Insulin resistance as a predictor for restenosis after coronary stenting.
The rationale of this study was to determine whether insulin resistance is an independent risk factor for restenosis after coronary stenting. Previous studies suggested that hyperinsulinemia may be an important risk factor for ischemic heart disease. Restenosis after coronary stenting is neointimal tissue proliferation and de-novo stenosis is atherosclerosis from the point of view of histology. However, it has not been determined whether insulin resistance is independently related to restenosis after coronary stenting. Clinical variables of unselected population of 110 patients were analyzed in multivariate logistic regression analyses for both restenosis and de-novo stenosis. Clinical, lesion-related, and procedural variables were analyzed by chi-square analysis, and relative risk. Multivariate logistic regression analysis showed that homeostasis model assessment insulin resistance (HOMA-IR) and HbA1c were associated with restenosis after coronary stenting (HOMA-IR; P=0.0447, HbA1c; P=0.0462), and HbA1c and low-density lipoprotein cholesterol (LDL-C) were associated with de-novo stenosis (HbA1c; P=0.0201, LDL-C; P=0.0204). Restenosis was influenced by insulin resistance [Relative Risk (RR) 2.06; 95 percent confidence interval (95%CI) 1.20 to 3.56], diabetes mellitus (DM: RR 1.92; 95%CI 1.25 to 2.95), and final minimal lumen diameter (RR 2.83; 95%CI 1.32 to 6.06). HOMA-IR and DM are the predictors of restenosis after coronary stenting, and HbA1c and LDL-C are the predictors of de-novo stenosis. These results may be reflected in histological differences between neointimal tissue proliferation as restenosis and atherosclerosis as de-novo stenosis.


The undescended testis: management after puberty.
The patient seen after puberty with an intra-abdominal unilateral undescended testis should have orchiectomy. The patient seen after puberty and before the age of 50 years with unilateral undescended testis in the inguinal region should have orchiectomy because the risk of death from malignancy exceeds the risk of anesthesia and orchiectomy.


The treatment of acute non-lymphocytic leukemia.
The treatment of acute nonlymphocytic leukemia involves a two stage approach. During the first stage, remission induction, cytotoxic drugs are administered to return hematopoiesis to normal. During the second stage, therapy is administered in an attempt to prolong the duration of remission. The clinical approaches and the problems incurred during these stages are not identical. At the time of diagnosis a decision must be made regarding whether or not the patient is likely to benefit from chemotherapy. If the answer is in the affirmative, then a decision must be made regarding the appropriate chemotherapeutic regimen. The optimal approach for the treatment of patients appears to vary depending on the age of the patient and whether or not there is a history of toxic exposure in the past. Overall remission rates vary from 40% to 85% depending upon the age of the patient and the patient's past history. Patients whose leukemia is induced into complete remission benefit from therapy administered after complete remission is attained. The optimal therapy, however, has not as yet been clearly defined. Conventional maintenance therapy appears to provide little benefit. On the other hand, the more intensive therapies are associated with substantial risk to the patient. The role of these modalities in the treatment of older patients is currently under investigation.


Cellular localization of GM1-ganglioside with biotinylated choleragen and avidin peroxidase in primary cultured cells from rat brain.
A new technique capable of demonstrating the presence and cellular localization of the ganglioside GM1 in primary cultured cells from the brains of newborn rats is described. The method is based on the highly specific binding of biotinylated choleragen to ganglioside GM1, and takes advantage of the high affinity of avidin for biotin. Thus, the biotinylated choleragen-ganglioside GM1 complex can be visualized by the use of avidin peroxidase. The results of this nonimmunologic method indicate that the concentration of ganglioside GM1 is much lower in culture astroglial cells than in neurons and oligodendroglial cells.


Nigella sativa oil extract: A natural novel specific conjugal transfer inhibitor of vancomycin resistance from vanA/B-resistant Enterococcus faecium to Staphylococcus aureus.
The emergence of vancomycin-resistant Staphylococcus aureus (VRSA) has been identified as one of the most challenging problems in healthcare settings worldwide. Specific conjugation inhibitors' development is critical in the fight against the spread of emerging VRSA. The impact of Nigella sativa oil on VR genes conjugal transfer from Enterococcus faecium (VREtfm) to vancomycin-sensitive S. aureus (VSSA) was investigated in this study. Enterococciwere isolated from retail broilers, fish, cows' milk, and human urine. VR E. faecalis and VREtfm VanA phenotypes were prevalent in retail broiler samples. The VREtfm isolates were dominant, exhibiting high levels of resistance to gentamycin and ciprofloxacin antibiotics, as well as the existence of both vanA and vanB genes and virulence traits (ESP+ , asa1+ ) as determined by PCR. Transconjugant VREtfm strains containing vanA/vabB and 20 kb plasmids (transfer frequency around 103 ) and carrying the Tn1546 transposon were identified. Tn1546 transposon transfer with its VR markers to VSSA was effectively inhibited in treated VREtfm donor strains with a sub-minimum inhibitory concentration of N. sativa oil. This work offers new insights for overcoming VR conjugal transfer utilizing natural N. sativa oil, as well as a suggestion for a novel specialized conjugation inhibitor that could effectively facilitate the difficulty of eliminating VR bacteria from healthcare settings.


Functional role, mechanisms of regulation, and therapeutic potential of regulator of G protein signaling 2 in the heart.
G protein-mediated signal transduction is essential for the regulation of cardiovascular function, including heart rate, growth, contraction, and vascular tone. Regulators of G protein Signaling (RGS proteins) fine-tune G protein-coupled receptor-induced signaling by regulating its magnitude and duration through direct interaction with the α subunits of heterotrimeric G proteins. Changes in the RGS protein expression and/or function in the heart often lead to pathophysiological changes and are associated with cardiac disease in animals and humans, including hypertrophy, fibrosis development, heart failure, and arrhythmias. This article focuses on Regulator of G protein Signaling 2 (RGS2), which is widely expressed in many tissues and is highly regulated in its expression and function. Most information to date has been obtained in biochemical, cellular, and animal studies, but data from humans is emerging. We review recent advances on the functional role of cardiovascular RGS2 and the mechanisms that determine its signaling selectivity, expression, and functionality. We highlight key unanswered questions and discuss the potential of RGS2 as a therapeutic target.


X-linked adrenoleukodystrophy caused by a novel mutation presenting with various phenotypes in a Taiwanese family.
X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder that primarily affects the white matter of central nervous system and the adrenal cortex. It is caused by mutations in the adenosine triphosphate-binding cassette, subfamily D, member 1 (ABCD1) gene that results in elevated plasma levels of very long chain fatty acids (VLCFAs). The disease is characterized by an unpredictable variation in phenotypic expressions, including childhood cerebral form (CCALD) and adrenomyeloneuropathy (AMN). Genetic analysis is a reliable method for the diagnosis of X-ALD. We reported a 46-year-old male admitted to Department of Neurology, Chang Gung Memorial Hospital with progressive paraparesis and Addison's disease, which was diagnosed when he was around 20-year-old. Plasma levels of VLCFA showed that his C26:0, C24:0/C22:0 and C26:0/C22:0 ratios were significantly elevated. A novel missense mutation (p.Arg163Cys) caused by the nucleotide change c.487C > T in exon 1 was identified in the ABCD1 gene of the proband and his subclinical family members. In this article, we reviewed the mutations that had been reported at the same position with different phenotypes. Given that the nerve conduction study (NCS) of the proband demonstrated a rare finding of demyelinating polyneuropathy with conduction blocks, we also reviewed the findings of NCS in patients with AMN in literature.


The effect of ligand on the kinetics of the sulfhydryl groups of human hemoglobin with p-mercuribenzoate.
The rate of reaction of PMB with the masked sulfhydryls of human hemoglobin derivatives correlates well with the extent of dissociation for various ligands. It is suggested that the alpha1beta2 dimer of hemoglobin participates in the slow step of the reaction with PMB.


Benzimidazoles and isosteric compounds as potent and selective factor Xa inhibitors.
Benzimidazoles and their isosteric compounds as factor Xa inhibitors are discussed.


Oral dyclonine hydrochloride mucilage versus tetracaine spray in electronic flexible laryngoscopy: A prospective, randomized controlled trial.
Topical anesthesia is important for electronic flexible laryngoscopy (EFL) utilization. We hypothesized that oral dyclonine hydrochloride mucilage (ODHM) is superior to tetracaine spray (TS) in patients undergoing EFL examination. This study included 932 patients randomized into either an ODHM or TS group, in which patients received either a single utilization of ODHM or TS administered via spray in three intervals. A 4.9 mm diameter flexible PENTAX-VNL-1570STK insertion tube placed into a Naso-Pharyngo-Laryngoscope (PENTAX Medical, Japan) was used in the procedure. Visual analogue scale (VAS) (0-10) was used to evaluate patient tolerance and procedure success by the operator, independently. Procedure time was also recorded. Both patients' and doctors' VAS scores were significantly higher in the ODHM group compared to the TS group. When subgroup analysis was made according to the procedure length (100 s), there was no significant difference in VAS between ODHM and TS groups in the short time procedure (≤100 s), while VAS in the ODHM group was higher compared to the TS in the long time procedure (>100 s), as assessed by both patients and doctors. A single use of ODHM seems to be superior to three doses of TS in patients undergoing EFL, specifically in procedures longer than 100seconds.


Treatment of bilateral choanal atresia in the premature infant.
An innovative technique for choanal atresia repair was used for a unique case of bilateral choanal atresia in a 28-week premature newborn. Endoscopic transnasal KTP laser was employed as an alternative to standard instrumentation to reach the very small atretic plate of a premature nose, providing good visualization of the operative field, thereby avoiding damage to the adjacent structures. The successful repair allowed for early extubation and avoidance of a tracheotomy. The clinical and surgical aspects of the case are discussed. With the likelihood of encountering more premature infants with choanal atresia given the improving neonatal intensive care, we propose that KTP laser repair be considered as an alternative to conventional procedures for this particular population.


Serum gamma-glutamyltransferase, oxidized LDL and mortality in the elderly.
Serum gamma-glutamyltransferase (GGT) is a liver enzyme involved in the metabolism of glutathione (GSH), a major antioxidant in humans. GGT is a risk factor for mortality in young and middle-aged individuals but this association has been poorly investigated in the elderly. We studied the relationship between GGT and all-cause mortality and tested whether oxidized low-density lipoproteins (oxLDL) modify this association in a cohort of 1038 elderly individuals. During the observation time (median 9 years), 401 individuals died. In a Cox regression model adjusting for potential confounders, GGT was an independent risk factor for all-cause mortality [HR (20U/L increase in serum GGT): 1.11, 95% CI 1.02-1.21, P = 0.02]. Furthermore, increasing levels of oxLDL amplified the risk excess for all-cause mortality associated with GGT (P for the effect modification = 0.003). In the elderly, serum GGT is an independent risk factor for all-cause mortality and circulating oxLDL amplify the magnitude of this association.


Identification of a feline coronavirus type I strain from a cat with feline infectious peritonitis by RT-pCR and phylogenetic analysis.
A case of feline infectious peritonitis (FIP) in an 11-month-old European shorthair cat is reported. The infected cat displayed loss of weight, respiratory distress, ascitis, anemia and died within 15 days after the first appearance of clinical signs. Lesions typical of a mixed form (effusive and non-effusive) of FIP were observed and by RT-PCR a feline coronavirus (FCoV) type I strain was detected in several tissues. The RT-PCR results were confirmed by sequence analysis of the amplified products. Phylogeny carried out on fragments of the M and S genes showed that the FCoV strain segregates with typical type I FCoVs.


Nonneoplastic lesions of the ovary in Fischer 344 rats and B6C3F1 mice.
The National Toxicology Program's pathology database on 2-year carcinogenicity studies was reviewed for nonneoplastic ovarian disease. Ovaries from 39,941 female Fischer rats and 41,444 female B6C3F1 mice were examined. A variety of inflammatory, degenerative, vascular, and proliferative lesions were documented and are described. The most common ovarian lesions in rats were cysts (6%). The most frequent ovarian lesions in mice were cysts (15%), acute inflammation (4%), degeneration (4%), vascular disease (2.5%), and atrophy (2%). There was no difference in incidence of ovarian disease between controls and treated animals. The frequency of ovarian disease in mice exceeded the frequency in rats in every category.


A Read/Write Mechanism Connects p300 Bromodomain Function to H2A.Z Acetylation.
Acetylation of the histone variant H2A.Z (H2A.Zac) occurs at active regulatory regions associated with gene expression. Although the Tip60 complex is proposed to acetylate H2A.Z, functional studies suggest additional enzymes are involved. Here, we show that p300 acetylates H2A.Z at multiple lysines. In contrast, we found that although Tip60 does not efficiently acetylate H2A.Z in vitro, genetic inhibition of Tip60 reduces H2A.Zac in cells. Importantly, we found that interaction between the p300-bromodomain and H4 acetylation (H4ac) enhances p300-driven H2A.Zac. Indeed, H2A.Zac and H4ac show high genomic overlap, especially at active promoters. We also reveal unique chromatin features and transcriptional states at enhancers correlating with co-occurrence or exclusivity of H4ac and H2A.Zac. We propose that differential H4 and H2A.Z acetylation signatures can also define the enhancer state. In conclusion, we show both Tip60 and p300 contribute to H2A.Zac and reveal molecular mechanisms of writer/reader crosstalk between H2A.Z and H4 acetylation through p300.


The application of color Doppler technology to the study of fetal swallowing.
To investigate the mechanics of fetal swallowing using color Doppler technology. The fetal face and a profile were imaged sagitally in ten fetuses at 36-41 weeks' gestation. Color-flow Doppler signals were superimposed on each gray-scale image to assess the direction and location of amniotic fluid (AF) flow with respect to anatomic structures of the fetal upper gastrointestinal and respiratory tracts during the act of swallowing. Further analysis of fetal swallowing movements was performed by a review of the ultrasonography videotapes at a slow speed. An initial stage of fetal swallowing was characterized by two to six sucking movements and the introduction of an AF bolus into the oral cavity. The soft palate superiorly and the tongue posteriorly and inferiorly obstructed the further flow of AF. The final stage of swallowing was characterized by low-frequency tongue movements, upward laryngeal and epiglottic movements, and narrowing of the lumen of the pharynx, directing the fluid bolus caudally. However, some AF was directed into the nasopharynx as well as the trachea. The swallowing pattern in the term fetus differs from that in the infant and adult, in that the oral and pharyngeal phases appear to be less completely developed.


Oberndorfer and his successors: from carcinoid to neuroendocrine carcinoma.
The year 2007 the centenary of Siegfried Oberndorfer's seminal description of special tumors of the small intestine which he called "Karzinoide Tumoren" (carcinoids). Their endocrine nature was suggested by Pierre Masson in 1914. The work of Friedrich Feyrter and later Anthony Pearse established the concept of a diffuse endocrine cell system. They suggested that there is a family of endocrine cells whose members originate at different sites in the organism and give rise to similar tumors, the carcinoids. Subsequent studies revealed that the individual members of the endocrine cell system are distinguished from each other by the expression of specific polypeptides (i.e., hormones). Common to all of these cells is the expression of general markers such as synaptophysin and chromogranin A. This led to the term neuroendocrine cell system and consequently neuroendocrine tumor. Although many tumors are similar in histological appearance, biologically they show heterogeneity, which has important implications for treatment. Therefore, efforts have been made to define the neuroendocrine neoplasms on the basis of features that discriminate the tumors with almost no risk/low risk of malignancy from low-grade and high-grade malignant tumors. For the gastroenteropancreatic neuroendocrine tumors, this resulted in a new World Health Organization classification that was recently followed by a tumor-nodes-metastasis classification.


Clinical study of modified Ivor-Lewis esophagectomy plus adjuvant radiotherapy for local control of stage IIA squamous cell carcinoma in the mid-thoracic esophagus.
To control the postoperative local recurrence is one of the critical factors to improve prognosis of patients with esophageal carcinoma. The aim of this study is to evaluate the effectiveness of modified Ivor-Lewis esophagectomy plus adjuvant radiotherapy for local control of stage IIA squamous cell carcinoma in the mid-thoracic esophagus. One hundred and twenty-five patients with stage IIA mid-thoracic esophageal squamous cell carcinoma who underwent modified Ivor-Lewis esophagectomy between June 1999 and June 2002 were included in the retrospective analysis. All the patients were evaluated within 3 years after surgery to detect tumor recurrence. Kaplan-Meier method was used to calculate the survival rate and logistic regression analysis was performed to identify risk factors of locoregional recurrence. The overall 3-year and 5-year survival rate in all patients was 58.4% and 43.2%, respectively. Tumor recurrence occurred in 61 patients (48.8%) within 3 years after operation. The median disease-free interval was 12.6 months. Thirty-three patients (26.4%) developed locoregional recurrence, 23 patients (18.4%) developed distant recurrence and 5 patients (4.0%) developed locoregional and distant recurrence simultaneously. Locoregional recurrence rate of patients with postoperative radiotherapy was significantly lower than that of those without postoperative radiotherapy (p<0.05). Logistic regression analysis showed that adjuvant radiotherapy (p=0.007) was an independent risk factor for tumor locoregional recurrence. Cox regression analysis showed that locoregional recurrence but not adjuvant radiotherapy was a relevant prognostic factor of patients with stage IIA esophageal cancer. Modified Ivor-Lewis esophagectomy with two-field lymph node dissection plus adjuvant radiotherapy might be an effective strategy to achieve local control of stage IIA mid-thoracic esophageal squamous cell carcinoma.


Is there a clinical need for a diagnostic test allowing detection of chain type-specific anti-A and anti-B?
Hemagglutination for detection and semiquantification of ABO antibodies is associated with large center-to-center variations and poor reproducibility. Because acceptance for transplantation and diagnosis of rejection in ABO-incompatible transplantation rely on the levels and specificity of ABO antibodies, reproducible tests that allow their detection and specificity determination are required. The level of chain type-specific anti-A and anti-B were analyzed in the sera of 44 healthy individuals of known ABO blood group using an enzyme-linked immunosorbent assay (ELISA) with polyacrylamide (PAA) conjugates of blood group A and B trisaccharides or Type 2 chain A and B tetrasaccharides. Selected sera were further analyzed by hemagglutination and in an ELISA with Types 1 to 4 chain A or B neoglycolipids (NGL) as antigens. Immunoglobulin (Ig)G anti-A and anti-B levels were higher (p ≤ 0.05) in blood group O than in B and A individuals. More IgM anti-A and anti-B cross-reactivity was detected in AB serum on PAA-conjugated A and B trisaccharides than on the tetrasaccharides. One of 11 blood group B and two of 12 A individuals had IgG antibodies binding the tetrasaccharide despite lack of, or very low reactivity with, the trisaccharides. IgG antibodies preferring the A and B Type 2 tetrasaccharides were of the IgG2 subclass. The NGL ELISA further supported the presence of chain type-specific anti-A and -B antibodies among nonsensitized, healthy individuals. An ELISA with structurally defined ABH antigens will allow the antibody class and fine specificity of ABO antibodies to be determined, which may improve risk assessment in ABO-incompatible transplantation.


Laparoscopic repair of vesicouterine fistula.
Vesicouterine fistulae are the least common type of urogenital fistulae found in women and are often the result of inadvertent bladder injury at the time of cesarean delivery. Few case reports exist on the management and repair of these fistulae. A 41-year-old woman with a history of three cesarean deliveries with persistent urinary incontinence who underwent laparoscopic repair of a vesicouterine fistula. Whereas in the past, these fistulae were predominantly repaired via a transvaginal or abdominal approach, vesicouterine fistulae can be successfully repaired endoscopically.


Genomic analysis of cultivated barley (Hordeum vulgare) using sequence-tagged molecular markers. Estimates of divergence based on RFLP and PCR markers derived from stress-responsive genes, and simple-sequence repeats (SSRs).
Three types of molecular markers have been compared for their utility in evaluating genetic diversity among cultivars of Hordeum vulgare. Restriction fragment length polymorphisms at 71 sites were scored with the aid of probes corresponding to stress-responsive genes from barley and wheat, coding for a low-molecular-weight heat shock protein, a dehydrin, an aldose reductase homolog, and a 18.9-kDa drought-induced protein of unknown function. Indexes of genetic diversity computed in the total sample and within groups of cultivars (two-rowed and six-rowed, winter and spring varieties) indicated high values of genetic differentiation ( F (ST) >15%). A second assessment of genetic diversity was performed by PCR amplification of genomic DNA using as primers 13 arbitrary oligonucleotides derived from sequences of the same stress-responsive genes. A high degree of polymorphism was uncovered using these markers also, but they yielded low values for F (ST) (<7%) among groups of cultivars. Finally, 15 different simple-sequence repeats (AC or AG) were amplified with primers based on unique flanking sequences. Levels of polymorphism and differentiation between groups of cultivars revealed by these markers were quite high. Ordination techniques applied to measures of genetic distance among cultivars demonstrated a remarkable ability of the RFLPs associated with stress-responsive genes to discriminate on the basis of growth habit. The correlation with production data for the cultivars in different environments was also significant. This "functional genomics" strategy was therefore as informative as the "structural genomics" (SSR-based) approach, but requires the analysis of fewer probes.


Risk factors associated with household transmission of SARS-CoV-2 in Negeri Sembilan, Malaysia.
Households are a significant venue for the transmission of SARS-CoV-2. We conducted a study to characterise the transmission dynamics and identify risk factors for household transmission of SARS-CoV-2 in Negeri Sembilan, Malaysia. This retrospective observational study included 185 families of paediatric COVID-19 cases from 1 February 2020 to 31 December 2020. We identified the index case for each household and gathered the socio-demographic, epidemiological investigation results and risk factors for household transmission from medical case records. The secondary attack rate was calculated, and logistic regression analyses were used to identify risk factors associated with secondary household transmission of SARS-CoV-2. Of the 848 household contacts, 466 acquired secondary infections, resulting in a secondary attack rate of 55%. The median age of the secondary cases was 12 years. Female household contacts and household contacts who slept in the same room with the index case were significantly associated with increased risk for COVID-19. Other independent risk factors associated with higher transmission risk in the household included an index case who was symptomatic, a household index case aged greater than 18 years and a male household index case. High rates of household transmission of COVID-19 were found, indicating households were a major setting of transmission of SARS-CoV-2. Our data provide insight into the risk factors for household transmission of SARS-CoV-2 in Malaysia.


Panhypopituitarism diagnosed in adulthood: Imaging findings of bone and other organs.
A 38-year-old man who was delivered in a breech position presented with delayed development of secondary sexual characteristics and malaise. He was diagnosed with panhypopituitarism caused by interruption of the pituitary stalk due to perinatal complications. Brain magnetic resonance imaging findings for pituitary stalk interruption syndrome are well-documented; however, reports of the imaging findings of the bones and several organs related to the effects of panhypopituitarism are limited. In this patient with anterior pituitary dysfunction, imaging revealed diverse sequelae, including delayed skeletal maturation, osteopenia, genital atrophy, fatty liver, and adrenal atrophy. Radiologists may find it difficult to discern complex imaging findings unless they are informed of the clinical course of the patient. Therefore, radiologists should coordinate with clinicians to arrive at a diagnosis.


Real-time guidance of thermal and ultrashort pulsed laser ablation in hard tissue using inline coherent imaging.
During tissue ablation, laser light can be delivered with high precision in the transverse dimensions but final incision depth can be difficult to control. We monitor incision depth as it progresses, providing feedback to ensure that material removal occurs within a localized target volume, reducing the possibility of undesirable damage to tissues below the incision. Ex vivo cortical and cancellous bone was ablated using pulsed lasers with center wavelengths of 1,064 and 1,070 nm, while being imaged in real-time using inline coherent imaging (ICI) at rates of up to 300 kHz and axial resolution of ∼6 µm. With real-time feedback, laser exposure was terminated before perforating into natural inclusions of the cancellous bone and verified by brightfield microscopy of the crater cross-sections accessed via side-polishing. ICI provides direct information about incision penetration even in the presence of intense backscatter from the pulsed laser and plasma emissions. In this study, ICI is able to anticipate structures 176 ± 8 µm below the ablation front with signal intensity 9 ± 2 dB above the noise floor. As a result, the operator is able to terminate exposure of the laser sparing a 50 µm thick layer of bone between the bottom of the incision to a natural inclusion in the cancellous bone. Versatility of the ICI system was demonstrated over a wide range of light-tissue interactions from thermal regime to direct solid-plasma transition. ICI can be used as non-contact real-time feedback to monitor the depth of an incision created by laser ablation, especially in heterogeneous tissue where ablation rate is less predictable. Furthermore, ICI can image below the ablation front making it possible to stop laser exposure to limit unintentional damage to subsurface structures such as blood vessels or nervous tissue.


[Effect of merocianina-540 in the fertilizing capacity of sperm correlated with the expression of 3-OH terminal fragments].
The packaging of heterochromatin during spermatogenesis has been correlated with the expression of residual apoptotic bodies (which stain with merocyanine A) that will impact on sperm function in the fertilization process; as well as the joint expression of the transmembrane translocation phosphatidyl serine and oligonucleosomes. To evaluate the expression of bodies stained with merocyanine in the functional processes of sperm and their level of agreement with apoptotic Annexin V and TUNEL biomarkers. We performed a prospective, cross, including 11,000 cells belonging to semen samples from infertile men, were evaluated according to WHO criteria (1999), bounded by the lines of Tygerberg. The biomolecular transformation processing of the membrane and the expression of oligonucleosomes in the terminal cascade of apoptosis were quantified by cytometry flow, using an argon lasser as a reading source of 480 nm, discriminating the degree of cellularity, both negative and positive for each indicators. Because of the study design was found low quantification in semen parameters, motility, morphology and sperm concentration. The average expression of cells [DNA-PI(+) / dUTP-FITC(+)] (quantification of TUNEL) and [Annexin-V(+) / PI(-)] was 36.5 +/- 17.4% and 31.2 +/- 17.4%, respectively. By comparing the expression of TUNEL without the effect of M540 bodies (36.3 +/- 1.7% vs. 36 +/- 1.7%) a significant difference was not determined. This study shows that there is a remnant of the primary processes of spermiation, which can take an important role in apoptotic and functional processes of the sperm. However, its expression does not affect measurement of biomarkers of apoptosis seminal, whose determination changed the diagnosis and functional perception of reproductive parameters in the sperm.


Single, high-dose local injection of bFGF improves thyroarytenoid muscle atrophy after paralysis.
Unilateral vocal fold paralysis (UVFP) induces hoarseness due to progressive atrophy of the denervated thyroarytenoid (TA) muscle. Therefore, treatments aimed at regenerating the atrophied TA muscle are required. Basic fibroblast growth factor (bFGF) is involved in muscle development and regeneration. This study aimed to elucidate the effects of bFGF injection on atrophied TA muscle. Animal research. A recurrent laryngeal nerve-paralysis rat model was established, and low- (200 ng) or high-dose (2,000 ng) bFGF or saline (control) was injected into the TA muscle 28 days later. The larynges were excised on day 1, 3, 7, 14, and 28 after treatment. The cross-sectional area of the TA muscle in normal and paralyzed sides was compared, and the Ki67-positive (Ki67+ ) dividing cells, paired box 7-positive (Pax7+ ) satellite cells (SCs), and myogenic differentiation-positive (MyoD+ ) myoblasts were counted. The TA muscle area of animals administered high-dose bFGF increased with time and was significantly larger than that of the saline-injected controls 28 days after treatment (P < .05). The counts of Ki67+ and Pax7+ cells were the highest on day 1, whereas the MyoD+ myoblast count was highest on day 7. These results suggest that bFGF administration into the denervated TA muscles compensated for the atrophied TA muscles by inducing proliferation of SCs and their differentiation to myoblasts. A single injection of high-dose bFGF augmented regeneration and differentiation of the atrophied TA muscle by enhancing proliferation and differentiation of muscle SCs, suggesting its possible clinical application in humans with UVFP. NA Laryngoscope, 130:159-165, 2020.


Dynamic "inline" images: context-sensitive retrieval and integration of images into Web documents.
Integrating relevant images into web-based information resources adds value for research and education. This work sought to evaluate the feasibility of using "Web 2.0" technologies to dynamically retrieve and integrate pertinent images into a radiology web site. An online radiology reference of 1,178 textual web documents was selected as the set of target documents. The ARRS GoldMiner image search engine, which incorporated 176,386 images from 228 peer-reviewed journals, retrieved images on demand and integrated them into the documents. At least one image was retrieved in real-time for display as an "inline" image gallery for 87% of the web documents. Each thumbnail image was linked to the full-size image at its original web site. Review of 20 randomly selected Collaborative Hypertext of Radiology documents found that 69 of 72 displayed images (96%) were relevant to the target document. Users could click on the "More" link to search the image collection more comprehensively and, from there, link to the full text of the article. A gallery of relevant radiology images can be inserted easily into web pages on any web server. Indexing by concepts and keywords allows context-aware image retrieval, and searching by document title and subject metadata yields excellent results. These techniques allow web developers to incorporate easily a context-sensitive image gallery into their documents.


Antimicrobial Susceptibility of Enterotoxigenic Escherichia coli from Diarrhoeic Neonatal Calves in Spain.
Enterotoxigenic Escherichia coli (ETEC) is one of the major pathogens involved in neonatal calf diarrhoea (NCD) causing high economic losses in dairy farms. Antibiotic treatment is common in cases of systemic illness caused by NCD, but antimicrobial susceptibility tests (AST) are usually not performed. Thus, the aim of this study was to characterize the antimicrobial susceptibility of ETEC strains obtained from calves with diarrhoea between 2018-2020. Faecal samples (n = 420) were analyzed to detect the typical ETEC virulence factors F5 and STa. Positive samples were cultured to identify and isolate ETEC strains (n = 41) and ASTs were performed. Our results are alarming since ETEC strains resistant to three or more families of antimicrobials were detected in all isolates. Only four antibiotics (ceftiofur, cefoperazone, cefquinome and gentamicin) presented efficacy against more than 90% of the ETEC strains, while the other ten antibiotics were effective against less than 40% of the strains. In addition, a high number of strains were resistant to most first-line antimicrobials used in veterinary practice. For this reason, when ETEC infection is suspected, an AST must always be performed to select the most appropriate antimicrobial in each case and to avoid the emergence of new resistance mechanisms.


[Improvement of the solubility behavior of problem drugs. 9. In vitro absorption studies using melting solidification products of iomeglamic acid].
By means of the absorption apparatus according to Fürst and Neubert the solid dispersions of the iomeglamic acid were studied with regard to their in vitro absorption properties. All products showed better half lives of transport in relation to the pure compound. This was in correlation to the solubility parameters.


An assessment of hysterosalpingosonography (HSSG) as a diagnostic tool for uterine cavity defects and tubal patency.
The value of hysterosalpingosonography (HSSG) as a diagnostic tool was evaluated in 76 patients and compared to hysteroscopic, laparoscopic, and/or hysterosalpingographic (HSG) findings. Saline solution and Dextran 60 were used as distension media. Patients were divided in three groups: group A (n = 22), patients submitted for control post-tubal electrocoagulation. Group B (n = 38), patients with a history of pathological metrorrhagias, and group C (n = 16) infertile women with possible tubal pathology. Comparison between the different diagnostic techniques for the evaluation of the uterine cavity and tubes was carried out. Our results indicated that HSSG had more sensitivity but less specificity than hysteroscopy or HSG in the diagnosis of uterine cavity pathology. Hysteroscopy seems to be the best technique for the diagnosis of endometrial pathology, and HSSG seems to be the most effective in the study of the myometrium. HSSG cannot be considered a reliable and accurate method for the diagnosis of tubal patency.


Genetic variant of HTR2A associates with risk of impulse control and repetitive behaviors in Parkinson's disease.
To determine the role of a serotonin 2A receptor gene (=HTR2A) variant in the development of impulse control and repetitive behaviors in Parkinson's disease. We performed a genetic association analysis to a cohort of 404 Korean patients with Parkinson's disease who had been enrolled in a previous study. Presence of impulse control and repetitive behaviors was screened using modified version of Minnesota Impulsive Disorders Interview and genotyping for HTR2A c.102T > C was performed using the TaqMan assay. The T allele, which is presumably linked to higher receptor expression, was marginally associated with impulse control and repetitive behaviors in Parkinson's disease; the genetic influence was significantly enhanced in the lower levodopa-equivalent-dose group, increasing the risk by 2.8 and 6.9 times in CT and TT carriers, respectively (p-trend = 0.011). There was no significant interaction between the c.102T > C variant and clinical risk variables such as sex, age at onset, total daily levodopa-equivalent-dose, use of dopamine agonist and daily dose of dopamine agonist. Our data support a possible contribution of genetic variation in the HTR2A to the susceptibility to impulse control and repetitive behaviors in Parkinson's disease.


Identifying lost surgical needles using radiographic techniques.
Many surgical procedures involve the use of very small surgical needles. In the event that a postoperative needle count is incorrect, traditionally an x-ray has been taken to find the needle. Little data exist to recommend the smallest surgical needle that can be identified with conventional radiographic techniques and the optimum technique for finding lost surgical needles. In this quality assurance project x-rays of various size surgical needles were taken. The smallest seen by the majority of observers was 17 mm. The radiographic technique of choice for optimum detection of lost surgical needles was imaging with a mobile image intensifier.


Organization and regulation of the arsenite oxidase operon of the moderately acidophilic and facultative chemoautotrophic Thiomonas arsenitoxydans.
Thiomonas arsenitoxydans is an acidophilic and facultatively autotrophic bacterium that can grow by oxidizing arsenite to arsenate. A comparative genomic analysis showed that the T. arsenitoxydans aioBA cluster encoding the two subunits of arsenite oxidase is distinct from the other clusters, with two specific genes encoding a cytochrome c and a metalloregulator belonging to the ArsR/SmtB family. These genes are cotranscribed with aioBA, suggesting that these cytochromes c are involved in arsenite oxidation and that this operon is controlled by the metalloregulator. The growth of T. arsenitoxydans in the presence of thiosulfate and arsenite, or arsenate, is biphasic. Real-time PCR experiments showed that the operon is transcribed during the second growth phase in the presence of arsenite or arsenate, whereas antimonite had no effect. These results suggest that the expression of the aioBA operon of T. arsenitoxydans is regulated by the electron donor present in the medium, i.e., is induced in the presence of arsenic but is repressed by more energetic substrates. Our data indicate that the genetic organization and regulation of the aioBA operon of T. arsenitoxydans differ from those of the other arsenite oxidizers.


Inhibition of the RNA polymerase-catalyzed synthesis of RNA by marcellomycin. Preferential interference of the inhibitor with the stabilization of the ternary promoter-RNA polymerase-nascent RNA complex.
Marcellomycin is a strong inhibitor of the Escherichia coli RNA polymerase-catalyzed synthesis of RNA from the strong A promoters of bacteriophage T7 DNA. Marcellomycin inhibits preferentially the last phase of transcription initiation. During this phase a stabilized ternary complex is formed consisting of RNA polymerase, DNA template, and a nascent RNA oligonucleotide about 11 nucleotides long, resulting from the extension of the RNA dinucleotide component of the corresponding early ternary complex. Marcellomycin is also responsible for minor inhibition of the formation of the open binary RNA polymerase-template complex, which serves as the precursor of the ternary complex. These findings suggest that marcellomycin may be a potentially useful tool in the study of the late stages of transcription initiation. The present findings may also contribute to a better overall understanding of the mode of drug action at the level of individual genes.


Interneurons in the human olfactory system in Alzheimer's disease.
The principal olfactory structures display Alzheimer's disease (AD) related pathology at early stages of the disease. Consequently, olfactory deficits are among the earliest symptoms. Reliable olfactory tests for accurate clinical diagnosis are rarely made. In addition, neuropathological analysis postmortem of olfactory structures is often not made. Therefore, the relationship between the clinical features and the underlying pathology is poorly defined. Traditionally, research into Alzheimer's disease has focused on the degeneration of cortical temporal projection neurons and cholinergic neurons. Recent evidence has demonstrated the neurodegeneration of interneuron populations in AD. This review provides an updated overview of the pathological involvement of interneuron populations in the human olfactory system in Alzheimer's disease.


Peripheral tissue energy metabolism during recovery from hypothermia after cardiopulmonary bypass: effect of amino-acid infusions.
We studied the effects of amino-acid administration on the leg exchange of energy substrates and amino-acids during recovery from hypothermia after open heart surgery. Glucose (G, n = 5), glucose and conventional amino-acids (CA, n = 5) or glucose and branched chain amino-acids (BC, n = 5) were infused during recovery from hypothermia after open heart surgery. The leg exchange of energy substrates and amino-acids were measured after arrival at the intensive care unit, after rewarming, and 2h and 4h after rewarming during increasing amino-acid intake. Despite a normal stress response to surgery, reflected by increased energy expenditure and increased concentrations of insulin and catabolic hormones, amino-acids had no effect on the leg exchange of branched chain amino-acids, glutamine, alanine and energy substrates. This suggests that the transport of amino-acids and energy substrates into the cell are impaired after hypothermic cardiopulmonary bypass and intracellular substrates are utilised for the increased demand for energy during rewarming.


A design of experiments concept for the minimization of nonspecific peptide adsorption in the mass spectrometric determination of substance P and related hemokinin-1.
Substance P and hemokinin-1 were predominantly examined by immunoassays with their limitation to differentiate appropriately between both peptides. The use of liquid chromatography coupled with tandem mass spectrometry is a promising, highly selective alternative. Adsorption processes have been identified in preliminary experiments to play a crucial role in the loss of mass spectrometry intensity of both peptides. Therefore, a design of experiments concept was created to minimize nonspecific peptide adsorption. For this purpose, the most critical influencing parameters-(1) the composition of the injection solvent as well as (2) the most suitable container material-were systematically and concordantly investigated. The addition of modifiers, such as formic acid, dimethyl sulfoxide, and organic solvents, to the injection solvent led to a substantial gain of intensity of substance P and hemokinin-1 compared to the start gradient as an injection solvent. Furthermore, the systematic investigation underlined the high impact of the container material, demonstrating polypropylene as the most favorable material. A conjoint injection solvent optimum was found to determine both peptides simultaneously by the conduction of a sweet-spot analysis. The experimental design substantially reduced nonspecific peptide adsorption and enabled the simultaneous and selective determination of endogenous substance P and hemokinin-1 plasma levels.


Identification and Preliminary Characterization of a Novel Single-Stranded DNA Binding Protein of Staphylococcus aureus Phage Phi11 Expressed in Escherichia coli.
Bacteriophage Phi11 harbors a gene, gp13, encoding the putative SSB protein (GenBank accession no. NC_004615.1). SSB proteins bind to and protect the single-stranded DNA molecules from nuclease digestion and are essential for the growth and metabolic activities of the organisms encoding them. In this investigation, we have carried out the cloning, recombinant expression, and purification of rGp13 for the first time in Escherichia coli. EMSA data indicated that the purified recombinant Gp13 protein was capable of binding to single-stranded DNA. The protein exhibited maximum binding activity at 32 °C. Furthermore, our bioinformatic analysis has revealed that Gp13 consists of an OB-fold, a characteristic of SSB proteins. However, the arrangement of the OB-fold is unique, being located in the C-terminal domain of Gp13. Despite the importance of SSB proteins in various metabolic processes as well as in various types of PCR, there are no reports on the purification and characterization of SSB proteins from staphylococcal bacteriophages. We expect that the purification and characterization of recombinant Gp13 will help us gain a better insight into its biological activity and make it available in large quantities for molecular biology work.


[Simplified methods in sampling and shipping of individual sera from mice and rats for serological checking of infections (author's transl)].
The usefulness of simplified techniques in sampling of individual mouse and rat sera and their shipping in wet state for serological checking of infections were described.


Effects of omega-3 fatty acids on arterial stiffness in patients with hypertension: a randomized pilot study.
Omega-3 fatty acids prevent cardiovascular disease (CVD) events in patients with myocardial infarction or heart failure. Benefits in patients without overt CVD have not been demonstrated, though most studies did not use treatment doses (3.36 g) of omega-3 fatty acids. Arterial stiffness measured by pulse wave velocity (PWV) predicts CVD events independent of standard risk factors. However, no therapy has been shown to reduce PWV in a blood pressure-independent manner. We assessed the effects of esterified omega-3 fatty acids on PWV and serum markers of inflammation among patients with hypertension. We performed a prospective, randomized; double-blinded pilot study of omega-3 fatty acids among 62 patients in an urban, safety net hospital. Patients received 3.36 g of omega-3 fatty acids vs. matched placebo daily for 3-months. The principal outcome measure was change in brachial-ankle PWV. Serum inflammatory markers associated with CVD risk were also assessed. The majority (71 %) were of Latino ethnicity. After 3-months, mean change in arterial PWV among omega-3 and placebo groups was -97 cm/s vs. -33 cm/s respectively (p = 0.36 for difference, after multivariate adjustment for baseline age, systolic blood pressure, and serum adiponectin). Non-significant reductions in lipoprotein-associated phospholipase A2 (LpPLA2) mass and high sensitivity C-reactive protein (hsCRP) relative to placebo were also observed (p = 0.08, and 0.21, respectively). High-dose omega-3 fatty acids did not reduce arterial PWV or markers of inflammation among patients within a Latino-predominant population with hypertension. NCT00935766 , registered July 8 2009.


Segregation frequency in microcephaly.
A total of 118 cases of microcephaly were clinically evaluated under two main groups: primary microcephaly (61 cases) and secondary microcephaly (57 cases). Secondary cases were generally characterized by convulsions, spasticity, and other congenital anomalies. Estimates of segregation frequency obtained separately in primary and secondary cases indicated that the primary consanguineous cases were most probably due to a single recessive gene. The segregation frequency was substantially less in other types, indicating much lower genetic risks in these cases.


Fracture of the penis.
Sporadic reports of penile fracture give the impression of a rare trauma. The value of diagnostic investigations is doubtful and treatment options are controversial. A Medline search from January 1966 to July 2001 using the terms 'fracture of penis', 'penile trauma' and 'coital injuries' was used to identify full texts of publications on fracture of the penis. Full texts of relevant references from these publications were also identified. Data extracted for review included authors, country and year of publication, number of cases in each report, aetiology, clinical features, investigations, treatment and outcome. In 183 publications 1331 cases were reported between January 1935 and July 2001. Most reports were from the Mediterranean region. The commonest causes were coitus and penile manipulations, especially masturbation. Most patients were in their fourth decade. Clinical features included sudden penile pain, detumescence, voiding difficulties, and penile swelling and deviation. Diagnosis was made mainly on clinical grounds. Associated injuries included urethral rupture. Predisposing factors included excessive force at coitus or manipulation, fibrosclerosis of the tunica albuginea and chronic urethritis. Most authors advocated early surgical repair using absorbable sutures. Complications of the injury included coital difficulty, urethral fistula, penile plaque and erectile dysfunction. Penile fracture is not rare. Radiological investigations are expensive and may delay treatment. Current management favours early surgical exploration to prevent complications.


Directed evolution of transketolase substrate specificity towards an aliphatic aldehyde.
Mutants of transketolase (TK) with improved substrate specificity towards the non-natural aliphatic aldehyde substrate propionaldehyde have been obtained by directed evolution. We used the same active-site targeted saturation mutagenesis libraries from which we previously identified mutants with improved activity towards glycolaldehyde, which is C2-hydroxylated like all natural TK substrates. Comparison of the new mutants to those obtained previously reveals distinctly different subsets of enzyme active-site mutations with either improved overall enzyme activity, or improved specificity towards either the C2-hydroxylated or non-natural aliphatic aldehyde substrate. While mutation of phylogenetically variant residues was found previously to yield improved enzyme activity on glycolaldehyde, we show here that these mutants in fact gave improved activity on both substrate types. In comparison, the new mutants were obtained at conserved residues which interact with the C2-hydroxyl group of natural substrates, and gave up to 5-fold improvement in specific activity and 64-fold improvement in specificity towards propionaldehyde relative to glycolaldehyde. This suggests that saturation mutagenesis can be more selectively guided for evolution towards either natural or non-natural substrates, using both structural and sequence information.


A C2-symmetric nickel diamine complex as an asymmetric catalyst for enecarbamate additions to butane-2,3-dione.
Butane-2,3-dione was activated towards nucleophilic addition of enecarbamates by a series of metal triflate complexes of a C2-symmetric diamine to give stereogenic, aldol-like, t-alcohols, a novel nickel(II) triflate complex was identified as a good catalyst for this asymmetric transformation, and an aquo nickel(II) complex was identified by XRD techniques.


Clinical role of the renal transplant biopsy.
Percutaneous needle core biopsy is the definitive procedure by which essential diagnostic and prognostic information on acute and chronic renal allograft dysfunction is obtained. The diagnostic value of the information so obtained has endured for over three decades and has proven crucially important in shaping strategies for therapeutic intervention. This Review provides a broad outline of the utility of performing kidney graft biopsies after transplantation, highlighting the relevance of biopsy findings in the immediate and early post-transplant period (from days to weeks after implantation), the first post-transplant year, and the late period (beyond the first year). We focus on how biopsy findings change over time, and the wide variety of pathological features that characterize the major clinical diagnoses facing the clinician. This article also includes a discussion of acute cellular and humoral rejection, the toxic effects of calcineurin inhibitors, and the widely varying etiologies and characteristics of chronic lesions. Emerging technologies based on gene expression analyses and proteomics, the in situ detection of functionally relevant molecules, and new bioinformatic approaches that hold the promise of improving diagnostic precision and developing new, refined molecular pathways for therapeutic intervention are also presented.


Age-related differences in novelty and target processing among cognitively high performing adults.
Previous research on age-related changes in ERP components in response to novel and target stimuli has not carefully controlled for differences in level of cognitive status between age groups, which may have contributed to the common findings of increased P3 latency, decreased P3 amplitude, and altered P3 scalp distribution. Here, cognitively high-performing (top third based on published norms) old, middle-aged, and young adults matched for IQ, education, and gender participated in a novelty oddball paradigm. There were no age-associated differences in P3 latency. Older adults had a larger, more anteriorly distributed P3 amplitude to all stimulus types, even repetitive standards, suggesting they may rely on increased resources and effortful frontal activity to successfully process any kind of visual stimulus. However, after controlling for this non-specific age-related processing difference, the amplitude and scalp distribution of the P3 component to novel and target stimuli were comparable across age groups, indicating that for cognitively high functioning elders there may be no age-related differences specific to the processing of novel and target events as indexed by the P3 component.


Effect of propranolol on secretin-induced gastrin release and secretin-induced tachycardia in patients with the Zollinger-Ellison syndrome.
The mechanism for secretin-induced gastrin release in the Zollinger-Ellison syndrome is uncertain. We evaluated whether the stimulatory effect of intravenous secretin on gastrin release was partly mediated through a beta-adrenergic stimulatory mechanism. Serum gastrin concentrations and heart rate were monitored in six patients with the Zollinger-Ellison syndrome. Secretin (2 clinical units/kg) increased mean serum gastrin concentrations from 1558 pg/ml basally to a peak of 3683 pg/ml (136% above baseline). This increase was not altered by pretreatment with 2 mg of propranolol intravenously, a dose which in previous studies blocked terbutaline-induced gastrin release. Secretin increased heart rate by 14 beats/min (20% above base-line) and this also was not altered by propranolol pretreatment. Thus, the stimulatory effects of secretin on gastrinoma cells and the heart do not appear to be mediated by beta-adrenergic receptors.


Stability of microsomal mono-oxygenase during incubations for the liver microsomal assay with S9 fractions of mouse liver under various inductions.
Aminopyrine-N-demethylase and p-nitroanisole-O-demethylase activities were determined in incubation mixtures for the liver microsomal assay at time zero and after 1 h of incubation in the conditions for the mutagenic assay. The experiments were performed with the S9 liver fraction of mice in the basal state and induced with sodium phenobarbital, beta-naphthoflavone or both. Lipid peroxidation was also determined. The experiments were repeated with female mice and also in the presence of styrene, as an example of a xenobiotic substance. The activity of pNAD was much more stable than that of APD in all the conditions tested. The pattern of stability, however, was similar for the two activities: more stable than controls with S9 fractions from beta-NF-induced mice, less stable than controls in PB-induced mice, intermediate between controls and PB-induced mice in those with combined induction by PB + beta NF. Styrene 50 mM in the incubation mixtures led to a marked inactivation of enzymic activity, similar in all cases and reaching about 90% in 1 h. S9 fractions from female mice gave enzymes slightly more stable in almost all cases. Lipid peroxidation was appreciably more elevated in basal than in induced animals. It was concluded that, for a mutagenesis test on an unknown xenobiotic, S9 fractions from mice following PB and beta-NF induction are to be preferred from the point of view of activation.


Reactive Template-Engaged Synthesis of NiSx/MoS2 Nanosheets Decorated on Hollow and Porous Carbon Microtubes with Optimal Electronic Modulation toward High-Performance Enzyme-like Performance.
As a promising cost-effective nanozyme, MoS2 nanosheets (NSs) have been considered as a good candidate for the enzyme-like catalysis. However, their catalytic activity is still restricted by the insufficient active sites and poor conductivity, and thus, the comprehensive performances are still unsatisfactory. To address these issues, herein, we design and fabricate an intelligent tubular nanostructure of hierarchical hollow nanotubes, which are assembled by NiSx/MoS2 NSs encapsulated into N-doped carbon microtubes (NiSx/MoS2@NCMTs). The N-doped carbon microtubes (NCMTs) serve as a conductive skeleton, integrating with NiSx/MoS2 NSs and ensuring their well-distribution, thereby maximally exposing more active sites. Additionally, the tube-like structure is favorable for increasing the mass transfusion to ensure their excellent catalytic performance. Profiting from their component and structural advantages, the obtained NiSx/MoS2@NCMTs exhibit a surprisingly enhanced enzyme-like activity. Based on these, a facile colorimetric sensing platform to detect H2O2 and GSH has been developed. This proposed approach can be expected to synthesize a series of tubular heterostructured MoS2-based composites, which will be widely applied in catalysis, energy storage, disease diagnosis, etc.


Regio- and stereoselective fungal oxyfunctionalisation of limonenes.
Selective transformations of limonene by asco- and basidiomycetes were investigated. On the shake flask scale, Penicillium citrinum hydrated R-(+)-limonene to a-terpineol [83% regioselectivity (rs), more than 80 mg l(-1) product yield], and Gongronella butleri catalysed the terminal oxidation to yield perillyl alcohol (60% rs, 16 mg l(-1)). On the laboratory bioreactor scale, Penicillium digitatum produced a peak concentration of 506 mg a-terpineol l(-1) in the fed-batch mode, equivalent to a theoretical yield of 67%, and no volatile by-products were found. Fusarium proliferatum transformed R-(+)-limonene enantiospecifically to cis-(+)-carveol (98.6% ee, more than 35 mg l(-1) product yield) and S-(-)-limonene predominantly to trans-(-)-carveol (96.3% ee). Pleurotus sapidus selectively dehydrogenised the accumulating trans-(-)-carveol to the corresponding enantiopure R-(-)-carvone. The results show that a careful selection of strain and bioprocess parameters may improve both the yield and the optical purity of a desired product.


Carbapenem-resistant Escherichia coli and Klebsiella pneumoniae isolates from Turkey with OXA-48-like carbapenemases and outer membrane protein loss.
Treatment options are limited in infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, with carbapenems generally preferred. Disturbingly, however, carbapenem-resistant strains are emerging worldwide. Here we report two clinical isolates, one Escherichia coli and one Klebsiella pneumoniae, each with high-level carbapenem resistance (imipenem minimum inhibitory concentration of 32 microg/mL). They were isolated following imipenem therapy from two hospital patients who had received imipenem therapy in different regions of Turkey. Both isolates produced OXA-48-like carbapenemases, enzymes so far reported only from Turkey. Both isolates also had group 1 CTX-M-type ESBLs and had lost major outer membrane proteins. OXA-48-like carbapenemases appear to be scattered in Turkey and surveillance to determine their prevalence is warranted.


Use of an ultrathin bronchoscope in the assessment of central airway obstruction.
To assess the utility of an ultrathin bronchoscope (UB) in the assessment of central airway obstruction (CAO). Prospective evaluation Tygerberg Hospital, a tertiary teaching hospital. Consecutive patients referred to the Lung Unit with CAO. Fiberoptic bronchoscopy (FOB) was performed with a prototype UB (Olympus BF XP40; Olympus Europe; Hamburg, Germany; outer diameter, 2.8 mm; working channel, 1.2 mm). The UB was used whenever a standard bronchoscope (SB) could not pass the obstruction or could not be tolerated by the patient. Data relating to indication and performance of FOB, patient demographics, utility in establishing a diagnosis, and planning definitive management were documented. Twenty-four patients (17 men; mean age, 46 years) were studied. Twelve patients (50%) had malignant CAO, 8 patients (33%) had benign tracheal stenosis, 3 patients (12.5%) had stent occlusion, and 1 patient (4%) had bilateral vocal cord paralysis. In 42% of patients, an initial attempt at passing the obstruction with an SB had failed. Vocal cords or trachea were involved in 62% of patients. The mean luminal occlusion was 84% of the total airway lumen (range, 50 to 100%). One complication (desaturation) led to early termination of FOB. In all but three patients with complete obstruction, the UB was able to pass the CAO and allowed assessment of the obstruction and the distal airways (87%). UB-FOB was useful and safe in the assessment of patients with CAO from both benign and malignant disease. It aided in establishing a diagnosis and/or planning of definitive management in all patients examined.


Gastrointestinal irritancy, antiinflammatory activity, and prostanoid inhibition in the rat. Differentiation of effects between nabumetone and etodolac.
Many nonsteroidal antiinflammatory drugs have the ability to cause gastrointestinal damage in both animals and man. The aim of the present study was to compare nabumetone, a nonacidic drug, with etodolac on rat gastric mucosal damage and prostanoid synthesis, while concurrently measuring prostanoid production during edema formation in a carrageenan model of paw inflammation. The results showed that both drugs inhibited paw exudate prostaglandin E2 and edema significantly, but they did not inhibit gastric prostanoid production 4 hr after dosing. Gastric damage, however, was observed with etodolac. Additional time-course studies showed that over a 4-hr period, etodolac, unlike nabumetone, markedly inhibited gastric mucosal prostaglandin E2 production, which was associated with gastric erosion formation. Further studies demonstrated that nabumetone did not induce gastrointestinal damage or blood loss when administered to rats in a high antiinflammatory oral dose. In contrast, etodolac produced marked gastrointestinal damage and bleeding, which was evident for up to 48 hr after the dose. It is suggested that nabumetone's favorable gastrointestinal irritancy profile may relate, in part, to its nonacidic nature and to its differential effects on prostanoid production.


Enhancement of a conducting polymer-based biosensor using carbon nanotube-doped polyaniline.
A biosensor with improved performance was developed through the immobilization of horseradish peroxidase (HRP) onto electropolymerized polyaniline (PANI) films doped with carbon nanotubes (CNTs). The effects of electropolymerization cycle and CNT concentration on the response of the biosensor toward H2O2 were investigated. It was found that the application of CNTs in the biosensor system could increase the amount and stability of the immobilized enzyme, and greatly enhanced the biosensor response. Compared with the biosensor without CNTs, the proposed biosensor exhibited enhanced stability and approximately eight-fold sensitivity. A linear range from 0.2 to 19 microM for the detection of H2O2 was observed for the proposed biosensor, with a detection limit of 68 nM at a signal-to-noise ratio of 3 and a response time of less than 5s.


Cor triatriatum sinister versus bowed septum primum in an infant with total anomalous pulmonary venous connection: a difficult imaging distinction.
In cor triatriatum sinister, a membrane divides the left atrium into a posterior chamber that receives the pulmonary veins and an anterior chamber that communicates with the mitral valve. With right-side chamber overload, the septum primum can separate from the muscular septum and bow toward the left atrial cavity, leading to a thin membrane within the left atrium and imaging findings that may mimic cor triatriatum. We report the multidetector CT findings of a 3-month-old infant with a supracardiac total anomalous pulmonary venous connection with a bowed septum primum. A description of the imaging findings that distinguish cor triatriatum and bowed septum primum will be discussed. This case demonstrates the usefulness of MDCT in the assessment of supracardiac vascular anomalies and intracardiac anatomy.


Natural course of the nodular bronchiectatic form of Mycobacterium Avium complex lung disease: Long-term radiologic change without treatment.
Although the incidence of Mycobacterium avium complex (MAC) lung disease is increasing, the long-term natural course of the nodular bronchiectatic form of MAC lung disease is not well described. The objective of our study is to evaluate long-term radiologic changes in untreated MAC lung disease by analyzing serial chest computed tomography (CT) scan findings. Of 104 patients with MAC lung disease, we selected 40 untreated nodular bronchiectatic MAC patients who underwent serial chest CTs without treatment for at least four years (mean = 6.23 years). Majority of patients have minimal symptoms. Two chest radiologists retrospectively reviewed initial and final chest CT scans. Each chest CT scan was scored for presence and extent of bronchiectasis, cellular bronchiolitis, consolidation, cavity, and nodule (maximum score: 30). Of 40 patients, 39 (97.5%) experienced a significant increase in overall CT score (overall difference = 4.89, p<0.001). On repeated measure analysis of variance analysis, cavity yielded the largest increase compared with cellular bronchiolitis (p = 0.013), nodule (p<0.001), and consolidation (p = 0.004). However, there was no significant difference in mean score change between cavity and bronchiectasis (p = 0.073). In analysis between radiologic parameters and the absolute number of involved segments, bronchiectasis showed most significant change compared with nodule (p<0.001) and consolidation (p<0.001). Most untreated nodular bronchiectatic MAC lung disease cases showed radiologic deterioration over long-term observation periods when we compared serial chest CT scans. Careful monitoring of MAC lung disease with serial chest CT scan can be beneficial in these untreated patients.


Recombinase-Dependent Mouse Lines for Chemogenetic Activation of Genetically Defined Cell Types.
Chemogenetic technologies, including the mutated human Gq-coupled M3 muscarinic receptor (hM3Dq), have greatly facilitated our ability to directly link changes in cellular activity to altered physiology and behavior. Here, we extend the hM3Dq toolkit with recombinase-responsive mouse lines that permit hM3Dq expression in virtually any cell type. These alleles encode a fusion protein designed to increase effective expression levels by concentrating hM3Dq to the cell body and dendrites. To illustrate their broad utility, we targeted three different genetically defined cell populations: noradrenergic neurons of the compact, bilateral locus coeruleus and two dispersed populations, Camk2a+ neurons and GFAP+ glia. In all three populations, we observed reproducible expression and confirmed that activation of hM3Dq is sufficient to dose-dependently evoke phenotypic changes, without extreme phenotypes associated with hM3Dq overexpression. These alleles offer the ability to non-invasively control activity of diverse cell types to uncover their function and dysfunction at any developmental stage.


Idiopathic synovial chondromatosis in two unusual sites: inferior radioulnar joint and ischial bursa.
Synovial chondromatosis is a rare disorder of unknown cause characterized by multiple calcific bodies in the vicinity of the affected joint. It is most commonly seen in the knee, hip, elbow, and shoulder. We describe three cases of synovial chondromatosis in two extremely uncommon sites, the inferior radioulnar joint and the ischial bursa, and review the literature on the subject. The characteristic radiographic appearance, even if in an uncommon location, should prompt the radiologist to suggest the correct diagnosis preoperatively.


Intravenous administration of sulpiride and heat sensation on the body surface.
Sulpiride was administered intravenously to 19 patients in a depressive or hallucinatory-paranoid state. The sensation of heat appeared characteristic as a side-effect of intravenous sulpiride when viewed in terms of frequency (arising in 13 of 19 cases), the site of occurrence (symmetrical, often on the ventral side in the upper half of the body), and the mode of occurrence (changes in the site in a short period of time). The fact that the mechanism of this heat sensation remains obscure makes caution advisable in using the drug.


Increased mature and immature CCR3 messenger RNA+ eosinophils in bone marrow from patients with atopic asthma compared with atopic and nonatopic control subjects.
Eosinophil infiltration of the bronchial mucosa is characteristic of asthma. Eosinophils differentiate from CD34(+) progenitors. Animal models suggest cooperation between IL-5 and eotaxin to allow rapid mobilization of a pool of bone marrow eosinophils followed by recruitment to the airway mucosa. The purpose of this study was to enumerate CD34(+) cell numbers in blood and bone marrow from atopic asthmatics and control subjects and to test the hypothesis that there is an increased bone marrow pool of CCR3(+) eosinophils in patients with atopic asthma, as compared with control subjects. Bone marrow aspirates and peripheral blood were obtained from volunteers with asthma and control volunteers. CD34(+) cell numbers were evaluated by flow cytometry, and eosinophil colony-forming activity was evaluated by methylcellulose cultures. Mature eosinophils, eosinophil myelocytes, metamyelocytes, and band forms (immature eosinophils) were enumerated by morphologic findings and immunocytochemistry for eosinophil cationic protein. CCR3 and eotaxin mRNA expression was examined by in situ hybridization, and protein expression was examined by immunocytochemistry. CCR3(+) cells were further identified with Chromotrope 2R staining. CD34(+) cell numbers in bone marrow were increased in atopic subjects. Numbers of eosinophil colony-forming units in blood and bone marrow did not differ between groups. Percentages of both mature and immature eosinophils were increased in bone marrow from patients with atopic asthma, but not atopic patients with no asthma or normal control subjects. CCR3 was expressed by immature and mature bone marrow eosinophils. Eotaxin was expressed by bone marrow cells from all 3 groups, but there was no increase in subjects with asthma. These findings suggest that in humans there is an increased bone marrow pool of CCR3(+) mature and immature eosinophils available for rapid mobilization in subjects with asthma but not in atopic subjects with no asthma.


Initial clinical experience with Single-Port robotic (SP r) left colectomy using the SP surgical system: description of the technique.
The daVinci Single-Port (SP) robot is a new robotic platform designed to overcome the challenges of Single-Incision Laparoscopic Surgery. The objective of this study is to demonstrate the feasibility and technical aspects of SP robotic (SP r) left colectomy using the SP platform. Under Institutional Review Board approval and registration on ClinicalTrials.gov, we performed SP rLeft colectomy using the daVinci SP surgical system on four patients. The primary end-point of this study was to report and describe the technical feasibility to perform SP rLeft colectomy. The secondary end-points included perioperative metrics and outcomes. Four patients underwent successful SP rLeft colectomy for diverticulitis through a single incision (average size: 4.4 cm) without intraoperative complications or conversions. The robot was docked 2.7 times on average (range 2-4). The average docking time was 8.4 min (range: 3-33 min). The mean estimated blood loss was 91 mL (range: 20-250 mL). There were no morbidities or mortalities. Patients were discharged on POD 2 and 3. We demonstrated in this initial clinical series the SP rLeft colectomy to be feasible and safe to perform in select patients. The SP robot's single-arm design and flexible instruments have shown to provide excellent visualization and retraction with minimal collisions. We predict that the SP robot will be widely utilized in the field of colorectal surgery as it becomes available to colorectal surgeons. Further experience and larger studies are needed to define the advantages and identify the problems with the SP rLeft colectomy.


High speed photo-mediated ultrasound therapy integrated with OCTA.
Photo-mediated Ultrasound Therapy (PUT), as a new anti-vascular technique, can promote cavitation activity to selectively destruct blood vessels with a significantly lower amount of energy when compared to energy level required by other laser and ultrasound treatment therapies individually. Here, we report the development of a high speed PUT system based on a 50-kHz pulsed laser to achieve faster treatment, decreasing the treatment time by a factor of 20. Furthermore, we integrated it with optical coherence tomography angiography (OCTA) for real time monitoring. The feasibility of the proposed OCTA-guided PUT was validated through in vivo rabbit experiments. The addition of OCTA to PUT allows for quantitative prescreening and real time monitoring of treatment response, thereby enabling implementation of individualized treatment strategies.


Right- and left-handedness of 2(1) symmetrical herringbone assemblies of benzene.
A universal method to determine handedness of 2(1) helical assemblies composed of planar aromatic molecules is proposed and demonstrated by taking P2(1)/c and Pbca crystals of benzene, the simplest aromatic molecule, as examples.


DNA methylation in promoter regions of red cell membrane protein genes in healthy individuals and patients with hereditary membrane disorders.
The methylation state of 5'-CG-3' sites is known to be linked to the regulation of promoter function by modulating DNA-protein interactions and to the structure of chromatin. As part of a project to determine methylation patterns in the human genome, we examined the methylation profiles of several genes for human erythroid membrane proteins: ELB42 (protein 4.2), EPB3 (band 3), SPTB gene (beta-spectrin), and ANK1 (ankyrin). The bisulfite protocol of the genomic sequencing method was applied. The number of 5'-CG-3' dinucleotides was the most abundant in SPTB and ANK1, much less in EPB3, and the least in ELB42. In the DNA of peripheral blood mononuclear cells from healthy individuals, the promoter regions of EPB3 and ELB42 were extensively methylated, but the SPTB and ANK1 promoters were totally unmethylated. We also investigated methylation profiles in peripheral blood mononuclear cells from patients with red cell membrane diseases, such as complete protein 4.2 deficiency due to ELB42 mutations, hereditary spherocytosis with EPB3 mutations, and hereditary elliptocytosis with SPTB mutations. The DNA methylation states in these genes of erythroid cells, which we obtained at the second phase of the 2-phase liquid culture of erythroid precursor cells in the peripheral blood, were essentially identical or very similar to those of peripheral blood mononuclear cells. In disease states, the DNA methylation profiles of these red cell membrane protein genes were essentially not different from those in healthy individuals (statistically not significant).


Contemporary management and outcomes for infants born with oesophageal atresia.
Reports on the management and outcome of rare conditions, such as oesophageal atresia, are frequently limited to case series reporting single-centre experience over many years. The aim of this study was to identify all infants born with oesophageal atresia in the UK and Ireland to describe current clinical practice and outcomes. This was a prospective multicentre cohort study of all infants born with oesophageal atresia and/or tracheo-oesophageal fistula in 2008-2009 in the UK and Ireland to record current clinical management and early outcomes. A total of 151 infants admitted to 28 paediatric surgical units were identified. Some aspects of perioperative management were universal, including oesophageal decompression, operative technique and the use of transanastomotic tubes. However, there were a number of areas where clinical practice varied considerably, including the routine use of perioperative chest drains, postoperative contrast studies and antireflux medication, with each of these being employed in 30-50 per cent of patients. There was a trend towards routine postoperative ventilation. The prospective methodology used in this study can help identify practices that all surgeons employ and also those that few surgeons use. Areas of clinical equipoise can be recognized and avenues for further research identified.


Initial experience of comparison between two slimmest single-use flexible ureteroscopes: Indoscope Sleek (Bioradmedisys™) Versus Uscope PU3033A (Pusen™): A single-center prospective study.
A single-use digital flexible ureteroscope (fURS) has become a cost-effective alternative option to reusable fURS. The requirement of large-diameter access sheath for passage of 9.5 Fr single-use fURS has not always achieved in the first attempt in all cases leading to stage stone clearance. Recently, two slimmest single-use digital disposable fURSs have been introduced by Bioradmedisys™ and Pusen™ to mitigate the accessibility problem, without or with small size access sheath. Primary objective was to compare in vivo performance and surgical outcomes with two single-use fURS: 7.5Fr Indoscope (Bioradmedisys™, Pune, India) and 7.5Fr Uscope PU3033A (Pusen, Zhuhai, China). 60 patients undergoing Retrograde Intrarenal Surgery (RIRS) with < 2 cm renal stones were prospectively randomized into: Group A (30 patients) for Indoscope and Group B (30 patients) for Uscope PU3033A. Pre-operative, intra-operative, and post-operative parameters were evaluated. In vivo visibility and maneuverability were rated on 5-point Likert scale by the operating surgeon. At one-month stone clearance was assessed with ultrasound and X-ray KUB. Data were analyzed using SPSS 23.0. Patient demographics and stone characteristics were comparable in both groups. Indoscope had significantly higher visibility (p < 0.05) than Uscope; however, the maneuverability scores were comparable between both the groups (p > 0.05). 28 patients in group A and 26 patients in group B achieved complete stone clearance (p = 0.38). Scope failure was observed in 1 case of group B (p = 0.31). We conclude that 7.5Fr Indoscope has better vision than 7.5Fr Uscope and the rest of in vivo performances were comparable with similar outcomes and complications among both scopes.


One-year monitoring of core biomarker and digestive enzyme responses in transplanted zebra mussels (Dreissena polymorpha).
A 12-month active biomonitoring study was performed in 2008-2009 on the Vesle river basin (Champagne-Ardenne, France) using the freshwater mussel Dreissena polymorpha as a sentinel species; allochthonous mussels originating from a reference site (Commercy) were exposed at four sites (Bouy, Sept-Saulx, Fismes, Ardre) within the Vesle river basin. Selected core biomarkers (acetylcholinesterase (AChE) activity, glutathione-S transferase (GST) activity, metallothionein concentration), along with digestive enzyme activities (amylase, endocellulase) and energy reserve concentrations (glycogen, lipids), were monitored throughout the study in exposed mussels. At the Fismes and Ardre sites (downstream basin), metallic and organic contamination levels were low but still high enough to elicit AChE and GST activity induction in exposed mussels (chemical stress); besides, chemical pollutants had no apparent deleterious effects on mussel condition. At the Bouy and Sept-Saulx sites (upstream basin), mussels obviously suffered from adverse food conditions which seriously impaired individual physiological state and survival (nutritional stress); food scarcity had however no apparent effects on core biomarker responses. Digestive enzyme activities responded to both chemical and nutritional stresses, the increase in energy outputs (general adaptation syndrome-downstream sites) or the decrease in energy inputs (food scarcity-upstream sites) leading to mid- or long-term induction of digestive carbohydrase activities in exposed mussels (energy optimizing strategy). Complex regulation patterns of these activities require nevertheless the use of a multi-marker approach to allow data interpretation. Besides, their sensitivity to natural confounding environmental factors remains to be precised.


Neutrophil fatty acid composition: effect of a single session of exercise and glutamine supplementation.
The fatty acid composition of immune cells appears to contribute to variations of cell function. The independent and combined effects of a single session of exercise (SSE) and glutamine supplementation (GS) on neutrophil fatty acid composition were investigated. Compared to control (no treatment given--i.e. neither SSE or GS), single session of exercise decreased myristic, palmitic and eicosapentaenoic (EPA) acids, and increased lauric, oleic, linoleic, arachidonic (AA) and docosahexaenoic (DHA) acids whereas glutamine supplementation combined with SSE (GS+SSE) increased oleic acid. Polyunsaturated/saturated fatty acid ratio and Unsaturation index were higher in neutrophils from the SSE and GS groups as compared with control. These findings support the proposition that SSE and GS may modulate neutrophil function through alterations in fatty acid composition.


Interferon in suction blister fluid from psoriatic lesions.
Interferon (IFN) (at least 16 units/ml) was demonstrated in suction blister fluid obtained from lesional skin in nine of thirteen patients with psoriasis vulgaris and in two patients with allergic contact dermatitis, but not in blister fluid from unaffected skin. IFN was detected in only three of the sera from the patients with psoriasis. The difference in results between the blister fluid and the sera from these patients was statistically significant (P less than 0.025). Evidence was obtained which indicated that the activity was probably IFN-gamma (immune IFN), but the additional presence of IFN-alpha in some of the fluids could not be excluded. The data indicate that IFN is produced locally in the psoriatic lesions, most likely by activated T lymphocytes.


Impact of HPV vaccination: health gains in the Italian female population.
Human papillomavirus (HPV) is the leading cause of cervical cancer and other malignant and benign neoplastic lesions. HPV vaccination has three potential goals: to prevent transmission, infection, and disease. At present, there are no available data about health consequences of HPV immunization in Italy. The aim of this study is to evaluate the effect of current HPV vaccination strategy in Italy. A multistate morbidity-mortality model was developed to estimate the infection process in a theoretical cohort of Italian women. The Markov process considered nine health states (health, anogenital warts, grade 1 and grade 2/3 cervical intraepithelial neoplasia, cervical cancer, anal cancer, death due to cervical cancer, anal cancer and other causes), and 26 transition probabilities for each age group. The model was informed with the available data in national and international literature. Effectiveness of immunization was assumed considering a literature review pertaining to models and vaccination coverage rates observed in Italy. Life expectancy (ex), Quality-Adjusted Life Years (QALYs), Disability-Adjusted Life Years (DALYs), and attributable risk (AR) were estimated for no intervention (cervical cancer screening) and vaccination strategies scenarios. The model showed that in a cohort of 100,000 Italian women the e0 is equal to 83.1 years. With current HPV vaccination strategy the e0 achieves 83.2 (+0.1) years. When HPV-related diseases are considered altogether, the QALYs increase from 82.7 to 82.9 (+0.2 QALYs) with no intervention and vaccination strategies respectively. DALYs decrease by 0.6 due to vaccination. Finally, AR is equal to 93 and 265 cases per 100,000 women in population and not vaccinated, respectively. When mortality due to cervical cancer is considered, HPV vaccination seems to have a low impact on health unit gains in the Italian female population. Conversely, when several HPV-related and cancer morbidity conditions are included, the effect of vaccination becomes quite remarkable.


Single-crystal X-ray diffraction and Raman spectroscopy studies of isobaric N2 adsorption in SOD-type metal-organic zeolites.
The two-step N(2) adsorption behaviour of sodalite-type Zn(II) 2-methylimidazolate and 3-methyl-1,2,4-triazolate has been comprehensively and accurately elucidated.


Evaluating compliance with process-related quality metrics and survival in oral cavity squamous cell carcinoma: Multi-institutional oral cavity collaboration study.
Process-related measures have been proposed as quality metrics in head and neck cancer care. A recent single-institution study identified four key metrics associated with increased survival. This study sought to validate the association of these quality metrics with survival in a multi-institutional cohort. Multicenter retrospective study of patients with oral cavity squamous cell (1/2005-1/2015). Baseline patient and disease characteristics and compliance with quality metrics was evaluated. Association between compliance with quality metrics with overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) was evaluated using Cox proportional hazards models. Failure to comply with two or more of the quality metrics was associated with worse OS, DFS, and DSS. Adherence to all or all but one of the quality metrics was found to be associated with improved survival. Process-related quality metrics are associated with increased survival in patients with oral cavity squamous cell carcinoma in a multi-institutional cohort.


Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype.
Nucleophosmin (NPM1) exon-12 gene mutations are the hallmark of a large acute myelogenous leukemia (AML) subgroup with normal karyotype, but their prognostic value in this AML subset has not yet been determined. We screened 401 AML patients with normal karyotype treated within the German AML Cooperative Group Protocol 99 (AMLCG99) study for NPM1 mutations. Results were related with partial tandem duplications within the MLL gene (MLL-PTD), Fms-like tyrosine kinase 3-length mutations (FLT3-LM), the tyrosine kinase domain of FLT3 (FLT3-TKD), NRAS, KIT, and CEBPA mutations and with clinical characteristics and outcome. NPM1 mutations were detected in 212 (52.9%) of 401 patients. Fourteen mutations, including 8 new variants, were identified. NPM1-mutated cases associated frequently with FLT3 mutations but rarely with other mutations. The NPM1-mutated group had a higher complete remission (CR) rate (70.5% vs 54.7%, P = .003), a trend to a longer overall survival (OS; median 1012 vs 549 days, P = .076), and significantly longer event-free survival (EFS; median 428 vs 336 days; P = .012). The favorable impact of NPM1 mutations on OS and EFS clearly emerged in the large group (264 [66.8%] of 395 cases) of normal-karyotype AML without FLT3-LM. This positive effect was lost in the presence of a concomitant FLT3-LM, since survival of the NPM1+/FLT3-LM+ double positive was similar to NPM1-/FLT3-LM+ cases. In conclusion, this study demonstrates that NPM1+/FLT3-LM- mutations are an independent predictor for a favorable outcome in AML with normal karyotype.


The specificity of Atlantic salmon antibodies made against the fish pathogen Vibrio salmonicida, establishing the surface protein VS-P1 as the dominating antigen.
The specificity of salmon (Salmo salar) antibodies made against the fish pathogen Vibrio salmonicida was studied. Salmon immunized with V. salmonicida emulisified in Freund's complete adjuvant produced antibodies which preferentially bound to a 40 KD outer surface molecule (VS-P1). Moreover, the bulk of the antibodies were specific for one particular epitope on VS-P1, defined by a mouse monoclonal antibody - as detected with a blocking ELISA. The data imply that salmon B cells mainly (90%) recognize one particular determinant on V. salmonicida and thus express a limited repertoire of antibody specificities against this pathogen.


Social network structure as a suicide prevention target.
The structure of relationships in a social network affects the suicide risk of the people embedded within it. Although current interventions often modify the social perceptions (e.g., perceived support and sense of belonging) for people at elevated risk, few seek to directly modify the structure of their surrounding social networks. We show social network structure is a worthwhile intervention target in its own right. A simple model illustrates the potential of interventions to modify social structure. The effect of these basic structural interventions on suicide risk is simulated and evaluated. Its results are briefly compared to emerging empirical findings for real network interventions. Even an intentionally simplified intervention on social network structure (i.e., random addition of social connections) is likely to be both effective and safe. Specifically, this illustrative intervention had a high probability of reducing the overall suicide risk, without increasing the risk of those who were healthy at baseline. It also frequently resolved stable, high-risk clusters of people at elevated risk. These illustrative results are generally consistent with emerging evidence from real social network interventions for suicide. Social network structure is a neglected, but valuable intervention target for suicide prevention.


Acute transient non-physiological over-sensing in the ventricle with a DF4 lead.
The DF-4 is a new defibrillator lead technology. We present two cases of non-physiological transient ventricular over-sensing in patients who underwent implantation of an ICD for secondary prevention. Case 1 had ventricular over-sensing during pacing threshold evaluation post defibrillation testing while Case 2 had the lead integrity alert triggered immediately post discharge with transient over-sensing. No lead-connector issues were found. Case 1 was likely due to improper venting of the header and trapped air. Case 2 was hypothesized to be due to intermittent header pin non-contact secondary to blood in the header. These cases reveal that DF-4 leads are subject to both reported and potentially novel causes of transient acute ventricular over-sensing.


Purification and properties of a soluble protein activator of rat liver squalene epoxidase.
A soluble rat liver protein, termed "supernatant protein factor" (SPF), that stimulates microsomal squalene epoxidase has been purified approximately 11,000-fold. The most highly purified preparation obtained by isoelectric focusing shows a single coincident peak for activity and protein (the isoelectric point, pI, was 6.74). SPF is about 95% pure, judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and it migrates to a position corresponding to an apparent molecular weight of 47,000. An amino acid analysis of SPF is presented, and the properties of SPF and of the various soluble protein activators of microsomal sterol biosynthesis described by other laboratories are compared.


Combination of dexanabinol and tempol in focal cerebral ischemia: is there a ceiling effect?
Because ischemic neuronal death is triggered by several parallel mechanisms, a combination of drugs active against individual death-promoting mechanisms may have synergistic effects. Dexanabinol is a noncompetitive NMDA antagonist with anti-inflammatory effects and tempol is a nitroxide antioxidant. Therefore, we explored whether their combined use results in smaller infarct volumes as compared with their individual administration. Rats underwent permanent middle cerebral artery occlusion (PMCAO) and were given vehicle, dexanabinol alone, tempol alone, or a combination of dexanabinol and tempol (n = 13 per group) 1 h later. Five animals in each group were evaluated with a motor rating scale 24 h after PMCAO and the infarct volumes were then measured. The remaining animals were examined with motor and behavioral scales up to 30 days after PMCAO and their infarct volumes were then determined. Motor disability and water maze latencies at all time points examined and infarct volumes at days 1 and 30 were significantly reduced in all active treatment groups when compared with vehicle. However, no significant differences were observed between the active treatment groups. In conclusions, combination therapy with dexanabinol and tempol does not appear to have additional neuroprotective effects compared to those conferred by each agent alone even when administered at optimal timing and dosing. Therefore, a ceiling neuroprotective effect that is impossible to overcome may exist.


Ichthyosiform changes in a patient with RAC1 mutation.
RAS-related C3 Botulinum Toxin Substrate 1 (RAC1) is a Rho GTPase that modulates numerous cellular functions including transcriptional regulation and actin-based structure turnover. Reported de novo RAC1 mutations are rare but generally manifest in developmental delay and brain malformations. In Rac1 knockout mice, a hairless phenotype has been observed, but little is known of other cutaneous phenotypes of RAC1 mutations. In this report, we describe the first known case of a RAC1 mutation with ichthyosiform changes.


Growth, fecundity and sex ratio of adult whaleworm (Anisakis simplex; Nematoda, Ascaridoidea, Anisakidae) in three whale species from the North-East Atlantic.
The growth rate, fecundity, and sex ratio of Anisakis simplex in minke whales (Balaenoptera acutorostrata), porpoises (Phocoena phocoena) and long-finned pilot whales (Globicephala melas) was studied on the basis of material from the North Atlantic. A total of 8,135 mature A. simplex were collected from 24 minke whales, 11 porpoises and eight pilot whales. For both males and females, the prevalence was 100% for all three host species, with a mean intensity of 1,727, 262 and 139, respectively. The mean body length of adult female A. simplex was 126 mm in minke whales, 71 mm in the porpoises and 73 mm in pilot whales; and for males the averages were, respectively, 106 mm, 57 mm and 68 mm. Eggs from the uteri of 32 females of length 87-176 mm collected in minke whale stomachs were counted in a Fuchs-Rosenthal chamber. Total egg production was measured in 14 females cultivated at sea. The female growth period was estimated to be 30-60 days, and apparently all eggs were shed during the last week of life. A female of size 150 mm produces approximately 1.5 million eggs. In the cultivation experiment, about 85% of the total egg production was shed during the first 3 days after spawning started.