thawed guinea-pig spermatozoa when the concentration of hamster spermatozoa ranged between 10 and 20 X 10(6)/ml. The beneficial factor of guinea-pig spermatozoa appeared to be from spermatozoa themselves, not from the vasal or epididymal fluids. The presence of follicular cells, blood serum, bovine serum albumin, or even polyvinylpyrrolidone in the media is essential for the capacitation and acrosome reaction of hamster spermatozoa. The components of guinea-pig spermatozoa appear to maintain the fertilizing capacity of hamster spermatozoa and stimulate the process of capacitation.


Seven Guiding Commitments: Making the U.S. Healthcare System More Compassionate.
Despite the current focus on patient centeredness, healthcare professionals face numerous challenges that impede their ability to provide compassionate care that ameliorates concerns, distress, or suffering. These include fragmentation and discontinuity of care, technologies that both help and hinder communication and relationship-building, burgeoning operational and administrative requirements, inadequate communication skills training, alarming rates of burnout, and increased cost and market pressures. A compassionate healthcare system begins with compassionate people, but the organizations in which they train and work must reliably enable them to express and act on their compassion rather than impede it. We present a set of guiding commitments and recommendations to foster a more compassionate healthcare system. We urge healthcare organizations to adopt these commitments and take action to embed compassionate care in all aspects of training, research, patient care and organizational life.


Cosmopolitanism through mobility: physical-corporeal or virtual-imagined?
In the context of increasing cross-border mobility and the associated interconnections and diversities, 'cosmopolitanism' has become a key concept in sociology. Understood as individual real-world orientation, many authors consider a central cause for cosmopolitanism in physical-corporeal mobility, in particular transnationally. However, the significance of virtual and imagined mobility, such as via television or the Internet, is increasingly emphasized. Nevertheless, it has so far been little examined how and with which relative strength physical-corporeal and virtual-imagined mobility are associated with cosmopolitan orientations. Unlike previous studies, the two forms of mobility are considered simultaneously. On the basis of existing studies and theoretical considerations, it is assumed that the dimension of global orientation is influenced rather by physical-corporeal than by virtual-imagined mobility, whereas the dimension of cultural openness is influenced rather by virtual-imagined than by physical mobility. One reason could be the different potential of the mobility forms to respond to perceived conflicts in the confrontation with the Other. The hypotheses are preliminary tested using data from an online survey that allows both to distinguish locals, (national) shuttles and transnationals, and to query media use. An exploratory principal component analysis confirmed, as in other studies, that global orientation and cultural openness are distinct dimensions. The results of the multivariate analyses largely support the hypotheses and indicate that in investigations of cosmopolitanism, the processes of identity-related self-categorization should be distinguished from pure socialization processes.


Increasing requests by adults with developmental disabilities using incidental teaching by peers.
A peer-delivered incidental-teaching procedure was used to instruct appropriate requesting in adults with moderate to severe mental retardation or autism. Three pairs of group-home residents participated in an incidental-teaching procedure to increase appropriate requesting, prompting, and responding of residents during lunch-preparation sessions. An increase in the number of incidental-teaching episodes during dinner was obtained, and remained high when lunch-making training sessions were withdrawn. In addition, during the incidental-teaching phase, an increase in appropriate requests and overall verbalizations occurred for the peer learners. Changes in appropriate requesting and overall verbalizations also remained higher than baseline when training was withdrawn.


Elevation of methylated DNA in KILLIN/PTEN in the plasma of patients with thyroid and/or breast cancer.
Around 80% of mutations in the PTEN gene have been reported to be associated with diseases such as Cowden syndrome, which is an autosomal dominant disorder associated with an increased risk of developing breast, thyroid, and endometrial neoplasms. Recent studies have also demonstrated that KILLIN, which is located proximally to PTEN, shares the same transcription start site, and is assumed to be regulated by the same promoter, but is transcribed in the opposite direction. In this regard, we postulate that there may be a connection between KILLIN/PTEN genes and breast and thyroid cancers. Using real-time quantitative polymerase chain reaction (qPCR), we found that expression of KILLIN, but not PTEN, was significantly decreased in 23 Chinese women with a personal history of breast and thyroid cancer or a personal history of breast cancer and a family history of thyroid cancer, or vice versa, and at least two persons in the family with thyroid cancer or at a young age <40 years, when compared with healthy controls (P<0.0001). No PTEN mutations were found in these 23 patients. We then developed a simple methylation-sensitive restriction enzyme digestion followed by real-time quantitative assay to quantify plasma methylated KILLIN/PTEN DNA in these patients. Plasma levels of methylated KILLIN/PTEN DNA were significantly increased in these patients when compared with healthy controls (P<0.05). This study shows that plasma methylated KILLIN/PTEN DNA was significantly elevated, suggesting hypermethylation of the KILLIN/PTEN promoter in breast and thyroid cancer patients.


Objective stress monitoring based on wearable sensors in everyday settings.
Monitoring people's stress levels has become an essential part of behavioural studies for physical and mental illnesses conducted within the biopsychosocial framework. There have been several stress assessment studies in laboratory-based controlled settings. However, the results of these studies do not always translate effectively to an everyday context. The current state of wearable sensor technology allows us to develop systems measuring the physiological signals reflecting stress 24/7 while capturing the context. In this paper, we present a stress monitoring system that provides objective daily stress measurements in everyday settings based on three physiological signals: electrocardiogram (ECG), photoplethysmogram (PPG), and galvanic skin response (GSR) using Shimmer3 ECG, Shimmer3 GSR+, and Empatica E4 wearable sensors. We perform controlled stress assessment experiments on 17 participants in which we successfully detect stress with a 94.55% accuracy for 10-fold cross-validation and an 85.71% accuracy for subject-wise cross-validation. In everyday settings, the system assesses stress with an 81.82% accuracy. We also examine whether motion artefacts affect stress assessment and filter the low-confidence readings to minimise false alarms.


A medley of midbrain maladies: a brief review of midbrain anatomy and syndromology for radiologists.
The midbrain represents the uppermost portion of the brainstem, containing numerous important nuclei and white matter tracts, most of which are involved in motor control, as well as the auditory and visual pathways. Notable midbrain nuclei include the superior and inferior colliculus nuclei, red nucleus, substantia nigra, oculomotor nuclear complex, and trochlear nucleus. In addition, white matter tracts include the brachium conjunctivum, medial and lateral lemniscus, spinothalamic tracts, and the fiber tracts within the cerebral peduncles. Although neurologically vital, many of these small midbrain nuclei and white matter tracts are not easily individually identified on neuroimaging. However, given their diverse functions, midbrain pathology often leads to distinct clinical syndromes. A review and understanding of the location and relationships between the different midbrain nuclei and fiber tracts will allow more precise correlation of radiologic findings with patient pathology and symptomatology. Particular syndromes associated with midbrain pathology include the Weber, Claude, Benedikt, Nothnagel, and Parinaud syndromes. The oculomotor and trochlear cranial nerves also reside at this level. An understanding of their functions as well as their projected courses from the midbrain towards the eye allows identification of distinct locations which are particularly vulnerable to pathology.


A centromeric DNA sequence colocalized with a centromere-specific histone H3 in tobacco.
Centromeres play an important role in segregating chromosomes into daughter cells, and centromeric DNA assembles specific proteins to form a complex referred to as the kinetochore. Among these proteins, centromere-specific histone H3 (CENH3) is one of the most characterized and found to be located only on active centromeres. We isolated four different CENH3-coding complementary DNAs (cDNAs), two from Nicotiana tabaccum and one each from the ancestral diploid species, Nicotiana sylvestris and Nicotiana tomentosiformis and raised an antibody against N-terminal amino acid sequences deduced from the cDNAs. Immunostaining with the antibody revealed the preferential centromere localization, indicating that the cDNAs cloned in this study encode authentic tobacco CENH3. A tobacco centromeric DNA sequence (Nt2-7) was also identified by chromatin immunoprecipitation cloning using the antibody.


Secondary enuresis and urological manifestations in children with ataxia telangiectasia.
Ataxia telangiectasia (AT) is a neurodegenerative cerebellar disorder, caused by mutations in the ATM gene, involved in DNA repair. Radiosensitivity, progressive ataxia, immune deficiency and malignancies, are well known symptoms, but urological manifestations are scarcely described. To characterize urologic manifestations in a large cohort of AT patients. Retrospective cross-sectional chart study comprising 52 AT patients followed at a National AT Center. 25% of the cohort (13 patients/8 males) had urologic symptoms, which presented at 11 ± 4.3 years. The most common symptom was secondary enuresis affecting 15% of the patients (8 children/4 males). Incontinence appeared at 8 ± 6.2 years of age, and resolved spontaneously within 15 ± 8.3 months in 6 patients. It preceded loss of ambulatory capacity by 1-2 years in 7 patients. Lumbosacral MRI were normal (4 children) and urine cultures (all) were negative. Urodynamic evaluation that was performed in only one patient revealed overactive bladder. Additional manifestations were macroscopic hematuria due to bladder telangiectasia in a 12-year-old, and renal cell carcinoma in a 22-year-old. Other manifestations unrelated to AT were neprolithiasis, vesico-ureteral reflux and scrotal pain, each in 1 patient. Transient secondary enuresis is a frequent finding in AT patients, heralding loss of ambulatory capacity, tough it's pathophysiological mechanism is largely no understood.


Highly elastomeric poly(glycerol sebacate)-co-poly(ethylene glycol) amphiphilic block copolymers.
Poly(glycerol sebacate) (PGS), a tough elastomer, has been proposed for tissue engineering applications due to its desired mechanical properties, biocompatibility and controlled degradation. Despite interesting physical and chemical properties, PGS shows limited water uptake capacity (∼2%), thus constraining its utility for soft tissue engineering. Therefore, a modification of PGS that would mimic the water uptake and water retention characteristics of natural extracellular matrix is beneficial for enhancing its utility for biomedical applications. Here, we report the synthesis and characterization of highly elastomeric poly(glycerol sebacate)-co-polyethylene glycol (PGS-co-PEG) block copolymers with controlled water uptake characteristics. By tailoring the water uptake property, it is possible to engineer scaffolds with customized degradation and mechanical properties. The addition of PEG results in almost 15-fold increase in water uptake capacity of PGS, and improves its mechanical stability under dynamic loading conditions. PGS-co-PEG polymers show elastomeric properties and can be subjected to serve deformation such as bending and stretching. The Young's modulus of PGS-co-PEG can be tuned from 13 kPa to 2.2 MPa by altering the amount of PEG within the copolymer network. Compared to PGS, more than six-fold increase in elongation was observed upon PEG incorporation. In addition, the rate of degradation increases with an increase in PEG concentration, indicating that degradation rate of PGS can be regulated. PGS-co-PEG polymers also support cell proliferation, and thus can be used for a range of tissue engineering applications.


Rapid and accurate detection of urinary pathogens by mobile IMS-based electronic nose: a proof-of-principle study.
Urinary tract infection (UTI) is a common disease with significant morbidity and economic burden, accounting for a significant part of the workload in clinical microbiology laboratories. Current clinical chemisty point-of-care diagnostics rely on imperfect dipstick analysis which only provides indirect and insensitive evidence of urinary bacterial pathogens. An electronic nose (eNose) is a handheld device mimicking mammalian olfaction that potentially offers affordable and rapid analysis of samples without preparation at athmospheric pressure. In this study we demonstrate the applicability of ion mobility spectrometry (IMS) -based eNose to discriminate the most common UTI pathogens from gaseous headspace of culture plates rapidly and without sample preparation. We gathered a total of 101 culture samples containing four most common UTI bacteries: E. coli, S. saprophyticus, E. faecalis, Klebsiella spp and sterile culture plates. The samples were analyzed using ChemPro 100i device, consisting of IMS cell and six semiconductor sensors. Data analysis was conducted by linear discriminant analysis (LDA) and logistic regression (LR). The results were validated by leave-one-out and 5-fold cross validation analysis. In discrimination of sterile and bacterial samples sensitivity of 95% and specificity of 97% were achieved. The bacterial species were identified with sensitivity of 95% and specificity of 96% using eNose as compared to urine bacterial cultures. These findings strongly demonstrate the ability of our eNose to discriminate bacterial cultures and provides a proof of principle to use this method in urinanalysis of UTI.


The Protective Effects of Enalapril Maleate and Folic Acid Tablets against Contrast-Induced Nephropathy in Diabetic Rats.
Renal vasoconstriction, oxidative stress, endothelial dysfunction, and apoptosis are the major causes of contrast-induced nephropathy (CIN). The aim of this study was to evaluate the protective effects of enalapril maleate and folic acid tablets on CIN in diabetic rats. Thirty-two Sprague-Dawley rats were divided into four groups: CIN (C), CIN + enalapril maleate (CE), CIN + folic acid (CF), and CIN + enalapril maleate and folic acid tablets (CEF). CE, CF, and CEF rats were treated orally with enalapril maleate, folic acid, or enalapril maleate and folic acid tablets, respectively, for 5 days. CIN was induced in all groups followed by analyzed biochemical parameters, oxidative stress markers, endothelial dysfunction parameters, renal histopathology, and TUNEL staining. Serum creatinine, blood urea nitrogen, and malondialdehyde levels were lower in the CEF group than in the C group. Homocysteine, superoxide dismutase, glutathione peroxidase, and nitric oxide levels were higher in the CEF group than in the C group. Histopathology scores and percentage of apoptotic kidney cells in the CEF group were significantly decreased compared with those in the C group. These results suggest that enalapril maleate and folic acid tablets have a protective effect against CIN in diabetic rats.


Two-color infrared predissociation spectroscopy of C₆H₆²⁺ isomers using helium tagging.
Two-color IR-IR isomer selective predissociation spectra of helium-tagged C6H6(2+) are presented. The dications are generated via electron bombardment of either benzene or 1,3-cyclohexadiene. After mass selection they are injected into a 2.6 K cold ion trap where the presence of a dense He buffer gas not only cools them but also leads to He attachment. The ion ensemble is exposed to one or two intense IR pulses from optical parametric oscillators (OPOs) (1200-3100 cm(-1)) before it is extracted, mass analyzed, and detected. On the basis of a comparison with theoretical predictions, the resulting spectral features allow us to separate and assign different isomers of C6H6(2+) dications. Compression of the ion cloud very close to the axis of the linear quadrupole trap and coaxial superposition of well-collimated laser beams results in the fragmentation of almost all helium complexes at specific wavelengths. This unique feature enables us to record fluence-dependent attenuation curves for individual absorption bands and thus determine not only absorption cross sections but also the composition of the ion mixture.


The Occurrence and Diversity of Waterborne Fungi in African Aquatic Systems: Their Impact on Water Quality and Human Health.
Currently, there is a worldwide growing interest in the occurrence and diversity of fungi and their secondary metabolites in aquatic systems, especially concerning their role in water quality and human health. However, this concern is hampered by the scant information that is available in the literature about aquatic fungi and how they affect water quality. There are only few published reports that link certain species of aquatic fungi to human health. The common aquatic fungal species that have been reported so far in African aquatic systems belong to the hyphomycetes kingdom. This paper thus aims to survey the information about the occurrence and factors that control the distribution of different species of fungi in African aquatic systems, as well as their effect on water quality and the possible metabolic pathways that lead to the formation of toxic secondary metabolites that are responsible for the deterioration of water quality. This review will also investigate the analytical and bioanalytical procedures that have been reported for the identification of different species of waterborne fungi and their secondary metabolites.


Implantation of an Intraosseous Transcutaneous Amputation Prosthesis Restoring Ambulation After Amputation of the Distal Aspect of the Left Tibia in an Arabian Tahr (Arabitragus jayakari).
Objective: This document is to report the clinical application and outcome of custom designed Intraosseous Transcutaneous Amputation Prosthesis (ITAP) in the left hind limb in a wildlife Arabian Tahr (Arabitragus jayakari). Sample Population: A 4-year-old, 15 kg Arabian female Tahr from the Omani Mammals Breeding Center. Method: The distal aspect of the left tibia was amputated due to trauma. A custom designed ITAP was inserted into the tibia 5 months after amputation. Two weeks after the surgery an exoprosthesis was attached to the limb. The outcome of the surgery was measured by means of assessments of the limb function and radiographic examination. Results: Fourteen days after surgery the exoprosthesis was attached. The animal was walking showing lameness grade 2/5 (AAEP lameness scale). Within three weeks lameness improved to grade 1/5. Skin integration with the ITAP was achieved within 28 days. The Tahr was successfully reunited with the breeding herd. Conclusion: Application of the ITAP to the left tibia of the Arabian Tahr resulted in positive functional outcomes. Six months post-surgery observations confirmed ambulation with grade 1/5 lameness was restored. The animal was reintroduced to the breeding group. Clinical Relevance: ITAP offers a viable option to restore functionality and ambulation in wildlife.


Cutaneous and hypersensitivity reactions associated with COVID-19 vaccination-a narrative review.
Vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV‑2) has become a major tool in the battle against the coronavirus disease 2019 (COVID-19) pandemic. Numerous products have been developed and more are to come. Vaccination success varies greatly between different countries. There are a number of different vaccine types, such as mRNA, DNA vaccines, adenovirus vector vaccines, and full-length spike protein nanoparticles with a special matrix. The different types may also cause a different spectrum of adverse events. With mass vaccination, post-marketing surveillance for product safety becomes increasingly important. In this review, we discuss possible hypersensitivity and cutaneous adverse events related to SARS-CoV‑2 vaccination-from local reactions like COVID arm to systemic and severe reactions like anaphylaxis. Vaccination may also induce or exacerbate preexisting disorders such as herpes zoster infection. This review should provide information to tailor, whenever possible, vaccination to patients' needs. It is a contribution to patient safety as well. There is general consensus that the benefits of SARS-CoV‑2 vaccination currently outweigh the risks of possible adverse events.


Radiofrequency ablation using BarRx for the endoscopic treatment of radiation proctopathy: a series of three cases.
Radiation proctopathy is a complication of pelvic radiotherapy, which occurs in patients treated for carcinoma of the prostate, rectum, urinary bladder, cervix, uterus, and testes. If it presents within 6 weeks to 9 months after therapy, it is called acute radiation proctitis/proctopathy (ARP), and if it occurs 9 months to a year after treatment, it is classified as chronic radiation proctitis/proctopathy (CRP). CRP occurs in 5%-20% of patients receiving pelvic radiation, depending on the radiation dose and the presence or absence of chemotherapy. In many cases, CRP resolves spontaneously, but in some, it can lead to persistent rectal bleeding. Other symptoms of CRP include diarrhea, mucoid discharge, urgency, tenesmus, rectal pain, and fecal incontinence. Despite the availability of several therapies, many patients fail to respond, and continue to suffer in their quality of life. Radiofrequency ablation (RFA) is a newer endoscopic technique that uses radiofrequency energy to ablate tissue. This is an emerging way to treat radiation proctopathy and other mucosal telangiectasia. We present three cases of radiation proctopathy treated with RFA at our institute and review the literature on treatment modalities for CRP. We were also able to find 16 other cases of CRP that used RFA, and review their literature as well as literature on other treatment modalities.


Constructive Feedback Teaching Strategy: A Multisite Study of Its Effectiveness.
The study purpose was to describe students' perceptions of feedback after participating in a teaching strategy designed to foster a view of feedback as an opportunity for improvement. Although delivering and receiving constructive feedback are essential to the role of the professional nurse, feedback has been identified as a trigger for incivility in academia and practice. Twelve nurse educators from the Quality and Safety Education for Nurses Academic Task Force, located at nine schools of nursing across the nation, implemented a presentation about giving and receiving constructive feedback in junior and senior courses. Five hundred twenty-three students submitted a total of 985 posts or essays in response to viewing the presentation; seven themes were identified. Viewing this teaching strategy enabled nursing students to develop an awareness of the opportunity that constructive feedback presents for professional development, self-improvement, teamwork and collaboration, and patient safety.


Comparative studies on the effect of cholesterol feeding on biliary composition.
The gallbaldder or hepatic bile from six species of animals had a uniformly low cholesterol content far below its maximum solubility. Cholesterol feeding for more than 1 month had little effect on the biliary composition in chickens, rabbits, and rats, but selectively doubled the absolute and relative concentration of cholesterol in the biles of hamsters, and increased the cholesterol concentration to a level of its maximum solubility in gallbladder bile of ground squirrels and hepatic bile of prairie dogs. The gallbladder bile of prairie dogs reached the boundary of metastable supersaturation of cholesterol and subsequently developed cholesterol crystals and gallstones. A circadian change of the relative concentration of bile acid, cholesterol, and phospholipid in the hepatic bile of the rats with chronic biliary drainage was also observed as a consequence of cholesterol feeding.


Intramuscular haemangioma of head and neck region.
Intramuscular haemangiomas are rare benign haemangiomas occurring within the skeletal muscle. These are uncommon tumours in the head and neck region and occur most frequently on the trunk and extremities. Fewer than 80 cases of intra-muscular haemangioma in the head and neck region have been reported in the literature. A case of intramuscular haemangioma of the sternocleidomastoid muscle is presented. The review of occurrence and natural history of such tumours is described and clinical and radiological presentation, histological classifications and treatment modalities are discussed.


The palliative value of surgical resection for carcinoma of the esophagus.
The authors review their experience with primary resection for carcinoma of the esophagus and compare the palliative results with those of a recently reported series of similar patients treated with radiotherapy alone. Between 1971 and 1977, 104 patients with carcinoma of the esophagus underwent resection as the primary therapy. The operative mortality was 7.7% (1.7% in the latter half of the series). At least 80% of the 104 patients had complete, continuing palliation of their dysphagia. Radiotherapy in a similar group of patients reported resulted in an 8% mortality from complications of the treatment and there was local recurrence of the tumour, usually associated with dysphagia, in 80%. The authors conclude that the palliation achieved with surgical resection is substantially better than that achieved with radical radiotherapy applied to a similarly staged group of patients with carcinoma of the esophagus.


Cross-whisker adaptation of neurons in the rat barrel cortex.
Neurons in the barrel cortex and the thalamus respond preferentially to stimulation of one whisker (the principal whisker) and weakly to several adjacent whiskers. Cortical neurons, unlike thalamic cells, gradually adapt to repeated whisker stimulations. Whether cortical adaptation is specific to the stimulated whisker is not known. The aim of this intracellular study was to determine whether the response of a cortical cell to stimulation of an adjacent whisker would be affected by previous adaptation induced by stimulation of the principal whisker and vice versa. Using a high-frequency stimulation that causes substantial adaptation in the cortex and much less adaptation in the thalamus, we show that cortical adaptation evoked by a train of stimuli applied to one whisker does not affect the synaptic response to subsequent stimulation of a neighboring whisker. Our data indicate that intrinsic mechanisms are not involved in cortical adaptation. Thalamic recordings obtained under the same conditions demonstrated that an adjacent whisker response was not generated in the thalamus, indicating that the observed whisker-specific adaptation results from diverging thalamic inputs or from cortical integration.


Malignant melanoma: differential diagnosis of pigmented lesions.
The incidence of melanoma is rising globally despite increased awareness. Familiarity with the clinical signs and certain risk factors for melanoma can result in early recognition, and potentially influence outcome. Unfortunately, there are several other cutaneous tumors, both malignant and benign, that resemble melanoma, and may confuse and possibly delay the diagnosis. This paper discusses the clinical characteristics of melanoma and its most common pigmented simulators.


Protein tango: the toolbox to capture interacting partners.
The evaluation of protein function in the context of the whole cell is crucial for understanding of living systems. In this context, the identification and modulation of protein-protein interactions in and outside cells is of ample importance. Several methods have been developed in the past years to detect and/or actively induce protein-protein interactions in living cells. As a result, tools are now available to manipulate intracellular events by reversible or irreversible cross-linking of proteins in a specific manner. These techniques open many new doors and enable the dissection of complicated protein networks. Herein we describe which cross-linkers and inducers of dimerization are out there and how to make use of this great toolbox.


[Recurrent pancreatitis in pediatric ulcerative colitis--a case report].
We report on a 12 years old girl with ulcerative colitis, who after a two years course of her disease developed a concomitant idiopathic pancreatitis. We discuss the causes of acute pancreatitis in childhood in view of the presented case summarizing the current literature. In the literature we found only two other children with ulcerative colitis and idiopathic pancreatitis. Both patients were colectomised as our patient did. Six months after colectomy she is still free of symptoms.


Chronic mucocutaneous candidiasis with deficient CD2 (E receptor) but normal CD3 mononuclear cells.
A case of chronic mucocutaneous candidiasis in a Malaysian child who subsequently developed disseminated tuberculosis and toxoplasmosis is described. The phenotype of her peripheral blood mononuclear cells showed discordance for her T cell markers. The presence of a subpopulation of CD2-/CD3+ mononuclear cells leading to an immunodeficiency state is consistent with failure of activation of CD2-mediated alternative pathway resulting in immunodeficiency. Such abnormal CD2-/CD3+ subpopulations have been described in lepromatous leprosy and foetal abortuses.


Monitoring of intra-abdominal pressure.
Intra-abdominal pressure monitoring is a very important parameter in the ICU setting, since pathological alterations of this value are significant and are responsible for functional alterations involving cardio-respiratory system, kidneys and central nervous system. Responsibility of the professional nurse in the ICU is to perform a tight and adequate monitoring of those patients who are at risk for a rise in intra-abdominal pressure.


Mapping the Magnetic Anisotropy at the Atomic Scale in Dysprosium Single-Molecule Magnets.
The anisotropy of the magnetic properties of molecular magnets is a key descriptor in the search for improved magnets. Herein, it is shown how an analytical approach using single-crystal polarized neutron diffraction (PND) provides direct access to atomic magnetic susceptibility tensors. The technique was applied for the first time to two Dy-based single-molecule magnets and showed clear axial atomic susceptibility for both DyIII ions. For the triclinic system, bulk magnetization methods are not symmetry-restricted, and the experimental magnetic easy axes from both PND, angular-resolved magnetometry (ARM), and theoretical approaches all match reasonably well. ARM curves simulated from the molecular susceptibility tensor determined with PND show strong resemblance with the experimental ones. For the monoclinic compound, comparison can only be made with the theoretically calculated magnetic anisotropy, and in this case PND yields an easy-axis direction that matches that predicted by electrostatic methods. Importantly, this technique allows the determination of all elements of the magnetic susceptibility tensor and not just the easy-axis direction, as is available from electrostatic predictions. Furthermore, it has the capacity to provide each of the anisotropic magnetic susceptibility tensors for all independent magnetic ions in a molecule and thus allows studies on polynuclear complexes and compounds of higher crystalline symmetry than triclinic.


Treatment of mild hypertension with urapidil or captopril.
The aim of this study was to compare the efficacy (lowering diastolic blood pressure to 90 mm Hg or less) of urapidil, a postsynaptic alpha-blocker with central action with that of captopril in a randomized, double-blind, multicenter study. Two hundred ninety-five essential hypertensives (WHO I/II) (140 male, 155 female, age 56-60 years) were treated for 12 weeks with either 30 to 90 mg urapidil bid or 12.5 to 50 mg captopril bid. Supine blood pressure values (mmHg, mean +/- SD) at the end of the 12-week treatment dropped for the urapidil group (n = 142) from 175/103 +/- 19/6 to 154/89 +/- 17/9 (P less than 0.001), and in the captopril group (n = 153) from 175/103 +/- 19/6 to 154/90 +/- 19/9 (P less than 0.001), corresponding to 62% urapidil and 58% captopril responder rates. The results demonstrate that the two antihypertensive medications with different modes of action control blood pressure with equal efficacy at three dose levels. A dose decrease was possible in 20% of each group, but a dose increase was necessary in 39% of urapidil and 44% of captopril group.


A new 5α,8α-Epidioxysterol from the soft coral Sinularia gaweli.
A new sterol, (22R,23R,24R)-5α,8α-epidioxy-22,23-methylene-24-methyl-cholest-6,9(11)-dien-3β-ol (1), and two known sterols, (22R,23R,24R)-5α,8α-epidioxy-22,23-methylene-24-methylcholest-6-en-3β-ol (2) and 24-methylenecholestane-1α,3β,5α, 6β,11α-pentol (3), were isolated from the soft coral Sinularia gaweli. The structure of sterol 1 was established by spectroscopic methods and by comparison of the spectral data with those of known analogues. The cytotoxicity of sterols 1-3 towards various tumor cells is reported.


Effects of three auxin-inducible LBD members on lateral root formation in Arabidopsis thaliana.
In Arabidopsis, two Auxin Response Factors (ARF7 and ARF19) and several Aux/IAAs regulate auxin-induced lateral root (LR) formation. As direct targets of ARF7 and ARF19, Lateral Organ Boundaries Domain 16 (LBD16), LBD29, and LBD18 have a biological function in the formation of lateral roots (LRs). However, the details of the functions of these three LBDs have remained unclear. Each single T-DNA insert mutant has been shown to have slightly fewer LRs than the wild type. We then created a triple mutant, which exhibited a dramatic defect in the LR formation. Our results show that the lbd mutations can lead to impairment in auxin-induced pericycle cell division and in the expression levels of some D-type cyclins (CYCDs). Simultaneously, Plethora (PLT) and PIN-formed (PIN), which have been well documented to promote cell mitotic activity and are required for auxin response effects, were down-regulated by these lbd mutations. Our results so far indicate that CYCDs, PLT, and PINs are the main targets of the LBDs. We believe that these three LBDs are involved in cell cycle progression of the pericycle in response to auxin. Overexpression of any of these three LBD genes in the triple mutant was found incapable of completely replacing the other two LBDs. The phenotypes of lbd29 mutants were not completely consistent with lbd16 or lbd18 mutants. This indicates that LBD29 may play a distinctive role compared with LBD16 or LBD18 and LBDs might play partially independent roles during the formation of LRs.


[Cervical lymph node inflammation in children].
One hundred and twenty seven cases of cervical lymph node infection were seen between 1974 and 1986 in children aged between 1 month and 10 years. The point of origin of the infection wa identified in 30% of cases and was, in decreasing order: cutaneous, in the cervico-cephalic region; pharyngo-tonsillar via the lymphatic structures of the pharynx or by direct effraction of the buccopharyngeal mucosa; and, finally, dental. The site of the secondary lymph node infection was generally below and behind the angle of the jaw and in some cases submandibular. Two thirds of cases progressed to suppuration and were evaluated bacteriologically. Four organisms were identified: Staphylococcus, very much in the majority. The origin of the infection was almost always cutaneous. There was a predilection for the child aged under 5 with a majority under 2. The streptococcus was in second place far behind the staphylococcus. The origin of the infection was pharyngo-tonsillar, with the beta-haemolytic streptococcus predominant, bucco-dental, with the alpha-haemolytic predominant, and a very small number of cases with a cutaneous origin. The age of these children was greater than in the staphylococcal infection group: the great majority were over 2 and all cases with a dental origin were aged over 5. There were a small number of anaerobic infections. In 2 of the 3 bacteriologically confirmed cases, the origin was pharyngo-tonsillar and development was obviously favored by the initial antibiotics prescribed. Management took into account the predominance of the staphylococcus, the resistance of this organism to penicillin G and its usual sensitivity to methicillin.(ABSTRACT TRUNCATED AT 250 WORDS)


In vitro rumen fermentation, microbial protein synthesis and composition of microbial community of total mixed rations replacing maize silage with red clover silage.
This study aimed to evaluate in vitro fermentation characteristics, microbial protein synthesis and microbial community composition when replacing maize silage (MS) with red clover silage (RCS) in total mixed rations (TMR) of dairy cows. Treatments included TMR containing forage (MS and RCS) and concentrates (0.75:0.25) with targeted proportions (dry matter (DM) basis) of RCS in TMR of 0.15 (RCS15 ), 0.30 (RCS30 ), 0.45 (RCS45 ), and 0.60 (RCS60 ), in substitution of MS. Samples of the TMR were incubated using the in vitro Ankom RF technique with a mixture of rumen fluid and buffer solution (1:2 v/v) for 8 and 24 hr. Gas production and total short-chain fatty acids concentration did not differ between diets, whereas ammonia-nitrogen concentration increased with increasing level of RCS. Acetate proportion was not affected by RCS level, but propionate showed a linear increase with increasing level of RCS at the expenses of butyrate. Branched fatty acids proportions linearly declined, reflecting a reduced deamination of true protein. Gene copy numbers of protozoa linearly decreased with increasing RCS levels, while total numbers of bacteria and methanogens were not affected by diet. The amylolytic bacteria Ruminobacter amylophillus and Prevotella bryantii showed evidence to increase with higher RCS levels after 8 hr and 24 hr, respectively, whereas no effects of diet where observed for the fibrolytic bacteria Ruminococcus albus, Ruminococcus flavefaciens and Fibrobacter succinogenes. Concentrations of purine bases, and total N production in liquid-associated microbes declined with increasing RCS levels, suggesting a negative impact of this feed on microbial growth. The findings of this study suggest that in general, microbial protein synthesis might be impaired by the substitution of MS by RCS, therefore caution should be taken when formulating diets for dairy cows using high levels of RCS as ingredient.


Role of temperature on isoproturon bioaccumulation and effects on two freshwater rooted macrophytes: Elodea densa and Ludwigia natans.
The effects of temperature on the bioaccumulation of the phenylurea herbicide isoproturon (IPU) and on the growth inhibition induced on two freshwater rooted macrophytes--Elodea densa and Ludwigia natans--were investigated using indoor microcosms. The experimental protocol was based on five temperatures (12, 16, 20, 24, and 28 degrees C) and two contamination levels of the water column (30 and 60 micrograms IPU.liter-1), plus a control condition. Variations in temperature had little effect on the decrease in [IPU] in the water column during the 21-day experiment. The IPU concentration in the two macrophyte species was not significantly modified by the large range of temperatures when results were expressed using the concentration criterion. IPU burdens in the E. densa cuttings, on the other hand, increased significantly when the temperature rose from 12 to 28 degrees C; small differences were observed between the two exposure conditions, in relation to the antagonistic effects of IPU and temperature on the growth of the cuttings. Bioconcentration factors in the plants (stems + leaves) were close to 10 and 13 after exposure to 30 and 60 micrograms IPU.liter-1, respectively.


Anomalous High-Temperature Magnetoresistance in a Dilute 2D Hole System.
We report an unusual magnetoresistance that strengthens with the temperature in a dilute two-dimensional (2D) hole system in GaAs/AlGaAs quantum wells with densities p=1.98-0.99×10^{10}/cm^{2} where r_{s}, the ratio between Coulomb energy and Fermi energy, is as large as 20-30. We show that, while the system exhibits a negative parabolic magnetoresistance at low temperatures (≲0.4 K) characteristic of an interacting Fermi liquid, a positive magnetoresistance emerges unexpectedly at higher temperatures, and grows with increasing temperature even in the regime T∼E_{F}, close to the Fermi energy. This unusual positive magnetoresistance at high temperatures can be attributed to the viscous transport of 2D hole fluid in the hydrodynamic regime where holes scatter frequently with each other. These findings give insight into the collective transport of strongly interacting carriers in the r_{s}≫1 regime and new routes toward magnetoresistance at high temperatures.


A Rare Case of Primary Sjogren's Syndrome Coexisting With Gilbert Syndrome.
Gilbert syndrome (GS) is an autosomal recessive inherited bilirubin metabolism disorder characterized by chronic unconjugated hyperbilirubinemia in the absence of hemolysis and liver disease. Primary Sjogren's syndrome (pSS), mainly occurring in women, is a common connective tissue disease (CTD) wherein bilirubin levels are generally reduced. We report a rare case of pSS coexisting with GS. A 35-year-old female patient presented to our hospital with pSS and chronic unconjugated hyperbilirubinemia, for which low-dose methylprednisolone was ineffective. The patient's liver function test results were normal, serological tests for hepatitis virus were negative, and abdominal ultrasound did not indicate abnormal liver morphology. Bone mineral density determination showed that the Z scores of the left femoral neck and lumbar spine were -1.9 and -2.6, respectively, with T scores of -2.1 and -2.8, respectively. Full-exon sequencing revealed a homozygous TA insertion in the TATA box (A(TA)7TAA) and a heterozygous base substitution from C to A at nucleotide position 686 in exon 1 (c.686C>A) in the uridine glucuronosyltransferase 1A1 (UGT1A1) gene. Therefore, the patient was diagnosed with pSS, GS, and osteoporosis. The dose of methylprednisolone was then reduced and gradually stopped, and treatment for osteoporosis was strengthened. To our knowledge, this is the first report of pSS with GS. It is important to clarify the cause of hyperbilirubinemia in patients with CTD, including pSS, which affects the formulation of correct treatment plans.


Ecto-protein kinase CK2, the neglected form of CK2.
Ecto-protein kinases, including protein kinase CK2 (former name, casein kinase 2), have been the focus of research for more than 30 years. At the beginning of the ecto-kinase research their identification was performed with substrates and inhibitors whose specificity under the current knowledge was rather limited. Since all currently known ecto-kinases, including ecto-CK2, have intracellular counterparts, one has to exclude that an ecto-localization originates from intracellular counterparts after cell damage. Protein kinase CK2 is involved in cellular key processes such as cell cycle progression, inhibition of apoptosis, DNA damage repair, differentiation and many other processes. CK2 is composed of two catalytic CK2α or CK2α' subunits and two non-catalytic CK2β subunits. Progress in the ecto-kinase and in particular ecto-CK2 studies was made with the use of transfected tagged CK2 subunits, which allowed to follow their individual transport and localization on the cell surface after transfection. Furthermore, immunofluorescence studies with antibodies against CK2 subunits as well as affinity chromatography with a binding partner of CK2 subunits have improved ecto-kinase research. The use of new and more specific inhibitors as well as of substrates, which do not cross the plasma membrane, have further improved the specificity for ecto-CK2. From the various substrates of ecto-CK2, it can be concluded that ecto-CK2 plays a role in Alzheimer disease, cell adhesion, platelet aggregation, immune response and cellular signalling. New tools and techniques, to study ecto-CK2 activity, are required to identify new substrates and thereby new functional implications for ecto-CK2.


Improving outcomes in the elderly after pressure ulcer repair.
Pressure ulcer repair with skin or muscle flaps may appear to close the wound, but elderly patients need extra precautions before and after surgery to improve the outcome. Nursing care of these patients include monitoring nutrition, removing devitalized tissue from the wound bed, providing proper pressure relief, administering proper patient positioning, and monitoring the flap.


Spontaneous basophilic foci of hepatocellular alteration in Fischer 344 female rats do not exclude iron.
Iron exclusion has been used to identify foci of hepatocellular alteration (FHA) in rats exposed to known carcinogens. This study investigates whether basophilic FHA occurring spontaneously in aged female Fischer 344 rats also exclude iron. Female rats 514-544 days of age were given supplemental iron by injection for 2 weeks prior to being killed. Serial sections of the liver stained with hematoxylin and eosin or Gomori's stain were examined. Seventy-five basophilic FHA were identified; none excluded iron. It may be possible to differentiate spontaneous basophilic FHA from carcinogen-induced, iron-excluding FHA by the use of this staining method.


[Proteases of swine small intestine enterocytes. Kinetics of substrate hydrolysis and inhibition of aminopeptidase N from brush border vesicles].
The kinetics of hydrolysis of L-leucine p-nitroanilide and some p-nitrophenylalanine dipeptides by vesicular aminopeptidase N from the porcine small intestine brush border membrane was studied. It was shown that the catalytic properties of the vesicular enzyme are very similar to those known for its solubilized counterpart. Both enzymes are inhibited by o-phenanthroline, ZnCl2 and puromycin with Ki = 10(-5)-10(-6) M. The data obtained offer new possibilities for investigating the role of aminopeptidase N in the amino acid and peptide transport across the enterocyte membrane.


Archaeal Nucleic Acid Ligases and Their Potential in Biotechnology.
With their ability to catalyse the formation of phosphodiester linkages, DNA ligases and RNA ligases are essential tools for many protocols in molecular biology and biotechnology. Currently, the nucleic acid ligases from bacteriophage T4 are used extensively in these protocols. In this review, we argue that the nucleic acid ligases from Archaea represent a largely untapped pool of enzymes with diverse and potentially favourable properties for new and emerging biotechnological applications. We summarise the current state of knowledge on archaeal DNA and RNA ligases, which makes apparent the relative scarcity of information on in vitro activities that are of most relevance to biotechnologists (such as the ability to join blunt- or cohesive-ended, double-stranded DNA fragments). We highlight the existing biotechnological applications of archaeal DNA ligases and RNA ligases. Finally, we draw attention to recent experiments in which protein engineering was used to modify the activities of the DNA ligase from Pyrococcus furiosus and the RNA ligase from Methanothermobacter thermautotrophicus, thus demonstrating the potential for further work in this area.


From bricks to bytes: faculty and student perspectives of online graduate nursing courses.
Four courses in an existing graduate primary care program were transformed and offered via interactive television with an online component. Data were collected from students taking any 1 of the 4 graduate nursing courses and from faculty teaching online to understand better the experiences associated with technology-based education. An online evaluation tool, the standard School of Nursing evaluation tool, and 2 focus groups-one a convenient sample of students from these 4 classes and the second a group of faculty engaged in online teaching-were all used for data collection. The primary advantages and disadvantages from both the student and the faculty perspective are described. Important considerations for initiation of online course work are included.


Septic Arthritis, Physitis, and Osteomyelitis in Foals.
Despite differences in etiology and diagnostics, the mainstay of therapy in the foal is similar to the adult: local lavage and/or debridement and local antimicrobial therapy. When musculoskeletal infection is concurrent with neonatal sepsis, the prognosis for survival is fair. When musculoskeletal infection is the primary problem, the prognosis is fair to good for survival of synovial, bony, and physeal infections with appropriate and aggressive local therapy. Recent literature may indicate that prognosis for survival and potential athleticism in foals that are treated expediently with local therapies and are without comorbidities may be more favorable than has been previously indicated.


[Long-term follow up of renal function after orthotopic liver transplantation].
Renal dysfunction in patients after the orthotopic liver transplantation (OLT) is frequent and it significantly contributes to the morbidity and mortality. The aim of our work was to assess the level of glomerular function (GFR) within the first to fifth year after OLT. Serum creatinine concentration (Skr), creatinine clearance (Ckr) and predicted value of creatinine clearance using the Cockcrofta a Gaulta formula (CG) were assessed in 75 patients. Normal values of the given parameters (Skr <110 umol/l, Ckr > or = 1.3 ml/s/1.73 m2) were found only in 16% of all patients. Significant decrease of GFR (Ckr < 0.5 ml/s/1.73 m2) was found in 24% of cases, acute renal failure, which required transitory haemodialysis developed in 4% of patients. In 60% of patients various degree of GFR decrease was found without the necessity of haemodialysis. Level of renal functions was not significantly related to the blood pressure or serum lipids concentration. An important factor appeared to be the level of renal function before OLT. Because the level of renal function after OLT can significantly influence the post transplantation development, regular follow up of GFR is recommended.


A robust hidden semi-Markov model with application to aCGH data processing.
Hidden semi-Markov models are effective at modelling sequences with succession of homogenous zones by choosing appropriate state duration distributions. To compensate for model mis-specification and provide protection against outliers, we design a robust hidden semi-Markov model with Student's t mixture models as the emission distributions. The proposed approach is used to model array based comparative genomic hybridization data. Experiments conducted on the benchmark data from the Coriell cell lines, and glioblastoma multiforme data illustrate the reliability of the technique.


The design and construction of an electrohydrodynamic cartesian robot for the preparation of tissue engineering constructs.
In this work we bring together replicating rapid prototyping technology with electrohydrodynamic phenomena to develop a device with the ability to build structures in three-dimensions while simultaneously affording the user a degree of designing versatility and ease that is not seen in conventional computer numerically controlled machines. An attempt at reproducing an actual human ear using polycaprolactone was pursued to validate the hardware. Five different polycaprolactone solution concentrations between 7-15 wt% were used and printing was performed at applied voltages that ranged from 1 to 6 kV and at flow rates from 5 µl/min to 60 µl/min. The corresponding geometrical and aesthetic features of the printed constructs were studied to determine the effectiveness of the device. The 15 wt% concentration at 60 µl/min under an applied electric field of 6 kV was identified as the best operating parameters to work with.


Velocity distribution for a two-dimensional sheared granular flow.
The velocity distribution for a two-dimensional collection of disks of number density n per unit area and radius a in a channel of width L is studied. The particle-particle collisions are considered to be inelastic with a coefficient of restitution e, while the particle-wall coefficients of restitution are inelastic with a tangential and normal coefficients of restitution, e(t) and e(n), respectively. The Knudsen number, which is the ratio of the channel width and the mean free path of the particles, is varied from Kn<<1 to Kn>>1. In the limit of high Knudsen number, the distribution function for the streamwise velocity is bimodal, as predicted by theory [J. Fluid Mech. 340, 3l9 (1997)]], and the scalings of the moments of the velocity distribution with the Knudsen number are in agreement with the theory. In the low Knudsen number limit, the distribution function for the streamwise velocity is a Gaussian if the coefficient of restitution is close to 1, but assumes the form of a "composite Gaussian" if the coefficient of restitution is not close to 1. The distribution function has a complex structure in the intermediate regime, where there are three maxima in the distribution function near the wall, while the distribution function is bimodal at the center. The granular temperature is accurately predicted by kinetic theory at the center of the channel, but there is dissipation at the wall due to inelastic particle-wall collisions, which results in a significant decrease in the temperature even when the coefficient of restitution is 0.9; this finding is in agreement with previous results with bumpy wall boundary conditions and with specular reflection conditions. The slip velocity at the wall has a power law dependence on the Knudsen number, and the exponent in this power law depends on the coefficients of restitution.


Diazoxide-Induced Neutropenia and Long-Term Follow-up in a Patient with Hyperinsulinemia-Hyperammonemia due to GLUD1 Mutation.
Hyperinsulinism/hyperammonemia (HI/HA) syndrome is caused by activating mutations in GLUD1 gene, and causes fasting as well as protein sensitive symptomatic hypoglycemia, in addition to persistently elevated plasma ammonia levels. First-line treatment is diazoxide, and most patients respond well to this agent, however side effects may be observed. The most frequent side effect of diazoxide is fluid retention and hypertrichosis, while hyperuricemia and hematologic side effects are observed less often. Herein, we report a case who had a heterozygous mutation of GLUD1 gene and who developed diazoxide related neutropenia 8 years after the start of treatment. On follow-up, leucopenia and mild neutropenia persisted and the treatment was changed to somatostatin analogues. However, she developed persistent severe symptomatic hypoglycemia and required diazoxide retreatment. A lower dose of diazoxide (6 mg/kg/day) successfully controlled hypoglycemia and cell counts increased even though they were not normalized. Neutropenia in current case presented after a long period of time of diazoxide use and this period is the longest defined in the literature. Long-term endocrine and hematologic follow-up of this patient up to 18 years old will also be presented.


Architecture of a lymphomyeloid developmental switch controlled by PU.1, Notch and Gata3.
Hematopoiesis is a classic system with which to study developmental potentials and to investigate gene regulatory networks that control choices among alternate lineages. T-cell progenitors seeding the thymus retain several lineage potentials. The transcription factor PU.1 is involved in the decision to become a T cell or a myeloid cell, and the developmental outcome of expressing PU.1 is dependent on exposure to Notch signaling. PU.1-expressing T-cell progenitors without Notch signaling often adopt a myeloid program, whereas those exposed to Notch signals remain in a T-lineage pathway. Here, we show that Notch signaling does not alter PU.1 transcriptional activity by degradation/alteration of PU.1 protein. Instead, Notch signaling protects against the downregulation of T-cell factors so that a T-cell transcriptional network is maintained. Using an early T-cell line, we describe two branches of this network. The first involves inhibition of E-proteins by PU.1 and the resulting inhibition of Notch signaling target genes. Effects of E-protein inhibition can be reversed by exposure to Notch signaling. The second network is dependent on the ability of PU.1 to inhibit important T-cell transcription factor genes such as Myb, Tcf7 and Gata3 in the absence of Notch signaling. We show that maintenance of Gata3 protein levels by Myb and Notch signaling is linked to the ability to retain T-cell identity in response to PU.1.


Studies on an alpha-amylase from a thermophilic bacterium. I. Purification and characterization.
An amylase-producing thermophilic bacterium was isolated from a Japanese hot spring. The thermophilic cells were gram-negative, nonsporulating, nonpigmented rods and were motile with flagella. Alpha-Amylase [EC 188.8.131.52) purified from the thermophile was studied. The enzyme was more heat-stable than the corresponding enzymes from mesophilic sources, and 50% loss of activity was observed after incubation for 1 hr at 90 degrees. The thermophilic enzyme resembled the corresponding mesophilic enzymes in many respects, such as kinetic parameters, physicochemical properties, and amino acid composition. The molecular weight of the enzyme was 50,000 and the enzyme contained 2 moles of half-cystine residues per mole of protein, but there were no disulfide crosslinkages. The alpha-helix content of the enzyme was estimated to be about 20% from CD spectra, a value similar to those of other alpha-amylases. The isoelectric point of the enzyme was at pH 9.2.


Morphine modulation of temporomandibular joint-responsive units in superficial laminae at the spinomedullary junction in female rats depends on estrogen status.
The influence of analgesic agents on neurons activated by stimulation of the temporomandibular joint (TMJ) region is not well defined. The spinomedullary junction [trigeminal subnucleus caudalis (Vc)/C(1-2)] is a major site of termination for TMJ sensory afferents. To determine whether estrogen status influences opioid-induced modulation of TMJ units, the classical opioid analgesic, morphine, was given to ovariectomized (OvX) rats and OvX rats treated for 2 days with low-dose (LE2) or high-dose (HE2) 17beta-estradiol-3-benzoate. Under thiopental anesthesia, TMJ units in superficial and deep laminae at the Vc/C(1-2) junction were activated by injection of ATP (1 mm) directly into the joint space. In superficial laminae, morphine inhibited evoked activity in units from OvX and LE2 rats in a dose-related and naloxone-reversible manner, whereas units from HE2 rats were not inhibited. By contrast, in deep laminae, morphine reduced TMJ-evoked unit activity similarly in all groups. Morphine reduced the background activity of units in superficial and deep laminae and resting arterial pressure similarly in all groups. Morphine applied to the dorsal surface of the Vc/C(1-2) junction inhibited all units independently of E2 treatment. Quantitative polymerase chain reaction and immunoblots revealed a similar level of expression for mu-opioid receptors at the Vc/C(1-2) junction in LE2 and HE2 rats. These results indicated that estrogen status differentially affected morphine modulation of TMJ unit activity in superficial, but not deep, laminae at the Vc/C(1-2) junction in female rats. The site(s) for estrogen influence on morphine-induced modulation of TMJ unit activity was probably outside the medullary dorsal horn.


Measurement of thrombopoiesis in rabbits using 75selenomethionine.
Incorporation of (75)selenomethionine ((75)SeM) has been used to study platelet production in rabbits. Radioactivity of platelets was low after the intravenous administration of (75)SeM and rose to a maximum approximately 3 days after administration. Platelet radioactivity was independent of concurrent plasma levels. The life span of rabbit platelets, as estimated with this technique, was 4-5 days. In vivo reutilization of (75)SeM previously incorporated into plasma proteins was not detected. In vitro incorporation of (75)SeM by platelets in platelet-rich plasma was not demonstrated. Acute hemorrhage 24 hr before administration of (75)SeM increased the incorporation of (75)SeM into platelets. Transfusion-induced thrombocytosis reduced the incorporation of (75)SeM to approximately 30% of that observed in control animals. Suppression of bone marrow function with nitrogen mustard resulted in decreased numbers of platelets in the circulation, and a decrease in incorporation of (75)SeM. Delayed appearance of (75)SeM was observed in circulating platelets during recovery from marrow suppression. Injection of 75-225 ml of plasma from thrombocytopenic donors into normal rabbits increased incorporation of (75)SeM into platelets while normal plasma did not have this effect. The rate of appearance of (75)SeM in circulating platelets appears to provide a sensitive and specific method for the study of production of platelets by megakaryocytes. The data suggest more rapid entry of platelets into the circulation, and a sustained increase in incorporation of (75)SeM into platelet protein after stimulation of platelet production. The results are consistent with the concept of a humoral agent (thrombopoietin) that acts on megakaryocytes to regulate platelet production.


Lipid production in aquatic plant Azolla at vegetative and reproductive stages and in response to abiotic stress.
The aquatic plant Azolla became increasingly popular as bioenergy feedstock because of its high growth rate, production of biomass with high levels of biofuel-producing molecules and ability to grow on marginal lands. In this study, we analysed the contribution of all organs of Azolla to the total yield of lipids at vegetative and reproductive stages and in response to stress. Triacylglycerol-containing lipid droplets were detected in all (vegetative and reproductive) organs with the highest level in the male microsporocarps and microspores. As a result, significantly higher total yields of lipids were detected in Azolla filiculoides and Azolla pinnata at the reproductive stage. Starving changed the yield and composition of the fatty acid as a result of re-direction of carbon flow from fatty acid to anthocyanin pathways. The composition of lipids, in regard the length and degree of unsaturation of fatty acids, in Azolla meets most of the important requirements for biodiesel standards. The ability of Azolla to grow on wastewaters, along with their high productivity rate, makes it an attractive feedstock for the production of biofuels.


Cardiovascular and renal developments: patent highlights January to June 2006.
Failure of the cardiovascular system is the main reason for mortality in industrialized countries, and is a major cause of chronic morbidity. As most of the numerous ways in which it can fail will manifest in the second half of life and are exacerbated by old age, this situation is not likely to change in the near future unless fundamentally new ways of treating or preventing hypertension, atherosclerosis, myocardial infarction, chronic heart failure and cardiac arrhythmia are found. This prospect keeps the pharmaceutical industry on a constant, intense search for new therapeutic targets, new drugs, and new ways to identify such targets and drugs, as well as monitoring patient responses to drugs. This summary highlights the most interesting developments seen in cardiovascular and renal patents (other than those claiming formulations or combinations of known drugs) published during the first half of 2006.


[High efficiency genome walking method for flanking sequences of cotton mitochondrial double-copy atpA gene based on optimized inverse PCR and TAIL-PCR].
Cloning of flanking sequences of double-copy gene is a challenge in molecular biology. We developed a method to solve this problem by combining an optimized inverse PCR (iPCR) with TAIL-PCR. First, Southern blotting analysis was used to determine a proper restriction enzyme that could obtain proper-length restriction fragments that contained the target gene. Then optimized iPCR was performed to amplify the restriction fragments that contained the separated copies of the gene. Based on the obtained sequences, TAIL-PCR was performed to amplify further flanking regions of the gene. With this method, we obtained all of the EcoR I restriction fragments (2.2-5.1 kb) and Hind III restriction fragments (8.5-11.7 kb) of mitochondrial atpA gene in cytoplasmic male sterile (CMS) line and maintainer line of Upland cotton. The results showed that this method was an efficient approach to clone flanking sequences of double-copy gene.


Visual function quality of life measure changes upon conversion to neovascular age-related macular degeneration in second eyes.
To determine changes in quality of life measures when choroidal neovascularization (CNV) developed in the second eye of patients with initially unilateral neovascular age-related macular degeneration (AMD). We analyzed responses to the 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ), 36-item Short Form Health Survey (SF-36), and Hospital Anxiety and Depression Scale (HADS) at baseline, and prior to and following second eye CNV diagnosis in 92 participants enrolled in two Submacular Surgery Trials. Paired t-tests for sample sizes over 30 and Wilcoxon signed-rank tests for sample sizes <30 were performed to compare scores. CNV development resulted in statistically and clinically significant changes in responses to 20 of 39 NEI-VFQ items, indicating visual function decline during a mean interval of 25 months. Little difference was noted between baseline scores and prior to CNV diagnosis, which averaged 8.9 months duration. Subscales demonstrated a statistically significant decline in general vision, near activities, distance activities, social functioning, role difficulties, dependency, and driving. There were minimal changes in the HADS and SF-36 scales. CNV development in the second eye had a dramatic effect on visual functioning based on patient responses to the NEI-VFQ questionnaire. Our investigation is believed to be the first study using data collected prospectively to demonstrate vision-related quality of life changes that resulted from development of CNV in AMD patients.