Several testis-expressed genes in the mouse t-complex have expression differences between wild-type and t-mutant mice.
The t-complex of the mouse occupies the proximal half of chromosome 17 and contains genes which have profound effects on spermatogenesis. Mutations of several loci in the t-complex appear to interact to cause male sterility or transmission ratio distortion (TRD). By cDNA screening or chromosomal walking we have identified seven genes, which are expressed in the germ cells of testis and map to various regions of the t-complex. These genes were named t-complex testis-expressed (Tctex) genes. An analysis of their expression patterns in testes from +/+, +/t, and t/t mice was done by in situ hybridization and by northern blotting. Six genes begin to be expressed at the pachytene stage: Three of them are more abundant at pachytene stage, while three others are more abundant at postmeiotic stages. One gene is expressed at all the stages of spermatogenesis. Interestingly, four Tctex genes show differences in the amount of transcript between wild-type and t-mutant testes. The chromosomal location and expression pattern imply that Tctex genes might be candidate genes for sterility or TRD.


Double aneuploidy with Edwards-Klinefelter syndromes (48,XXY,+18) of maternal origin: prenatal diagnosis and molecular cytogenetic characterization in a fetus with arthrogryposis of the left wrist and aplasia of the left thumb.
To present the prenatal diagnosis and molecular investigation of the parental origin and mechanism of nondisjunction underlying an 48,XXY,+18 karyotype in a fetus with congenital abnormalities, and to review the literature. A 42-year-old woman was referred for amniocentesis at 18 weeks of gestation because of advanced maternal age. Prenatal ultrasound revealed bilateral choroid plexus cysts. Amniocentesis revealed a karyotype of 48,XXY,+18. The parental karyotypes were normal. Level II ultrasound revealed a flexion contracture deformity of the left wrist with absence of the thumb. The pregnancy was terminated at 22 weeks of gestation. A 332 g male fetus was delivered with clenched hands, arthrogryposis of the left wrist, aplasia of the left thumb, micrognathia, low-set ears, hypertelorism, rocker-bottom feet, and a normal penis. Quantitative fluorescent polymerase chain reaction assays using polymorphic DNA markers showed a triallelic pattern with a dosage ratio of 1:1:1 (paternal:maternal:maternal) for chromosome 18-specific markers, and a monoallelic pattern of a single maternal allele for chromosome X-specific markers. The fetus inherited two copies of two different maternal alleles on chromosome 18, and two copies of a single maternal allele on chromosome X. The molecular result, along with the karyotype of 48,XXY,+18, was consistent with the occurrence of nondisjunction of chromosome 18 in a maternal meiosis I error and nondisjunction of chromosome X in a maternal meiosis II error or less likely a postzygotic mitotic error. The present case provides evidence that abnormal separation of chromosomes 18 and X resulting in double aneuploidy may occur in different cell divisions, and such an occurrence is related to advanced maternal age.


[Systemic review of the safety and efficacy of fast-track surgery combined with laparoscopy in radical gastrectomy for gastric cancer].
To conduct a systemic review of the safety and efficacy of fast-track surgery combined with laparoscopy in radical gastrectomy for gastric cancer. The databases, including CNKI, Wangfang, VIP, PubMed, EMBASE and Cochrane Library, were searched to collect randomized controlled trials(RCTs) or clinical controlled trials(CCTs) on the comparison of fast-track surgery combined with laparoscopy versus fast-track surgery or laparoscopy separately used in radical gastrectomy for gastric cancer between January 1994 and December 2012. After data were extracted, meta-analysis was conducted by using RevMan 5.1.0 software. A total of 3 RCTs and 2 CCTs, involving 524 patients, were included. There were 257 patients in the study group and 267 patients in the control group. Compared with the control group, the study group had earlier first flatus(SMD=-1.29, 95%CI:-2.17 to -0.40, P<0.05), shorter postoperative hospital stay(WMD=-1.72,95%CI:-2.56 to -0.89, P<0.05) and lower postoperative complication rate(OR=0.51, 95%CI:0.31 to 0.84, P<0.05). However, no significant differences were found in operation time, harvested lymph node number, intraoperative blood loss and hospital charge(P>0.05). Fast-track surgery combined with laparoscopy in radical gastrectomy for gastric cancer can accelerate postoperative rehabilitation by promoting postoperative bowel function recovery, and decreasing postoperative hospital stay and complication rate.


Present status and performance of SPring-8 front ends.
SPring-8 front ends have a novel structure which makes it easy to rearrange them and exchange the components. The structure has a common support for all the components except X-ray beam-position monitors and lead collimators. The alignment of the common support as well as the components was carried out with an accuracy of 0.25 mm in the vertical and horizontal directions. Replaceable pumping systems have also been placed on the common support and have achieved a vacuum of 2 x 10(-8) Pa at the upstream part of the front ends without synchrotron radiation. During the commissioning with synchrotron radiation, the pumping systems displayed good pumping-down characteristics. Commissioning has been successfully performed for four standard in-vacuum X-ray undulators and three bending-magnet-beamline front ends up to July 1997. Measurements of temperature rise show that absorber, pre-slits and XY slits can handle the anticipated maximum heat load at a ring current of 100 mA.


Retinopathy screening in patients with type 1 diabetes diagnosed in young age using a non-mydriatic digital stereoscopic retinal imaging.
Diabetic retinopathy seriously impairs patients' quality of life, since it represents the first cause of blindness in industrialized countries. To estimate prevalence of retinopathy in young Type 1 diabetes patients using a non-mydriatic digital stereoscopic retinal imaging (NMDSRI), and to evaluate the impact of socio-demographic, clinical, and metabolic variables. In 247 young patients glycated hemoglobin (HbA1c), gender, age, pubertal stage, presence of diabetic ketoacidosis (DKA), HLA-DQ heterodimers of susceptibility for Type 1 diabetes, and β-cell autoimmunity at clinical onset were considered. At retinopathy screening, we evaluated age, disease duration, pubertal stage, body mass index (BMI-SDS), insulin requirement, HbA1c levels, other autoimmune diseases, diabetes-related complications, serum concentrations of cholesterol and triglycerides, systolic and diastolic blood pressure. Retinopathy was found in 26/247 patients: 25 showed background retinopathy, and 1 had a sight-threatening retinopathy. A significant relationship between retinopathy and female gender (p=0.01), duration of disease ≥15 yr (p<0.0001), serum triglycerides levels >65 mg/dl (p=0.012) and mean HbA1c ≥7.5% or >9% (p=0.0014) were found at the multivariate logistic analysis. Metabolic control is the most important modifiable factor and promotion of continuous educational process to reach a good metabolic control is a cornerstone to prevent microangiopathic complications. Symptoms appear when the complication is already established; a screening program with an early diagnosis is mandatory to prevent an irreversible damage.


[Infiltrating transitional carcinoma of the bladder. (1st part). Preoperative or neoadjuvant chemotherapy. Our experience with 38 patients followed-up for a prolonged period].
Analysis of the evolution of 37 patients treated with neoadjuvant chemotherapy + radical cystectomy and bilateral lymphadenectomy. Patients were followed until death, and survivors between 43 and 68 months. Twenty-six patients died. Twenty of them within 24 months after treatment and 6 after 2 years. Five did not undergo surgery due to fast tumour progression during the interval scheduled for cytostatics administration. Bladder removal was rejected in 5 cases after a significant loco-regional progression was shown by laparotomy. Initially, bladder was preserved in 12 patients after TUR + chemotherapy, and in 8 patients when cCR was observed: 1 died due to a disease unrelated cause. 1 was lost after 16 months with no evidence of vesical cancer or metastasis. 3 presented distant dissemination. 3 are alive and have no evidence of tumour. 1 pCR died of metastasis. 1 cPR required radical cystectomy and died of metastasis. Of the 2 cases defined as sCR, one had to undergo radical cystectomy and remains disease-free while the other one died of metastasis. Radical cystectomy was performed in 15 cases. Three remain tumour-free, 2 were lost. to follow-up and 10 died (3 for disease-unrelated causes and 7 as a consequence of their condition). Nodes affectation were present in 54%. Metastasis was found in 57.3% and 17.3% had local relapse. The pre-operative chemotherapy regime examined has not contributed to prolong the metastasis-free interval in the group of patients studied.


Preventive Behavior Intentions for Polycystic Ovary Syndrome in Young Students.
Objective: Polycystic ovary syndrome (PCOS) is among the most common, yet treatable causes of infertility. This study explored how South Korean female college students' health beliefs and knowledge of PCOS are associated with their preventive behavior intentions. Methods: Data for this cross-sectional study were collected using an online survey of 328 female university students from July 25 to August 30, 2020. Data were analyzed using the chi-squared test and t-test, Pearson's r, and hierarchical multiple regression analysis. Results: The average age of participants was 21.67 years, 7.3% of whom had been diagnosed with PCOS. Perceived disability (β = 0.30, P < 0.001) and perceived benefit (β = 0.26, P < 0.001) of health behavior were associated with preventive behavior intentions. However, knowledge was not a significant factor. Conclusions: Health beliefs are related to the preventive behavior intentions of women with PCOS. Education to strengthen health beliefs should be provided to female university students.


Small-Area Estimation of Smoke-Free Workplace Policies and Home Rules in US Counties.
The workplace and home are sources of exposure to secondhand smoke, a serious health hazard for nonsmoking adults and children. Smoke-free workplace policies and home rules protect nonsmoking individuals from secondhand smoke and help individuals who smoke to quit smoking. However, estimated population coverages of smoke-free workplace policies and home rules are not typically available at small geographic levels such as counties. Model-based small-area estimation techniques are needed to produce such estimates. Self-reported smoke-free workplace policies and home rules data came from the 2014-2015 Tobacco Use Supplement to the Current Population Survey. County-level design-based estimates of the two measures were computed and linked to county-level relevant covariates obtained from external sources. Hierarchical Bayesian models were then built and implemented through Markov Chain Monte Carlo methods. Model-based estimates of smoke-free workplace policies and home rules were produced for 3134 (of 3143) US counties. In 2014-2015, nearly 80% of US adult workers were covered by smoke-free workplace policies, and more than 85% of US adults were covered by smoke-free home rules. We found large variations within and between states in the coverage of smoke-free workplace policies and home rules. The small-area modeling approach efficiently reduced the variability that was attributable to small sample size in the direct estimates for counties with data and predicted estimates for counties without data by borrowing strength from covariates and other counties with similar profiles. The county-level modeled estimates can serve as a useful resource for tobacco control research and intervention. Detailed county- and state-level estimates of smoke-free workplace policies and home rules can help identify coverage disparities and differential impact of smoke-free legislation and related social norms. Moreover, this estimation framework can be useful for modeling different tobacco control variables and applied elsewhere, for example, to other behavioral, policy, or health related topics.


A reassessment of the phylogenetic utility of genus-level morphological characters in the family Bogidiellidae (Crustacea, Amphipoda), with description of a new species of Eobogidiella Karaman, 1981.
Bogidiellidae is the most diverse and cosmopolitan family of stygobiotic amphipods, and inhabits a variety of subterranean biotopes, especially interstitial habitats. While the family is characterized by considerable sexual dimorphism, this dimorphism has adversely affected our understanding of the systematics of the group. Most species have restricted geographic ranges and occur in difficult to sample habitats, so it is common for individual species descriptions to be based on a single sex. In this work we revisit an analysis of morphological characters in an attempt to clarify their phylogenetic utility in resolving taxonomic relationships among genera by introducing a new species, two additional characters, and phylogenetic statistical support values. Eobogidiella venkataramani sp. n., from a spring fed brook in the Shirawati River basin along the escarpment of the Western Ghats (Karnataka, India) differs from the only known congener, Eobogidiella purmamarcensis, from Argentina, in the structure of mouthparts, the shape and ornamentation on gnathopods and characters of the telson. Our phylogenetic analyses indicate that the available morphological characters are not sufficient to resolve phylogenetic relationships within Bogidiellidae, thus these characters alone cannot be used to determine the phylogenetic placement of Eobogidiella venkataramani sp. n. within the family. Nevertheless, Eobogidiella venkataramani sp. n. shares diagnostic characters with Eobogidiella, supporting placement of the new species in this genus. Our findings point towards a critical need to resolve relationships within the family using molecular approaches, along with the development of a suite of additional morphological characters for Bogidiellidae. This is the third species of Bogidiellidae from southern India.


Iron-induced susceptibility effect at the globus pallidus causes underestimation of flow and volume on dynamic susceptibility contrast-enhanced MR perfusion images.
Age-related iron accumulation in extrapyramidal nuclei causes T2 shortening, which may result in decreased signal intensity in these areas on MR images. Because the dynamic susceptibility contrast-enhanced technique uses heavily T2*- or T2-weighted images, the iron-induced susceptibility may have direct impact on perfusion imaging. The purpose of this study was to assess the effect of iron-induced susceptibility on the calculated perfusion parameters. The difference of this effect between gradient-echo and spin-echo sequences was also assessed. Dynamic susceptibility contrast-enhanced MR perfusion imaging data of 12 patients were used for this study. Perfusion images were obtained using a single shot spin-echo echo-planar imaging sequence in seven patients and a gradient-echo echo-planar imaging sequence in five patients. Region of interest measurements of relative cerebral blood flow, relative cerebral blood volume, and mean transit time were obtained at various parts of the gray matter, including the globus pallidus, putamen, caudate nucleus, thalamus, and cerebral cortex of temporal, frontal, and occipital lobes. The baseline signal intensity on the source images and the magnitude of signal change (DeltaR2* or DeltaR2) were also assessed. The globus pallidus had statistically significantly lower values of relative cerebral blood flow, relative cerebral blood volume, baseline signal intensity, and magnitude of signal change compared with other parts of the gray matter for both gradient-echo and spin-echo sequences (P <.05). Underestimations of these values were more prominent for the gradient-echo than for the spin-echo sequence. Little variance in the measured mean transit time was noted. Iron-induced susceptibility effect may lead to underestimation of relative cerebral blood flow and relative cerebral blood volume in the basal ganglia.


Application of locked nucleic acids to improve aptamer in vivo stability and targeting function.
Aptamers are powerful candidates for molecular imaging applications due to a number of attractive features, including rapid blood clearance and tumor penetration. We carried out structure-activity relationship (SAR) studies with the Tenascin-C binding aptamer TTA1, which is a promising candidate for application in tumor imaging with radioisotopes. The aim was to improve its in vivo stability and target binding. We investigated the effect of thermal stabilization of the presumed non-binding double-stranded stem region on binding affinity and resistance against nucleolytic degradation. To achieve maximal thermal stem stabilization melting experiments with model hexanucleotide duplexes consisting of unmodified RNA, 2'-O-methyl RNA (2'-OMe), 2'-Fluoro RNA (2'-F) or Locked Nucleic Acids (LNAs) were initially carried out. Extremely high melting temperatures have been found for an LNA/LNA duplex. TTA1 derivatives with LNA and 2'-OMe modifications within the non-binding stem have subsequently been synthesized. Especially, the LNA-modified TTA1 derivative exhibited significant stem stabilization and markedly improved plasma stability while maintaining its binding affinity to the target. In addition, higher tumor uptake and longer blood retention was found in tumor-bearing nude mice. Thus, our strategy to introduce LNA modifications after the selection procedure is likely to be generally applicable to improve the in vivo stability of aptamers without compromising their binding properties.


A bacteriological study of rampant caries in children.
We undertook a microbiological study, in children, of dental plaque from sound surfaces or associated with rampant caries, both black-colored and unstained. Improved selective media allowed for the enumeration of bacteria belonging to specific genera or species present in plaque samples. A nearly similar bacterial distribution was found in both types of rampant caries. Aciduric flora, Streptococcus mutans, Veillonella, and Lactobacillus predominated in plaque over the lesions, whereas extracellular polysaccharide-producing streptococci other than S. mutans, as well as Actinomyces, were more abundant in plaque from sound surfaces. However, more lactobacilli and Actinomyces were recovered from pigmented lesions than from the unstained ones. These findings suggest that the microbial flora associated with black-pigmented lesions did not strongly differ from that observed over unstained caries lesions.


CKD and bladder problems in children.
Approximately 35% of children with CKD who require renal replacement therapy have a significant urological abnormality, including posterior urethral valves, a neuropathic bladder, prune belly syndrome, Hinman syndrome, or severe vesicoureteral reflux. In such children, abnormal bladder function can have a significant deleterious effect on the renal function. In children with bladder outlet obstruction, bladder compliance and capacity often are abnormal, and a sustained intravesical pressure of >40 cm H(2)O impedes drainage from the upper urinary tract. Consequently, in these conditions, regular evaluation with renal sonography, urodynamics, urine culture, and serum chemistry needs to be performed. Pediatric urological care needs to be coordinated with pediatric nephrologists. Many boys with posterior urethral valves have severe polyuria, resulting in chronic bladder overdistension, which is termed as valve bladder. In addition to behavioral modification during the day, such patients may benefit from overnight continuous bladder drainage, which has been shown to reduce hydronephrosis and stabilize or improve renal function in most cases. In children with a neuropathic bladder, detrusor-sphincter-dyssynergia is the most likely cause for upper tract deterioration due to secondary vesicoureteral reflux, hydronephrosis, and recurrent urinary tract infection (UTI). Pharmacologic bladder management and frequent intermittent catheterization are necessary. In some cases, augmentation cystoplasty is recommended; however, this procedure has many long-term risks, including UTI, metabolic acidosis, bladder calculi, spontaneous perforation, and malignancy. Nearly half of children with prune belly syndrome require renal replacement therapy. Hinman syndrome is a rare condition with severe detrusor-sphincter discoordination that results in urinary incontinence, encopresis, poor bladder emptying, and UTI, often resulting in renal impairment. Children undergoing evaluation for renal transplantation need a thorough evaluation of the lower urinary tract, mostly including a voiding cystourethrogram and urodynamic studies.


Histologic and biochemical alterations predict pulmonary mechanical dysfunction in aging mice with chronic lung inflammation.
Both aging and chronic inflammation produce complex structural and biochemical alterations to the lung known to impact work of breathing. Mice deficient in surfactant protein D (Sftpd) develop progressive age-related lung pathology characterized by tissue destruction/remodeling, accumulation of foamy macrophages and alteration in surfactant composition. This study proposes to relate changes in tissue structure seen in normal aging and in chronic inflammation to altered lung mechanics using a computational model. Alterations in lung function in aging and Sftpd -/- mice have been inferred from fitting simple mechanical models to respiratory impedance data (Zrs), however interpretation has been confounded by the simultaneous presence of multiple coexisting pathophysiologic processes. In contrast to the inverse modeling approach, this study uses simulation from experimental measurements to recapitulate how aging and inflammation alter Zrs. Histologic and mechanical measurements were made in C57BL6/J mice and congenic Sftpd-/- mice at 8, 27 and 80 weeks of age (n = 8/group). An anatomic computational model based on published airway morphometry was developed and Zrs was simulated between 0.5 and 20 Hz. End expiratory pressure dependent changes in airway caliber and recruitment were estimated from mechanical measurements. Tissue elements were simulated using the constant phase model of viscoelasticity. Baseline elastance distribution was estimated in 8-week-old wild type mice, and stochastically varied for each condition based on experimentally measured alteration in elastic fiber composition, alveolar geometry and surfactant composition. Weighing reduction in model error against increasing model complexity allowed for identification of essential features underlying mechanical pathology and their contribution to Zrs. Using a maximum likelihood approach, alteration in lung recruitment and diminished elastic fiber density were shown predictive of mechanical alteration at airway opening, to a greater extent than overt acinar wall destruction. Model-predicted deficits in PEEP-dependent lung recruitment correlate with altered lung lining fluid composition independent of age or genotype.


Transcription factor Sp1 activates the expression of the mouse tenascin-X gene.
Tenascin-X (TNX) is an extracellular matrix protein that is prominent in the heart and muscle. We previously showed that TNX is expressed in fibroblast cells in culture. To elucidate the molecular basis of the TNX gene expression, the promoter region of the mouse TNX gene (mTnx) has been characterized. The two adjacent transcription initiation sites were identified at 68 and 67 bp upstream of the previously known 5'-untranslated exon. Transient transfection of L and 293T cells with 5'-deletion constructs of the promoter region linked to the luciferase reporter revealed that the region (-141 to -136) containing a transcription factor Sp1-binding element contributes to the expression of mTnx. Site-directed mutagenesis of the Sp1-binding region confirmed this result. Electrophoretic mobility shift analysis using nuclear extracts obtained from the cells demonstrated that a distinct Sp1-DNA complex is formed at the element. Our results show that Sp1 plays a critical role in the gene expression of mTnx.


Detoxification of the explosive 2,4,6-trinitrotoluene in Arabidopsis: discovery of bifunctional O- and C-glucosyltransferases.
Plants, as predominantly sessile organisms, have evolved complex detoxification pathways to deal with a diverse range of toxic chemicals. The elasticity of this stress response system additionally enables them to tackle relatively recently produced, novel, synthetic pollutants. One such compound is the explosive 2,4,6-trinitrotoluene (TNT). Large areas of soil and groundwater are contaminated with TNT, which is both highly toxic and recalcitrant to degradation, and persists in the environment for decades. Although TNT is phytotoxic, plants are able to tolerate low levels of the compound. To identify the genes involved in this detoxification process, we used microarray analysis and then subsequently characterized seven uridine diphosphate (UDP) glycosyltransferases (UGTs) from Arabidopsis thaliana (Arabidopsis). Six of the recombinantly expressed UGTs conjugated the TNT-transformation products 2- and 4-hydroxylaminodinitrotoulene, exhibiting individual bias for either the 2- or the 4-isomer. For both 2- and 4-hydroxylaminodinitrotoulene substrates, two monoglucose conjugate products, confirmed by HPLC-MS-MS, were observed. Further analysis indicated that these were conjugated by either an O- or C-glucosidic bond. The other major compounds in TNT metabolism, aminodinitrotoluenes, were also conjugated by the UGTs, but to a lesser extent. These conjugates were also identified in extracts and media from Arabidopsis plants grown in liquid culture containing TNT. Overexpression of two of these UGTs, 743B4 and 73C1, in Arabidopsis resulted in increases in conjugate production, and enhanced root growth in 74B4 overexpression seedlings. Our results show that UGTs play an integral role in the biochemical mechanism of TNT detoxification by plants.


[Drivers' random controls and population's recent drug use monitoring].
Substance abuse, particularly among young people, does not seem to have the tendency to decrease. Our knowledges on this phenomenon are manifold and they validly compete to address the actions of contrast. Nevertheless, it would seem profit to be able to have further informations, to place side by side to those already existing, with the aim to improve the surveillance of the phenomenon. For this purpose, in the present paper we propose a monitoring model based on the results of random controls on road, carried out by the Police (or by the Hospital) in relationship to the road safety. The representativeness of the data that we could get this way appears elevated as an hight percentage of the population own the driver's licence. As it is shown, these controls could be both individual and related to drivers' pools of biological samples. This last approach would seem to be more practicable since problems relating to the drivers' privacy would be avoided.


Protein kinase C-dependent supply of secretory granules to the plasma membrane.
To elucidate the mechanism for supplying secretory granules to the cell membrane, chromaffin cells isolated from the bovine adrenal medulla were observed by the evanescent wave microscopy after staining their granules with acridine orange. The secretory granules showed only a very small fluctuation, indicating their docking to the plasma membrane. The rate and range of movement increased greatly by application of botulinum toxin A or C. The number of secretory granules docked to the plasma membrane significantly decreased by botulinum toxin C. Conversely, the number increased greatly by activation of protein kinase C with phorbol 12,13-dibutyrate (PDBu). In the presence of an anti-actin reagent cytochalasin D, no increasing effect of PDBu on the number of docked granules was observed. While in the presence of an anti-mitotic reagent, colchicine, a clear increasing effect of PDBu was observed. The final step for supplying granules to the plasma membrane in endocrine cells is concluded to be mediated by a phosphorylation-dependent and actin-based transport system.


Nitrate Reductase in Barley Roots under Sterile, Low Oxygen Conditions.
Levels of nitrate reductase activity (EC 220.127.116.11.) as high as 11 mumoles nitrite produced/hour gram fresh weight were found in barley (Hordeum vulgare cv. Compana) roots grown under low oxygen conditions. Roots of plants given identical treatment under sterile conditions did not develop the high levels of nitrate reductase activity. The results suggest that the buildup of particulate, reduced viologen-utilizing nitrate reductase reported in barley roots may be caused by bacterial contamination. The nitrate reductase activity in roots grown under low oxygen conditions was not specific for reduced nicotinamide adenine dinucleotide like the assimilatory nitrate reductase (EC 220.127.116.11.) normally found in aerated plant roots.


Sebaceous carcinoma arising in nevus sebaceus.
A 53-year-old woman had had a pale-brown lesion on her right cheek and neck from birth. Since she was about 40 years old, part of the lesion had gradually elevated and increased in size. At the first examination, there was a huge mass measuring 110 x 70 x 35 mm on the right cheek. A wide local excision of the area including a superficial parotidectomy and submandibular lymph node dissection was performed, followed by full thickness skin grafting. Histological examination of the tumor revealed an invasive dermal neoplasm characterized by lobes that were composed of foamy cells stained with Sudan-IV mixed with many atypical cells showing remarkable variation in the shapes and sizes of their nuclei. The surrounding epithelial changes were consistent with nevus sebaceus. From these findings, the gigantic tumor was diagnosed as a sebaceous carcinoma arising in nevus sebaceus.


Lateral shifting of the first metatarsal head in hallux valgus surgery: effect on sesamoid reduction.
Thirty feet with hallux valgus (HV) having grade 2 and 3 sesamoid stations on AP radiographs were examined after Lindgren-Turan oblique distal metatarsal osteotomy with a minimum follow-up of 12 months. Adductor tendon release from the lateral sesamoid was not performed to determine the isolated effect of distal metatarsal osteotomy on metatarsosesamoidal reduction. Of the 30 feet, 20 (67%) had reduced and 10 (33%) unreduced sesamoids at the follow-up. Ultimately, distal metatarsal osteotomy (DMO) with lateral shifting of the first metatarsal head more than 7.2 mm was found to reduce the sesamoids in the great majority of the cases (95% CI 7.243-9.757). Sesamoid release is redundant for metatarsosesamoidal reduction if sufficient lateral shift of the first metatarsal head over the sesamoids is accomplished.


[Corrigendum] miR‑29b overexpression induces cochlear hair cell apoptosis through the regulation of SIRT1/PGC‑1α signaling: Implications for age‑related hearing loss.
Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that the bar charts shown in Fig. 4A and B, which were intending to have shown the RT‑qPCR and western blot analyses of SIRT1 and PGC‑1α in HEI‑OC1 cells, respectively, under different experimental conditions were apparently identical. Similarly, in Fig. 5, the histograms shown in Fig. 5C and D, which were intending to have shown the RT‑qPCR and western blot analyses, respectively, of SIRT1 and PGC‑1α in HEI‑OC1 cells subjected to different treatments were also apparently identical. The authors have re‑examined their data, and realize that the data properly belonging to the protein expression levels had been wrongly used to show the mRNA levels, and therefore Figs. 4A and 5C were presented incorrectly in these figures. The revised versions of Figs. 4 and 5, containing the correct data for the RT‑qPCR experiments in Figs. 4A and 5C, are shown on the next page. These errors did not affect the major conclusions reported in the paper. All the authors have agreed to this corrigendum, and thank the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this. The authors regret these errors went unnoticed during the compilation of the figures in question, and apologize to the readership for any confusion that this may have caused. [the original article was published in International Journal of Molecular Medicine 38: 1387‑1394, 20186 DOI: 10.3892/ijmm.2016.2735].


Electron Microscopy Revealed Massive Lipid Droplets in Cardiomyocytes in a Patient with Cardiogenic Shock Following a Fulminant Type 1 Diabetes Mellitus.
A 52-year-old man with consciousness disorder following a 2-day history of general fatigue, diarrhea, vomiting and excessive thirst was admitted to our hospital. Severe hyperglycemia (1,739 mg/dL) with a slightly elevated HbA1c level (6.9%), ketonuria and low C-peptide level (0.07 ng/mL) confirmed the diagnosis of fulminant type 1 diabetes mellitus (FT1DM). Following sudden unexplained cardiogenic shock shortly after the initiation of insulin therapy with no evidence of myocardial ischemia assessed by coronary angiography, the patient was supported with percutaneous venoarterial extracorporeal membrane oxygenation. Electron microscopic analysis of the myocardium revealed massive lipid droplets without the infiltration of inflammatory cells. His left ventricular function began to recover during the following days and returned to a normal level on day 14. Currently, the impact of FT1DM on intramyocardial lipid deposition is poorly understood. However, this case suggests that even short-term exposure to high concentrations of glucose can be responsible for lipotoxicity followed by severe cardiac dysfunction.


Ethyl 1-(butan-2-yl)-2-(2-meth-oxy-phen-yl)-1H-benzimidazole-5-carboxyl-ate.
In the title compound, C(21)H(24)N(2)O(3), the mean planes of the benzene ring and the benzimidazole ring system form a dihedral angle of 69.94 (7)°. The ethyl group atoms of the ethano-ate fragment are disordered over two sets of sites, with refined occupancies of 0.742 (6) and 0.258 (6). In the crystal, there are weak C-H⋯N hydrogen bonds which connect mol-ecules into chains along the b axis. A weak inter-molecular C-H⋯π inter-action is also observed.


Cognate gene clusters govern invasion of host epithelial cells by Salmonella typhimurium and Shigella flexneri.
The enteric pathogens Salmonella typhimurium and Shigella flexneri differ in most virulence attributes including infectivity, pathology and host range. We have identified a new assemblage of genes responsible for invasion properties of Salmonella which is remarkably similar in order, arrangement and sequence to the gene cluster controlling the presentation of surface antigens (spa) on the virulence plasmid of Shigella. In Salmonella, this chromosomally encoded complex consists of over 12 genes, mutations in which abolish bacterial entry into epithelial cells. Although these genera use distinct invasion antigens, a non-invasive spa mutant of Salmonella could be rescued by the corresponding Shigella homolog. While spa promotes equivalent functions in Shigella and Salmonella, this constellation of genes has been acquired independently by each genus and displays motifs used by diverse antigen export systems including those required for flagellar assembly and protein secretion.


[Tracheal stenosis by extrinsic compression: a case of anterior cervical hypertrophic osteophytosis].
Anterior Cervical Hypertrophic Osteophytosis (ACHO) is a clinical entity caused by degenerative changes of the cervical spine. ACHO may also be found in Diffuse Idiopathic Skeletal Hyperostosis (DISH)1-3, Ankylosing Spondylitis and Post-traumatic Osteophytogenesis. In a minority of cases it may lead to oesophagical manifestations and less commonly, to respiratory complaints. The authors report the case of a 75-year-old male with a personal history of chronic tophaceous gout and chronic obstructive lung disease. The patient presented with a history of progressive worsening of dyspnoea and dysphagia (for solid food) as well as foreign body sensation at the cervical level. On general examination, the patient presented with slightly diminished breath sounds and an increased expiratory time. On rheumatologic examination, the patient had moderate limitation of all cervical movements, crepitating knees and multiple gout tophi in both hands. Cervical plain radiographs showed large anterior osteophytes at the level of C4 and C5. Flexible videobronchoscopy was also performed, showing an angle of distortion in the upper third of the tracheal wall, caused by extrinsic compression. These changes were confirmed by cervical CT scan which also documented an anterior sliding of the oesophagus due to large anterior cervical osteophytes. Videofluoroscopic swallow study revealed the presence of paradoxal contraction of the cricopharyngeal muscle. The patient was treated with a non-steroidal anti-inflammatory drug (NSAID) and a skeletal muscle relaxant. Dysphagia improved but not the respiratory symptoms. Although there was indication for surgical removal of the hypertrophic osteophytes, the patient refused surgery and continues to be followed-up regularly at our outpatient clinic.


[Construction and immunogenicity of recombinant adenovirus tandem expressing M and GP5 of porcine reproductive and respiratory syndrome virus].
The M protein gene of porcine reproductive and respiratory syndrome virus amplified by PCR was tandem linked with its GP5 gene in shuttle vector in correct frame, resulting in shuttle vector pShuttle-CMV-M-GP5. The positive clone was identified by PCR and further confirmed by sequencing. The constructed plasmid was linearized with Pme I and co-transformed BJ5183 host bacteria with pAdEasy-1 to produce recombinant adenovirus DNA by homologous recombination. Then the adenovirus DNA was linearized with Pac I and transfected into HEK-293A cells to obtain recombinant adenovirus. The specific expression of target proteins by the recombinant adenovirus was verified by indirect immuno-fluorescence assay (IFA) with monoclonal antibodies against M and GP5.The results showed that the tandem linked M with GP5 could be co-expressed by adenovirus vector. Mice immunized with the constructed recombinant adenovirus induced strong humoral immunity (ELISA antibody and virus neutralizing antibody) and cellular immunity (lymphocyte proliferation and CTL responses). The results showed that the recombinant adenovirus has strong immunogenicity and provided the basis for the further experiments in pigs.


Function of multiple sclerosis-protective HLA class I alleles revealed by genome-wide protein-quantitative trait loci mapping of interferon signalling.
Interferons (IFNs) are cytokines that are central to the host defence against viruses and other microorganisms. If not properly regulated, IFNs may contribute to the pathogenesis of inflammatory autoimmune, or infectious diseases. To identify genetic polymorphisms regulating the IFN system we performed an unbiased genome-wide protein-quantitative trait loci (pQTL) mapping of cell-type specific type I and type II IFN receptor levels and their responses in immune cells from 303 healthy individuals. Seven genome-wide significant (p < 5.0E-8) pQTLs were identified. Two independent SNPs that tagged the multiple sclerosis (MS)-protective HLA class I alleles A*02/A*68 and B*44, respectively, were associated with increased levels of IFNAR2 in B and T cells, with the most prominent effect in IgD-CD27+ memory B cells. The increased IFNAR2 levels in B cells were replicated in cells from an independent set of healthy individuals and in MS patients. Despite increased IFNAR2 levels, B and T cells carrying the MS-protective alleles displayed a reduced response to type I IFN stimulation. Expression and methylation-QTL analysis demonstrated increased mRNA expression of the pseudogene HLA-J in B cells carrying the MS-protective class I alleles, possibly driven via methylation-dependent transcriptional regulation. Together these data suggest that the MS-protective effects of HLA class I alleles are unrelated to their antigen-presenting function, and propose a previously unappreciated function of type I IFN signalling in B and T cells in MS immune-pathogenesis.


Oral health of a Brazilian population on renal dialysis.
The purpose of this study was to assess the oral health of patients with chronic renal failure (CRF) undergoing hemodialysis in Brazil. A dentist examined 160 subjects aged 40 to 85 years of age. Data was collected on dental caries, use of and need for dentures, oral mucosa, periodontal disease and temporomandibular joint status. All subjects were interviewed about their socioeconomic status, dental and medical history, and oral hygiene habits. Most subjects had hypertension (49.4%); used the public service for their medical care (69.4%); had a middle school educational level (83.1%); and did not complain of xerostomia (60.0%). The majority used private oral healthcare services and used a toothbrush only for oral hygiene. The mean DMFT was 26.0 (standard deviation 7.7). Most individuals did not wear dentures, but needed some type of prosthesis. Lesions of the oral mucosa (3.1%), signs (2.5%) and symptoms (3.8%) of temporomandibular dysfunction could be observed in only a few patients. The oral health of the subjects examined was poor. These persons needed their oral condition monitored by a dentist and their oral disease treated as well as receiving instruction on oral hygiene.


[Dosimetry with phantom for total body irradiation(TBI)].
Total body irradiation(TBI) is being used as a method of preparation for bone marrow transplantation(BMT). In TBI, the dose calculation is based on dosimetry using a phantom. We measured the basic dose with a phantom using a 10 MV X-rays. We confirmed the accuracy of the dose calculation performed in our facilities and investigated a method of more accurate dosimetry. We measured the variation in dose according to the size of the phantom and the depth using a tough water phantom, and examined the difference in TMR according to SCD, field size, and size of the phantom. Consequently, the dose has been changed regardless of the size of the phantom at larger than 80 x 30 x 30 cm(3), and it is about 1% larger than 30 x 30 x 30 cm(3). Also TMR has changed according to various conditions, including the size of the phantom, field size, and SCD. Therefore, it was found that dosimetry using the 30 x 30 x 30 cm(3) phantom leads to underestimation in dose calculation, and there is no difference in dose between the field size of 151.5 x 160 cm(2) and 151.5 x 80 cm(2). It is also necessary to consider the effect of the vertical size of the phantom.


[Targeting therapy using a monoclonal antibody against tumor vascular endothelium].
Recent studies have revealed that the targeting therapy using monoclonal antibody against tumor associated antigens did not have a clinically satisfactory effect due to various physiological characters of tumor. We propose a novel approach targeting tumor vascular endothelium to solve the inefficiency of common tumor missile therapy. In this study, the tissue distribution of anti-tumor vascular endothelium monoclonal antibody (TES-23) produced by immunizing with plasma membrane vesicles obtained from isolated rat tumor-derived endothelial cells (TECs) was assessed in various tumor-bearing animals. Radiolabeled TES-23 dramatically accumulated in KMT-17 fibrosarcoma, a source of isolated TECs after intravenous injection. In Meth-A fibrosarcoma, Colon-26 adenocarcinoma in BALB/c mice and HT-1080 human tumor tissue in nude mice, radioactivities of 125I-TES-23 were also up to fifty times higher than those of control antibody with little distribution to normal tissues. Furthermore, immunostaining of human tissue sections showed specific binding of TES-23 on endothelium in esophagus and colon cancers. These results indicate that tumor vascular endothelial cells express a common antigen in different tumor types of various animal species. In order to clarify the efficacy of TES-23 as a drug carrier, an immunoconjugate, composed of TES-23 and neocarzinostatin, was tested for its antitumor effect in vivo. The immunoconjugate (TES-23-NCS) caused a marked regression of the tumor, KMT-17 in rats and Meth-A in mice. Thus, from a clinical view, TES-23 would be a novel drug carrier because of its high specificity to tumor vascular endothelium and its application to many types of cancer.


Inhibition by interferon of herpes simplex virus type 1-activated transcription of tat-defective provirus.
The herpes simplex virus type 1 (HSV-1)-mediated transactivation of human immunodeficiency virus type 1 (HIV-1) provirus was studied in cell lines containing either integrated tat-defective HIV-1 provirus (HNHIVdt4 cells) or the tat-defective HIV-1 provirus, and a plasmid in which the expression of human alpha 2 interferon (HuIFN-alpha 2) was under the control of the HIV-1 long terminal repeat (LTR) (HNHIV alpha 1 cells). In both cell lines, transcription of the HIV-1 provirus was below the limits of detection, but it could be induced effectively by transfection with a HIV-1 tat-expression plasmid. In HNHIV alpha 1 cells, HuIFN-alpha 2 was induced concomitantly with HIV-1 provirus, although these cells synthesized only low levels of IFN constitutively. In contrast, infections with HSV-1 activated transcription of HIV-1 provirus only in HNHIVdt4 cells but not in HNHIV alpha 1 cells. Similarly in a transient expression assay, HSV-1 up-regulated expression of a HIV LTR-CAT (chloramphenicol acetyltransferase gene) plasmid in HNHIVdt4 but not in HNHIV alpha 1 cells. No major differences could be detected in the expression of HSV-1 immediate-early (IE) genes IE175 and IE110 (which are essential for the activation of HIV-1 LTR) in HNHIVdt4 and HNHIV alpha 1 cells to account for the inability of HSV-1 to induce HIV-1 in HNHIV alpha 1 cells. However, major differences were observed in the binding pattern of NF-kappa B-specific nuclear proteins to the enhancer region of the HIV-1 LTR: whereas binding of the 45-kDa NF-kappa B-specific nuclear protein was detected in nuclear extracts from HNHIVdt4 cells, no protein binding was seen in extracts from HNHIV alpha 1 cells. These results suggest an alternate mechanism by which IFN may alter the expression of cellular and viral genes.


Treatment for Chiari 1 malformation (CIM): analysis of a pediatric surgical series.
Children may present a peculiar picture of CIM, as syncopes and acute paraparesis. In a series of 99 children operated for CIM at FINCB there were no major surgical morbidity nor mortality. The preoperative symptoms improved more in this pediatric series than in the adult cases treated at the same institution in the same period; a reason could be the shorter duration of symptoms and another the children plasticity. An untreated nonsyndromic craniosynostosis was present in 10 cases. In our hands, the results of the limited extradural decompression were poor. In some CIM associated with psychiatric symptoms an unexpected improvement was observed after tonsilar resection. The associated Syringomyelia reduced in more than 80% of children and disappeared in a significant number. The rare associated tethered cord (5%) needed a double treatment, detethering by itself being insufficient to treat also tonsillar descent. The clinical symptoms are often more serious in children than in the adults, but the results of surgery, especially on the syrinx, are better.


An unusual cause of pelvic pain: struma ovarii.
A 22 year old female patient presented with a three month history of pelvic discomfort and dysmenorrhoea. A pelvic MRI demonstrated a large mass measuring 10 x 6 cm in size. On T1 and T2 weighted images the mass was noted to be predominantly cystic. The mass also contained peripheral solid components as well as a large fat fluid level. Following excision, histological examination revealed a lesion with mature teratomatous elements but with a significant component (> 50%) being composed of mature thyroid tissue. A 2cm area within the lesion had the morphological pattern of a classical papillary thyroid carcinoma. A diagnosis of struma ovarii was made. Struma ovarii is a rare ovarian neoplasm generally arising in a teratoma and accounts for less than 1% all ovarian neoplasms. Here we present the above case of struma ovarii in a young patient and discuss the radiological characteristics of the disease.


[Health sector reform in Peru: Law, governance, universal coverage, and responses to health risks].
In 2013, Peru initiated a reform process under the premise of recognizing the nature of health as a right that must be protected by the state. This reform aimed to improve health conditions through the elimination or reduction of restrictions preventing the full exercise of this right, and the consequent approach aimed to protect both individual and public health and rights within a framework characterized by strengthened stewardship and governance, which would allow system conduction and effective responses to risks and emergencies. The reform led to an increase in population health insurance coverage from 64% to 73%, with universalization occurring through the SIS affiliation of every newborn with no other protection mechanism. Health financing increased by 75% from 2011, and the SIS budget tripled from 570 to 1,700 million soles. From 2012 to May 2016, 168 health facilities have become operational, 51 establishments are nearing completion, and 265 new projects are currently under technical file and work continuity with an implemented investment of more than 7 billion soles. Additionally, this reform led to the approval of the Ministry of Health intervention for health emergencies and strengthened the health authority of the ministry to implement responses in case of risks or service discontinuity resulting from a lack of regional or local government compliance with public health functions.


Recurrent malignant epitheloid schwannoma of the lower lip.
The authors describe a case of recurrent malignant epitheloid schwannoma of the lower lip. Histologically, the tumor was composed of fibroblast-like spindle cells in compact fascicles and areas of epitheloid growth, combined with demonstration of S-100, GFAP and NF positivity, which is characteristic for this type of tumor. The therapy consisted of a combination of surgery and radiotherapy and the patient was followed-up since the disease was diagnosed. A local re-operation had to follow the first surgical intervention consisting of a radical excision of tumor in the lower lip together with suprahyoid neck dissection six months later. After the first operation, the patient received a radiation therapy with a total dosage of 12 Gy in seven fractions to the tumor area of the lower lip. After the second operation, an external radiotherapy with total dosage of 50 Gy was applied. Despite the complex intensive therapy, the patient died of metastases into lungs, liver and spine 37 months after the initiation of the therapy (Fig. 2, Ref. 17). Full Text (Free, PDF) www.bmj.sk.


Impact of exercise and a complex environment on hippocampal dendritic morphology, Bdnf gene expression, and DNA methylation in male rat pups neonatally exposed to alcohol.
Alcohol exposure in utero can result in Fetal Alcohol Spectrums Disorders (FASD). Measures of hippocampal neuroplasticity, including long-term potentiation, synaptic and dendritic organization, and adult neurogenesis, are consistently disrupted in rodent models of FASD. The current study investigated whether third trimester-equivalent binge-like alcohol exposure (AE) [postnatal days (PD) 4-9] affects dendritic morphology of immature dentate gyrus granule cells, and brain-derived neurotrophic factor (Bdnf) gene expression and DNA methylation in hippocampal tissue in adult male rats. To understand immediate impact of alcohol, DNA methylation was measured in the PD10 hippocampus. In addition, two behavioral interventions, wheel running (WR) and environmental complexity (EC), were utilized as rehabilitative therapies for alcohol-induced deficits. AE significantly decreased dendritic complexity of the immature neurons, demonstrating the long-lasting impact of neonatal alcohol exposure on dendritic morphology of immature neurons in the hippocampus. Both housing conditions robustly enhanced dendritic complexity in the AE animals. While Bdnf exon I DNA methylation was lower in the AE and sham-intubated animals compared with suckle controls on PD10, alterations to Bdnf DNA methylation and gene expression levels were not present at PD72. In control animals, exercise, but not exercise followed by housing in EC, resulted in higher levels of hippocampal Bdnf gene expression and lower DNA methylation. These studies demonstrate the long-lasting negative impact of developmental alcohol exposure on hippocampal dendritic morphology and support the implementation of exercise and complex environments as therapeutic interventions for individuals with FASD. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 708-725, 2017.


Actinomycin D: inhibition of respiration and glycolysis.
Actinomycin D inhibited respiration and anaerobic glycolysis of human leukemic leukocytes and lowered the adenosine triphosphate content of the cells. Inhibitory effects on respiration and on RNA synthesis could not be dissociated from one another over a wide range of drug concentrations. Actinomycin D also impaired protein synthesis, probably by decreasing the availability of adenosine triphosphate and by inhibiting messenger RNA.


Early Locoregional Breast Surgery and Survival in de novo Metastatic Breast Cancer in the Multicenter National ESME Cohort.
The aim was to evaluate the impact of local surgery performed during the year after MBC diagnosis on patients' outcomes from a large reallife cohort. Locoregional treatment for patients with MBC at the time of diagnosis remains debated. Women with newly diagnosed, de novo stage IV MBC and who started MBC treatment between January 2008 and December 2014 in one of the 18 French Comprehensive Cancer Centers were included (NCT03275311). The impact of local surgery performed during the first year on overall survival (OS) and progression-free survival (PFS) was evaluated by the Cox proportional hazards model in a 12 month-landmark analysis. Out of 16,703 patients in the ESME database, 1977 had stage IV MBC at diagnosis, were alive and progression-free at 12 months and eligible for this study. Among them, 530 (26.8%) had received primary breast cancer surgery within 12 months. A greater proportion of patients who received surgery had less than 3 metastatic sites than the no-surgery group (90.8% vs 78.2%, P < 0.0001). Surgery within 12 months was associated with treatment with chemotherapy, HER2-targeted therapy (89.1% vs 69.6%, P < 0.0001) and locoregional radiotherapy (81.7% vs 32.5%, P < 0.0001). Multivariable analyses showed that surgery performed within 12 months was associated with longer OS and PFS (adjusted HR [95%CI] = 0.75 [0.61-0.92] and 0.72 [0.63-0.83], respectively), which were also affected by pattern and number of metastatic sites, histological subtype, and age. In the large ESME cohort, surgery within 1 year after de novo MBC diagnosis was associated with a significantly better OS and PFS.


Surface modifications and molecular imprinting of polymers in medical and pharmaceutical applications.
Recent developments in the field of biomaterials are based on molecular design of polymers with improved surface and bulk properties. Novel techniques of surface modification by addition of tethered chains can lead to materials with the ability to recognize biological and pharmaceutical compounds. Methods based on molecular imprinting can increase the recognition capabilities of such systems. Chain tethering can also can improve the mucoadhesive behavior of a delivery device and the effectiveness of a drug by allowing targeting and localization of a drug at a specific site. Acrylic-based hydrogels are well-suited for mucoadhesion due to their flexibility and nonabrasive characteristics which reduce damage-causing attrition to the tissues in contact. However, the adhesive and drug delivery capabilities of these devices can continue to be improved as presently known bioadhesive materials are modified and more bioadhesive materials are discovered. Tethering of long PEG chains on PAA hydrogels and their copolymers can be achieved by grafting reactions involving thionyl chloride, followed by PEG grafting. The ensuing materials exhibit mucoadhesive properties due to enhanced anchoring of the chains with the mucosa. Theoretical calculations can lead to optimization of the tethered structure.


Clinical features of cross-reactivity of food allergy caused by fruits.
Fruits are increasingly recognized as a cause of food allergy. The wide cross-reactivity among these foods has been extensively studied. In this review we will focus on studies addressing the clinical relevance of cross-reactivity among fruits, the diagnostic management of patients complaining of reactions to multiple fruits, and adequate dietary recommendations.


A randomised controlled trial comparing Rapid Rhino Mannheim and Netcell series 5000 packs following routine nasal surgery.
To determine whether there is a difference in discomfort between Netcell Series 5000 and Rapid Rhino Mannheim 8.0 cm (Cat. No. 800) packs used after routine nasal surgery, whilst in situ and during removal. This was tested in a single blind, randomised controlled trial at the ENT Department, Royal Devon & Exeter Hospital. Adults aged 16-65 undergoing nasal septal surgery and trimming of inferior turbinates. Patients were excluded if they were undergoing revision surgery, taking anticoagulants, or had a history of sino-nasal disease or trauma. Thirty nine entered and 32 completed the study. The intervention was a different nasal pack in each side of the nose, removed the morning after surgery. Pain experienced by patients while packs are in situ and on removal as recorded on a standard unmarked 100 mm visual analogue scale. There was no difference in the pain scores whilst in situ. Rapid Rhino Mannheim was more painful on removal (difference = 10.6 mm, p < 0.001, Wilcoxon signed ranks test). Rapid Rhino Mannheim packs do not confer a benefit over Netcell Series 5000 packs after routine nasal surgery.


Unilateral Ocular Manifestations of Vogt-Koyanagi-Harada Disease.
To describe a case of unilateral Vogt-Koyanagi-Harada (VKH) disease and associated multimodal imaging. Retrospective case report. A 50-year-old Hispanic male presented with three days of painless decreased vision in his left eye, headache, and decreased hearing. His visual acuity was 20/20 in the right eye and counting fingers in the left eye. Examination of his right eye was unremarkable. Funduscopic examination of his left eye revealed multiple serous retinal detachments. Fluorescein angiography demonstrated late multifocal pinpoint hyperfluorescence in his left eye and a diagnosis of VKH disease was made. He was treated with oral prednisone. Serial re-examination demonstrated resolution of the serous retinal detachments and a taper of his oral prednisone was initiated with improvement of his visual acuity to 20/25. Our patient had imaging and a clinical course that was consistent with VKH disease. This unilateral presentation may represent a clinical variant of VKH disease.


Regulation of the Biosynthesis of Ent-Kaurene from Mevalonate in the Endosperm of Immature Marah macrocarpus Seeds by Adenylate Energy Charge.
The rate of kaurene biosynthesis from mevalonate in a cell-free enzyme preparation from the endosperm of immature seeds of Marah macrocarpus is regulated by adenylate energy charge. The response curve is typical of a biosynthetic energy-utilizing sequence in which the rate of biosynthesis increases sharply as the energy charge is increased above 0.80. ADP proved to be an effective inhibitor of this process. AMP gave no inhibition at concentrations up to 2 mm and orthophosphate gave no inhibition up to 15 mm. Measurement of the pool sizes of intermediates in the sequence showed that the presence of ADP caused an increase in the levels of 5-phosphomevalonate and 5-pyrophosphomevalonate and a decrease in the levels of isopentenyl pyrophosphate and kaurene. These results indicate that pyrophosphomevalonate decarboxylase is the enzyme most subject to regulation by adenylate energy charge. The rate of conversion of isopentenyl pyrophosphate to kaurene and the rate of utilization of mevalonate by mevalonate kinase were not influenced by variations in the adenylate energy charge.


Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis.
Previously published meta-analyses exploring the effect of statins on stroke incidence included 20,000 patients and found a 2% to 30% risk reduction. It is not clear whether this is attributable to low-density lipoprotein-cholesterol (LDL-C) reduction. Statin trials have now included >90,000 patients. We have determined the effect of statins and LDL-C reduction on stroke prevention. We performed a systematic review and meta-analysis of all randomized trials testing statin drugs published before August 2003. The trials were identified using a computerized PubMed search. We analyzed separately statin effect on incident strokes and on carotid intima-media thickness (IMT) according to LDL-C reduction. The relative risk reduction for stroke was 21% (odds ratio [OR], 0.79 [0.73 to 0.85]), with no heterogeneity between trials. Fatal strokes were reduced but not significantly: by 9% (OR, 0.91 [0.76 to 1.10]). There was no increase in hemorrhagic strokes (OR, 0.90 [0.65 to 1.22]). Statin size effect was closely associated with LDL-C reduction. Each 10% reduction in LDL-C was estimated to reduce the risk of all strokes by 15.6% (95% CI, 6.7 to 23.6) and carotid IMT by 0.73% per year (95% CI, 0.27 to 1.19). Statins may reduce the incidence of all strokes without any increase in hemorrhagic strokes, and this effect is mainly driven by the extent of between-group LDL-C reduction. Carotid IMT progression also strongly correlated with LDL-C reduction.


"Cleanse" detoxification diet program in Appalachia: Participant characteristics and perceived health effects.
Introduction Numerous detoxification or "detox" diets purport to eliminate toxins from the body, help with weight loss, and improve health. Despite the claims of proponents, few of these programs have evidence of effectiveness. They often have significant associated costs and may have potential for harm, but they seem to be quite popular. Members of a community in Appalachia were invited to participate as a group in one such diet (called a "cleanse"). We conducted a study to explore characteristics of people who chose to complete the program, including their motivations and their perceptions of the health effects related to participation. Methods Those who volunteered to participate were educated on this program's definition of a "clean" diet through an information session and were given written guidelines. The diet was to last 21 days, and instructions were outlined as to which foods were allowed and which were to be eliminated. This study evaluated participants in two cohorts (June 2014 and January 2015). Individuals who registered for the study were asked to complete three anonymous surveys: one pretest before beginning the program (PRE), one roughly 1 week after completion (1wPOST), and one follow-up 8 weeks after the end of the diet period (8wPOST). Descriptive statistics, Skillings-Mack test, and Wilcoxon signed rank test were used to analyze results. Results Thirty-four individuals completed the PRE surveys, 15 individuals completed the 1wPOST surveys (44% of those completing the PRE surveys), and 8 individuals completed the 8wPOST surveys (24% of those completing the PRE surveys). Comparing results from the PRE, 1wPOST, and 8wPOST surveys, there were significant overall differences seen in the following health characteristics: cravings for sweet/salty foods (p=0.03), "giving in" to cravings (p=0.04), energy levels (p=0.001), and sleep quality (p=0.0001). These differences seen were between the PRE and 1wPOST surveys. Weight satisfaction and overall health did not show any overall significant differences. Conclusions While participants in Appalachia could benefit from a program that could improve health, this program's participants did not share socioeconomic characteristics reflective of most people from that area. Most were college-educated females with a reported family income and level of education that were higher than the average population. Self-reported health characteristics related to cravings, energy levels, and sleep quality demonstrated overall significant improvements from the PRE to the 1wPOST surveys. This exploratory study provides insight into the popularity of such programs. While measurement rather than self-report of clinical outcomes would be needed to more definitively determine the effects of this program, it would be worthwhile to explore further in an experimental study the outcomes identified in this study as being affected (cravings, energy, sleep, and weight).


UNC-51-like kinase regulation of fibroblast growth factor receptor substrate 2/3.
UNC-51-like kinases (ULK) are members of an evolutionarily conserved sub-family of ubiquitously expressed serine/threonine-specific protein kinases. Here we report that fibroblast growth factor receptor substrate (FRS) 2/3 are novel ULK2 carboxy-terminal domain interacting proteins. FRS2/3 are homologs that function as adaptor proteins to mediate signaling of multiple receptor tyrosine kinases. ULK2 interacts with the phospho-tyrosine binding (PTB) domain of FRS2/3. We demonstrate that siRNA targeting ULK2 in mouse P19 cells results in elevated FGFR1 mediated FRS3 and SHP2 tyrosyl phosphorylation. In addition, RNAi-mediated decrease in ULK2 causes increased interaction between FGFR1 and FRS3. ULK2 phosphorylates FRS2/3 in vitro, suggesting that ULK2 mediated phosphorylation may be a mechanism of FRS2/3 regulation. The data presented support a model in which ULK2, by interaction with FRS2/3 and inhibition of SynGAP, functions to negatively regulate tyrosyl phosphorylation of signaling proteins downstream of FGFR1.


Directly diode-pumped holmium fiber lasers.
Sensitizer-free holmium-doped silica and fluoride mid-infrared fiber lasers are pumped using a high-power diode laser operating at 1148 nm. A maximum output power of 162 mW at 2.86 microm was produced at a slope efficiency of 24% using Ho(3+), Pr(3+)-doped fluoride fiber. Using Ho(3+)-doped silica fiber, a maximum output power of 55 mW at 2.1 microm was generated at a slope efficiency of 27%, a value limited by the presence of pump excited state absorption.


[Mrakia curviuscula sp. Nov.--a new species of psychrophilic yeasts from forest substrates].
Seven strains with similar characteristics from the laboratory collection of yeasts isolated from forest substrates collected in the central part of European Russia corresponded to none of the known yeast species. Based on the study of their life cycle, physiological characteristics, and the nucleotide composition of DNA and taking into account the data of PCR analysis with universal primers, the strains were ascribed to a new psychrophilic yeast species, Mrakia curviuscula sp. nov.


Testis-specific human small heat shock protein HSPB9 is a cancer/testis antigen, and potentially interacts with the dynein subunit TCTEL1.
Searching EST databases for new members of the human small heat shock protein family, we recently identified HSPB9, which is expressed exclusively in testis as determined by Northern blotting (Kappé et al., Biochim. Biophys. Acta 1520, 1-6, 2001). Here we confirm this testis-specific expression pattern by RT-PCR in a larger series of normal tissues. Interestingly, while screening HSPB9 ESTs, we also noted expression in tumours, which could be verified by RT-PCR. Protein expression of HSPB9 was also detected in normal human testis and various tumour samples using immunohistochemical staining. We thus conclude that HSPB9 belongs to the steadily growing number of cancer/testis antigens. To get a better understanding of the function of HSPB9, we performed a yeast two-hybrid screen to search for HSPB9-interacting proteins. TCTEL1, a light chain component of cytoplasmic and flagellar dynein, interacted in both the yeast two-hybrid system and in immunoprecipitation experiments with HSPB9. Additionally, immunohistochemical staining showed co-expression of HSPB9 and TCTEL1 in similar stages of spermatogenesis and in tumour cells. The possible functional significance of this interaction is discussed.


Fund raising from a volunteer's perspective.
Dick Rathgeber recently volunteered to lead a major fund raising drive for the Salvation Army in Austin, Texas. Of the $3.6 million effort, Rathgeber personally solicited $2.2 million, receiving pledges from nearly 80 percent of the calls he made. Although he has been a volunteer fund raiser for only four years, he obviously is successful at it. "It's a noble calling," says Rathgeber. "I've been richly blessed in my life, and this is my way of giving some of it back." The following article was adapted from a speech Rathgeber gave to attendees of NAHD's Region 5 Conference in San Antonio this past spring by Pat Korbus, writer for Seton Medical Center in Austin, Texas.


[Assessment of physical status of patients with mandibular fractures by bioimpedance analysis].
The study shows the results of assessing the trophic status with the help of bioelectrical impedance in 78 patients with mandibular fractures. Deviations from ideal body weight were found in 47% of cases, body weight deficit in 24% of patients, risk to nutritional insufficiency, increase in fat mass in 23% of cases. The average values of the lean mass were lower than their physiological norm. The tendency to a more pronounced deviation of body composition indicators from the norm may be a marker of the inadequacy of the patient's individual response to therapy. For each patient it is necessary to carry out rehabilitation measures aimed at correcting body weight, increasing muscle tissue, basic metabolism which will prevent the progression of weight loss and the development of complications. The use of adequate nutrition and physiotherapy increases the effectiveness of complex treatment, effectively helps the normalization of somatic conditions, has an important impact on the favorable outcome of the underlying disease, affects the motivational component of physical activity with the formation of adequate approaches to a healthy lifestyle.


CLINICAL PRESENTATIONS, MICROBIOLOGY, AND FACTORS AFFECTING MANAGEMENT OUTCOMES IN LENS ABSCESS WITH CONCURRENT ENDOPHTHALMITIS.
To describe the clinical presentations, microbiology, and factors affecting management outcomes in lens abscess with concurrent endophthalmitis. A retrospective, consecutive, noncomparative series including cases of endophthalmitis with concurrent lens abscess from January 2017 to May 2021. This study included 102 eyes, predominantly male (71.6%). All cases were posttrauma. The mean age noted was 30.47 ± 19.51 years. Presenting vision was logMAR 3.02 ± 0.74 (median 3.5, Snellen 20/63245). A favorable anatomical outcome was seen in 63 eyes (61.8%), while a final favorable functional outcome was seen in 51 eyes (50%). The mean follow-up duration was 10.04 ± 10.87 months (median 4.5). Final vision was logMAR 2.13 ± 1.32 (median 2.7, Snellen 20/10023) (P < 0.0001). The mean follow-up duration was 10.04 ± 10.87 months (median 4.5). Increasing age (OR 1.04, P = 0.02), female sex (OR 7.91, P = 0.007), initial intervention of vitrectomy instead of limited vitreous biopsy (OR 11.72, P = 0.009), and a negative vitreous culture (OR 14.28, P = 0.0004) predicted a favorable anatomical outcome. Absence of a corneal infiltrate (OR 11.11, P = 0.003) and initial intervention of vitrectomy instead of a limited vitreous biopsy (OR 21.96, P < 0.0001) predicted a favorable functional outcome. Culture positivity was seen in 56.9% of the cases. Gram-positive organisms were predominant (n = 41) followed by Gram-negative organisms (n = 12) and fungi (n = 10). Lens abscess can present concurrently with traumatic endophthalmitis. Management should involve the complete removal of the crystalline lens along with a pars plana vitrectomy for optimal outcomes.


Onset of Alcohol Dehydrogenase Synthesis during Microsporogenesis in Maize.
During male gametophyte development the synthesis of several proteins occurs from transcripts of the haploid genome. Alcohol dehydrogenase (ADH1), a developmentally regulated protein, was chosen for study to determine the stage at which its synthesis was initiated and the pattern of its synthesis during microsporogenesis. The ability of ADH to reduce p-nitro blue tetrazolium chloride in situ was used as an indicator of enzyme activity. Maize strains heterozygous for adh1 were utilized to provide an internal control, 50% of the grains being adh1(+) and 50% being adh1(-). No ADH activity was detectable when tetrads were first formed after meiosis. Activity was initially detected soon after the tetrads began to break apart but before the microspores in the tetrads had completely separated. The transcription of the adh1 gene from the haploid genome must thus occur very soon after meiosis is completed. ADH activity increases at a constant rate thereafter until microspore mitosis when an increase in the rate takes place which lasts until generative cell division. Thereafter, there is a marked decrease in the rate of accumulation of ADH activity.


Polyamine oxidase from water hyacinth: purification and properties.
Polyamine oxidase was purified to homogeneity from leaves of water hyacinth by the criterion of sodium dodecyl sulfate gel electrophoresis (SDS disc PAGE). The enzyme showed a high specificity for spermidine and spermine (K(m) values 28 micromolar and 20 micromolar, respectively). The optimal pH of the enzyme for both spermidine and spermine was 6.5. The molecular weight of the enzyme estimated by Sephadex G-200 gel filtration was 87,000, while SDS disc PAGE gave a single band at the molecular weight of 60,000. Octamethylenediamine and quinacrine were strong inhibitors of the enzyme, but p-chloromercuribenzoate was without effect. A prosthetic group in the enzyme was identified as flavin adenine dinucleotide.


Viruses and oral diseases in HIV-infected individuals on long-term antiretroviral therapy: What are the risks and what are the mechanisms?
As a result of the extension of life span produced by increasing access to combined antiretroviral therapy, people living with HIV/AIDS (PLWH) face new challenges from comorbidities. Although advances in medical care for HIV infection have dramatically reduced opportunistic infections and AIDS-defining cancers, some non-AIDS-defining cancers (NADC) and specific oral diseases such as periodontitis and salivary gland disease are now more prevalent. Cancer prevention is, therefore, a priority issue in care of PLWH, stressing both restoration of immune function and reduction of non-HIV cancer risk factors (tobacco in all its forms; areca nut; heavy alcohol consumption; diets lacking antioxidant vitamins and minerals; and oncogenic virus infections) through specific interventions, especially tobacco and areca nut cessation and alcohol moderation. Detection of oral high-risk human papillomaviruses (HR-HPV) and the universal preventive HPV vaccination among PLWH should be promoted to reduce the malignancy burden, along with routine oral examinations which remain the cheapest, most reliable, most reproducible, and non-invasive tool to identify suspicious lesions. Also, considerations of oral inflammation and periodontal health are important to replication and gene expression of viruses in the mouth. Considering that a key risk factor for this scenario is the presence of oncogenic virus infection such as several members of the human herpesvirus and human papillomavirus families, here we analyze the variables involved in the seeming increase in comorbidities in PLWH.


Aminoglycoside and glycopeptide renal toxicity in intensive care patients studied by proton magnetic resonance spectroscopy of urine.
Aminoglycoside and glycopeptide antibiotics are responsible for renal toxicity. In most cases, the nephrotoxicity is limited to a reversible tubular injury, but an acute and sustained renal failure may occur. The aim of our study was to explore the renal function of patients given these antimicrobial agents with proton magnetic resonance spectroscopy of urine. This technique is able to detect, in urine samples, a wide range of metabolites reflecting renal tubular function. The variables assessed by magnetic resonance spectroscopy were compared with the routine markers of renal function: creatinine, urea, and 24-hr urine volume. Prospective clinical study. Intensive care unit. All patients in an intensive care unit receiving an aminoglycoside and/or a glycopeptide were included in the study if they presented with signs of renal dysfunction. All experiments were performed on urine samples collected for the routine follow-up of these patients. Proton spectra were acquired with water suppression, and the peak intensity of each metabolite was reported in relationship to the intensity of the creatinine peak. The ratio values obtained by magnetic resonance spectroscopy were compared with the values of creatininemia and blood urea obtained routinely by biochemistry and with the value of the 24-hr urine volume by logistic regression and general linear models. This statistical analysis showed that the ratio of dimethylamine to creatinine was highly correlated with creatininemia. Dimethylamine is an osmolyte released from the medullar region of the kidney. Thus, our study demonstrated that nephrotoxicity from aminoglycosides and glycopeptides is not limited to proximal tubular toxicity but also may involve the medullar region (Henle loop and collecting duct) of the nephron.


Growth of piezoelectric water-free GeO2 and SiO2-substituted GeO2 single-crystals.
Using the slow-cooling method in selected fluxes, we have grown spontaneously nucleated single-crystals of pure GeO(2) and SiO(2)-substituted GeO(2) materials with the α-quartz structure. These piezoelectric materials were obtained in millimeter size as well-faceted, visually colorless, and transparent crystals. Cubic-like or hexagonal prism-like morphology was identified depending on the chemical composition of the single-crystals and on the nature of the flux. Both the silicon substitution rate and the homogeneity of its distribution were estimated by Energy Dispersive X-ray spectroscopy. The cell parameters of the flux-grown GeO(2) and Ge(1-x)Si(x)O(2) (0.038 ≤ x ≤ 0.089) solid-solution were deduced from their X-ray powder diffraction pattern. As expected, the cell volumes decrease as the silicon content substitution increases. A room temperature Infrared spectroscopy study confirms the absence of hydroxyl groups in the as-grown crystals. Unlike what was observed for hydrothermally grown GeO(2) crystals, these flux-grown oxide materials did not present any phase transition before melting as pointed out by a Differential Scanning Calorimetry study. Neither a α-quartz/β-quartz transition as encountered in SiO(2) near 573 °C nor a α-quartz to rutile transformation were detected for these GeO(2) and Ge(1-x)Si(x)O(2) single-crystals.


Safety and performance of TCI pumps in a magnetic resonance imaging environment.
Target controlled infusion (TCI) devices can be associated with significant safety concerns when used during magnetic resonance imaging (MRI). We tested the safety and compatibility of newer TCI systems in a 3-Tesla MRI environment. Two Asena PK and two Agilia TCI pumps were used to administer TCI propofol (at target blood concentrations of 0.5 and 6.0 μg.ml⁻¹) using the Marsh model under magnetic fields of up to 50 G with a T2-weighted sequence. We assessed the devices for projectile risk, accuracy of drug delivery, alarm function and effects on MR image quality. Both devices did not demonstrate any significant deflection at the tested field strengths, and performed within acceptable limits (cumulative error in total delivered volume < 3%; maximum 10-min interval error < 10%). The Asena pump caused minor artefacts on MR images. The TCI pumps tested perform well and safely implement pharmacokinetic software in a high magnetic field.


Multidimensional scaling of nasal voice quality.
Listeners judged the dissimilarity of pairs of synthesized nasal voices that varied on 3 dimensions. Separate nonmetric multidimensional scaling (MDS) solutions were calculated for each listener and the group. Similar 3-dimensional solutions were derived for the group and each of the listeners, with the group MDS solution accounting for 83% of the total variance in listeners' judgments. Dimension 1 ("Nasality") accounted for 54% of the variance, Dimension 2 ("Loudness") for 18% of the variance, and Dimension 3 ("Pitch") for 11% of the variance. The 3 dimensions were significantly and positively correlated with objective measures of nasalization, intensity, and fundamental frequency. The results of this experiment are discussed in relation to other MDS studies of voice perception, and there is a discussion of methodological issues for future research.


A prospective evaluation of the value of intrapartum biophysical and Doppler parameters in identifying the potentially compromised fetus.
This study was designed to evaluate the use of the biophysical profile and umbilical arterial Doppler in early labour in identifying the potentially compromised fetus. Two hundred and forty-two women attending the labour suite in early labour were studied. One hundred and fifty-one were in spontaneous labour and the remaining 91 had labour induced. All women had intrapartum biophysical profile assessment and umbilical arterial Doppler performed. Umbilical arterial Doppler and fetal movements were variously identified as being independently and significantly associated with adverse perinatal outcomes. Positive predictive values for adverse outcomes were however poor. Umbilical arterial Doppler used individually or in combination with clinical risk, gave no advantage over the use of clinically assigned risk alone in identifying fetuses at risk of subsequent adverse outcome. The assignment of clinical risk on admission in labour remains the most predictive 'test' for identifying the fetus at risk of subsequent adverse outcome. The routine addition of intrapartum biophysical parameters and umbilical arterial Doppler as methods of assessment is not justified.


Low-dose intralesional injection of 5-fluorouracil and triamcinolone reduces tissue resident memory T cells in chronic eczema.
Tissue resident memory T (TRM) cells have been reported to play a significant role in the pathogenesis and relapse of chronic eczema. To compare the efficacy and safety of the intralesional injection of 5-fluorouracil (5-FU) and triamcinolone (TA) with those associated with TA alone for the treatment of chronic eczema. A total of 168 patients were randomized to 5-FU+TA or TA groups and received a one-time intralesional injection of 5-FU+TA or TA only. Biopsies were collected before and 2 wk after treatment for evaluation of histopathological changes. All patients were followed up monthly for up to 1 year. No serious adverse event was observed in either group. Although the mean atopic dermatitis severity index scores and effective rates were comparable between the two groups after 2 wk of treatment, the relapse rate was significantly lower in the 5-FU+TA group than in the TA group. Histological examination showed significantly fewer CD8+ and CD103+ T cells but not CD4+ T cells in the 5-FU+TA group. One-time intralesional injection of 5-FU+TA is effective and safe for chronic eczema treatment and can further reduce the retention of TRM cells in the lesional skin and the relapse rate of chronic eczema.


Ethanol-induced oxidative stress is associated with EGF receptor phosphorylation in MCF-10A cells overexpressing CYP2E1.
Breast cancer is the most common cancer and the second leading cause of cancer-related mortality worldwide. The etiology of breast cancer is very diverse and ethanol (EtOH) consumption is a well-established risk factor for breast cancer in women. However, the mechanism by which EtOH exerts its carcinogenic activity in breast tissue remains unknown. CYP2E1 is known to metabolize ethanol and produce reactive oxygen species (ROS), including superoxide in epithelial cells. Therefore, in the present studies, we investigated whether there is an increase in ROS following overexpression of CYP2E1 in MCF-10A cells. We found that 30 and 100 mM EtOH increased ROS levels after 2 h treatment in CYP2E1 overexpressing cells. Based on these results and our previous studies with ROS-producing chemicals, we also examined epidermal growth factor receptor (EGFR) activation following exposure to ethanol. We found that there was an increase in phosphorylation of pY1086 EGFR after 18 h EtOH treatment in CYP2E1 overexpressing cells. These studies support a hypothesis that EtOH might increase human mammary cell activation, via an EGFR-dependent signaling mechanism associated with oxidative stress.


Obesity and asthma: a coincidence or a causal relationship? A systematic review.
Epidemiological data has established increasing adiposity as a risk factor for incident asthma. However, the mechanisms underlying the association between obesity and asthma are incompletely understood. In the present paper, we review current knowledge of possible mechanisms mediating the observed association between obesity and asthma. Systematic literature review. Obesity and asthma share some etiological factors, such as a common genetic predisposition and effects of in utero conditions, and may also have common predisposing factors such as physical activity and diet. Obesity results in important changes in the mechanical properties of the respiratory system which could explain the occurrence of asthma. However, there are also plausible biological mechanisms whereby obesity could be expected to either cause or worsen asthma. These include co-morbidities such as gastro-oesophageal reflux, complications from sleep-disordered breathing, breathing at low lung volumes, chronic systemic inflammation, and endocrine factors, including adipokines and reproductive hormones. Obesity related asthma is in general not associated with eosinophilic airway inflammation, and adipokines are likely to play important roles in the inflammatory pathogenesis of asthma in obese individuals. The association between obesity and asthma is not straightforward, and further knowledge is clearly needed, as understanding the underlying mechanisms may lead to new therapeutic options for this high-risk part of the asthma population.


Hyperosmolar Potassium (K+) Treatment Suppresses Osteoarthritic Chondrocyte Catabolic and Inflammatory Protein Production in a 3-Dimensional In Vitro Model.
The main goal of this study was to provide a proof-of-concept demonstrating that hyperosmolar K+ solutions can limit production of catabolic and inflammatory mediators in human osteoarthritic chondrocytes (OACs). A 3-dimensional in vitro model with poly(ethylene glycol) diacrylate (PEGDA) hydrogels was used. Catabolic and pro-inflammatory protein production from encapsulated OACs was assessed following culture for 1 or 7 days in the presence or absence of 80 mM K+ gluconate, 80 mM sodium (Na+) gluconate, or 160 mM sucrose, each added to culture media (final osmolarity ~490 mOsm). Relative to untreated controls, OACs treated with hyperosmolar (80 mM Na+ gluconate or 160 mM sucrose) solutions produced lower levels of catabolic and inflammatory mediators in a marker- and time-dependent manner (i.e., MMP-9 after 1 day; MCP-1 after 7 days ( P ≤ 0.015)). In contrast, OAC treatment with 80 mM K+ gluconate reduced catabolic and inflammatory mediators to a greater extent (both the number of markers and degree of suppression) relative to untreated, Na+ gluconate, or sucrose controls (i.e., MMP-3, -9, -13, TIMP-1, MCP-1, and IL-8 after 1 day; MMP-1, -3, -9, -13, TIMP-1, MCP-1, and IL-8 after 7 days ( P ≤ 0.029). Hyperosmolar K+ solutions are capable of attenuating protein production of catabolic and inflammatory OA markers, providing the proof-of-concept needed for further development of a K+-based intra-articular injection for OA treatment. Moreover, K+ performed significantly better than Na+- or sucrose-based solutions, supporting the application of K+ toward improving irrigation solutions for joint surgery.


Further investigations on the transport mechanism of cephalexin and ampicillin across rat jejunum.
The transport mechanisms of cephalexin (CEX) and ampicillin (AB-PC) across rat jejunum were examined using the electrophysiological technique in vitro. From the experiments under the short-circuit condition, it became evident that the specific transport system participates in the mucosal-to-serosal transport of CEX, while AB-PC is transport only by the simple diffusion. In addition, the transport routes of these drugs were examined using the voltage-clamp technique. Salicylate, a model drug of the weak electrolyte, was transported mainly via a paracellular route, while CEX, in the absence of Na, penetrated the membrane via two routes, i.e. the transcellular route and the paracellular route. Similar result was obtained as to AB-PC. So it seems to be likely that these two drugs diffuse through the intestinal epithelium via the similar pathways in the Na-free condition.


Behaviour change to treat overactive bladder syndrome.
Overactive bladder syndrome has a negative impact on quality of life. This article discusses a definition of the condition and its the prevalence and aetiology, as well as some of the more common behavioural therapies. Although there is a good evidence base for bladder retraining, there is often conflicting research to support other interventions including caffeine reduction, the amount and types of fluid recommended, smoking cessation and weight reduction. A standardised approach from a national level is needed; nurses also need to demonstrate more robustly the effectiveness of their interventions.


Management of relapse and survival in advanced stage Hodgkin's disease: the EORTC experience.
The EORTC Lymphoma Cooperative Group and the Pierre and Marie Curie Group conducted a multicentre randomised trial on clinical stages IIIB-IV Hodgkin's disease from 1981-1986. Two hundred seven patients were registered and 192 randomised. Actuarial survival at five years for the whole group was 68%. Induction chemotherapy with eight cycles of MOPP resulted in more patients with progressive disease and fewer partial responders than a combination of MOPP and ABVD, for an equal complete remission rate. Half of the partial responders went into complete remission after radiotherapy. At five years there was no significant survival difference between the arms. Progression was recorded in 39 patients of whom only 4 survived. Relapses were most frequent in previously involved unirradiated areas. For 46 relapsed patients, including 21 early relapses within 18 months of start of treatment, the four-year survival rate was 53%. When complete remission was reached, whether early or late with combination chemotherapy or after additional radiotherapy, prognosis was independent of the way in which it was achieved. All efforts should be taken to reach a complete remission for initially progressing patients and for partial responders.


Regional vasodilating effects of spirapril diacid and enalapril diacid in anesthetized dogs.
The acute regional hemodynamic effects of spirapril diacid, a novel nonsulfhydryl angiotensin-converting enzyme inhibitor, and enalapril diacid at an equidepressor dose were examined in anesthetized dogs by simultaneously measuring renal, coronary, vertebral arterial and aortic blood flow. Spirapril diacid (30 micrograms/kg, i.v.) lowered aortic pressure and increased aortic and renal blood flow associated with no marked change in heart rate, myocardial contractility, vertebral and coronary blood flow in a similar manner to enalapril diacid (30 micrograms/kg, i.v.). Both inhibitors thus produced an increase in stroke volume and a decrease of the rate-pressure product. The decrease of renal vascular resistance after administration of both agents was greater than that in vertebral and coronary vascular beds. A relatively more prolonged renal vasodilatation and a shortened coronary vasodilatation were seen with spirapril diacid as compared with enalapril diacid, despite practically identical reductions in total peripheral resistance. Each of the drugs markedly inhibited the pressor and renal vasoconstrictor responses to angiotensin I. These results indicate that the two inhibitors exhibit a similar profile of regional differences in vasodilatory effects, although they might display different durations of regional vasodilatation.


HDHD1, which is often deleted in X-linked ichthyosis, encodes a pseudouridine-5'-phosphatase.
Pseudouridine, the fifth-most abundant nucleoside in RNA, is not metabolized in mammals, but is excreted intact in urine. The purpose of the present work was to search for an enzyme that would dephosphorylate pseudouridine 5'-phosphate, a potential intermediate in RNA degradation. We show that human erythrocytes contain a pseudouridine-5'-phosphatase displaying a Km ≤ 1 μM for its substrate. The activity of the partially purified enzyme was dependent on Mg2+, and was inhibited by Ca2+ and vanadate, suggesting that it belonged to the 'haloacid dehalogenase' family of phosphatases. Its low molecular mass (26 kDa) suggested that this phosphatase could correspond to the protein encoded by the HDHD1 (haloacid dehalogenase-like hydrolase domain-containing 1) gene, present next to the STS (steroid sulfatase) gene on human chromosome Xp22. Purified human recombinant HDHD1 dephosphorylated pseudouridine 5'-phosphate with a kcat of 1.6 s-1, a Km of 0.3 μM and a catalytic efficiency at least 1000-fold higher than that on which it acted on other phosphate esters, including 5'-UMP. The molecular identity of pseudouridine-5'-phosphatase was confirmed by the finding that its activity was negligible (<10% of controls) in extracts of B-cell lymphoblasts or erythrocytes from X-linked ichthyosis patients harbouring a combined deletion of the STS gene (the X-linked ichthyosis gene) and the HDHD1 gene. Furthermore, pseudouridine-5'-phosphatase activity was 1.5-fold higher in erythrocytes from women compared with men, in agreement with the HDHD1 gene undergoing only partial inactivation in females. In conclusion, HDHD1 is a phosphatase specifically involved in dephosphorylation of a modified nucleotide present in RNA.


Effect of oxygen tension on NMR spin-lattice relaxation rate of blood in vivo.
Spin-lattice relaxation rate (1/T1) was measured in the left (LV) and right (RV) ventricular cavities in four conscious normal humans and four anesthetized greyhound dogs breathing spontaneously. Inspired oxygen concentration (FIO2) was varied in five steps from 21 to 100%. In dogs, blood was sampled from indwelling catheters in the pulmonary artery and aorta for measurement of PO2. Saturation-recovery and inversion-recovery tomographic images of the ventricular cavities were obtained supine during quiet breathing using a whole-body NMR scanner operating at a static magnetic field strength of 0.15 Tesla. From FIO2 21 to 100%, 1/T1 of LV increased by 11.6% in humans and 9.6% in dogs. In dogs, 1/T1 increased by 2.8% per 100 mm Hg increase in aortic PO2 (r greater than 0.87). There was no correlation in dogs between 1/T1 in RV and pulmonary artery PO2. The LV/RV 1/T1 ratio in dogs increased by 4% per 100 mm Hg increase in the LV-RV PO2 difference, and by 8% in humans as FIO2 increased from 21 to 100%. A rise in dissolved oxygen concentration increases NMR spin-lattice relaxation rates of blood in vivo to a small but significant extent.


Peripheral cytokines profile in Parkinson's disease.
Higher levels of proinflammatory cytokines are found in Parkinson's disease (PD) patient's brains and inflammation is thought to be a major contributor to the neurodegeneration. During the inflammatory process, microglial release of proinflammatory cytokines act on the endothelium of blood-brain barrier (BBB) cells to stimulate upregulation of adhesion molecules. Consequently, this upregulation leads to the recruitment of passing T cells and monocytes, which express the counter receptors, that then go on to release more cytokines [Whitton, P.S., 2007. Inflammation as a causative factor in the aetiology of Parkinson's disease, Br. J. Pharmacol. 50, 963-976; Kortekaas, R., Leenders, K.L., Van Oostrom, J.C., Vaalburg, W., Bart, J., Willemsen, A.T., Hendrikse, N.H., 2005. Blood-brain barrier dysfunction in parkinsonian midbrain in vivo, Ann. Neurol. 57, 176-179]. In addition, a systemic inflammatory response results in the production of cytokines which circulate in the blood and communicate with neurons within the brain. Thus, a central inflammatory reaction interacts with peripheral blood mononuclear cells (PBMCs) modulating immune activity. The present study investigates levels of production and expression of cyto/chemokines by PBMCs in PD patients. Basal and LPS-induced levels of MCP-1, RANTES, MIP-1alpha, IL-8, IFNgamma, IL-1beta and TNFalpha were significantly higher in PD patients than in HC subjects (p<0.001), as determined by RT-PCR and Elisa methods. Cyto/chemokine levels were significantly correlated with UPDRS III and H/Y stage (p<0.001). The Pearson's correlation coefficient (R) was also used to assess the strength of the relationship between NF-kappaBp65 levels and all studied cyto/chemokines and between NF-kappaBp65, UPDRS III and H/Y score in PD patients. The overall results strengthen and extend the knowledge of the peripheral dysregulation in the cytokine network associated with PD.