Randomized clinical trial of morbidity after D1 and D3 surgery for gastric cancer.
A randomized comparison of D1 (level 1 lymphadenectomy) and D3 (levels 1, 2 and 3 lymphadenectomy) dissection was performed to evaluate morbidity and effects on survival from gastric cancer. A total of 221 patients were studied after resection for gastric cancer, 110 after D1 surgery and 111 after D3 surgery. The morbidity rate was higher after D3 than after D1 resection (17.1 (95 per cent confidence interval (c.i.) 10.1 to 24.1) versus 7.3 (95 per cent c.i. 2.4 to 12.2) per cent respectively; P = 0.012). The difference was largely related to abdominal abscess (8.1 per cent after D3 versus none after D1 resection; P = 0.003). The D3 group had an anastomotic leak rate of 4.5 per cent whereas there was no leakage in the D1 group (P = 0.060). All anastomotic leaks were minor and were managed non-operatively with nutritional support. Patients who had D3 resection had longer operating times, greater blood loss and postoperative drain outputs, and more patients needed blood transfusion. There was no death in either group. The hospital stay was longer after D3 than D1 surgery (mean(s.d.) 19.6(13.9) (range 10-98) versus 15.0(4.0) (range 10-30) days; P = 0.001). Extended lymphadenectomy for gastric cancer is associated with more complications than limited lymphadectomy but this does not lead to significant mortality.


Activation of the alternative pathway of complement by Malassezia ovalis (Pityrosporum ovale).
Activation of C3 and factor B in normal human serum by P. ovale was demonstrated using a standard unidirectional immunoelectrophoresis technique. Activation of complement by the alternative (properdin) pathway is a possible mechanism by which P. ovale may mediate an inflammatory response.


Roentgenological investigation of cavernous sinus structure with special reference to paracavernous cranial nerves.
We have evaluated the anatomical structure of cavernous sinuses in parasellar blocks obtained from adult cadavers to gain clinically useful information. Ten microdissectional studies of parasellar blocks (20 sides of cavernous sinus) were carried out with special emphasis on the course of paracavernous cranial nerves (3rd to 6th). These were also examined on plain radiographs. Secondly, CT investigations of the cavernous sinuses (notably as to paracavernous cranial nerves) were undertaken in twenty clinical cases having presumed parasellar lesions and in three parasellar blocks from cadavers. The results from microdissectional studies and plain radiographs were as follows. It was found that the 3rd cranial nerve entered the lateral wall of the cavernous sinus close to the antero-inferior part of the posterior clinoid on lateral projection. The 4th cranial nerve, on the other hand, entered near the postero-inferior portion of the posterior clinoid on the same view. Variations in Parkinson's triangle were fairly often noted, although marked asymmetry was not seen in individual cases. From CT findings, it was found that a postenhanced, magnified direct coronal study was essential for identifying paracavernous cranial nerves more clearly. The 3rd and 5th cranial nerves were fairly well identified on axial and coronal projections. Careful radiological investigation including plain skull radiographs & CT seems to be of value for those who diagnose or treat parasellar lesions.


The current landscape of coronavirus-host protein-protein interactions.
In less than 20 years, three deadly coronaviruses, SARS-CoV, MERS-CoV and SARS-CoV-2, have emerged in human population causing hundreds to hundreds of thousands of deaths. Other coronaviruses are causing epizootic representing a significant threat for both domestic and wild animals. Members of this viral family have the longest genome of all RNA viruses, and express up to 29 proteins establishing complex interactions with the host proteome. Deciphering these interactions is essential to identify cellular pathways hijacked by these viruses to replicate and escape innate immunity. Virus-host interactions also provide key information to select targets for antiviral drug development. Here, we have manually curated the literature to assemble a unique dataset of 1311 coronavirus-host protein-protein interactions. Functional enrichment and network-based analyses showed coronavirus connections to RNA processing and translation, DNA damage and pathogen sensing, interferon production, and metabolic pathways. In particular, this global analysis pinpointed overlooked interactions with translation modulators (GIGYF2-EIF4E2), components of the nuclear pore, proteins involved in mitochondria homeostasis (PHB, PHB2, STOML2), and methylation pathways (MAT2A/B). Finally, interactome data provided a rational for the antiviral activity of some drugs inhibiting coronaviruses replication. Altogether, this work describing the current landscape of coronavirus-host interactions provides valuable hints for understanding the pathophysiology of coronavirus infections and developing effective antiviral therapies.


Comparative characterization of TEMPO-oxidized cellulose nanofibril films prepared from non-wood resources.
Three non-wood celluloses, hemp bast holocellulose, and commercial bamboo and bagasse bleached kraft pulps, were oxidized by 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated oxidation in water at pH 10. The water-insoluble TEMPO-oxidized celluloses thus obtained were converted to aqueous dispersions of TEMPO-oxidized cellulose nanofibrils (TOCNs) and then to self-standing TOCN films. Weight recovery ratios of the TEMPO-oxidized celluloses decreased to 70-80% and their carboxylate contents reached 1.5-1.7mmolg(-1) by the TEMPO-mediated oxidation. The viscosity-average degrees of polymerization remarkably decreased from 800-1100 to 200-480 by partial depolymerization occurring during the oxidation, depending on the non-wood celluloses used as the starting materials. The average lengths and widths of the TOCNs were estimated to be 500-650nm and 2.4-2.9nm, respectively, from their atomic force microscopy images. The self-standing TOCN films had high light-transparencies (>87% at 600nm), high tensile strengths (140-230MPa), high Young's moduli (7-11MPa), low coefficients of thermal expansion (4-6ppmK(-1)) in spite of low densities of 1.4-1.7gcm(-3). In particular, the TOCN films prepared from the hemp bast holocellulose had clearly high works of fracture (~30MJm(-3)), whereas those prepared from other two non-wood celluloses had 2-8MJm(-3).


Therapy for male couples experiencing relationship problems and sexual problems.
This article examines four issues that need to be explored by the therapist as possible causes of stress for a male couple: stereotypic male roles, stereotypic sexual roles, homophobia, which includes the "coming out" process, and sexual dysfunctions. These issues can cause anxiety and stress, which may in turn cause relationship problems for a male couple. The role of the therapist is clarified and suggestions for treatment are given.


Badister Clairville 1806: A new species and new continental record for the nominate subgenus in Amazonian Perú (Coleoptera, Carabidae, Licinini).
Badister (Badister) amazonussp. n. is described from Perú, Loreto, 1.0 km SW Boca del Rio Samiria, Vigilante Post 1, 130m, "04°40.5'S, 074°18.9'W" its type locality. It is known also from two other localities in Loreto Department, Perú, in both the Varzea and Igapó river systems. This new species is sufficiently different that a new informal higher taxon, the amazonus species complex, is recognized. An updated key to the Western Hemisphere species of subgenus Badister is provided.


Repurposing a neurodegenerative disease drug to treat Gram-negative antibiotic-resistant bacterial sepsis.
The emergence of polymyxin resistance in carbapenem-resistant and extended-spectrum β-lactamase (ESBL)-producing bacteria is a critical threat to human health, and alternative treatment strategies are urgently required. We investigated the ability of the hydroxyquinoline analog ionophore PBT2 to restore antibiotic sensitivity in polymyxin-resistant, ESBL-producing, carbapenem-resistant Gram-negative human pathogens. PBT2 resensitized Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa to last-resort polymyxin class antibiotics, including the less toxic next-generation polymyxin derivative FADDI-287, in vitro. We were unable to select for mutants resistant to PBT2 + FADDI-287 in polymyxin-resistant E. coli containing a plasmid-borne mcr-1 gene or K. pneumoniae carrying a chromosomal mgrB mutation. Using a highly invasive K. pneumoniae strain engineered for polymyxin resistance through mgrB mutation, we successfully demonstrated the efficacy of PBT2 + polymyxin (colistin or FADDI-287) for the treatment of Gram-negative sepsis in immunocompetent mice. In comparison to polymyxin alone, the combination of PBT2 + polymyxin improved survival and reduced bacterial dissemination to the lungs and spleen of infected mice. These data present a treatment modality to break antibiotic resistance in high-priority polymyxin-resistant Gram-negative pathogens.


Dialkylzinc-assisted alkynylation of nitrones.
[reaction: see text]. Reaction of nitrones with terminal alkynes takes place readily in the presence of a substoichiometric amount of diethylzinc in toluene, affording N-propargyl-hydroxylamines in excellent yields and purity.


Assessment of subclinical cardiovascular alterations in nonfunctioning adrenal incidentalomas.
Adrenal incidentalomas have been associated with increased cardiovascular risk and have a prevalence as high as 10%. This study aims to evaluate carotid- intima media thickness (CIMT), left ventricular mass, and epicardial adipose tissue thickness in nonfunctioning adrenal incidentaloma patients and compare their results with healthy controls. Patients who were referred to the endocrinology clinic for adrenal incidentaloma between 2014 and 2019 were assessed with 1 mg dexamethasone suppression test, 24-h urine metanephrines and normetanephrines, plasma aldosterone to renin ratio. Age and gender-matched subjects without an adrenal mass formed the control group. Left ventricular mass, epicardial adipose tissue thickness, and CIMT of both groups were measured. A total of 41 adrenal incidentaloma patients (21 female, 52.5%) and 40 healthy controls (19 female, 46.3%) were included in the study. Patients with adrenal incidentalomas had increased CIMT. No differences were observed in left ventricle mass or epicardial adipose tissue thickness. There was no correlation between CIMT and adenoma size or serum cortisol (p = 0.2 and p = 0.6, respectively). There was a statistically significant correlation between CIMT and age (p = 0.016, r = 0.295). HBA1c (p = 0.001) and age (p = 0.05) were independently associated with CIMT in regression analysis. Adrenal incidentaloma patients need to be monitored for cardiac dysfunction. CIMT may be used to evaluate adrenal incidentaloma patients for early cardiovascular risk.


[Correction of irregular astigmatism with intracorneal ring segments].
Management of irregular astigmatism with intracorneal rings segments is an intrastromal additive technique developed initially for myopia but eventually popularized for keratoconus and post LASIK ectasia. ICR's are indicated for rigid contact lens intolerance, as an alternative to corneal transplantation. The mechanism of action is complex and involves biomechanical changes leading to a centering and a flattening of the ectasia. The surgical procedure has become much easier thanks to the use of femtosecond lasers. Individualized implantation strategies, based on each patient's topographic and tomographic pattern, are constantly evolving. Patients' refraction and vision are usually improved in more than 70% of cases. Complications remain very rare. Intracorneal ring segments can often be combined with other types of keratoplasty, usually in a sequential fashion, so as to optimize functional results.


Functionalization of α-C(sp3 )-H Bonds in Amides Using Radical Translocating Arylating Groups.
α-C-H arylation of N-alkylamides using 2-iodoarylsulfonyl radical translocating arylating (RTA) groups is reported. The method allows the construction of α-quaternary carbon centers in amides. Various mono- and disubstituted RTA-groups are applied to the arylation of primary, secondary, and tertiary α-C(sp3 )-H-bonds. These radical transformations proceed in good to excellent yields and the cascades comprise a 1,6-hydrogen atom transfer, followed by a 1,4-aryl migration with subsequent SO2 extrusion.


Redefining the Gender Gap in Urology Authorship: An 18-Year Publication Analysis.
Academic authorship is a critical productivity metric used for academic promotion. To characterize temporal changes in female representation in academic authorship in ten primary urology journals as the complement of female urologists is increasing. Publication records were retrieved from 2002 to 2020 for the ten urology journals with the highest impact factor. The names of all authors were gathered and gender was inferred using first names. Trends in first and last/senior authorship by gender were evaluated overall, within journals, and by geographic region. A total of 59,375 articles were analyzed, of which 94.1% had gender information for the first author and 94.2% had gender information for the last author. The percentage of overall female authors increased positively from 17.2% (95% highest density interval [HDI] 12.9-21.4%) in 2002 to 27.2% (HDI 21.7-33.6%; p < 0.01) in 2020. Overall female first authorship increased from 15.2% (95% HDI 11.0-19.5%) to 28.5% (95% HDI 21.8-35.6%; p < 0.01). There was also significant growth for female senior authors from 10.4% (95% HDI 7.6-13.5%) to 18.6% (95% HDI 13.6-23.8%; p < 0.01). Assessment of journal-specific changes revealed that Neurourology and Urodynamics (12.6%, 95% HDI 9.9-15.1%) and The Journal of Sexual Medicine (16.2%, 95% HDI 13.6-19.0%) had significantly higher growth in female authorship when compared to Journal of Endourology (7.2%, 95% HDI 5.5-8.7%) and Urologic Oncology (4.5%, 95% HDI 2.0-6.8%; p < 0.05). Although overall female authorship increased between 2002 and 2020, women remain underrepresented in urology authorship. The percentage of females in senior (last) author positions is less than the percentage of females in first author positions. Journal-specific differences can probably be attributed to gender-based differences in subspecialized fields. In this study, we characterized the underrepresentation of women as authors in urology journals and analyzed the change in female authorship for ten academic urology journals over the course of 18 years. Although the proportion of female authors has increased over that time, the percentage of females in senior authorship roles is less than the percentage of females in first author positions.


A novel model of large vessel ischemic stroke in rabbits: microcatheter occlusion of the posterior cerebral artery.
The rabbit small clot embolic model for large vessel occlusion (LVO) is well established, yet has limitations. Blind introduction of autologous thrombus often fails to completely occlude a target vessel and, when successful, the precise timing of occlusion and revascularization is difficult to control. Studies of cellular biology and neuroimaging of acute reversible cerebral ischemia (ie, penumbral tissue) would benefit from a rabbit model in which LVO can be reliably induced, easily confirmed, and in which the time of occlusion and revascularization can be precisely controlled. Transfemoral 1.5 F microcatheterization of the posterior cerebral artery (PCA) was performed in anesthetized rabbits (n=7) using fluoroscopic guidance. LVO with the wedged microcatheter was maintained for 30-210 min followed by reperfusion. Diffusion-weighted and T2 fluid-attenuated inversion recovery (FLAIR) MRI was performed 3 h after catheter removal on a 3 T scanner. Post-mortem histopathologic analysis of brain tissue was performed using triphenyltetrazolium chloride (TTC). Placing of the 1.5 F microcatheter tip in the PCA was successful in all seven animals. Infarct size on matched diffusion-weighted and TTC sections was strongly correlated (r(2)=0.86). Transient PCA occlusion of 30-60 min resulted in infarction of the ipsilateral hippocampus and thalamus, sparing the cortex, while more prolonged occlusion (180-210 min) resulted in cortical infarction as well. Image-guided microcatheter induction of PCA occlusion in rabbits can consistently produce time-dependent infarction of cortical and subcortical structures that is reliably detected by diffusion-weighted MRI, and thus may be a useful model for therapeutic studies in acute ischemic stroke.


Optical coherence tomography and intravascular ultrasound imaging of bioabsorbable magnesium stent degradation in porcine coronary arteries.
Absorbable metallic stents (AMS) composed of magnesium alloy were designed to complete degradation within 90-120 days. Among the potential advantages of these stents, when compared to conventional stents, are the elimination of late stent thrombosis, chronic inflammation, and artifacts during noninvasive imaging. Magnesium-based AMS were deployed in juvenile domestic pig coronary arteries. Angiography, optical coherence tomography (OCT), and intravascular ultrasound (IVUS) were performed before and after implant and then at 28 days and 3 months following stenting. The animals were sacrificed at 28 days or 3 months following stent implantation. Stented vessels were harvested and analyzed by histomorphometry. Over time, OCT, IVUS, and histologic images revealed a progressive degradation of the stents. Mean stent strut width in the OCT images after implantation was 0.24+/-0.032 mm, then decreased to 0.12+/-0.007 mm (P<.0001) at 28 days and to 0.151+/-0.032 mm at 3 months (P<.0001 vs. implant, P=.078 vs. 28 days). Magnesium-based AMS degrade over a 3-month time period in a porcine model. Its structure is not apparent by angiography but is well-visualized by OCT and IVUS. OCT allowed quantitative assessment of stent degradation.


Intravenous selenium modulates L-arginine-induced experimental acute pancreatitis.
Oxidative stress is understood to have a critical role in the development of acinar injury in experimental acute pancreatitis. We have previously demonstrated that compound multiple antioxidant therapy ameliorates end-organ damage in the intra-peritoneal L-arginine rat model. As the principal co-factor for glutathione, selenium is a key constituent of multiple antioxidant preparations. The intention of this study was to investigate the effect of selenium on pancreatic and remote organ injury in a well-validated experimental model of acute pancreatitis. Male Sprague-Dawley rats were randomly allocated to one of 3 groups (n=5/group) and sacrificed at 72 hours. Acute pancreatitis was induced by 250 mg per 100 g body weight of 20% L-arginine hydrochloride in 0.15 mol/L sodium chloride. Group allocations were: Group 1, control; Group 2, acute pancreatitis; Group 3, selenium. Serum amylase, anti-oxidant levels, bronchoalveolar lavage protein, lung myeloperoxidase activity, and histological assessment of pancreatic injury. L-arginine induced acute pancreatitis characterised by oedema, neutrophil infiltration, acinar cell degranulation and elevated serum amylase. Selenium treatment was associated with reduced pancreatic oedema and inflammatory cell infiltration. Acinar degranulation and dilatation were completely absent. A reduction in bronchoalveolar lavage protein content was also demonstrated. Intravenous selenium given 24 hours after induction of experimental acute pancreatitis was associated with a reduction in the histological stigmata of pancreatic injury and a dramatic reduction in broncho-alveolar lavage protein content. Serum selenium fell during the course of experimental acute pancreatitis and this effect was not reversed by exogenous selenium supplementation.


Effect of electronic versus print format and different reading resources on knowledge acquisition in the third-year medicine clerkship.
Many medical students have access to electronic and print resources. It is not known if the format or the choice of resources effects knowledge acquisition over an entire clerkship. To determine if the format (electronic or print) or choice of reading materials is associated with knowledge acquisition during the 3-year internal medicine clerkship. This was a prospective cohort study. During the last week of the clerkship, students took the National Board of Medical Examiners (NBME) exam and completed a survey ranking the reading materials used. One hundred and fourteen 3rd-year internal medicine clerkship students participated. The most commonly reported resources were UpToDate (99%), a review or question book (93%), and Harrison's Principles of Internal Medicine (82%). Multivariate analysis showed a significant beneficial effect of any use of Harrison's (linear regression, p < .04, absolute difference 3 points, SD = 1.4) on NBME score. The format of the most important resource-electronic (61%) or print (39%)-did not predict the NBME score, p > .80. The format (electronic or print) of resources did not appear to effect NBME score in the medicine clerkship. A secondary analysis showed the use of Harrison's textbook was associated with improved knowledge acquisition.


Interdigitating dendritic cell sarcoma: a report of four paediatric cases and review of the literature.
To report a series of four paediatric cases of interdigitating dendritic cell sarcoma (IDCS) and add to the known extranodal sites of occurrence for this tumour. Neoplasms derived from interdigitating dendritic cells are rare, with only 33 cases being reported in the literature (Medline search). These tumours usually occur in lymph nodes in the adult population. The patients were a 10-year-old girl with a large soft tissue mass bulging into the left chest, a 12-year-old girl with a right paraspinal mass, a 21-month-old boy with generalized lymphadenopathy and hepatosplenomegaly and a 6-year-old girl with a large bladder mass. Paraffin blocks and haematoxylin and eosin slides were available in all cases. In addition, immunohistochemistry and electron microscopy were performed. A diagnosis of IDCS was made in all cases. The diagnosis of IDCS can rarely be entertained on clinical information alone. Microscopically, there is a wide spectrum of features. Thus, immunohistochemistry and electron microscopy are crucial in making the diagnosis. The differential diagnosis includes inflammatory pseudotumour, follicular dendritic cell sarcoma, true histiocytic lymphoma, malignant Langerhans cell histiocytosis, anaplastic large-cell lymphoma, melanoma, and a range of sarcomas. IDCS displays aggressive behaviour and approximately half of the patients die of the disease.


Transient hydrops fetalis of the donor fetus in twin-twin transfusion syndrome after therapeutic amnioreduction.
We present a case of twin-twin transfusion syndrome associated with transient hydrops fetalis observed in the donor after therapeutic amnioreduction at 22 weeks of gestation. After the amnioreduction, the bladder of the donor could be visualized and the donor subsequently began to make amniotic fluid, with spontaneous regression of hydrops fetalis. It is suspected that after therapeutic amnioreduction, intrauterine hemodynamic changes occurred and the donor developed transient hydrops fetalis due to volume overload.


Antioxidant and hepatoprotective effects of Ajuga nipponensis extract by ultrasonic-assisted extraction.
To investigate suitable condition for extraction of the active components from Ajuga nipponensis (A. nipponensis). Orthogonal experimental design was used to determine the optimal extraction parameters for ecdysterones and flavonoids. Finally, the hepatoprotective abilities of A. nipponensis extracts were evaluated by CCl4-induced animal models. Maximum yields of flavonoids (7.87 ± 0.10) mg/g and ecdysterones (0.73 ± 0.02) mg/g could be obtained when the extraction time was 50 min, the extraction temperature was 60 °C, and the ratio of sample to 70% (v/v) ethanol was 1:20 (w/w). The antioxidant property of A. nipponensis was correlated to the concentration of its extracts. At 5 mg/mL, A. nipponensis extract scavenged 84.8% of DPPH radical and had absorbance values of 2.43 ± 0.04 reducing power. Upon CCl4-induced liver injury, glutamic oxaloacetic transaminase and glutamic pyruvic transaminase decreased significantly after the mice were treated with A. nipponensis. Histological researches also explained that A. nipponensis reduced the extent of liver lesions induced by CCl4. A. nipponensis exhibited potent antioxidant activity in chemical experimental models and hepatoprotective effect against CCl4-induced liver damage.


Uvomorulin-catenin complex: cytoplasmic anchorage of a Ca2+-dependent cell adhesion molecule.
The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins, named catenins, which are structurally related in different cell types of various species. This complex formation connects uvomorulin and cytoskeletal structures and might, moreover, be involved in other adhesion-dependent mechanisms.


Alpha-receptor-mediated modulation of 3H-noradrenaline release from rat brain cortex synaptosomes.
The effects of oxymetazoline and noradrenaline (in the presence of desipramine) on the release of 3H-noradrenaline from rat brain cortex synaptosomes were studied using a superfusion technique. Both drugs (at 1 micrometer concentrations) were found to reduce the depolarization-induced (15 mM K+) release of 3H-noradrenaline. The release-modulating effect of noradrenaline was antagonized by phentolamine and yohimbine. The data provide direct evidence for the hypothesis that alpha-receptors modulating the release of noradrenaline are localized on varicosities of central noradrenergic neurones.


Surgical management of severely displaced pediatric seat-belt fracture-dislocations of the lumbar spine associated with occlusion of the abdominal aorta and avulsion of the cauda equina: a report of two cases.
Case report. To present 2 cases of fracture-dislocations of the lumbar spine associated with injury to the aorta and avulsion of the cauda equina and present recommendations regarding urgent management of these injuries. The "seat-belt syndrome" was first described by Garrett and Braunstein in 1962 to describe intraabdominal visceral injuries with fractures of the lumbar spine. Although this syndrome has been described in previously, there have been no reported cases of pediatric patients with significant injury to the abdominal aorta. We present 2 seat-belt injuries occurring within a 4 month period at a pediatric trauma center with significantly displaced lumbar fracture-dislocation, abdominal aortic occlusion, and complete neurologic injury. Rigid fixation of the spinal fracture dislocation in both cases was delayed since these patients were deemed to be hemodynamically unstable. Aggressive mobilization, wound care, and pulmonary toilet were possible after stabilization of the spine. Despite this, 1 patient eventually died. These cases need to be managed according to principles established in the treatment of extremity fractures with vascular and neurologic injuries. That is, early rigid fixation of the fracture to protect the vascular repair.


Late maternal age and postdate pregnancy.
Charts of 443 postdate pregnancies were reviewed to determine the effect of late maternal age on pregnancy outcome. There were significantly more low 1-minute Apgar scores, intrapartum decelerations, and cesarean sections in the group of women greater than 35 years old. Use of oxytocin percentages and the results were similar with regard to both groups. Five-minute Apgar scores also were similar. Women greater than 35 years of age are less able to be delivered of postdate infants with optimal outcomes, but it is still safe to allow them to exceed 42 weeks' gestation.


Fitness of the pMV158 replicon in Streptococcus pneumoniae.
Promiscuous, rolling-circle replication plasmid pMV158 determines tetracycline resistance to its host and can be mobilized by conjugation. Plasmid pLS1 is a deletion derivative of pMV158 that has lost its conjugative mobilization ability. Both plasmids replicate efficiently and are stably inherited in Streptococcus pneumoniae. We have analyzed the effect of pMV158 and pLS1 carriage on the bacterial growth rate. Whereas the parental plasmid does not significantly modify the cell doubling time, pLS1 slows down the growth of the bacterial host by 8-9%. The bases of the differential burden caused by pMV158 and pLS1 carriage are not yet understood. The negligible cost of the pMV158 parental natural plasmid on the host might explain the prevalence of small, multicopy, rolling-circle replication plasmids, even though they lack any selectable trait.


The self-rated Inventory of Depressive Symptomatology for screening prenatal depression.
To examine whether the self-reported version of the Inventory of Depressive Symptomatology (IDS-SR), which is used for major depression, is a reliable tool for screening and assessment of prenatal depression. Between June 2006 and July 2008, pregnant women attending a teaching hospital in São Paulo, Brazil, completed the Portuguese version of the IDS-SR. Trained psychologists diagnosed depression via the Primary Care Evaluation of Mental Disorders questionnaire, which is based on the Diagnostic and Statistical Manual of Mental Disorders IV. Of 543 participants, 60 (11%) were diagnosed with depression. The Cronbach α of the IDS-SR was 0.89, and the area under the ROC curve was 0.8. The IDS-SR cutoff score at 30 gave a sensitivity and specificity of 78% and 76%, respectively, for diagnosis of prenatal depression. Exploratory and confirmatory analyses revealed a 2-factor structure for the IDS-SR, characterized by symptoms of "mood/cognition" and "irritability/anxiety/pain". The IDS-SR gave satisfactory internal consistency and accuracy for diagnosing prenatal depression, showing that it can improve early diagnosis and treatment of this condition, thereby minimizing the burden. In addition, a 2-factor model was found to account for depressive symptomatology during pregnancy, which will be useful for developing further depression subscales specific to prenatal depression.


Structure and antigenicity of the major specific glycolipid antigen of Mycobacterium leprae.
Earlier we reported on the presence of a specific phenolic glycolipid (Phenolic Glycolipid-I) in Mycobacterium leprae, and in infected armadillo tissues (Hunter, S. W., and Brennan, P. J. (1981) J. Bacteriol. 147, 728-735). It had an inherent oligosaccharide, composed of 3-O-Me-rhamnose, 2,3-di-O-Me-rhamnose, and 3,6-di-O-Me-glucose, glycosidically linked to the phenol substituent. The structure of the oligosaccharide has now been determined, by partial acid hydrolysis, permethylation, 1H NMR, and 13C NMR as: 3,6-di-O-Me-Glcp(1 beta leads to 4)2,3-di-O-Me-Rhap(1 alpha leads to 2)3-O-Me-Rhap1 alpha leads to phenol (assuming that the glucose substituent is in the D-enantiomeric configuration, and the two methylated rhamnoses are L). Acid hydrolysis of deacylated Phenolic glycolipid-I yielded a phenolic phthiocerol "core," and mass spectrometry and proton NMR of the permethylated core suggested the following structure: (formula, see text) Combined gas-liquid chromatography-mass spectrometry showed three tetramethyl branched "mycocerosic" acids, C30, C32 and C34, with molecular weights (as methyl esters) of 466, 494, and 522, respectively. These are esterified to the hydroxyl functions of the branched glycolic chain. Evidence is also presented that the glycolipid is immunologically active, reacting with rabbit antisera to M. leprae and with sera from lepromatous leprosy patients.


Preparation and gas storage of high surface area microporous carbon derived from biomass source cornstalks.
Microporous carbon (MC) with a high surface area has been prepared from cornstalks through carbonization and KOH activation. The surface area of the obtained product varies to some extent but the pore size of the material remains within the micropore region as the concentration of KOH activating agent is increased. The MC we prepared exhibits H2 adsorption capacities up to 4.4 wt% at 77K and this material is also able to adsorb considerable amounts of CH4 and CO2. The high adsorption capacities for gases are attributed to the relatively narrow pore size and the high surface area of the porous carbon material.


Gold nanostar-based voltammetric sensor for chromium(VI).
This paper presents an electrochemical sensor for Cr(VI) (chromate ion) in water. A disposable screen-printed electrode was modified with gold nanostars (AuNSs) that were synthesized by Good's buffer method. Linear sweep voltammetry (LSV) was employed for the detection of Cr(VI) in 0.1 M sulfuric acid solution. The AuNSs are shown to provide higher current response to Cr(VI) than spherically shaped gold nanoparticles. The sensor gives the strongest response at a scan rate of 0.05 V (vs Ag/AgCl) and exhibits minimal interference from other electroactive species. The linear range extends from 10 to 75,000 ppb, and the limit of detection is 3.5 ppb. This is well below the provisional guideline value given by the World Health Organization. Excellent recoveries (ranging between 95 and 97%) were found when analyzing contaminated ground water samples obtained from a site situated in Wellesley, MA. Graphical abstract Schematic presentation of preparation of gold nanostars (AuNS) on carbon paste screen printed electrode (CPSPE) by drop casting and electrochemical detection of chromium (VI) using linear sweep voltammetry (LSV).


Economic evaluation of Optilume, a drug-coated balloon for recurrent anterior male urethral stricture.
We aim to conduct an economic evaluation of the Optilume urethral drug-coated balloon (DCB) compared with endoscopic management for the treatment of recurrent anterior male urethral stricture in England. A cohort Markov model was developed to estimate the costs and savings to the NHS over a 5-year time horizon of adopting Optilume for the treatment of anterior urethral male stricture versus current endoscopic standard of care. A scenario analysis was conducted which compared Optilume to urethroplasty. Probabilistic and deterministic sensitivity analyses were performed to estimate the impact of uncertainties in model parameters. When compared with current endoscopic standard of care Optilume resulted in an estimated cost saving of £2502 per patient if introduced in the NHS for the treatment of recurrent anterior male urethral stricture. In the scenario analysis, the use of Optilume compared with urethroplasty resulted in an estimated cost saving of £243. Results were robust to changes in individual input parameters as demonstrated in the deterministic sensitivity analyses, with the monthly probability of symptom recurrence associated with endoscopic management the only exception. Probabilistic sensitivity analysis results demonstrated that Optilume was cost saving in 93.4% of model iterations, when running 1000 iterations. Our analysis suggests that the Optilume urethral DCB treatment can be a cost-saving alternative management option for the treatment of recurrent anterior male urethral stricture within the NHS in England.


Poor health-related quality of life in postural orthostatic tachycardia syndrome in comparison with a sex- and age-matched normative population.
The effect of postural orthostatic tachycardia syndrome (POTS) on health-related quality of life (HrQoL) remains poorly studied. Here, we sought to compare the HrQoL in individuals with POTS to a normative age-/sex-matched population. Participants enrolled in the Australian POTS registry between 5 August 2021 and 30 June 2022 were compared with propensity-matched local normative population data from the South Australian Health Omnibus Survey. The EQ-5D-5L instrument was used to assess HrQoL across the five domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) with global health rating assessed with a visual analog scale (EQ-VAS). A population-based scoring algorithm was applied to the EQ-5D-5L data to calculate utility scores. Hierarchical multiple regression analyses were undertaken to explore predictors of low utility scores. A total of 404 participants (n = 202 POTS; n = 202 normative population; median age 28 years, 90.6% females) were included. Compared with the normative population, the POTS cohort demonstrated significantly higher burden of impairment across all EQ-5D-5L domains (all P < 0.001), lower median EQ-VAS (p < 0.001), and lower utility scores (p < .001). The lower EQ-VAS and utility scores in the POTS cohort were universal in all age groups. Severity of orthostatic intolerance symptoms, female sex, fatigue scores, and comorbid diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome were independent predictors of reduced HrQoL in POTS. The disutility in those with POTS was lower than many chronic health conditions. This is the first study to demonstrate significant impairment across all subdomains of EQ-5D-5L HrQoL in the POTS cohort as compared with a normative population. ACTRN12621001034820.


Serpentine fibula--polycystic kidney syndrome and Melnick-Needles syndrome are different disorders.
We report on the third patient with serpentine fibula-polycystic kidney syndrome. Main features in the three reported cases were growth retardation, abnormal face, hirsutism, short neck, bowed forearms and lower legs due to bowed radii and elongated serpentine fibulae, and metatarsus adductus. Two patients including our own were deaf. All were mentally normal, all were female and sporadic. In addition, we report on a girl with Melnick-Needles syndrome and illustrate the similarities and differences between these syndromes.


Smoking mediates the effect of conscientiousness on mortality: The Veterans Affairs Normative Aging Study.
This study examined the relationship between conscientiousness and mortality over 18 years and whether smoking behavior mediated this relationship. We utilized data from the Veterans Affairs Normative Aging Study on 1349 men who completed the Goldberg (1992) adjectival markers of the Big Five. Over the 18-year follow-up, 547 (41%) participants died. Through proportional hazards modeling in a structural equation modeling framework, we found that higher levels of conscientiousness significantly predicted longer life, and that this effect was mediated by current smoking status at baseline. Methodologically, we also demonstrate the effectiveness of using a structural equation modeling framework to evaluate mediation when using a censored outcome such as mortality.


Unveiling the Role of the Tumor Microenvironment in the Treatment of Follicular Lymphoma.
Follicular lymphomas (FL) are neoplasms that resemble normal germinal center (GC) B-cells. Normal GC and neoplastic follicles contain non-neoplastic cells such as T-cells, follicular dendritic cells, cancer associated fibroblasts, and macrophages, which define the tumor microenvironment (TME), which itself is an essential factor in tumor cell survival. The main characteristics of the TME in FL are an increased number of follicular regulatory T-cells (Treg) and follicular helper T-cells (Tfh), M2-polarization of macrophages, and the development of a nodular network by stromal cells that creates a suitable niche for tumor growth. All of them play important roles in tumor angiogenesis, inhibition of apoptosis, and immune evasion, which are key factors in tumor progression and transformation risk. Based on these findings, novel therapies have been developed to target specific mutations present in the TME cells, restore immune suppression, and modulate TME.


Auditory nerve activity and cochlear morphology after noise exposure.
Four chinchillas were exposed for 5 days to an octave band of noise centered at 4 kHz and having an SPL of 86 dB. After a recovery period of approximately 6 months, behavioral audiograms were obtained and auditory nerve fiber activity was recorded. The animals were killed and the cochleas embedded in plastic to obtain a surface preparation and 1 mu radial sections of the organ of Corti. Behavioral threshold shifts ranged from 5 to 20 dB at frequencies between 4 and 11 kHz. Auditory nerve fiber thresholds were elevated up to 70 dB for units with characteristic frequencies between 4 and 14 kHz. Units with higher and lower characteristic frequencies had normal thresholds. Cochleagrams showed narrow lesions of inner and/or outer hair cells over approximately a 1 mm distance. A comparison of the three realms of data revealed the following: (1) The greatest threshold shifts from the noise exposure were seen in the single nerve fiber thresholds while the smallest shifts were seen in the behavioral thresholds, (2) the greatest behavioral and neural threshold shifts and greatest cochlear damage occurred 1 octave above the center frequency of the noise exposure, and (3) based on the frequency-place map of the chinchilla cochlea, the range of fibers with elevated thresholds exceeded the extent of the OHC lesion. A number of anatomical changes were seen that effectively increased the extent of the damage found in the chochleagram. These changes included: distortions in the surface topography of the organ of Corti affecting the orientation of IHC; missing pillar cells in the presence of normal OHC and/or IHC and protrusion of the IHC cuticular plate into the subtectorial space.


[The occurrence of Chorioptes bovis in bovines in the region of São Carlos, State of São Paulo (author's transl)].
The finding of Chorioptes bovis, the agent of corioptic mange in bovines in the region of São Carlos, State of São Paulo. A description of clinical aspects and treatments is given.


Evaluation of a phosphate management protocol to achieve optimum serum phosphate levels in hemodialysis patients.
To evaluate the effectiveness of a protocol designed to optimize serum phosphate levels in patients undergoing regular hemodialysis (HD). Randomized, controlled trial. Hemodialysis units at Barts and the London NHS Trust and satellite units. Thirty-four clinically stable adults undergoing regular HD with a serum phosphate level >1.8 mmol/L on at least one occasion within 4 months of starting the study. Management of serum phosphate using a specially designed phosphate management protocol during a 4-month study period implemented by a renal dietitian and renal pharmacist compared with standard practice. Change in serum phosphate levels in both groups after 4 months. Patients managed using the phosphate management protocol had a significantly greater reduction in serum phosphate levels compared with patients receiving standard practice (-0.22 +/- 0.67 mmol/L vs. +0.19 +/- 0.32 mmol/L, P = 0.03). The phosphate management protocol was effective, and its implementation was associated with significantly better serum phosphate control in patients undergoing regular HD.


Characterization of aerosol associated non-polar organic compounds using TD-GC-MS: a four year study from Delhi, India.
Aerosol associated Non-Polar Organic Compounds (NPOCs)--25 n-alkanes, 17 Polycyclic Aromatic Hydrocarbons (PAHs), and 3 Isoprenoid hydrocarbons--have been identified and quantified in PM10 samples collected over four years in time sequence (2006-2009), using Thermal Desorption Gas Chromatography Mass Spectrometry, in Delhi region. Established organic markers, associated diagnostic parameters, and molecular diagnostic ratios were used to assess and discern the contributing biogenic, petrogenic and pyrogenic sources to NPOCs. Analysis show that anthropogenic contributions to NPOCs exhibit increase from 2006 to 2009. Distribution profiles of NPOCs were significantly affected by change in season. Lower concentrations of NPOCs during summer months, and higher during winter, once scaled to Planetary Boundary Layer height, suggests that contributing sources were most active during summer months. During monsoon season high mass fractions of Total n-alkanes (ppm), Total PAHs (ppm), and Black carbon (BC) % alludes at the role of differential washout process involving hydrophilic and hydrophobic fractions of ambient aerosols. Significantly high, four year average concentrations of TPAH and BC signify the dominance of pyrogenic source contributions to PM10. High correlation between monthly mean concentrations of TPAH and BC (R(2)=0.75) suggests that besides common emission source, they are also contributed, individually, by exclusive independent sources.


A sensitive H2O2 biosensor based on carbon nanotubes/tetrathiafulvalene and its application in detecting NADH.
Reduced nicotinamide adenine dinucleotide (NADH) plays a pivotal role in the electron-transfer chain of biological system. Analysis of many biological markers is based on the detection of the enzymatically generated NADH. In this paper, a sensitive hydrogen peroxide (H2O2) biosensor, fabricated by carbon nanotubes (CNTs)/tetrathiafulvalene (TTF)/horseradish peroxidase (HRP), was applied for detecting the NADH in a buffer containing methylene blue (MB) at low operating potential of - 0.3 V (vs. Ag/AgCl). Since the NADH could be oxidized by MB to release H2O2, the electrochemical biosensor enables to detect the NADH in the MB buffer. And the low working potential made the biosensor avoid the interference from other electroactive substances. Linear response ranges from 10 μM to 790 μM, with a sensitivity of 4.76 μA mM-1 and a detection limit of 1.53 μM were obtained under the optimum conditions. The proposed sensor provided a promising approach for sensitively detecting the NADH.


Loss of Hsp67Bc leads to autolysosome enlargement in the Drosophila brain.
Hsp67Bc is a small heat shock protein found in Drosophila melanogaster. Apart from performing a function (common for all small heat shock proteins) of preventing aggregation of misfolded proteins, it is involved in macroautophagy regulation alongside the Starvin protein. Overexpression of the D. melanogaster Hsp67Bc gene has been shown to stimulate macroautophagy in S2 cell culture. Nonetheless, it has been unknown how the absence of the Hsp67Bc gene may affect it. Here, we studied the effect of Hsp67Bc gene deletion on the macroautophagy induced by the pathogenic Wolbachia wMelPop strain in D. melanogaster. We detected Wolbachia inside autophagic vacuoles in fly neurons, thereby proving that these endosymbionts were being eliminated via macroautophagy. Nevertheless, we did not register any difference in brain bacterial load between Hsp67Bc-null and control flies at all tested stages of ontogenesis. Moreover, the abundance of autophagic vacuoles was similar between neurons of the mutant and control flies, yet the cross-sectional area of autolysosomes on ultrathin sections was more than 1.5-fold larger in Hsp67Bc-null fly brains than in the control line. Our findings suggest that the product of the Hsp67Bc gene does not participate in the initiation of endosymbiont-induced macroautophagy but may mediate autophagosome maturation: the deletion of the Hsp67Bc gene leads to the increase in autolysosome size.


Automated, solid-phase coupling of rhodamine dye acids to 5' amino oligonucleotides.
A convenient method has been developed for directly labeling the 5' amino group of oligonucleotides on solid-support with rhodamine dyes.


The use of lactic acid bacteria to reduce mercury bioaccessibility.
Mercury in food is present in either inorganic [Hg(II)] or methylmercury (CH3Hg) form. Intestinal absorption of mercury is influenced by interactions with other food components. The use of dietary components to reduce mercury bioavailability has been previously proposed. The aim of this work is to explore the use of lactic acid bacteria to reduce the amount of mercury solubilized after gastrointestinal digestion and available for absorption (bioaccessibility). Ten strains were tested by addition to aqueous solutions containing Hg(II) or CH3Hg, or to food samples, and submission of the mixtures to gastrointestinal digestion. All of the strains assayed reduce the soluble fraction from standards of mercury species under gastrointestinal digestion conditions (72-98%). However their effectiveness is lower in food, and reductions in bioaccessibility are only observed with mushrooms (⩽68%). It is hypothesized that bioaccessible mercury in seafood forms part of complexes that do not interact with lactic acid bacteria.


Congenital cystic dilatation of the intrahepatic bile ducts (Caroli's disease).
With reference to a patient with Caroli's disease (segmentally dilatated intrahepatic bile ducts), the clinical features of this rare but serious disease are described. The condition differs from other cystic dilatations of the bile ducts in that only the intrahepatic bile ducts are involved. Its pathogenesis is obscure. It is suspected that an embryonic developmental disorder in the wall of the bile ducts causes cysts via physiological periodical increases of pressure. The diagnosis is made accidentally by cholangiography via the T-drain during or after cholecystectomy. When Caroli's disease is suspected, echography can be a valuable diagnostic aid.


Factors contributing to variability in drug pharmacokinetics. II. Drug distribution.
Many factors determine the distribution of a drug within the body. All factors may be altered in physiological and pathological states, and this may result in a need to change either the dose of the drug administered or the dosage interval. Changes in plasma protein binding may also alter the interpretation of the relationship between total plasma drug concentration and drug effect, and in such circumstances the free drug concentration may provide a better guide to optimal therapy.


An immunochemical examination of acetylaminofluorene-modified poly(dG-dC) X poly(dG-dC) in the Z-conformation.
Immunization of rabbits with a complex of methylated bovine serum albumin and N-2-acetylaminofluorene (AAF)-modified poly(dG-dC) X poly(dG-dC), a polynucleotide that can assume the Z-DNA conformation, yielded several populations of antibodies specific for Z-DNA determinants. The Z-DNA determinants were analyzed by examination of the antisera and of antibody preparations purified on immunoadsorbents. The following was found: AAF-poly(dG-dC) X poly(dG-dC) shared Z-DNA determinants in common with poly(dG-dC) X poly(dG-dC) in 3.0 M NaCl, poly(dG-m5dC) X poly(dG-m5dC) in 1.5 M NaCl, and brominated poly(dG-dC) X poly(dG-dC) in 0.2, 1.5, and 3.0 M NaCl. Included among the antibodies induced by these determinants was a subpopulation whose reaction with brominated poly(dG-dC) X poly(dG-dC) was sensitive to increased ionic strength. Another distinct population of antibodies recognized determinants present on AAF-poly(dG-dC) X poly(dG-dC) but not on the other Z-DNAs. Only a small portion of this population was specific for the AAF moiety; the greater part appeared to recognize Z-DNA-associated conformational characteristics that were unique to AAF-poly(dG-dC) X poly(dG-dC). These findings are consistent with the existence of a continuum of Z-DNA determinants, which might be capable of functioning as recognition signals for regulatory DNA-binding proteins.


Langerhans cells do not express alternative macrophage activation-associated CC chemokine (AMAC)-1.
We have cloned a novel human CC chemokine, alternative macrophage activation-associated CC chemokine (AMAC)-1 that is highly homologous to macrophage inflammatory protein (MIP)-1alpha. In contrast to MIP-1alpha, AMAC-1 is induced in macrophages by Th2-associated cytokines IL4, IL13, and IL10 in vitro; in addition, AMAC-1 is expressed by Th1-suppressive alveolar macrophages in vivo. Surprisingly, however, AMAC-1 is also expressed by GM-CSF-induced, in vitro monocyte-derived dendritic cells when treated by IL4. Here, we present a detailed analysis of AMAC-1 expression in monocyte-derived dendritic cells in vitro and show that the prime dendritic cells in vivo, i.e. epidermal Langerhans cells, do not express AMAC-1 mRNA. In conclusion, AMAC-1 is a novel CC chemokine whose Th2-associated expression pattern in alternatively activated suppressor macrophages in vivo and in vitro and its absence from epidermal Langerhans cells in vivo suggest that it may be involved in inhibition of Th1 reactions and in tolerance induction.


Epidural analgesia after scoliosis surgery: electrophysiologic and clinical assessment of the effects of bupivacaine 0.125% plus morphine versus ropivacaine 0.2% plus morphine.
To study the electrophysiologic and clinical effects of epidural morphine combined with either bupivacaine 0.125% or ropivacaine 0.2%. Comparative, randomized, double-blind study. Intensive care unit and hospital ward of a university hospital. 18 adult ASA physical status I and II patients with degenerative or idiopathic scoliosis, undergoing posterior spinal fusion with instrumentation. Patients received epidural administration of 10-mL bolus of either bupivacaine or ropivacaine followed by a 6-mL/h infusion for 48 hours of unlabeled local anesthetic. In all patients, epidural morphine 5 mg was added daily. Assessment was focused mainly on somatosensory cortical evoked potentials, soleus H-reflex, and F waves. These electrophysiologic data were recorded before and after epidural medications. Second, respiratory rate, Paco(2), visual analog score (VAS), and side effects such as postoperative nausea and vomiting (PONV), gastrointestinal (GI) transit delay, and urinary retention were noted. Bupivacaine 0.125% + morphine was given to 9 patients, and ropivacaine 0.2% + morphine was given to 9 other patients. H-reflex, F waves, and somatosensory cortical evoked potential recording remained unchanged across the time of assessment. Respiratory rate and Paco(2) values were normal. VASs were indifferently low at rest, but they were lower with bupivacaine than with ropivacaine on mobilization. The frequency of PONV was indifferently high. No altered GI transit or urinary retention was noted. After epidural administration during the study conditions, bupivacaine 0.125% and ropivacaine 0.2% combined with morphine allow for neurologic examination.


Novel quinazolin-sulfonamid derivatives: synthesis, characterization, biological evaluation, and molecular docking studies.
In the design of novel drugs, the formation of hybrid molecules via the combination of several pharmacophores can give rise to compounds with interesting biochemical profiles. A series of novel quinazolin-sulfonamid derivatives (9a-m) were synthesized, characterized and evaluated for their in vitro antidiabetic, anticholinergics, and antiepileptic activity. These synthesized novel quinazolin-sulfonamid derivatives (9a-m) were found to be effective inhibitor molecules for the α-glycosidase, human carbonic anhydrase I and II (hCA I and hCA II), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) enzyme, with Ki values in the range of 100.62 ± 13.68-327.94 ± 58.21 nM for α-glycosidase, 1.03 ± 0.11-14.87 ± 2.63 nM for hCA I, 1.83 ± 0.24-15.86 ± 2.57 nM for hCA II, 30.12 ± 3.81-102.16 ± 13.87 nM for BChE, and 26.16 ± 3.63-88.52 ± 20.11 nM for AChE, respectively. In the last step, molecular docking calculations were made to compare biological activities of molecules against enzymes which are achethylcholinesterase, butyrylcholinesterase and α-glycosidase.Communicated by Ramaswamy H. Sarma.


Intraoperative Doppler assessment of gastric tube perfusion in esophagogastroplasty.
Intraoperative Doppler ultrasonography is a non-invasive method with a great potential for the assessment of perfusion in surgery. This study aimed to determine the accuracy of Doppler ultrasonography in the assessment of blood flow on the top of an Akiyama-fashioned stomach tube for esophagus substitution. A secondary point of interest was the real length gained after construction of the gastric tube. The Ivor-Lewis two stage gastro-esophagectomy was performed in 22 patients with carcinoma of the lower third of the esophagus. Vascularization of the gastric tube was assessed in every patient by Doppler sonographies after every separate step of stomach mobilization. Control arteriographies were performed at 4 major steps of mobilization to evaluate the accuracy of Doppler measurements. Doppler assessment showed a sensitivity of 50 to 95%, specificity of up to 97% and overall accuracy between 95% and 75% during the separate steps of construction of the gastric tube. An approximate length of 4 cm was gained after the final mobilization and tubularization of the stomach. Our clinical trial revealed an excellent agreement between the results of Doppler sonography and arteriography. Doppler sonography proved to be a precise technique for the evaluation of stomach perfusion, especially for the needs of tissue viability assessment of the stomach tube in esophageal surgery.


Optical and Piezoelectric Study of KNN Solid Solutions Co-Doped with La-Mn and Eu-Fe.
The solid-state method was used to synthesize single phase potassium-sodium niobate (KNN) co-doped with the La3+-Mn4+ and Eu3+-Fe3+ ion pairs. Structural determination of all studied solid solutions was accomplished by XRD and Rietveld refinement method. Electron paramagnetic resonance (EPR) studies were performed to determine the oxidation state of paramagnetic centers. Optical spectroscopy measurements, excitation, emission and decay lifetime were carried out for each solid solution. The present study reveals that doping KNN with La3+-Mn4+ and Eu3+-Fe3+ at concentrations of 0.5 mol % and 1 mol %, respectively, improves the ferroelectric and piezoelectric behavior and induce the generation of optical properties in the material for potential applications.


Artificial proteins as allosteric modulators of PDZ3 and SH3 in two-domain constructs: A computational characterization of novel chimeric proteins.
Artificial multidomain proteins with enhanced structural and functional properties can be utilized in a broad spectrum of applications. The design of chimeric fusion proteins utilizing protein domains or one-domain miniproteins as building blocks is an important advancement for the creation of new biomolecules for biotechnology and medical applications. However, computational studies to describe in detail the dynamics and geometry properties of two-domain constructs made from structurally and functionally different proteins are lacking. Here, we tested an in silico design strategy using all-atom explicit solvent molecular dynamics simulations. The well-characterized PDZ3 and SH3 domains of human zonula occludens (ZO-1) (3TSZ), along with 5 artificial domains and 2 types of molecular linkers, were selected to construct chimeric two-domain molecules. The influence of the artificial domains on the structure and dynamics of the PDZ3 and SH3 domains was determined using a range of analyses. We conclude that the artificial domains can function as allosteric modulators of the PDZ3 and SH3 domains. Proteins 2016; 84:1358-1374. © 2016 Wiley Periodicals, Inc.


Peripheral arterial disease in hemodialysis patients 10 years later.
Patients with chronic kidney disease (CKD) on hemodialysis present high cardiovascular comorbidity. Peripheral arterial disease (PAD) is associated with higher mortality and the interest in its early detection and treatment is increasing. The objective of this study is to determine the frequency and severity of symptomatic PAD, and to establish its relationship with mortality in HD patients that have received treated early and compare them with a cohort of our center already reported. Retrospective study on a cohort of incident patients since 2014 and followed up until December 2019. Demographic data, cardiovascular risk, the presence of symptomatic PAD at baseline and during follow-up were collected. Trophic lesions were graded using the Rutherford scale. Initially, there were 91 patients and 7 cases that were not included in the study were lost to follow-up. Age 64 ± 16 years, men 51.6% (47/91). The percentage of baseline PAD was 10.7% (9/84). During a median follow-up of 35 months (20-57), the diagnosis of PAD increased to 25% (21/84). Half of the patients with PAD 52.38% (11/21) obtained a score greater than 3 in the Rutherford Clinical Classification, which corresponds to severe disease. 13/21 patients required reoperation due to recurrence of symptoms (61.9% of cases with PAD). The development of PAD was significantly associated with: an elevated index of Charlson (3.9±2.1 vs. 7.7 ± 3.5; P = 0.001),being male (19 vs. 2; P = 0.001), diabetic (no: 7; yes: 15; P = 0.001) and with a history of chronic ischemic heart disease (no: 13; yes: 8; P = 0.001), 38.1% (8/21) had ischemic heart disease in patients who developed PAD, while in the absence of PAD the presence of ischemic heart disease was 9.5% (6/63). Furthermore, more than half (66.7% [14/21]) of those who developed PAD were diabetic. Univariate analysis showed that age, C reactive protein, albumin, and number of surgical interventions, but not PAD, were associated with mortality. In the multivariate analysis adjusted for other factors, only C reactive protein was related to overall survival Exp β: 2.17; P = 0.011; CI (1.19-3.97). Regarding cardiovascular mortality, in the multivariate Cox analysis, only PAD was related to mortality of cardiovascular origin Exp β: 1.73; P = 0.006; CI (1.17-2.56). A significant number of patients on hemodialysis develop PAD requiring peripheral vascular surgery. PAD was not associated with overall mortality in our cohort, but it did show an association with cardiovascular mortality. Prospective studies with a larger sample size are necessary. New surgical treatments and Follow-up by vascular surgeons could improve the severity of PAD and the long-term prognosis.


Moc-31, fibronectin and CEA in the differential diagnosis of malignant effusions: an immunocytochemical study.
In discriminating benign and malignant origins of cytologically suspicious effusion smears a panel of antibodies against carcinoembryonic antigen (CEA), Fibronectin (F) and MOC-31 was used with immuno-cytochemical techniques. One hundred and thirty seven effusions were studied of which 107 had a malignant and 30 a benign aetiology as determined by clinical and histological examination. Cytologically 24 were diagnosed as benign, 97 as malignant and 14 as suspicious. Staining for F was positive in all effusions of benign and 3 of malignant origin. MOC-31 was positive in 95 (88.8%) of effusions of malignant origin but none of benign origin. Positive CEA was observed in 43% of effusions of malignant origin and in 10 of benign origin. The combination of MOC-31 positivity measured the sensitivity and specificity of the cytological examination in cases where the cytological examination result was suspicious as did F positivity improve the sensitivity for a benign origin of the effusion. Positivity or negativity for CEA is less valuable than the other parameters.


[Encephalomyelitis of atypical course probably caused by Echovirus 7].
The authors report a cases of encephalomyelytis caused probably by ECHO7 virus which was isolated from the cerebrospinal fluid after 45 days of disease. During 120 days 4 relapses of the disease were observed associated with severe general and neurological signs and cerebral coma which ultimately was the cause of death.


From behavior theory to behavior therapy: the contributions of behavioral theories and research to the advancement of behavior therapy.
As we approach the latter years of the twentieth century, a century that witnessed the birth of the behavior therapy movement, it becomes increasingly important to understand the forces that shaped the development, advancement, and success of behavior therapy. This paper is an introduction to a series of articles analyzing how major behavioral theories and research have contributed to the advancement of behavior therapy. In view of the fact that many behavior therapists have lost touch with the relation between behavior theory and behavior therapy and the challenges of the "cognitive revolution", we argue that the field would benefit conceptually and practically from integrating and utilizing the resources provided by recent advances in basic behavioral theory and research. The articles in this symposium attempt to build conceptual, methodological, and practical bridges to help behavior therapists recognize and utilize basic behavioral research and concepts.


Down Syndrome Candidate Region 1 Isoform 1L regulated tumor growth by targeting both angiogenesis and tumor cells.
Angiogenesis is critical for solid tumor growth beyond its minimal size. Previously, we reported that Down Syndrome Candidate Region 1 isoform 1L (DSCR1-1L) was one of the most up-regulated genes in endothelial cells induced by VEGF and histamine, and regulated endothelial cell proliferation, migration and angiogenesis. However, it was not known whether DSCR1-1L played a role in tumor growth. In this study, we found that DSCR1-1L shRNAs significantly inhibited the growth of transplanted melanoma in mice and its associated tumoral angiogenesis. In the gain of function assay, overexpression of DSCR1-1L cDNA in mouse endothelium is sufficient to significantly increase the tumor initiation induced by carcinogen, the growth of xenografted tumor, and the tumor metastasis in our endothelially-expressed DSCR1-1L transgenic mice, in which angiogenesis was induced. It was the first time to find that DSCR1-1L was also expressed in various tumor cells. DSCR1-1L shRNAs inhibited, but overexpression of DSCR1-1L cDNA increased, the tumor cell proliferation and migration. Most recently, we reported that DSCR1-1L modulated angiogenesis by down-regulation of VE-cadherin expression. Here, we found that DSCR1-1L down-regulated the expression of E-cadherin. Hence, DSCR1-1L is an excellent therapeutic target for cancers by regulation of both the endothelial and tumor cells through down-regulating (V)E-cadherin. DSCR1-1L shRNAs have the potential to be developed for clinical application.


Effects of maternal smoking during pregnancy on offspring blood pressure in late adolescence.
Previous studies suggest that maternal smoking during pregnancy is associated with elevated offspring blood pressure during childhood. We aimed to investigate whether this association remained in late adolescence and, if so, whether it could be attributed to an intrauterine effect or to familial confounding. We used a national cohort of 87,223 young Swedish men born between 1983 and 1988 with information on both maternal smoking during pregnancy and blood pressure at military conscription. The cohort included 780 full brothers discordant for maternal smoking. Generalized estimation equations were used to estimate regression coefficients (β) with 95% confidence intervals (95% CIs). We found a small but significant increase in both SBP and DBP for young men whose mothers had been daily smokers during pregnancy compared with sons of nonsmoking mothers: 0.26 (95% CI 0.09 to 0.44) and 0.45 mmHg (95% CI 0.31 to 0.59) for SBP and DBP, respectively. In a within-sibling analysis comparing full brothers discordant for maternal smoking exposure, point estimates were similar but not statistically significant: 0.85 (95% CI -0.19 to 1.90) for DBP and 0.81 (-0.56 to 2.19) for SBP. Maternal smoking during pregnancy is associated with a small but statistically significant increase in offspring blood pressure in late adolescence. Because the association does not appear to be explained by familial confounding, our results support an intrauterine effect of prenatal smoking exposure on blood pressure in late adolescence.


Karyotypic heterogeneity and clonal evolution in squamous cell carcinomas of the head and neck.
Head and neck squamous cell carcinomas (HNSCC) are often characterized by complex karyotypic changes, and a substantial proportion of the reported tumors have shown intratumor heterogeneity in the form of cytogenetically related (40%) or unrelated clones (20%). In order to study intratumor heterogeneity and to distinguish the temporal order of chromosome rearrangements in these tumors, two or more samples from different areas of the same tumor were separately examined in 19 HNSCC, yielding karyotypes from a total of 42 tumor samples. Intrasample heterogeneity was observed in 16 samples. Two samples displayed both related and unrelated multiple clones, four samples showed only multiple unrelated clones, and the remaining 10 samples had only related subclones. Intersample heterogeneity was detected in all but one tumor. Five tumors showed both cytogenetically related and unrelated multiple clones, 11 were found to have only related subclones, and the remaining two tumors showed only unrelated clones. Clonal evolution could be assessed in 13 tumors. A comparison of chromosome imbalances in different subclones from these tumors suggests that partial or entire loss of 3p, 8p, 9p, and 18q and gain of genetic material from 3q and 8q are likely to be early genetic events. In contrast, loss of 1q, 6p, 7q, and chromosome 10, as well as gain of chromosome arms 5p and 7p, are most probably later genetic events. One of the examined tumors contained two highly complex clones that were cytogenetically unrelated, indicating that this tumor had a multicellular origin.


EGFR-induced suppression of HPV E6/E7 is mediated by microRNA-9-5p silencing of BRD4 protein in HPV-positive head and neck squamous cell carcinoma.
EGFR upregulation is an established biomarker of treatment resistance and aggressiveness in head and neck cancers (HNSCC). EGFR-targeted therapies have shown benefits for HPV-negative HNSCC; surprisingly, inhibiting EGFR in HPV-associated HNSCC led to inferior therapeutic outcomes suggesting opposing roles for EGFR in the two HNSCC subtypes. The current study aimed to understand the link between EGFR and HPV-infected HNSCC particularly the regulation of HPV oncoproteins E6 and E7. We demonstrate that EGFR overexpression suppresses cellular proliferation and increases radiosensitivity of HPV-positive HNSCC cell lines. EGFR overexpression inhibited protein expression of BRD4, a known cellular transcriptional regulator of HPV E6/E7 expression and DNA damage repair facilitator. Inhibition of EGFR by cetuximab restored the expression of BRD4 leading to increased HPV E6 and E7 transcription. Concordantly, pharmacological inhibition of BRD4 led to suppression of HPV E6 and E7 transcription, delayed cellular proliferation and sensitised HPV-positive HNSCC cells to ionising radiation. This effect was shown to be mediated through EGFR-induced upregulation of microRNA-9-5p and consequent silencing of its target BRD4 at protein translational level, repressing HPV E6 and E7 transcription and restoring p53 tumour suppressor functions. These results suggest a novel mechanism for EGFR inhibition of HPV E6/E7 oncoprotein expression through an epigenetic pathway, independent of MAPK, but mediated through microRNA-9-5p/BRD4 regulation. Therefore, targeting EGFR may not be the best course of therapy for certain cancer types including HPV-positive HNSCC, while targeting specific signalling pathways such as BRD4 could provide a better and potentially new treatment to improve HNSCC therapeutic outcome.


Scapula motor control training with Proprioceptive Neuromuscular Facilitation in chronic subacromial impingement syndrome: A case report.
Shoulder complaints have high re-occurrence rates and scapular control seems to be a major influencing factor in sub-acromial impingement syndromes (SIS). Scapular dyskinesia disrupts the scapulohumeral rhythm, altering biomechanical loads on the rotator cuff in shoulder movements. As a result, this disturbs the natural healing process. Proprioceptive Neuromuscular Facilitation (PNF) seems to be a promising treatment approach because it has a focus on motor learning. This case report seeks to illustrate the clinical reasoning and feasibility of applying the comprehensive nature of PNF in a patient who was not responsive to standard physiotherapy. A 47-year-old male, a former professional handball player, was diagnosed with a SIS based upon a rotator-cuff tendinopathy, scapular dyskinesia and degeneration of supraspinatus tendon. The patient presented complaints of right sided shoulder pain in overhead activities and in reaching behind the back. PNF-based motor-control training was provided over a period of five weeks. This approach included specified PNF-pattern exercises with specific PNF-facilitation principles and techniques. The results were improvements beyond the minimal clinical important difference and/or minimal detectable change for physical functioning, pain, range of motion, and functional disability of the shoulder. PNF provided an opportunity for motor control training, restored altered movement patterns in the patient's daily life activities. The approach addressed motor learning effects and structural impairments. PNF-patterns have been described as: "mimicking functional activities" from daily life and from sports. In cases where standard strengthening and mobilization exercises are not effective, a specified PNF-based therapy has shown to be a feasible alternative.


Cytochemical localization of small intestinal glycoconjugates by lectin histochemistry in controls and subjects with cystic fibrosis.
Human mucosal glycoconjugates were examined in normal small intestinal biopsies from five control subjects using six different fluorescein-conjugated lectins: Triticum vulgare agglutinin (WGA), Ulex europaeus agglutinin I (UEA1), Ricinus communis agglutinin I (RCA1), glycin max-soy bean agglutinin (SBA), Dolichus biflorus agglutinin (DBA), and Arachis hypogaea peanut agglutinin (PNA). These plant agglutinins bind to specific nonreducing end-terminal carbohydrate residues. Only the lectins derived from WGA, which produced the strongest staining, and UEA1 consistently bound to both intestinal goblet cell mucin and epithelial cell microvillar membranes. The intensity of lectin binding was greatest in the upper villus and diminished down towards the crypt, being weakest in the crypt base. Similar histochemical studies carried out on small bowel biopsies from five patients with cystic fibrosis revealed no major qualitative differences between the intestinal glycoconjugates in normal subjects and those with cystic fibrosis. These results suggest that glycoconjugate biosynthesis of human intestinal goblet cell mucin and epithelial cell membranes may be complete and hence full differentiation achieved only when these cells have migrated out of the crypt and onto the villus.


A cost-effectiveness analysis of intraoperative autologous transfusion in adolescent idiopathic scoliosis surgery: a single-centre retrospective study.
Intraoperative autologous transfusion (IAT) has been used in scoliosis surgery for decades; however, its cost-effectiveness remains debatable. This study aimed to evaluate the cost-effectiveness of IAT in adolescent idiopathic scoliosis (AIS) surgery and identify risk factors of massive intraoperative blood during this surgery. The medical records of 402 patients who underwent AIS surgery were reviewed. The patients were divided into different groups according to the intraoperative blood loss volume (group A: ≥500 to < 1000 mL, B: ≥1,000 to < 1,500 mL, and C: ≥1,500 mL) and whether IAT was used (i.e., IAT and no-IAT groups). The volume of blood loss, volume of transfused allogeneic red blood cells (RBC), and RBC transfusion costs were analysed. Univariate and multivariate logistic regression analyses were used to identify the independent risk factors of massive intraoperative blood loss (≥ 1,000 mL and ≥ 1,500 mL). A receiver operating characteristic (ROC) curve was used to analyse the cut-off values of the factors contributing to massive intraoperative blood loss. In group A, no significant difference was observed in the volume of allogeneic RBC transfused during and after procedure between the IAT and no-IAT groups; however, total RBC transfusion costs was significantly higher in the IAT group. In groups B and C, the patients in the IAT group compared with those in the no-IAT group had a lower volume of allogeneic RBC transfused during the operation and on the first day after the operation. However, in group B, the total RBC transfusion cost in the patients who used IAT was significantly higher. In group C, total RBC transfusion cost in the patients who used IAT was significantly lower. The number of fused vertebral levels and Ponte osteotomy were found to be independent risk factors for massive intraoperative blood loss. ROC analysis showed that more than eight and 10 fused vertebral levels predicted ≥ 1,000 mL and ≥ 1,500 mL intraoperative blood loss, respectively. The cost-effectiveness of IAT in AIS was related to the volume of blood loss, and when the blood loss volume was ≥ 1,500 mL, IAT was cost-effective, drastically reducing the demand for allogeneic RBC and total RBC transfusion cost. The number of fused vertebral levels and Ponte osteotomy were independent risk factors for massive intraoperative blood loss.


Management of Carotid Blowout from Radiation Necrosis.
Although the incidence of carotid blowout has decreased with the advent of better reconstructive techniques, it remains a real risk after major head and neck surgery, especially in an irradiated field. A systematic, multidisciplinary approach incorporating appropriate history and physical examination, adequate resuscitation, diagnostic computed tomography, and diagnostic and therapeutic angiography can manage most of these patients in a safe and effective manner. Surgery has a limited role in acute management, although surgical techniques are useful both for prevention of this problem and for wound management after carotid blowout.


Evaluation of the anti-Trypanosoma cruzi activity in vitro and in vivo of silibinin and silibinin in association to benznidazole.
Chagas disease (CD) is endemic in Latin America. Drugs available for its treatment are benznidazole (BZ)/nifurtimox (NF), both with low efficacy in the late infection and responsible for several side effects. Studies of new drugs for CD among natural products, and using drug combinations with BZ/NF are recommended. Silibinin (SLB) is a natural compound that inhibits the efflux pump (Pgp) of drugs in host cell membranes, causes death of trypanosomatids, has anti-inflammatory activity, and was never assayed against T. cruzi. Here, in vitro and in vivo activities of SLB, SLB+BZ, and BZ against T. cruzi Y strain were evaluated. Cytotoxicity of SLB in VERO cells by the MTT method revealed IC50 of 250.22 μM. The trypanocidal activity evaluated by resazurin method in epimastigotes showed that SLB 25 μM inhibited parasite growth. SLB IC50 and selectivity index (SI) for amastigote were 79.81 μM and 3.13, respectively. SLB100+BZ10 showed higher parasite inhibition (91.44%) than SLB or BZ. Swiss mice infected with Y strain were treated with SLB, SLB+BZ, and BZ. Parasitemia was evaluated daily and 90, 180, and 240 days after treatment in surviving animals by hemoculture, blood qPCR, and after euthanasia, by qPCR in heart tissue. SLB monotherapy was not able to control the parasitemia/mortality of the animals. Parasitological negativation of 85.7-100% was observed in the experimental groups treated with SLB+BZ. Although SLB had shown activity against T. cruzi in vitro, it was not active in mice. Thus, the results of the therapeutic effect observed with SLB+BZ may be interpreted as a result from BZ action.


[Polymorphisms of angiotensin converting enzyme and angiotensin II type 1 receptors genes and the state of regional hemodynamics in borderline arterial hypertension in young men].
Relationship between polymorphisms of ACE and ATR1 genes to morphological and functional states of cardiovascular system was studied in young men with borderline hypertension living in north-west region of Russia. Prevalences of ACE DD and ATR1 AC genotypes were 46 and 54%, respectively. There were no significant correlations between genotypes studied and parameters of central, intracardiac, ophthalmic hemodynamics, as well as presence and severity of albuminuria. Compared with other gene combinations simultaneous carriers of DD and CC genotypes had significantly more pronounced changes of target organs.


A randomized controlled trial investigating the efficacy and safety of switching from a protease inhibitor to nevirapine in patients with undetectable viral load.
To assess the antiviral efficacy and safety of switching from a protease inhibitor (PI) to nevirapine in patients with long-term HIV-1 RNA suppression on PI-containing regimens, and to assess its influence in the adherence to treatment. In an open-label multicentre study, 160 HIV-infected patients with undetectable viral load for at least 6 months on a PI-containing regimen were randomized to either continue with their PI regimen (n=79) or replace PI with nevirapine (n=81). Clinical assessment included plasma HIV-1 RNA, blood chemistry, haematology, lymphocyte counts and adverse events reports. Adherence to treatment and lipodystrophy syndrome were assessed by patient self-reporting. Treatment efficacy was equivalent in the two arms, for patients with viral loads either above or below 100 000 HIV-1 RNA copies/mL. The increase in CD4 cell count was significant in both arms (P<0.00001) but the average CD4 cell count at 48 weeks was slightly higher in the nevirapine arm (596 vs. 569; P=0.1588). The number of patients with severe hypertriglyceridaemia (>400 mg/dL) after 48 weeks of treatment decreased in the nevirapine arm (from 11 to six), but increased in the PI arm (from four to 11) and led to treatment discontinuation in two patients. Lipodystrophy changes increased in 15% of patients in the PI arm but decreased in 4% of patients in the nevirapine arm. Finally, although adherence was similar in the two arms, patients reported that it required significantly less effort to stay on treatment in the nevirapine arm. Conclusions The results indicate that switching from PI to nevirapine is as effective as continuing with PI for maintaining viral control, even in patients with baseline viral load above 100,000 copies/mL. In addition, reductions in hypertriglyceridaemia and lipodystrophy and in the effort required to stay on treatment were observed.


Determinants of VO(2) kinetics at high power outputs during a ramp exercise protocol.
To determine the relationship between the additional, nonlinear increase in oxygen uptake (Delta VO(2)) that occurs at high power outputs during a ramp cycle ergometer test, on one hand; and possible explanatory mechanisms of the phenomenon, such as cardiorespiratory work, blood lactate, fitness level, or muscle fiber distribution, on the other. Ten healthy, sedentary young adults (age (mean +/- SEM), 22 +/- 1 yr) were chosen as subjects. A muscle biopsy specimen was taken from the vastus lateralis of the right leg to determine fiber type distribution by immunohistochemical identification of myosin heavy chain (MHC) isoforms. During the ramp tests (power output increases of 5 W every 15-s interval), the ventilatory threshold (VT) and lactate threshold (LT) were measured. We defined Delta VO(2) as the difference between "true" VO(2) values observed at the maximal power output (VO(2)obs) and those expected (VO(2)exp) from the previous linear VO2:power output relationship below the VT. A nonlinear increase was observed in VO2 (Delta VO(2) = 239 +/- 79 mL x min(-1), P < 0.05 for VO(2)obs vs VO(2)exp), which was significantly correlated with the percentage of type IIX fibers (r = 0.80, P < 0.05). No other correlations were found between Delta VO(2) and possible explanatory mechanisms. A greater percentage of type IIX fibers is associated with a higher excess VO(2) at high power outputs (above VT).


Survival outcome of salvage hepatectomy in patients with local, recurrent hepatocellular carcinoma who underwent radiofrequency ablation as their first treatment.
Local recurrence is a specific problem after radiofrequency ablation of small hepatocellular carcinoma, and additional treatment is an important issue. We aimed to investigate the outcome of salvage hepatectomy in patients who develop local, recurrent hepatocellular carcinoma after treatment with radiofrequency ablation. From 2001-2013, we reviewed 58 patients from 6 university hospitals with local, recurrent hepatocellular carcinoma who underwent salvage hepatectomy after their initial radiofrequency ablation treatment. Pathologic characteristics and prognostic factors influencing overall survival were analyzed. Noncurative resection, des-gamma carboxy prothrombin levels >40 mAU/mL, and multiple preceding treatments before salvage hepatectomy were negative prognostic factors for overall survival. The 5-year survivals for the prognostic factors were 0%, 24%, and 30%, respectively, after salvage hepatectomy, and 0%, 54%, and 54% after initial radiofrequency ablation treatment, respectively. As for the pathologic finding of local, recurrent hepatocellular carcinoma after radiofrequency ablation, vascular invasion was observed frequently in patients with increases in des-gamma carboxy prothrombin levels and with multiple preceding treatments before salvage hepatectomy with a frequency of 59% and 53%, respectively (P < .01 and .05). Noncurative resection, increases in serum des-gamma carboxy prothrombin, and multiple preceding treatments were prognostic factors for subsequent salvage hepatectomy; nevertheless, survival outcomes were still acceptable when a curative salvage hepatectomy was performed. Increases in serum des-gamma carboxy prothrombin and multiple preceding treatments were positive predictors for pathologic vascular invasion. These factors should be taken into consideration when selecting treatment modalities for locally recurrent hepatocellular carcinoma following radiofrequency ablation. Repetition of unsuccessful, loco-regional treatment would appear to decrease the potential survival.


Epidemiology of premature ejaculation.
Accumulating evidence suggests that premature ejaculation is the most common sexual symptom. This review focuses on the epidemiology of premature ejaculation from geographical and medical perspectives. In the past year many articles have been published using the data from the Global Study of Sexual Attitudes and Behaviors, a large survey that investigated various aspects of sex and relationships among 27 500 men and women aged 40-80 years. Despite some methodological bias, discussed herein, a prevalence of more than 21% seems a realistic figure for premature ejaculation. Premature ejaculation is the most prevalent sexual dysfunction in every country.


Sweet's Syndrome Presenting in Concordance with Acute Coronary Syndrome.
Acute febrile neutrophilic dermatosis (Sweet's syndrome) is typically characterized by an acute onset of erythematous papules, plaques, and nodules in a febrile patient. This dermatosis is classically accompanied by leukocytosis and neutrophilia, and has had reported associations with various underlying etiologies including drug reactions, malignancies, infections, autoimmune disorders, and inflammatory bowel diseases. However, most cases of acute febrile neutrophilic dermatosis are idiopathic. We present a unique case of Sweet's syndrome in a patient with concurrent acute myocardial infarction.


Comparative fading responses induced by mivacurium, cisatracurium, and d-tubocurarine in the evoked muscular compound action potentials of the cat.
It has been suggested that the different degrees of fade induced by nondepolarizing neuromuscular blocking agents in repetitive muscular contractions may be due to the varying affinities or binding kinetics of presynaptic nicotinic receptors. We compared the degree of fade induced by mivacurium, cisatracurium, and d-tubocurarine in the cat muscular compound action potential (mCAP). In 21 cats, mCAPs of the gastrocnemius muscle were evoked by paired (conditioning and test stimuli) and 2 Hz train-of-four (TOF) sciatic nerve stimulation. The interval between the paired stimuli was changed stepwise from 7 to 1000 ms. The ratios of the amplitude evoked by test stimulus to that evoked by the conditioning stimulus (M2/M1 ratios) and TOF ratios were measured. After baseline variables had been obtained, the cat received either mivacurium (0.08 mg x kg(-1), n = 7), cisatracurium (0.05 mg x kg(-1), n = 7), or d-tubocurarine (0.5 mg x kg(-1), n = 7). A series of M2/M1 ratios and TOF ratios were measured at various levels of partial block during recovery. At 10% of baseline amplitude, all agents significantly depressed the M2/M1 ratios (i.e., fade) at relatively longer intervals of paired stimuli (mivacurium, > or = 100 ms; cisatracurium. > or = 40 ms; and d-tubocurarine, > or = 20 ms), when compared with baseline. The order of activity to produce fade was mivacurium < cisatracurium < d-tubocurarine. A similar result was obtained in TOF ratios measured at various levels of neuromuscular block. Our results suggest that mivacurium shows a lesser degree of fade during partial neuromuscular block than cisatracurium and d-tubocurarine.


Influence of basil (Ocimum basilicum Lamiaceae) addition on functional, technological and sensorial characteristics of fresh cheeses made with organic buffalo milk.
The inclusion of basil in the development of fresh cheeses made with organic buffalo milk was studied. The treatments were: 0 (without basil), 2.5, 5.0 and 7.5 g dried basil/kg of cheese. The cheeses were stored under refrigeration at 4 ± 1 °C during 21 days. The addition of basil did not modify fat, protein, moisture and mineral content of cheeses. The total polyphenol content and antioxidant activity of cheeses increased with basil addition at day one, with a significant reduction in cheeses with 21 days of storage. Cheeses with basil presented higher antioxidant activity and lower pH. The inclusion of basil changed hardness and chewiness, but not influenced springiness and cohesiveness. The microstructure was less homogeneous in cheeses with basil. Cheese with 2.5 and 5.0 g dried basil/kg cheese were preferred by consumers. Thus, the basil improves functional and modify technological characteristics of fresh cheeses and presented good acceptability.


Toll signal pathway activating eicosanoid biosynthesis shares its conserved upstream recognition components in a lepidopteran Spodoptera exigua upon infection by Metarhizium rileyi, an entomopathogenic fungus.
Eicosanoids play crucial roles in mediating immune responses in insects. Upon a fungal infection, Toll signal pathway can mediate immune responses of Spodoptera exigua, a lepidopteran insect, by activating eicosanoid biosynthesis. However, upstream signal components of the Toll signal pathway activating eicosanoid biosynthesis remain unclear. This study predicted pattern recognition receptors (PRRs) and serine proteases (SPs) as upstream components of the Toll pathway with reference to known signal components of Manduca sexta, another lepidopteran insect. S. exigua infected with Metarhizium rileyi, an entomopathogenic fungus, activated phospholipase A2 (PLA2) and phenoloxidase (PO) enzymes along with marked increases of expression levels of genes encoding three specific antimicrobial peptides, cecropin, gallerimycin, and hemolin. Among ten Toll receptors encoded in the genome of S. exigua, seven Toll genes were associated with immune responses against fungal infection by M. rileyi through individual RNA interference (RNAi) screening. In addition, two Spätzles (ligands of Toll receptor) were required for Toll signaling against the fungal infection. All predicted upstream components of the Toll pathway were inducible by the fungal infection. Individual RNAi screening showed that three PRRs (βGRP-1, βGRP-2, and GNBP3) and five SPs (ModSP, HP21, HP5, HP6, and HP8) were required for immune responses of S. exigua mediated by Toll signal pathway against the fungal infection. However, two PO-activating proteases (PAP1 and PAP3) were not required for PLA2 activation, although they were required for PO activation. These results suggest that PRRs and SPs conserved as upstream components in Toll signal pathway play crucial roles in triggering eicosanoid biosynthesis of S. exigua to mediate various immune responses against fungal infection.


Phosphopyridoxal complexes with histamine and histidine. (2) The influence of presumed complex on histidine decarboxylase activity in rat gastric mucosa.
It was found that in vitro, histidine and histamine form a complex compound with pyridoxal-5'-phosphate (PLP). The purpose of the present experiments was to find whether formation of this complex can influence histidine decarboxylase activity. It was found that excess PLP inhibits rat's gastric mucosa histidine decarboxylase activity in vitro. The inhibitory action of PLP depends on the histidine concentration and is independent on the amount of crude enzyme preparation. The histidine-PLP complex did not influence enzyme activity. The possible mechanisms of the inhibitory action of PLP on histidine decarboxylase activity are discussed.


Are We Ready for Clinical Therapy based on Cerebral Autoregulation? A Pro-con Debate.
Cerebral autoregulation (CA) is a physiological mechanism that maintains constant cerebral blood flow regardless of changes in cerebral perfusion pressure and prevents brain damage caused by hypoperfusion or hyperperfusion. In recent decades, researchers have investigated the range of systemic blood pressures and clinical management strategies over which cerebral vasculature modifies intracranial hemodynamics to maintain cerebral perfusion. However, proposed clinical interventions to optimize autoregulation status have not demonstrated clear clinical benefit. As future trials are designed, it is crucial to comprehend the underlying cause of our inability to produce robust clinical evidence supporting the concept of CA-targeted management. This article examines the technological advances in monitoring techniques and the accuracy of continuous assessment of autoregulation techniques used in intraoperative and intensive care settings today. It also examines how increasing knowledge of CA from recent clinical trials contributes to a greater understanding of secondary brain injury in many disease processes, despite the fact that the lack of robust evidence influencing outcomes has prevented the translation of CA-guided algorithms into clinical practice.


[Evaluation of therapeutic success by patients with anxiety disorders after inpatient psychotherapy].
To identify factors influencing the subjective assessment of patients regarding the outcome of in-patient psychotherapy for anxiety disorders. A total of 231 patients were tested at admission, discharge and 1-year follow-up in a multi-center study. Subjective outcome assessment was measured with the revised German version of the Helping Alliance Questionnaire. The use of the term "outcome satisfaction" is discussed. Patient outcome assessment did not correlate with age, sex, or education, or with duration or severity of illness or duration of treatment. Outcome assessment was closely connected with therapy success. Reaching a low symptom level ("clinical significance") had a higher impact than a high pre-post-difference ("statistical significance"). Anxiety patients give a generally positive assessment of their therapy outcome, which is most determined by symptom-related treatment success. The differentiation of "clinical" and "statistical significance" of success is of importance for the patient's subjective view of the therapy outcome.


Beta-glucuronidase activity in dried blood spots: Reduced technique with biochemical parameters determined.
Mucopolysaccharidoses (MPS) occur due to deficiency in the activity of enzymes that catalyze the breakdown of glycosaminoglycans. MPS VII is caused by deficiency of the beta-glucuronidase enzyme (GUSB). This study aimed to enhance the technique to measure GUSB activity by reducing the amount of reagents and the size of the DBS, as well as to determine some biochemical parameters of enzyme of healthy individuals. The measurement of GUSB in 3 and 1.2mm DBS (with reagents reduced 2.5- and fourfold) was correlated and the precision of the technique was tested. Optimal pH, Km and Vmax, and thermostability parameters were determined and time and temperature of sample storage were established. The correlations among the techniques were significant. Although the correlation coefficient was similar, fourfold reduction was selected. pH4.4 had the highest enzyme activity. GUSB's Km was 1.25mM, while Vmax was 594.48nmol/h/mL. After pre-incubation of the sample at 60°C, its activity dropped from 100% to 15.8% at 120min. GUSB activity significantly decreased after 45days of storage at 4, 25, and 37°C. This research allowed a previously described technique for MPS VII diagnosis to be adapted for smaller amounts of sample and reagents. That will facilitate the use of smaller amounts of samples, which may be used for other techniques and to save material. Given the importance of early MPS VII diagnosis due to the severity of the disease, using reliable diagnostic techniques in DBS is essential.


Limonoids from the fruits of Melia azedarach and their cytotoxic activities.
Thirty-one limonoids and one tirucallane-type triterpenoid were isolated from the fruits of Melia azedarach (Meliaceae). The structures of 14 of these isolated compounds were elucidated on the basis of spectroscopic analyses and comparison with literature. All of these compounds were evaluated for their cytotoxic activities against HL60, A549, AZ521, and SK-BR-3 human cancer cell lines. Meliarachin C (IC50 0.65 μM) and 3-O-deacetyl-4'-demethyl-28-oxosalannin (IC50 2.8 μM) exhibited potent cytotoxic activity against HL60 cells, and this was demonstrated mainly due to the induction of apoptosis by flow cytometry. Western blot analysis suggested that both compounds induced apoptosis via both the mitochondrial and death receptor-mediated pathways. In addition, 25 compounds were evaluated for their inhibitory effects against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells.