Can Young Children Ignore Irrelevant Events, or Subevents, During Verb Learning?
Children learning a verb may benefit from hearing it across situations (e.g., Behrend, 1995; Childers, 2011; Fisher et al, 1994; Pinker, 1989). At the same time, in everyday contexts, situations in which a verb is heard will be interrupted by distracting events. Using Structural Alignment theory as a framework (e.g., Gentner & Namy, 2006), Study 1 asks whether children can learn a verb when irrelevant, interleaved events are present. Two½- and 3½-year-old children saw dynamic events and were randomly assigned to one of three experimental conditions (differing in orders of events), or one of two control conditions. They extended the verbs in the experimental conditions, and not the control conditions. Three ½-year-olds were more successful than 2½-year-olds, though the younger children could extend verbs. A more difficult task is segmenting dynamic action into subevents that could be relevant for a verb (e.g., finding "chopping" in a cooking scene). In Study 2, 2½-, 3½- and 4½-year-old children were assigned to experimental conditions in which relevant events flowed into irrelevant events (or vice versa), or to a control. Two½-year-olds failed to extend the verbs at test, differing from the older children; children in experimental conditions extended the verbs while children in the control condition did not. Altogether, these results show children can ignore irrelevant events (and subevents), and extend new verbs by 3½ years. Results are important to understand learning in everyday contexts in which verbs are heard in varied situations over time.


Morphology of the Myocardium after Experimental Bone Tissue Trauma and the Use of Extracellular Vesicles Derived from Mesenchymal Multipotent Stromal Cells.
The effect of extracellular vesicles (EVs) of various origins on the heart structures in the time of health and disease has been well studied. At the same time, data on the distribution of EVs throughout the body after introduction into the tissues and the possibility of the influence of these EVs on organs distant from the injection site are practically absent. It is also necessary to note a certain inconsistency in the results of various researchers: from articles on the direct absorption of EVs derived from mesenchymal multipotent stromal cells (MSC EVs) by cardiomyocytes to the data that the heart is inherently immune to drug delivery mediated by nanoparticles. In this regard, the morphological changes in the myocardium of outbred rabbits of both sexes weighing 3-4 kg were studied at various times after experimental trauma of the bone tissue in the proximal condyle of the tibia (PCT) and the use of MSC EVs. As a result of modeling the PCT defect, rabbits develop myocardial edema in the heart muscle by the 3rd day, their lymphatic vessels expand, and then, on the 7th day, the blood vessels become dilated. In the myocardium, the relative and absolute contents of neutrophils, erythrocytes, and macrophages increase, but the percentage of lymphocytes decreases. By day 10, almost all of these changes return to their initial values. The detected transformations of the myocardium are most likely due to the ingress of detritus with the blood flow from the PCT. The use of MSC EVs to influence the regeneration of damaged tissue of PCT promotes earlier dilatation of the blood vessels of the heart with pronounced diapedesis of erythrocytes or even hemorrhages, prolongation of edema, the formation of blood clots in vessels with obliteration of their lumen, sclerotic transformation of vascular walls and paravascular tissues. In the myocardium, the number density of neutrophils, the percentage of lymphocytes, and neutrophils become smaller, with a simultaneous increase in the relative numbers of erythrocytes and macrophages, and changes in the content of macrophages remained until the end of the observation-up to 10 days after the surgery. The discovered effect of MSC EVs is most likely associated with the suppression of the activity of the inflammatory process in the PCT area, which, in turn, was caused by a longer ingress of detritus with blood flow into the myocardium. The absence of statistically significant differences between changes in the myocardium of the left and right ventricles may indicate that both detritus from the surgical site and MSC EVs affect the heart spreading through the coronary artery system.


Molecular cloning, characterization and expression of the heat shock protein 60 gene from the human pathogenic fungus Paracoccidioides brasiliensis.
A gene encoding the heat shock protein (HSP) 60 from Paracoccidioides brasiliensis (Pb) was cloned and characterized. The hsp60 gene is composed of three exons divided by two introns. Structural analysis of the promoter detected canonical sequences characteristic of regulatory regions from eukaryotic genes. The deduced amino acid sequence of the Pb hsp60 gene and the respective cloned cDNA consists of 592 residues highly homologous to other fungal HSP60 proteins. The hsp60 gene is present as a single copy in the genome, as shown by Southern blot analysis. The HSP60 protein was isolated from Pb yeast cellular extracts. N-terminal amino acid sequencing of HSP60 confirmed that the cloned hsp60 gene correlated to the predicted protein in Pb. HSP60 expression appeared to be regulated during form transition in Pb, as different levels of expression were detected in in vitro labeling of cells and northern blot analysis. The complete coding region of Pb hsp60 was fused with plasmid pGEX-4T-3 and expressed in Escherichia coli as a glutathione S-transferase-tagged recombinant protein. The protein reacted with a mouse monoclonal antibody raised to a human recombinant HSP60. Western immunoblot experiments demonstrated that the recombinant protein and the native HSP60 were recognized by sera from humans with paracoccidioidomycosis (PCM).


[Therapeutic results in hyperthyroid patients from the Bern endemic goiter region].
Among 239 hyperthyroid patients from the Bernese endemic goiter area referred to specialist, 66% were found to have Graves' disease (MB), 12% hyperthyroid autonomous adenoma ( AAH ) and 22% multinodular toxic goiter (HK). 189 (79%) of these 239 patients have been followed up 5.4 +/- 3.8 years after the last treatment. At the time of follow-up, 146 patients (77%) were euthyroid without additional treatment. 97 of these (51%) became euthyroid after a single, initial treatment (41% of the MB, 83% of the AAH and 67% of the HK). 68 patients (36%) developed recurrences, in some cases several (48% of the MB, 4% of the AAH and 15% of the HK). These recurrences occurred in 56% of cases treated with carbimazole, in 19% of the thyroidectomies and in 11% of the radioiodine treated cases. 30% of the recurrences occurred two or more years after the last treatment. At the time of follow-up, 40 patients (21%) were found to be hypothyroid (23% of the MB, 13% of the AAH and 21% of the HK). However, only 20 of these patients had been treated properly with 1-thyroxin; the other 20 were either insufficiently treated or not at all. Hypothyroidism has been observed in 27 (25%) patients after thyroidectomy and in 13% (23%) patients after radioiodine. No complications were recorded after radioiodine or under carbimazole treatment. After surgery, 2.8% of the patients had recurrent nerve palsy and 2.8% permanent hypoparathyroidism. The present data are in accordance with those published from outside the goiter areas.(ABSTRACT TRUNCATED AT 250 WORDS)


Can corrections spread misinformation to new audiences? Testing for the elusive familiarity backfire effect.
Misinformation often continues to influence inferential reasoning after clear and credible corrections are provided; this effect is known as the continued influence effect. It has been theorized that this effect is partly driven by misinformation familiarity. Some researchers have even argued that a correction should avoid repeating the misinformation, as the correction itself could serve to inadvertently enhance misinformation familiarity and may thus backfire, ironically strengthening the very misconception that it aims to correct. While previous research has found little evidence of such familiarity backfire effects, there remains one situation where they may yet arise: when correcting entirely novel misinformation, where corrections could serve to spread misinformation to new audiences who had never heard of it before. This article presents three experiments (total N = 1718) investigating the possibility of familiarity backfire within the context of correcting novel misinformation claims and after a 1-week study-test delay. While there was variation across experiments, overall there was substantial evidence against familiarity backfire. Corrections that exposed participants to novel misinformation did not lead to stronger misconceptions compared to a control group never exposed to the false claims or corrections. This suggests that it is safe to repeat misinformation when correcting it, even when the audience might be unfamiliar with the misinformation.


A longitudinal study of anteroposterior growth changes in the palatine rugae.
Palatine rugae have been used as internal dental cast reference points for quantification of tooth migration. Some, but not all, investigators have reported the medial rugal region to be stable or to show predictable change. The purpose of this study was to use the longitudinal data base of the Child Research Council of Denver to examine the anteroposterior stability of the medial rugal region. Dental casts of 20 females and 21 males with untreated normal Angle Class I occlusions were selected. Time intervals measured were: T1--primary teeth erupted, T2--earliest cast with permanent first molars erupted, T3--earliest cast with canines and pre-molars erupted, and T4--ages 16 to 22. Distinctive left and right anterior and posterior rugae which appeared on all four casts were identified, the medial ends marked, and the anteroposterior distances measured. The data were evaluated with the paired t test, repeated-measures ANOVA, and Tukey's multiple comparison procedure. From T1--T4, the medial rugal region increased 1.4 +/- 0.6 mm in females and 2.3 +/- 0.8 mm in males. Only two cases showed a trend toward stability. There were no significant differences by side. Significant increases in size occurred between T2 and T3 for females and males and between T3 and T4 for males. Analysis of these data indicates that the medial rugal region increases significantly in anteroposterior length, but not uniformly between the sexes across observation times. Such changes are characteristic of general craniofacial growth and suggest that the rugal region is responding to the differential growth of the underlying bone. Therefore, medial rugal landmarks appear not to be stable reference points for tooth migration research.


Prognostic features of signal transducer and activator of transcription 3 in an ER(+) breast cancer model system.
The aberrantly expressed signal transducer and activator of transcription 3 (STAT3) predicts poor prognosis, primarily in estrogen receptor positive (ER(+)) breast cancers. Activated STAT3 is overexpressed in luminal A subtype cells. The mechanisms contributing to the prognosis and/or subtype relevant features of STAT3 in ER(+) breast cancers are through multiple interacting regulatory pathways, including STAT3-MYC, STAT3-ERα, and STAT3-MYC-ERα interactions, as well as the direct action of activated STAT3. These data predict malignant events, treatment responses and a novel enhancer of tamoxifen resistance. The inferred crosstalk between ERα and STAT3 in regulating their shared target gene-METAP2 is partially validated in the luminal B breast cancer cell line-MCF7. Taken together, we identify a poor prognosis relevant gene set within the STAT3 network and a robust one in a subset of patients. VEGFA, ABL1, LYN, IGF2R and STAT3 are suggested therapeutic targets for further study based upon the degree of differential expression in our model.


[Perforation of esofagic mucosa for enteric tube: case report].
This study is a case report of a patient that was submitted to implant of enteric tube (ET) in the ICU, being evidenced false passage in proximal esophagus during endoscopic procedure, demonstrating tunnel for the submucosa. A 77 years old woman, transferred to ICU, where ET was installed (due to difficulty of being carried through both nostrils) being confirmed its position through thoraco-abdominal x-ray. The patient remained around 10 days with the ET, receiving diet, without any alteration. In the 10th day she was evolved with melena and reduction of the values of Hb/Ht, without hemodynamic repercussion. Submitted to the high digestive endoscopic that evidenced ulcer injury to bulbar, of about 2.5 cm, with signals of former bleeding. During the examination, a false passage of the ET in proximal esophagus was visualized: 2 cm below of the crico-faring, tunnel for the submucosa possibly for all above-mentioned segments, following its habitual passage until gastric chamber. Patients of high risk for esophagus perforation for ET installation can be identified and well-taken care of adjusted they can be used. If to occur perforation, this must be identified how much so early possible, for adequate treatment. The adequate treatment depends of each case and same the clinical therapy can be appropriate in selected cases.


Late phase of repolarization is autoregenerative and scales linearly with action potential duration in mammals ventricular myocytes: a model study.
Scaling of action potential (AP) duration (APD) in mammals of different size is a rather complex phenomenon, dominated by a regulatory type mechanism of ion channels expression. By means of simulations performed on six published mathematical models of cardiac ventricular APs of different mammals, it is shown that AP repolarization is autoregenerative in its later phase (ARRP) and that the duration of such phase scales linearly with APD. For each AP, a 3-D instantaneous time-voltage-current surface is constructed, which has been recently described in a more simplified model. This representation allows us to measure ARRP and to study the contribution to it for different ion currents. It has been found that the existence of an ARRP is not intrinsic to cardiac models formulation; one out of the six models does not show this phase. A linear correlation between ARRP duration and APD in the remaining models is also found. It is shown that ARRP neither simply depend on AP shape nor on APD. Though I(K1) current seems to be the main responsible for determining and modulating this phase, the mechanism by which ARRP scales linearly with APD remains unclear and raises further questions on the scaling strategies of cardiac repolarization in mammals.


Dentinogenic ghost cell tumor - A case report and review of literature.
Dentinogenic ghost cell tumor (DGCT) was first described by Praetorius et al. in 1981 and now believed to be the tumor counterpart of the calcifying odontogenic cyst (COC). DGCT is an extremely rare odontogenic tumor and accounts for only 2% to 14% of all COCs. A case of DGCT in a 40-year-old female patient is being reported.


Image-guided brachytherapy (IGBT) combined with whole pelvic intensity-modulated radiotherapy (WP-IMRT) for locally advanced cervical cancer: a prospective study from Chiang Mai University Hospital, Thailand.
A report of preliminary results and toxicity profiles using image-guided brachytherapy (IGBT) combined with whole pelvic intensity-modulated radiation therapy (WP-IMRT) for locally advanced cervical cancer. Fifteen patients with locally advanced cervical cancer were enrolled into the study. WP-IMRT was used to treat the Clinical Target Volume (CTV) with a dose of 45 Gy in 25 fractions. Concurrent cisplatin (40 mg/m(2)) was prescribed during radiotherapy (RT) on weekly basis. IGBT using computed tomography was performed at the dose of 7 Gy × 4 fractions to the High-Risk Clinical Target Volume (HR-CTV). The mean cumulative doses - in terms of equivalent dose of 2 Gy (EQD2) - of IGBT plus WP-IMRT to HR-CTV, bladder, rectum, and sigmoid colon were 88.3, 85.0, 68.2 and 73.6 Gy, respectively. In comparison with standard (point A prescription) dose-volume histograms, volume-based image-guided brachytherapy improved the cumulative doses for bladder of 67%, rectum of 47% and sigmoid of 46%. At the median follow-up time of 14 months, the local control, metastasis-free survival and overall survival rates were 93%, 100% and 93%, respectively. No grade 3-4 acute and late toxicities were observed. The combination of image-guided brachytherapy and intensity-modulated radiotherapy improved the dose distribution to tumor volumes and avoided overdose in OARs which could be converted in excellent local control and toxicity profiles.


The PstI/RsaI and DraI polymorphisms of CYP2E1 and head and neck cancer risk: a meta-analysis based on 21 case-control studies.
CYP2E1 encodes a member of the cytochrome P450 superfamily of enzymes which play a central role in activating and detoxifying many carcinogens and endogenous compounds thought to be involved in the development of cancer. The PstI/RsaI and DraI polymorphism are two of the most commonly studied polymorphisms of the gene for their association with risk of head and neck cancer, but the results are conflicting. We performed a meta-analysis using 21 eligible case-control studies with a total of 4,951 patients and 6,071 controls to summarize the data on the association between the CYP2E1 PstI/RsaI and DraI polymorphism and head and neck cancer risk, especially by interacting with smoking or alcohol. Compared with the wild genotype, the OR was 1.96 (95% CI: 1.33-2.90) for PstI/RsaI and 1.56 (95% CI: 1.06-2.27) for DraI polymorphism respectively. When stratified according to ethnicity, the OR increased in the Asians for both polymorphisms (OR = 2.04, 95% CI: 1.32-3.15 for PstI/RsaI; OR = 2.04, 95% CI: 1.27-3.29 for DraI), suggesting that the risk is more pronounced in Asians. Our meta-analysis suggests that individuals with the homozygote genotypes of PstI/RsaI or DraI polymorphism might be associated with an increased risk of head and neck cancer, especially in Asians.


Product-related emphasis of skin disease information online.
In 2000, 41 million people searched for medical information online. The quality of that information is unregulated, variable, and not well studied. To quantify and compare the numbers and types of Internet sites matched for 10 diverse skin conditions through different search systems. Search strategies were performed at 6-month intervals via Netscape Navigator, using 3 search engines and 1 directory. Ten skin conditions were chosen to represent common (psoriasis and eczema), cosmetic (wrinkles and cellulite), difficult-to-treat (alopecia, mastocytosis, granuloma annulare, and xanthoma), and uncommon (dermatitis herpetiformis and epidermolysis bullosa) problems. Search strings were designed to generate lists of Web sites that provide educational or product-related information. Results were compared. The Saint Louis University information technology server, July 9, 1999, December 16, 1999, and February 5, 2000. Comparisons of the total number, top 10 ranking, and type (educational vs product-related) of sites that matched through different search systems at 6-month intervals. The total number of matched sites for different skin conditions varied up to 100-fold. This number increased by 30% to 316% between July and December 1999. The largest number of Web sites related to wrinkles, followed by Web sites related to common conditions. Product-related sites outnumbered educational sites, especially for common and cosmetic conditions. Although there were differences in the total number of sites found through different search engines, the ratios of product-related to educational sites were similar. Different search engines yielded different top 10 match lists for the same condition. The top 10 lists included higher proportions of educational sites than the total match lists for all conditions except cellulite. Within the top 10 lists, the rank order of well respected sites varied by search engine used and changed over time. Patients are increasingly accessing the growing body of data available through the Internet. Most Web sites contain information related to products. Until standards are enacted to govern the distribution of online medical information, consumers are at risk for obtaining misinformation and buying ineffective products. To better guide patients, physicians must become familiar with this ever-changing information.


[After-care of the patient with myocardial infarct].
Patients after myocardial infarction are at a substantial risk for recurrent cardiac events; therefore, an optimal patient care is of great importance. Early revascularisation is one important contributor to the prognosis after myocardial infarction. Antithrombotic agents, betablockers, and ACE-inhibitors also contribute significantly to the improved outcome after myocardial infarction. Reduction of risk factors, in particular cessation of smoking and lowering of lipids are of highest importance to improve the prognosis after myocardial infarction.


Flavobacterium filum sp. nov., isolated from a wastewater treatment plant in Korea.
A Gram-negative bacterium, designated strain EMB34(T), was isolated from a wastewater treatment plant in Korea. Growth was observed between 10 and 40 degrees C (optimum, 25-35 degrees C) and between pH 6.0 and 9.5 (optimum, pH 7.5-8.0). The cells were non-motile rods, linked with extracellular fibrils. The predominant fatty acids of strain EMB34(T) were iso-C(15 : 0), C(15 : 0), iso-C(15 : 1) G, iso-C(16 : 0) 3-OH and iso-C(15 : 0) 3-OH and the strain contained phosphatidylethanolamine and phosphatidylinositol as the polar lipids. The G+C content of the genomic DNA was 34.2 mol% and the major quinone was menaquinone-6. Comparative 16S rRNA gene sequence analyses showed that strain EMB34(T) formed a distinct phyletic line within the genus Flavobacterium. The levels of 16S rRNA gene sequence similarity with other Flavobacterium species were less than 94.5 %. On the basis of phenotypic, chemotaxonomic and molecular data, it is clear that strain EMB34(T) represents a novel species within the genus Flavobacterium, for which the name Flavobacterium filum sp. nov. is proposed. The type strain is EMB34(T) (=KCTC 12610(T)=DSM 17961(T)).


The influence of dopaminergic system inhibition on biosynthesis of gonadotrophin-releasing hormone (GnRH) and GnRH receptor in anoestrous sheep; hierarchical role of kisspeptin and RFamide-related peptide-3 (RFRP-3).
This study aimed to explain how prolonged inhibition of central dopaminergic activity affects the cellular processes governing gonadotrophin-releasing hormone (GnRH) and LH secretion in anoestrous sheep. For this purpose, the study included two experimental approaches: first, we investigated the effect of infusion of sulpiride, a dopaminergic D2 receptor antagonist (D2R), on GnRH and GnRH receptor (GnRHR) biosynthesis in the hypothalamus and on GnRHR in the anterior pituitary using an immunoassay. This analysis was supplemented by analysis of plasma LH levels by radioimmunoassay. Second, we used real-time polymerase chain reaction to analyse the influence of sulpiride on the levels of kisspeptin (Kiss1) mRNA in the preoptic area and ventromedial hypothalamus including arcuate nucleus (VMH/ARC), and RFamide-related peptide-3 (RFRP-3) mRNA in the paraventricular nucleus (PVN) and dorsomedial hypothalamic nucleus. Sulpiride significantly increased plasma LH concentration and the levels of GnRH and GnRHR in the hypothalamic-pituitary unit. The abolition of dopaminergic activity resulted in a significant increase in transcript level of Kiss1 in VMH/ARC and a decrease of RFRP-3 in PVN. The study demonstrates that dopaminergic neurotransmission through D2R is involved in the regulatory pathways of GnRH and GnRHR biosynthesis in the hypothalamic-pituitary unit of anoestrous sheep, conceivably via mechanisms in which Kiss1 and RFRP-3 participate.


Implantable cardioverter-defibrillators and pregnancy: a safe combination?
The purpose of this investigation was to evaluate the outcome of pregnancy in women with implantable cardioverter-defibrillators (ICDs). A multicenter retrospective analysis was performed on women with an ICD who became pregnant. Data were collected on 44 patients. The mean age and ejection fraction at the time of the initial ICD implant were 25.6+/-4.9 years and 49.8+/-9.7%, respectively. The mean follow-up after the ICD implant was 4.8+/-2.8 years. Forty-two women had abdominally implanted generators, and 2 had a prepectoral device. Thirty had epicardial lead sensing systems, and 14 had transvenous. Thirty-six (82%) experienced no complications, and 8 (18%) had a medical or device-related complication. The ICD-related problems included tenderness at the ICD pocket scar (2 patients), generator migration (1), and pericarditis secondary to the epicardial patches (1). Medical complications were pulmonary embolism (1), therapeutic abortion (1), worsening hyperthyroidism (1), congestive heart failure (1), and weight loss (1). Thirty-seven women delivered vaginally, and 7 underwent cesarean section. Thirty-nine babies were born healthy, 1 was stillborn, 2 were small for gestational age, 1 had transient hypoglycemia, and 1 woman had a therapeutic abortion unrelated to the ICD. During pregnancy, 33 women received no ICD therapy, 8 had 1 shock, 1 had 5 discharges, 1 had 11 shocks, and 1 had 5 shocks. The total number of shocks during pregnancy ranged from 0 to 11, with an average of 0.66+/-1.9 discharges. Five women had 7 additional pregnancies without an ICD shock. The mere presence of an ICD should not defer a women from becoming pregnant unless she has an underlying structural cardiac disease that is considered a contraindication. Pregnancy does not increase the risk of major ICD-related complications or result in a high number of ICD discharges.


CD27 and CD40 inhibit p53-independent mitochondrial pathways in apoptosis of B cells induced by B cell receptor ligation.
B cells in the germinal center are known to undergo apoptosis after B cell receptor (BCR) ligation, a process relevant to immunological tolerance. Human CD27 is a B cell co-stimulatory molecule. The aim of this study was to compare the effects of CD27 and CD40 signals on BCR-mediated apoptosis of B cells. BCR ligation activated mitochondrial apoptotic pathways including down-regulation of Bcl-X(L), dissipation of mitochondrial transmembrane potential, release of cytochrome c, and activation of caspase-9. Each of these effects was significantly inhibited by CD27 and CD40. Bik expression was weakly but significantly down-regulated by CD27 but up-regulated by CD40. BCR ligation resulted in p53 activation including its phosphorylation at Ser(15), nuclear translocation, and target gene p53AIP1 induction. CD27 and CD40 clearly suppressed these processes. Analyses that used dominant-negative p53 variants revealed a low but still substantial level of BCR-mediated apoptosis and intact mitochondria-mediated apoptotic pathway. These pathways were further inhibited by CD27 and CD40, although the cells showed no p53 phosphorylation or p53AIP1 expression. Our results suggested that, at the mitochondrial level, CD27 and CD40 co-stimulatory signals regulated the p53-amplified apoptotic pathway in B cells through the inhibition of p53-independent apoptotic pathway primarily induced by BCR ligation.


Tissue-specific and light-dependent expression within a family of nuclear-encoded sigma-like factors from Zea mays.
The principal transcription machinery functioning in chloroplasts of higher plants is encoded in two subcellular compartments. Subunits of the RNA polymerase catalytic core are plastid encoded, while sigma factors required for promoter recognition are encoded in the nucleus. We have isolated nuclear-encoded cDNAs, sig1, sig2, and sig3, specifying three sigma factors from maize (Zea mays). The three deduced polypeptides have extensive sequence identity with the principal sigma factors of eubacteria. Two of the maize cDNAs, sig1 and sig3, encode NH2-terminal transit peptides which direct the uptake of a heterologous protein into chloroplasts in vitro. Transcripts for the sig3 gene were more abundant in green leaves than in roots and in light-treated seedlings than in dark-grown seedlings. In contrast, sig1 transcripts were readily detectable in all tissues examined. Thus, at least two promoter-selectivity factors function with the maize chloroplast RNA polymerase, one of which is constitutively expressed and the other is light activated.


The effect of anakinra to nephrotoxicity with cisplatin induced in rats: Biochemical, gene expression and histopathological evaluation.
Oxidative stress and interleukin-1 beta (IL-1β) have been reported to play a role in the pathogenesis of nephrotoxicity induced by cisplatin. The objective of this study was to investigate the effect of anakinra, which is an IL-1β receptor antagonist, on cisplatin-induced nephrotoxicity in rats, through biochemical, gene expression and histopathological analyses. The study was designed with 4 groups. For 1 week, the control group (C) and the cisplatin (Cis) group received distilled water, while the cisplatin + anakinra 50 (Cis + ANA50) group and the cisplatin + anakinra 100 (Cis + ANA100) group were intraperitoneally administered 50 mg/kg and 100 mg/kg of anakinra, respectively. The Cis, Cis + ANA50 and Cis + ANA100 groups were intraperitoneally injected with a 2.5 mg/kg dose of cisplatin for 7 days. After sacrifice, the kidney tissue of each rat was extracted for the assessment of the malondialdehyde (MDA) and total glutathione (tGSH) levels, and for gene expression analyses of IL-1β. The kidney tissues were histopathologically evaluated. Statistical analyses of the data were performed using one-way analysis of variance (ANOVA). The administration of cisplatin (the Cis group) yielded a higher level of MDA (4.75 ±0.25 nmol/mL; p < 0.001) and lower levels of tGSH (1.80 ±0.35 mg/L; p < 0.001) compared to other groups. Cisplatin also increased IL-1β gene expression (6.33 ±0.27 gene expression levels; p < 0.001) compared to other groups. The impact of anakinra on the MDA and tGSH levels, and on IL-1β gene expression induced by cisplatin was observed as a reversal of these findings (p < 0.05). Anakinra better prevented an increase of the levels of MDA and IL-1β at a dose of 100 mg/kg compared to a 50 mg/kg dose. Anakinra prevents oxidative kidney damage induced by cisplatin, in a dose-dependent manner. This result suggests that anakinra may be useful in the treatment of cisplatin-induced kidney damage.


Prediction of respiratory symptoms by peripheral blood neutrophils and eosinophils in the First National Nutrition Examination Survey (NHANES I).
To examine specific cellular markers of inflammation in peripheral blood (neutrophils and eosinophils) and their relationship to respiratory symptoms, we used data from the First National Health and Nutrition Examination Survey (NHANES I). Cross-sectional data were available on a random sample of 6,913 adults aged 30 to 74 years who had American Thoracic Society-National Heart, Lung, and Blood Institute questionnaire information on respiratory symptoms and illnesses, including asthma, chronic bronchitis, dyspnea (grade 3), chronic cough, and chronic phlegm. Information was available on age, race, smoking status, peripheral blood leukocyte count, and differential cell count. These data were analyzed using logistic regression controlling for age, race, sex, and cigarette smoking. Physician-diagnosed asthma was significantly associated only with the eosinophil count (p = 0.001). Physician-diagnosed bronchitis was significantly associated with the neutrophil count (p = 0.012) and marginally associated with the eosinophil count (p = 0.072). Chronic phlegm was also significantly associated with both the eosinophil count (p = 0.049) and the neutrophil count (p = 0.041). Grade 3 dyspnea (p = 0.049) was only significantly associated with the neutrophil count. These data suggest that both peripheral blood neutrophils and eosinophils are associated with a broad range of respiratory symptoms and that the eosinophil may play a role in nonasthmatic respiratory inflammation.


Computer-aided drug design: lead discovery and optimization.
Over the past decade, there have been remarkable advances in the area of computer-aided drug design (CADD), which has been applied at almost all stages in the drug discovery pipeline. The generation of initial lead compounds and the subsequent optimization aimed at improving potency and pharmacological properties are the core activities among all. The development in these aspects over the past years will be the focus of this review.


[Folate deficiency, cancer and congenital abnormalities. Is there a connection?].
The biochemical role of folate is in the interconversion of one-carbon units in intermediary metabolism; a process in which a methyl group is formed de novo. The methyl group is subsequently transferred to adenosylmethionine, which is an important methyl donor in the methylation of DNA. A negative correlation exists between the intake of folate in pregnancy and the occurrence of neural tube defects and certain malignant brain tumours in children. Numerous clinical studies have pointed to an association between folate status in adults and both the occurrence of cancer and the premalignant changes, cervical dysplasia, bronchial metaplasia, and colorectal adenomas. Folate deficiency may cause chromosomal damage, due to impaired DNA synthesis or repair. Moreover, decreased production of adenosylmethionine may influence the expression of developmental genes and of oncogenes and/or tumour suppressor genes through disturbed methylation of DNA.


Cohesin and Cdk1: an anaphase barricade.
Separation of sister chromatids at anaphase in metazoan cells requires only the cleavage of the kleisin subunit of centromeric cohesin, but efficient poleward movement of separated sisters requires the associated loss in Cdk1 activity. Activation of the anaphase-promoting complex/cyclosome ensures these events are coordinated.


A major human immunodeficiency virus type 1-initiated killing pathway distinct from apoptosis.
We have investigated the relative contribution of apoptosis or programmed cell death (PCD) to cell killing during acute infection with T-cell-tropic, cytopathic human immunodeficiency virus type 1 (HIV-1), by employing diverse strategies to inhibit PCD or to detect its common end-stage sequelae. When Bcl-2-transfected cell lines were infected with HIV-1, their viability was only slightly higher than that of control infections. Although the adenovirus E1B 19-kDa protein has been reported to be a stronger competitor of apoptosis than Bcl-2, it did not inhibit HIV-mediated cell death better than Bcl-2 protein. Competition for Fas ligand or inactivation of the Fas pathway secondary to intracellular mutation (MOLT-4 T cells) also had modest effects on overall cell death during acute HIV infection. In contrast to these observations with HIV infection or with HIV envelope-initiated cell death, Tat-expressing cell lines were much more susceptible (200% enhancement) to Fas-induced apoptosis than controls and Bcl-2 overexpression strongly (75%) inhibited this apoptotic T-cell death. PCD associated with FasR ligation resulted in the cleavage of common interleukin-1beta-converting enzyme (ICE)-protease targets, poly(ADP-ribose) polymerase (PARP) and pro-ICE, whereas cleaved products were not readily detected during HIV infection of peripheral blood mononuclear cells or T-cell lines even during periods of extensive cell death. These results indicate that one important form of HIV-mediated cell killing proceeds by a pathway that lacks the characteristics of T-cell apoptosis. Our observations support the conclusion that at least two HIV genes (env and tat) can kill T cells by distinct pathways and that an envelope-initiated process of T-cell death can be discriminated from apoptosis by many of the properties most closely associated with apoptotic cell death.


Posterior Hip Precautions Do Not Impact Early Recovery in Total Hip Arthroplasty: A Multicenter, Randomized, Controlled Study.
Posterior hip precautions have been routinely prescribed to decrease dislocation rates. The purpose of this study was to determine whether the absence of hip precautions improved early recovery after total hip arthroplasty via the posterolateral approach. Patients undergoing total hip arthroplasty via the posterolateral approach at 3 centers were enrolled. Patients meeting the selection criteria were randomized to standard hip precautions (SHP) or no hip precautions (NHP) for 6 weeks following surgery. HOOS Jr, Health State visual analog score, and rate of pain scores were recorded preoperatively and in subsequent postoperative visits; dislocation episodes were also noted. Standard statistical analysis was performed. From 2016 to 2017, 159 patients were randomized to SHP and 154 patients were randomized to NHP. Controlling for the center at which the surgery was performed, the only difference in outcome scores between the 2 groups was at 2 weeks; the NHP group had a lower HOOS Jr score when compared to the SHP group (P = .03). There was no difference in outcome scores at any other time points when compared to preoperative assessments. In the SHP group, there were 2 recorded dislocations (1.3%) and 1 in the NHP group (0.7%; P = .62). In this multicenter, randomized, controlled study, the absence of hip precautions in the postoperative period did not improve subjective outcomes which may be explained by the self-limiting behavior of NHP patients. Furthermore, with the numbers available for the study, there was no difference in the rate of dislocation between the 2 groups.


Quantification of hepatitis B surface antigen and E antigen: correlation between Elecsys and architect assays.
Quantification of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) and their change model during treatment are emerging as a useful tool for assessing the outcome of hepatitis B virus (HBV) infection and predicting the efficacy of antiviral therapy. The aim of this study was to compare the performance of the Elecsys and Architect assays for HBsAg and HBeAg quantification. Quantification of HBsAg and HBeAg, determined by these two assays, were assessed in 1292 sera from patients with chronic hepatitis B(CHB). HBeAg quantification in serum was performed by calibrating the results through HBeAg Paul-Ehrlich international (PEI) reference standard. The HBV genotype was determined by direct sequencing and phylogenetic analysis. Of 1292 samples, the distribution of genotype was 514 (39.78%) genotype B, 776 (60.06%) genotype C, 2 (0.16%) genotype D. The results of HBsAg and HBeAg quantification between the Architect and Elecsys assays were significantly correlated (HBsAg: r = 0.939; HBeAg: r = 0.987), independent of HBV genotype and treatment phase. The mean differences between the two methods (the log10 [Elecsys] - the log10 [Architect]) were 0.075 log10 IU/mL and -0.149 log10 PE IU/mL in quantifying HBsAg and HBeAg, respectively. This study demonstrates a high correlation between the Elecsys and the Architect assays in quantifying HBsAg and HBeAg, regardless of HBV genotype. Both the two assays can be used to monitor the HBsAg and HBeAg levels in patients with chronic hepatitis B.


Are lipid mediators implicated in the production of pro- and anti-inflammatory cytokines during cardiopulmonary bypass graft with extracorporeal circulation?
In this study the authors assessed the sequential release of lipid mediators (TXB2, PGE2, 6-keto-PGF1alpha, LTB4, LTC4, PAF), pro-inflammatory cytokines (IL-6, IL-8, TNF-alpha) and anti-inflammatory cytokines (IL-4, IL-10) in 17 patients undergoing coronary artery bypass graft (CABG) with extracorporeal circulation (ECC). Time course of appearance of inflammatory mediators revealed the early and transient increase in lipid mediator plasma concentrations (6-keto-PGF1alpha, LTB4, LTC4, PAF) whereas cytokines (IL-6, IL-8, IL-10) were involved only in late pre- and post-operative periods. No variation of TXB2, PGE2, IL-4 and TNF-alpha levels were found. No correlation was documented between the levels of lipid mediators and pro- or anti-inflammatory cytokines suggesting that lipidic compounds are not implicated in the genesis of cytokines which appear much later involved. Despite the common use of high doses of aprotinin (a non-specific enzyme inhibitor) in hope to abrogate the inflammatory response to cardiopulmonary bypass procedure, this study reports the persistent release of several inflammatory compounds that might be involved in the post-CABG multiple organ failure syndromes.


Treatment of rheumatoid arthritis: new therapeutic approaches with biological agents.
Rheumatoid arthritis is a chronic polyarthritis leading to joint destruction and remarkable disability. Current therapies have various degrees of efficacy, but toxicity frequently limits their long-term use. Furthermore, treatment of refractory rheumatoid arthritis includes increasing disease-modifying antirheumatic drugs dosage, using combination therapy, and adding or increasing the posology of corticosteroids. Although the etiology of the disease remains unknown, our increasing knowledge of the mechanisms underlying pathogenic events in rheumatoid synovitis, has provided opportunities to specifically target cell surface markers or cytokines involved in the inflammatory response. The objective of this review is to describe the different therapeutic approaches with biological agents that are either being utilized or are under development. Some of these products reflect the evolving capacity for the biotechnology industry to synthesize and humanize therapeutic agents: anti-tumor necrosis factor (TNF) alpha monoclonal antibodies (MoAb) and recombinant TNF-receptor construct appear to be validated tools. These treatments alone, or in combination with methotrexate are very effective in rheumatoid patients. Data from clinical trials and issues related to mechanisms of action, potential toxicity, and future perspectives for these novel therapeutic options are considered in this review. Anti-cytokine treatment include other interesting approaches to interfere with on-going inflammatory processes, such as the use of recombinant human interleukin (IL)1 receptor antagonist, or recombinant human IL10. T cell constimulatory blockade, induction of apoptosis in the synovial tissue, and gene therapy could represent future strategies in rheumatoid disease.


[Manual suture versus/or mechanical suture from the German viewpoint].
There is a definite increase in the application of stapled sutures in the gastrointestinal tract and the lung. This is due to high level of technical perfection of modern staplers whose preceding models were actually already developed at the beginning of this century. The introduction of circular staplers since approx. 1978/79 has resulted in a true breakthrough for gastrointestinal tract surgery. Thanks to these circular staplers surgeons have been especially innovative regarding the principles of reconstruction. Thus the procedures for the formation of substitute stomachs (Roux-Y and pouch, interposition and pouch) allow an unprecedented degree of standardization and offer new physiological perspectives. The use of circular staplers in the rectum is generally accepted. However, a recent development concerning manual sutures using medium-term absorbable suture material should not be disregarded.


Serum osteocalcin concentrations in Paget's disease of bone.
Total body scintiscans, serum alkaline phosphatase estimations, and serum osteocalcin radioimmunoassays were performed in 49 consecutive patients with Paget's disease of bone. Eleven were receiving calcitonin (salmon synthetic) at the time of the study. The serum alkaline phosphatase activities were elevated in all but one patient, with the highest value almost 50 times the upper limit of the reference range. Serum osteocalcin concentrations were elevated in 53% of patients and normal in the rest. The highest serum osteocalcin value was 4.2 times the upper limit of the reference range. The correlation coefficient between the extent of skeletal involvement and serum osteocalcin level was .70, while that between skeletal involvement and serum alkaline phosphatase level was .55. In spite of the better correlation between bone scintiscans and serum osteocalcin level, osteocalcin measurements are diagnostically less useful than serum alkaline phosphatase estimations in patients with Paget's disease of bone.


Vitamin C enhances chemosensitization of esophageal cancer cells in vitro.
Chemotherapy is increasingly utilised in multimodal protocols to try and improve outcomes. Cisplatin and 5-fluorouracil (5-Fu) are the mainstay of chemotherapeutic regimens, and an understanding of sensitivity and resistance of esophageal cancer to these agents is of considerable clinical importance. Antioxidants may modulate the response to chemotherapy, and in this study we examined the effect of vitamin C on 5-Fu and cisplatin cytotoxicity and related pathways in the esophageal cancer cell lines OE33 and SKGT-4. The antiproliferative effect of antitumor agents was measured by the MTT assay, and the transcription factors NF-kappaB and AP-1 pathways were assessed by electrophoretic mobility gel shift assay. 5-Fu and cisplatin demonstrated marked morphological changes and decreased cell proliferation. A combination of vitamin C with 5-Fu or cisplatin exerted a significantly enhanced cytotoxic effect compared to both drugs individually. Treatment of esophageal cancer cells with 5-Fu and cisplatin induced NF-kappaB and AP-1 activation. Pretreatment with vitamin C inhibited 5-Fu or cisplatin induced NF-kappaB nuclear translocation and DNA binding activity, but vitamin C had no effect on IkappaB-alpha protein levels. Vitamin C also inhibited 5-Fu- and cisplatin-induced AP-1 activation. Our data demonstrate that vitamin C enhances the antitumor activity of 5-Fu and cisplatin, in part by inhibiting translocation of NF-kappaB and AP-1, and sensitizes cancer cells to drug-induced cell death. The data suggest that vitamin C supplementation may improve the efficacy of chemotherapy for esophageal cancer.


Disappearance of Anterior Cervical Corpectomy Cage.
Although cage subsidence and dislodgement are not uncommon in anterior cervical spine surgery, missing cages have seldom been reported. This is the first report of the disappearance of a metallic corpectomy cage after anterior cervical fusion. A 63-year-old man, who had a history of ankylosing spondylitis and diabetes mellitus, was involved in a motor vehicle accident that broke his neck. The traumatic C6 burst fracture caused myelopathy and instability, which required surgery. He then underwent anterior C6 corpectomy with circumferential fixation, including anterior plating and posterior lateral mass screws from C5-C7. There was a significant improvement in neurological function after the surgery and he could ambulate independently. However, upon a visit at six months postoperation, there was dislodgement of the anterior cervical plate and cage. An attempt to revise the anterior fusion construct was made subsequently, but this surgery could only remove the plate. The metallic cage was left in place during the revision surgery because it was firmly incorporated into the C5 and C7 vertebra and could hardly be adjusted intraoperatively. There were no other interventions during the interval. Upon his visit at 23 months after the initial surgery, the metallic cage was missing. No examinations could locate the cage anywhere in the body, including 36-inch radiographs that demonstrated completely the disappearance of the metallic corpectomy cage. The posterior arthrodesis seemed stable and the patient had no dysphagia or any other gastrointestinal symptoms. The process of the disappearance of the corpectomy cage was never noticed by the patient and he remains free of symptoms to date. The complete dislodgement of a cervical corpectomy cage that was placed anteriorly could happen without symptoms. The cage might have been expelled during bowel movements and caused little problem. Failure to achieve arthrodesis in anterior cervical fusion, therefore, must be closely monitored.


Structure of the Threonine-Rich Extensin from Zea mays.
Chymotryptic digestion of a threonine-rich hydroxyproline-rich glycoprotein (THRGP) purified from the cell surface of a Zea mays cell suspension culture gave a peptide map dominated by the hexadecapeptide TC5: Thr-Hyp-Ser-Hyp-Lys-Pro-Hyp-Thr-Pro-Lys-Pro-Thr-Hyp-Hyp-Thr-Tyr, in which the repetitive motif Ser-Hyp-Lys-Pro-Hyp-Thr-Pro-Lys is homologous with the dominant decamer of P1-type dicot extensins: Ser-Hyp-Hyp-Hyp-Hyp-Thr-Hyp-Val-Tyr-Lys, modified by a Lys for Hyp substitution at residue 3, a Val-Tyr deletion at residues 8 and 9, and incomplete post-translational modification of proline residues. One of the minor peptides (TC1) contained the 8-residue sequence: Thr-Hyp-Ser-Hyp-Hyp-Hyp-Hyp-Tyr corresponding to the C-terminal tail (judging from the recently isolated maize cDNA clone MC56) which is homologous with the major repetitive motif of the ;P3' class of dicot extensins. Direct peptide sequencing defined potential glycosylated regions on the THRGP corresponding to clone MC56 and showing that glycosylated and nonglycosylated domains alternate with high regularity. The THRGP is not in the polyproline-II conformation, judging from circular dichroic spectra, but nevertheless is an extended rod, from electron microscopic data. HF-solvolysis of cell walls from maize coleoptile, root, and root tip released deglycosylated THRGP detected on sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblots with high titer rabbit polyclonal antibodies raised against the intact THRGP. In a quantitative enzyme-linked immunosorbent assay, these antibodies cross-reacted 20% with tomato P1 extensin, and 18% with anhydrous hydrogen fluoride-deglycosylated P1. These results, together with other previously published data, show that maize THRGP is homologous with the dicot P1 extensins and, as such, is the first extensin isolated from a graminaceous monocot.


Discrete wavelet transform de-noising in eukaryotic gene splicing.
This paper compares the most common digital signal processing methods of exon prediction in eukaryotes, and also proposes a technique for noise suppression in exon prediction. The specimen used here which has relevance in medical research, has been taken from the public genomic database - GenBank. Here exon prediction has been done using the digital signal processing methods viz. binary method, EIIP (electron-ion interaction psuedopotential) method and filter methods. Under filter method two filter designs, and two approaches using these two designs have been tried. The discrete wavelet transform has been used for de-noising of the exon plots. Results of exon prediction based on the methods mentioned above, which give values closest to the ones found in the NCBI database are given here. The exon plot de-noised using discrete wavelet transform is also given. Alterations to the proven methods as done by the authors, improves performance of exon prediction algorithms. Also it has been proven that the discrete wavelet transform is an effective tool for de-noising which can be used with exon prediction algorithms.


Kimura's disease and ankylosing spondylitis: A case report.
Ankylosing spondylitis (AS) and Kimura's disease (KD) which is quite rare are both chronic inflammatory diseases. Recently we encountered a patient who suffered from KD and AS, and some of his family members also suffer from AS. We, therefore, investigated this unique case and conducted the family-based whole exome sequencing to explore the possible genetic alterations. Here, we reported a case of a 44-year-old Chinese man with multiple painless masses all over his body and a back pain for 32 years. His uncle and sister were diagnosed with AS. The diagnosis of KD was based on the patient's clinical features and the biopsy of the neck masses. The diagnosis of AS was based on the patient's clinical features, HLA-B27(+) and the radiologic changes of sacroiliac joints. The genetic test showed that ARPC1B gene which was associated with recurrent infections, auto-inflammatory changes and elevated IgE levels was mutated in this patient. Neck masses were removed by surgery. Systemic glucocorticoid, nonsteroidal anti-inflammatory agents, combined with cyclosporine were orally administered, and Etanercept was injected subcutaneously. The masses disappeared rapidly after surgery combined with systemic glucocorticoid, but relapsed shortly after the therapy was discontinued. Low dose glucocorticoid, cyclosporine and Etanercept could keep both KD and AS remained long-term remission. Our experience suggests that low dose glucocorticoid, cyclosporine and Etanercept could be beneficial for the patient with KD and AS. The mutation of ARPC1B gene in this case, which is associated with immunologic disturbance, may increase the susceptibility of KD.


Cardiac tumors: the 17-year experience of pediatric cardiology department.
Primary cardiac tumork may be benign or malignant and may arise anywhere in the endocardium, myocardium or pericardium. They are rare in pediatric age-groups, with a prevalence in autopsy findings of 0.0017 to 0.28%; most are benign, malignant tumors accounting for only 10% of the total. The purpose of this paper is to report the 17-year (1989-2006) experience of primary cardiac tumors in a single center. The clinical data and histopathological diagnoses were collected from a retrospective chart review. We identified 12 patients, with a mean age at diagnosis of 23 months, in two cases diagnosed in the fetal period. The frequent cause of referral was tuberous sclerosis, followed by a cardiac murmur. The diagnosis of primary cardiac tumor was based on echocardiography and/or magnetic resonance imaging. The patients all underwent 24-hour electrocardiographic Holter monitoring, and the most common finding was nonspecific repolarization abnormalities. The most frequent cardiac tumor was rhabdomyoma (67%), usually associated with tuberous sclerosis, followed by fibroma (17%) and fibroelastoma (8%) Although biopsy is the diagnostic gold standard, it was only performed in two patients. Surgical removal of the tumor was performed in a single patient (with fibroelastoma) due to the perceived risk of pulmonary embolization. In our population, the most frequent tumor was rhabdomyoma associated with tuberous sclerosis. Most patients were asymptomatic, and the diagnosis was made in routine observations on patients with tuberous sclerosis or with a cardiac murmur. A histopathological diagnosis is only warranted in the rarest forms of cardiac tumors.


Clinical and ECG variables to predict the outcome of genetic testing in hypertrophic cardiomyopathy.
Knowledge on the influence of specific genotypes on the phenotypic expression of hypertrophic cardiomyopathy (HCM) is emerging. The objective of this study was to evaluate the genotype-phenotype relation in HCM patients and to construct a score to predict the genetic yield based to improve counseling. Unrelated HCM patients who underwent genetic testing were included in the analysis. Multivariate logistic regression was performed to identify variables that predict a positive genetic test. A weighted score was constructed based on the odds ratios. In total, 378 HCM patients were included of whom 141 carried a mutation (global yield 37%), 181 were mutation negative and 56 only carried a variant of unknown significance. We identified age at diagnosis <45 years, familial HCM, familial sudden death, arrhythmic syncope, maximal wall thickness ≥20 mm, asymmetrical hypertrophy and the absence of negative T waves in the lateral ECG leads as significant predictors of a positive genetic test. When we included these values in a risk score we found very high correlation between the score and the observed genetic yield (Pearson r = 0.98). MYBPC3 mutation carriers more frequently suffered sudden cardiac death compared to troponin complex mutations carriers (p = 0.01) and a similar trend was observed compared to MYH7 mutation carriers (p = 0.08) and mutation negative patients (p = 0.11). To conclude, a simple score system based on clinical variables can predict the genetic yield in HCM index patients, aiding in counseling HCM patients. MYBPC3 mutation carriers had a worse outcome regarding sudden cardiac death.


Supernumerary impacted teeth in a patient with SOX2 anophthalmia syndrome.
SOX2 anophthalmia syndrome characteristically presents as anophthalmia or microphthalmia, with various extraocular symptoms, such as hypogonadotropic hypogonadism, brain anomaly, and esophageal abnormalities. In this report, we describe a patient with SOX2 anophthalmia syndrome complicated with a dental anomaly, multiple supernumerary impacted teeth, and persistence of deciduous teeth. Multiple supernumerary teeth are usually not solitary symptoms, but indicate systemic syndrome such as cleidocranial dysplasia. In odontogenesis, many transcriptional factors, such as BMPs, FGFs, and Wnts, play significant roles and SOX2 is known to interact with some of them. The role of SOX2 in dental development remains unknown, however, multiple supernumerary teeth can be considered as extraocular symptoms of SOX2 anophthalmia syndrome, rather than the coincidence of two rare diseases.


Sodium glucose co-transporter 2 inhibitors: blocking renal tubular reabsorption of glucose to improve glycaemic control in patients with diabetes.
The kidney plays a central role in the regulation of plasma glucose levels, although until recently this has not been widely appreciated or considered a target for therapeutic intervention. The sodium glucose co-transporter type 2 (SGLT2) located in the plasma membrane of cells lining the proximal tubule mediates the majority of renal glucose reabsorption from the tubular fluid, which normally prevents the loss of glucose in the urine. Competitive inhibitors of SGLT2 that provoke the renal excretion of glucose have been discovered, thereby providing a unique mechanism to potentially lower the elevated blood glucose levels in patients with diabetes. To explore the physiology of SGLT2 action and discuss several SGLT2 inhibitors that have entered early clinical development. All publicly available data were identified by searching the internet for 'SGLT2' and 'SGLT2 inhibitor' through 1 November 2007. Published articles, press releases and abstracts presented at national and international meetings were considered. Sodium glucose co-transporter type 2 inhibition is a novel treatment option for diabetes, which has been studied in preclinical models and a few potent and selective SGLT2 inhibitors have been reported and are currently in clinical development. These agents appear to be safe and generally well tolerated, and will potentially be a beneficial addition to the growing battery of oral antihyperglycaemic agents.


Intracranial presentation of systemic Hodgkin's disease.
Intracranial involvement by Hodgkin's disease is rare. We report a patient with Hodgkin's disease who had intracranial disease at presentation. We also review the literature pertaining to intracranial Hodgkin's disease. Using the key words "Hodgkin's disease" and "central nervous system (CNS) disease", we searched the Pubmed and Cancerlit databases. References were systematically reviewed and data regarding the following variables was extracted: age, gender, signs and symptoms at presentation, histology of Hodgkin's disease, cerebrospinal fluid analysis, stage and treatment. Only 36 cases of intracranial Hodgkin's disease were identified in the literature. Intracranial Hodgkin's disease at presentation is even more uncommon with only 8 reported cases. Most cases of intracranial involvement by Hodgkin's disease occur at the time of relapse. The most common presenting feature of intracranial Hodgkin's disease is a cranial nerve palsy with brain parenchyma being the most common intracranial site of involvement. Mixed cellularity histology is the most frequent subtype of Hodgkin's disease among these patients and the median survival following intracranial presentation is 46 months. Treatment has varied extensively but includes whole brain radiation with or without combination chemotherapy. Our literature review suggests that the prognosis is not dismal with appropriate treatment.


Novel Insight into the Serum Sphingolipid Fingerprint Characterizing Longevity.
Sphingolipids (SLs) are structural components of the lipid bilayer regulating cell functions. In biological fluids, their distribution is sex-specific and is at variance in aging and many disorders. The aim of this study is to identify SL species associated with the decelerated aging of centenarians. SLs, extracted from serum of adults (Ad, 35-37 years old), aged (Ag, 75-77 years old) and centenarian (C, 105-107 years old) women were analyzed by LC-MS/MS in combination with mRNA levels in peripheral blood mononuclear cells (PBMCs) of SL biosynthetic enzymes. Results indicated in Ag and C vs. Ad a comparable ceramides (Cers) increase, whereas dihydroceramide (dhCer) decreased in C vs. Ad. Hexosylceramides (HexCer) species, specifically HexCer 16:0, 22:0 and 24:1 acyl chains, increased in C vs. Ag representing a specific trait of C. Sphingosine (Sph), dihydrosphingosine (dhSph), sphingosine-1-phosphate (S1P) and dihydrosphingosine-1-phosphate (dhS1P), increased both in Ag and C vs. Ad, with higher levels in Ag, indicating a SL fine-tuning associated with a reduced physiological decline in C. mRNA levels of enzymes involved in ceramide de novo biosynthesis increased in Ag whereas enzymes involved in sphingomyelin (SM) degradation increased in C. Collectively, results suggest that Ag produce Cers by de novo synthesis whereas C activate a protective mechanism degrading SMs to Cers converting it into glycosphingolipids.


Estimating and projecting HIV prevalence and AIDS deaths in Tanzania using antenatal surveillance data.
The Estimations and Projections Package (EPP 2005) for HIV/AIDS estimates and projects HIV prevalence, number of people living with HIV and new HIV infections and AIDS cases using antenatal clinic (ANC) surveillance data. The prevalence projection produced by EPP can be transferred to SPECTRUM, a demographic projection model, to calculate the number of AIDS deaths. This paper presents estimates and projections of HIV prevalence, new cases of HIV infections and AIDS deaths in Tanzania between 2001 and 2010 using the EPP 2005 and SPECTRUM soft-wares on ANC data. For this study we used; the 1985-2004 ANC data set, the 2005 UN population estimates for urban and rural adults, which is based on the 2002 population census, and results of the 2003 Tanzania HIV Indicator Survey. The ANC surveillance sites were categorized into urban and rural areas on the basis of the standard national definitions of urban and rural areas, which led to 40 urban and 35 rural clinic sites. The rural and urban epidemics were run independently by fitting the model to all data and on level fits. The national HIV prevalence increased from 0% in 1981 to a peak of 8.1% in 1995, and gradually decreased to 6.5% in 2004 which stabilized until 2010. The urban HIV epidemic increased from 0% in 1981 peaking at 12.6% in 1992 and leveled to between 10.9% and 11.8% from 2003 to 2010. The rural epidemic peaked in 1995 at 7.0% and gradually declined to 5.2% in 2004, and then stabilized at between 5.1% and 5.3% from 2005 to 2010. New infections are projected to rise steadily, resulting in 250,000 new cases in 2010. Deaths due to AIDS started in 1985 and rose steadily to reach 120,000 deaths in 2010, with more females dying than men. The fact that the number of new infections is projected to increase steadily to reach 250,000 per year in 2010 calls for more concerted efforts to combat the spread of HIV infection particularly in the rural areas where the infrastructure needed for prevention programmes such as counseling and testing, condom accessibility and AIDS information is less developed.


[Chromosomes isolation from scallop oocytes].
A methodology for chromosome isolation from non fertilized oocytes of Euvola ziczac and Nodipecten nodosus is presented. It solves most of the common problems found during preparation of samples such as the high yolk concentration, chromosome condensation and the loss of biological material during solution changes.


Isolated fallopian tube torsion: a series of six cases.
Isolated Fallopian tube torsion is a rare gynecological cause of acute lower abdominal pain. Currently, there are no pathognomonic symptoms, clinical findings, imaging or laboratory characteristics for this condition, and the diagnosis can rarely be made before operation. We have identified six cases of isolated Fallopian tube torsion treated over a period of 3 years. It was observed that acute onset of abdominal pain with gastrointestinal symptoms can be the initial presenting features. Clinical and laboratory findings included positive peritoneal signs, fever, tachycardia and leucocytosis. Most of the women had preoperative ultrasound showing tubular adnexal masses of heterogeneous echogenicity with cystic component and the presence of free fluid. In contrast to the belief that isolated Fallopian tube torsion is more common in the right side, in five of our cases it occurred in the left side.


So-called sclerosing hemangioma of the lung with nuclear inclusion bodies. Immunohistochemical study of a case.
A so-called sclerosing hemangioma of the lung was removed from a 45-year-old woman after a follow-up of 15 years. In addition to the histology of solid, hemorrhagic, papillary and sclerosing patterns, two types of various-sized, irregularly shaped spaces were found to be lined by either small cells with a high N/C ratio (L1 cells) or large, eosinophilic or foamy cells (L2 cells). These spaces (L1 and L2 spaces) were often alternately arranged. Clusters of L1 cells or L2 cells were also observed in solid-pattern areas with or without lumen formation. Eosinophilic nuclear inclusion bodies (NIB) were exclusively found among L2 cells. L2 cells as well as NIB-containing cells showed an immunohistochemical reactivity similar to that of type II pneumocytes (i.e., positive cytokeratin, epithelial membrane antigen (EMA), surfactant apoprotein, alpha-1-antitrypsin and nonspecific cross-reacting antigen). L1 cells were immunohistochemically similar to solidly growing cells (S cells) which showed positive EMA, alpha-1-antitrypsin and vimentin. These results are consistent with the view that NIB are a good marker for type II pneumocytes in so-called sclerosing hemangioma, and that the two characteristic types of spaces were formed in different ways, thus favoring the theory that S cells are an immature form of type II pneumocytes.


Genomic evolution and transmission of Helicobacter pylori in two South African families.
Helicobacter pylori infects the stomachs of one in two humans and can cause sequelae that include ulcers and cancer. Here we sequenced the genomes of 97 H. pylori isolates from 52 members of two families living in rural conditions in South Africa. From each of 45 individuals, two H. pylori strains were isolated from the antrum and corpus parts of the stomach, and comparisons of their genomes enabled us to study within-host evolution. In 5 of these 45 hosts, the two genomes were too distantly related to be derived from each other and therefore represented evidence of multiple infections. From the remaining 40 genome pairs, we estimated that the synonymous mutation rate was 1.38 × 10(-5) per site per year, with a low effective population size within host probably reflecting population bottlenecks and immune selection. Some individuals showed very little evidence for recombination, whereas in others, recombination introduced up to 100-times more substitutions than mutation. These differences may reflect unequal opportunities for recombination depending on the presence or absence of multiple infections. Comparing the genomes carried by distinct individuals enabled us to establish probable transmission links. Transmission events were found significantly more frequently between close relatives, and between individuals living in the same house. We found, however, that a majority of individuals (27/52) were not linked by transmission to other individuals. Our results suggest that transmission does not always occur within families, and that coinfection with multiple strains is frequent and evolutionarily important despite a fast turnover of the infecting strains within-host.


Efficacy and safety of self-start therapy in women with recurrent urinary tract infections.
We evaluated the efficacy of self-start therapy in women with recurrent urinary tract infections. Women with recurrent urinary tract infections received a dip slide urine culture kit and 6 tablets of norfloxacin (400 mg.). At each symptomatic urinary tract infection episode the patient performed a culture and initiated therapy. The culture was returned and the patient was resupplied with another kit and norfloxacin. Patients were seen 5 to 9 days and 4 to 6 weeks after therapy to assess treatment outcome. A total of 34 women were enrolled in the study and were evaluable for treatment outcomes. Six women followed for 74 months were asymptomatic and 9 followed for 103 months had no infections. A total of 28 women followed for 355 months had 84 symptomatic episodes and 25 had 67 urinary tract infections. Patients had symptomatic episodes at a rate of 2.8 per patient-year (range 0 to 9) and infections at a rate of 2.3 per patient-year (range 0 to 9). The greatest risk of symptoms of infection or infection occurred in the first 3 months and among patients with a higher rate of infection before entering the study. Of the 84 symptomatic episodes 78 (92%) responded clinically. Of 78 cultured episodes 11 (14%) were negative. The remaining 67 cultured documented infections were cured microbiologically 5 to 7 days after therapy. No adverse effects occurred. The annual cost unaccompanied by a symptomatic episode was $86 and $259 if symptomatic episodes occurred. Intermittent self-start therapy is effective, safe and economical in women with recurrent urinary tract infections.


Zhibitai and low-dose atorvastatin reduce blood lipids and inflammation in patients with coronary artery disease.
Atorvastatin decreases blood lipids but is associated with side effects. Zhibitai is a traditional Chinese medicine used to treat blood lipid disorders. The objective of this study is to evaluate the lipid-lowering effect, antiinflammatory effect, and adverse events of zhibitai combined to atorvastatin in patients with coronary heart diseases (CHDs). Patients with CHD (n = 150) were randomized to: zhibitai 480 mg + atorvastatin 10 mg (ZA10 group), atorvastatin 20 mg (A20 group), and atorvastatin 40 mg (A40 group). Lipid profile, cardiotrophin-1 (CT-1), and C-reactive protein (CRP) were measured after 4 and 8 weeks of treatment. Self-reported side effects, liver function, kidney function, and creatine kinase levels were monitored. After 8 weeks, triglycerides, total cholesterol (TC), LDL-cholesterol (LDL-C), and apolipoprotein B100 (ApoB100) levels were decreased in the ZA10 group (-64%, -37%, -46%, and -54%, respectively, compared with baseline), and these changes were similar to those of the A40 group (P > 0.05). CT-1 and high sensitivity-C reactive protein (hs-CRP) levels were significantly decreased in the ZA10 group after 4 and 8 weeks (4 weeks: -73% and 96%; 8 weeks: -89% and -98%; all P < 0.01), without differences among the 3 groups (P > 0.05). After 8 weeks of treatment, adverse events (abdominal distention, nausea, vomiting, and hunger) were found in 4, 5, and 7 patients in the ZA10, A20, and A40 groups, respectively. ZA10 significantly reduced triglycerides, TC, LDL-C, ApoB, CT-1, and hs-CRP levels in patients with CHD, similar to the effects of A40 and A20, but ZA10 lead to fewer adverse events.


Superstructure MOF as a framework to composite MoS2 with rGO for Li/Na-ion battery storage with high-performance and stability.
Metal sulfides, one kind of electrode material with very high theoretical capacity, have been widely studied for use in lithium and sodium ion batteries. However, there are some problems hindering their applications in electrodes, such as low conductivity and volume expansion. The MOF introduces metals with different coordination strengths into an existing MOF structure, which improves the performance of the electrode to a certain extent. In this paper, Fe/Zn bimetallic MOF rod-like superstructure was prepared based on Ostwald theory. Accompanied by sulfuration, the MOF was effectively combined with MoS2 and GO, and the objective materials Fe7S8-C/ZnS-C@MoS2/rGO composites were successfully prepared. The MOF material provides a good frame and an efficient electron transport path, while the robust rGO wall effectively inhibits the pulverization of materials during the lithium/sodium intercalation/escalation courses. This particular material exhibited excellent cycling and rate capability performance when used in Li/Na-ion batteries. When used in Li-batteries, the electrode material delivered a specific capacity of 1598.3 mA h g-1 at 0.1 A g-1 and remained at 1196.7 mA h g-1 even after about 100 cycles and further exhibited a specific capacity of 368.68 mA h g-1 at the current rate of 5 A g-1 even after 1000 cycles, respectively. As for sodium batteries, these electrode materials exhibited an initial reversible capacity of 1053.6 mA h g-1 at 0.1 A g-1 and the reversible capacity was still as high as 592.2 mA h g-1 after 200 cycles. It is perhaps that this composite material with its particular architecture and composition is greatly beneficial for electron transfer and Li/Na ion diffusion. In the repeated physicochemical/nutrifying process, the appropriate distance between adjacent MOFs is of great help in preventing volume changes and thus improving the electrochemical performance.


A Mild Phenotype Caused by Two Novel Compound Heterozygous Mutations in CEP290.
CEP290 is a ciliary gene frequently mutated in ciliopathies, resulting in a broad range of phenotypes, ranging from isolated inherited retinal disorders (IRDs) to severe or lethal syndromes with multisystemic involvement. Patients with non-syndromic CEP290-linked disease experience profound and early vision loss due to cone-rod dystrophy, as in Leber congenital amaurosis. In this case report, we describe two novel loss-of-function heterozygous alterations in the CEP290 gene, discovered in a patient suffering from retinitis pigmentosa using massive parallel sequencing of a molecular inversion probes library constructed for 108 genes involved in IRDs. A milder phenotype than expected was found in the individual, which serves to prove that some CEP290-associated disorders may display preserved cone function.


Hunt's 'sincere' words only strike a false note.
The first strike by NHS staff over pay in more than 30 years - and the first by members of the Royal College of Midwives in its history - will hopefully force ministers to rethink their decision to freeze pay rates for 1.3 million health service staff. Those taking part in Monday's four-hour stoppage and this week's 'work-to-rule' deserve great credit for making a sacrifice so that everyone in the NHS may benefit.


Effects of saffron on homocysteine, and antioxidant and inflammatory biomarkers levels in patients with type 2 diabetes mellitus: a randomized double-blind clinical trial.
Type 2 diabetes mellitus (T2DM) is one of the most common health problems worldwide. Studies have shown that saffron and its derivatives may have therapeutic potentials in T2DM through reducing plasma glucose. The present study aimed to evaluate the effects of saffron extract on serum anti-inflammatory and antioxidant variables in T2DM patients. This was a double-blind randomized clinical trial conducted on 64 T2DM patients. Participants received either 15 mg of saffron or placebo capsules (two pills per day) for 3 months. Anthropometric indices, homocysteine, serum anti-inflammatory and antioxidant variables and dietary intake were assessed pre- and post-intervention. After 3 months of treatment, interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) increased significantly in both group (p<0.05). No significant differences were observed for total antioxidant capacity (TAC), malondialdehyde (MDA), high sensitivity C-reactive protein (hs-CRP) and interleukin 10(IL-10) after the treatment period (p>0.05). Homocysteine decteased significantly in control group (p<0.05). Our results showed no improvement in homocystein levels, antioxidant status and inflammatory biomarkers in T2DM patients after treatment with saffron.


Immunocytochemical studies on the formation and repair of O6-alkylguanine in rat tissues.
The immunocytochemical visualization of the carcinogen-DNA adducts O6-ethylguanine (O6-etGua) and O6-methylguanine (O6-meGua) in histological sections of a large series of rat tissues, including liver, pancreas, testis and oesophagus, is described. In the liver of rats treated with N-ethyl-N-nitrosourea (ENU), N-nitrosodiethylamine (NDEA) or N-nitrosodimethylamine (NDMA), large differences were found in the formation and/or repair of O6-alkylGua between different cell types, between hepatocytes of different localization, and also between normal and precancerous hepatocytes. Heterogeneity of O6-etGua formation and repair was also found in pancreatic tissue of rats treated with ENU. O6-etGua was relatively persistent in nonparenchymal liver cells, pancreatic islet cells, spermatogonia, renal glomeruli and smooth-muscle cells. Our aim is to extend the immunocytochemical analysis to other DNA adducts, and ultimately to human tissues.


Phosphate overload accelerates vascular aging in uremic patients.
Vascular calcification is a very common event in atients affected by diabetes and chronic kidney disease (CKD). Recently, it has been well documented that abnormalities in mineral and bone metabolism in CKD patients are associated with increased morbidity and mortality. Elevated serum phosphate and calcium-phosphate product levels play an important role in the pathogenesis of vascular mineralization in uremic patients and also appear to be associated with increased cardiovascular mortality. Together with classical passive precipitation of calcium-phosphate in soft tissues, during the last decade it has been demonstrated that inorganic phosphate may cause extraskeletal calcification directly through a real "ossification" of the tunica media in the vasculature of CKD patients. Therefore, control of phosphate retention is now an even more crucial target of treatment in patients affected by chronic kidney disease.


Zero valent metal loaded silica nanoparticles for the removal of TNT from water.
Silica nanoparticles with a surface area of 673.60 m2/g and particle size of 8-12 nm were prepared using aerogel process (AP) followed by super critical drying. Zero valent Fe, Co, Pt, and bimetallic Fe/Pt and Fe/Co were loaded using an incipient wetness impregnation technique and subsequent reduction. Scanning electron microscopy-energy dispersive X-ray (SEM-EDX) and transmission electron microscopy-energy dispersive X-ray (TEM-EDX) characterizations indicated fine dispersion of iron on AP-SiO2 +Fe system. Prepared nanoparticles were evaluated for the adsorptive removal of 2,4,6-trinitrotoluene (TNT) from water. Surface area normalized rate constant values indicated the adsorptive removal potential of prepared nanoparticles to be: AP-SiO2 + Fe/Co > AP-SiO2 + Fe > CM (commercial) SiO2 + Fe > AP-SiO2 + Co > AP-SiO2 + Fe/Pt > AP-SiO2 + Pt. Lower pH helped in accelerating the reactive removal of TNT on zero valent iron loaded silica. AP-SiO2 + Fe/Co system showed the maximum adsorption potential (74 mg/g) after five cycles.


Dynamic nuclear polarization enhanced nuclear magnetic resonance and electron spin resonance studies of hydration and local water dynamics in micelle and vesicle assemblies.
We present a unique analysis tool for the selective detection of local water inside soft molecular assemblies (hydrophobic cores, vesicular bilayers, and micellar structures) suspended in bulk water. Through the use of dynamic nuclear polarization (DNP), the (1)H NMR signal of water is amplified, as it interacts with stable radicals that possess approximately 658 times higher spin polarization. We utilized stable nitroxide radicals covalently attached along the hydrophobic tail of stearic acid molecules that incorporate themselves into surfactant-based micelle or vesicle structures. Here, we present a study of local water content and fluid viscosity inside oleate micelles and vesicles and Triton X-100 micelles to serve as model systems for soft molecular assemblies. This approach is unique because the amplification of the NMR signal is performed in bulk solution and under ambient conditions with site-specific spin labels that only detect the water that is directly interacting with the localized spin labels. Continuous wave (cw) electron spin resonance (ESR) analysis provides rotational dynamics of the spin-labeled molecular chain segments and local polarity parameters that can be related to hydration properties, whereas we show that DNP-enhanced (1)H NMR analysis of fluid samples directly provides translational water dynamics and permeability of the local environment probed by the spin label. Our technique therefore has the potential to become a powerful analysis tool, complementary to cw ESR, to study hydration characteristics of surfactant assemblies, lipid bilayers, or protein aggregates, where water dynamics is a key parameter of their structure and function. In this study, we find that there is significant penetration of water inside the oleate micelles with a higher average local water viscosity (approximately 1.8 cP) than in bulk water, and Triton X-100 micelles and oleate vesicle bilayers mostly exclude water while allowing for considerable surfactant chain motion and measurable water permeation through the soft structure.


Data-driven head motion correction for PET using time-of-flight and positron emission particle tracking techniques.
Positron emission tomography (PET) is susceptible to patient movement during a scan. Head motion is a continuing problem for brain PET imaging and diagnostic assessments. Physical head restraints and external motion tracking systems are most commonly used to address to this issue. Data-driven methods offer substantial advantages, such as retroactive processing but typically require manual interaction for robustness. In this work, we introduce a time-of-flight (TOF) weighted positron emission particle tracking (PEPT) algorithm that facilitates fully automated, data-driven head motion detection and subsequent automated correction of the raw listmode data. We used our previously published TOF-PEPT algorithm Dustin Osborne et al. (2017), Tasmia Rahman Tumpa et al., Tasmia Rahman Tumpa et al. (2021) to automatically identify frames where the patient was near-motionless. The first such static frame was used as a reference to which subsequent static frames were registered. The underlying rigid transformations were estimated using weak radioactive point sources placed on radiolucent glasses worn by the patient. Correction of raw event data were achieved by tracking the point sources in the listmode data which was then repositioned to allow reconstruction of a single image. To create a "gold standard" for comparison purposes, frame-by-frame image registration based correction was implemented. The original listmode data was used to reconstruct an image for each static frame detected by our algorithm and then applying manual landmark registration and external software to merge these into a single image. We report on five patient studies. The TOF-PEPT algorithm was configured to detect motion using a 500 ms window. Our event-based correction produced images that were visually free of motion artifacts. Comparison of our algorithm to a frame-based image registration approach produced results that were nearly indistinguishable. Quantitatively, Jaccard similarity indices were found to be in the range of 85-98% for the former and 84-98% for the latter when comparing the static frame images with the reference frame counterparts. We have presented a fully automated data-driven method for motion detection and correction of raw listmode data. Easy to implement, the approach achieved high temporal resolution and reliable performance for head motion correction. Our methodology provides a mechanism by which patient motion incurred during imaging can be assessed and corrected post hoc.


Fixation of the acetabular component. The case for cement.
The long-term success rate of cemented sockets in total hip arthroplasty has been well documented in patients who are 60 years of age and older and who have had a followup of as many as 16 years. The failures with cemented sockets have been observed in young patients, patients with poor bone stock (rheumatoid and dysplastic hips) with metal backed components, and in revision surgery with loss of acetabular bone. Ranawat et al have shown that most mechanical failures of cemented socket fixation within 10 years of primary operation is attributable to failure to achieve a good fixation initially of the cement and bone. Volumetric wear of the polyethylene of a cemented socket against a 22- or 28-mm femoral head is compared with the metal backed cemented and noncemented cups. The increase in volumetric polyethylene particles with metal backed cemented sockets and noncemented sockets will induce histiocytic response. The mechanism of histiocytic invasion should be similar for cemented all polyethylene sockets and noncemented sockets. It manifests itself in the cemented socket as global radiolucency when the socket is loose and as osteolysis when it is well fixed for noncemented and cemented sockets. If the number of particles coming out in a noncemented and hybrid total hip replacement are greater, osteolysis would be expected to increase with longer followup. The technique of cemented polyethylene sockets requires organization of the surgical team and hypotensive epidural anesthesia. Under these conditions the procedure is very reproducible. As far as cost is concerned, the all polyethylene socket is significantly less expensive. It seems that cemented total hip replacement is most suitable and perhaps is the right kind of operation for treating osteoarthritis of the hip for patients who are 60 years of age and older because the procedure is reproducible, the quality of arthroplasty is excellent, and it is durable, lasting as many as 15 years in 90% to 95% of the cases.


Preliminary analysis of mortality associated with rituximab use in autoimmune diseases.
Normal antibodies and pathogenic autoantibodies are produced by B-cells and plasma cells. Rituximab is a chimeric monoclonal antibody that targets the CD20 molecule on cells that express them on their surface and kills them. Rituximab has been increasingly used to treat several autoimmune diseases. Studies on fatal outcomes associated with rituximab therapy are lacking. A comprehensive and detailed analysis in which the multiple factors that could contribute to a fatal outcome in all the autoimmune diseases in which rituximab has been used would be cumbersome, lack uniformity and would prove difficult in making certain definitive conclusions and comparisons, but more importantly it would not allow to provide specific precautions and recommendations to prevent mortality. Hence, autoimmune mucocutaneous blistering diseases (AMBD) were used as model to study fatal outcomes in patients treated with rituximab between 2000 and 2013, using uniform 13 criteria. Fatal outcomes were found in 14 patients with autoimmune blistering diseases out of 134 patients (10.4%). Patients died due to infections (75%), gastrointestinal (17%) and cardiac events (8%). Causes of death were reported in 101 patients with other autoimmune diseases out of 4320 with a mortality rate of 2.4%. Among them, 44 patients (43.6%) died from infections. A statistical analysis of the data demonstrated that a statistically significant higher mortality rate was observed in patients with AMBD compared to patients with other autoimmune diseases. Similarly, a statistically significant higher rate of death due to infections was reported in patients with AMBD compared to patients with other autoimmune diseases. Use of systemic corticosteroids and immunosuppressive agents as concomitant therapy with rituximab enhanced immunosuppression. In many patients, B-cells were depleted for prolonged periods, even after clinical recovery was observed. Although its main action is depletion of B-cells, rituximab has a significant impact on the immune and inflammatory systems, directly and indirectly and thus enhances susceptibility to infection. These preliminary data suggests that physicians using rituximab to treat autoimmune diseases should monitor their patients closely, especially their B-cell levels until they return to normal, be vigilant for possible sources of infection, and be aware of potential fatal outcomes.


Infrared spectroscopy and theory of the formaldehyde cation and its hydroxymethylene isomer.
Pulsed discharges in supersonic expansions containing the vapor of different precursors (formaldehyde, methanol) produce the m/z = 30 cations with formula [H2,C,O]+. The corresponding [H2,C,O]+ Ar complexes are produced under similar conditions with argon added to the expansion gas. These ions are mass selected in a time-of-flight spectrometer and studied with infrared laser photodissociation spectroscopy. Spectra in the 2300-3000 cm-1 region produce very different vibrational patterns for the ions made from different precursors. Computational studies with harmonic methods and various forms of anharmonic theory allow detailed assignment of these spectra to two isomeric species. Discharges containing formaldehyde produce primarily the corresponding formaldehyde radical cation, CH2O+, whereas those with methanol produce exclusively the cis- and trans-hydroxymethylene cations, HCOH+. The implications for the interstellar chemistry of these cations are discussed.


The effect of antidepressants on ethylmorphine and imipramine N-demethylation in rat liver microsomes.
The effects of single and multiple doses of desipramine, amitriptyline or citalopram on the rat liver microsomal cytochrome P-450 level and on the rate of ethylmorphine and imipramine demethylation in-vitro have been investigated. Desipramine, amitriptyline or citalopram when given to rats as a single dose, did not affect the level of cytochrome P-450 in the liver microsomes, however, there was a tendency towards acceleration of imipramine, and particularly ethylmorphine, demethylation. Prolonged administration of desipramine and citalopram, but not amitriptyline, elevated the microsomal level of cytochrome P-450 and accelerated the rate of ethylmorphine demethylation. All the drugs investigated, when given chronically, inhibited the rate of imipramine demethylation. Since demethylation of ethylmorphine and imipramine in a CO atmosphere was inhibited by ca 90% for the former and only by 58% for the latter, it can be assumed that prolonged administration of the drugs investigated has two different effects on the oxygenase systems in rat liver microsomes: on the one hand they stimulate the cytochrome P450 oxygenase system involved in ethylmorphine demethylation and, on the other, they inhibit the other microsomal oxygenase system involved in demethylation of imipramine.


Reproductive hormones, hepatic deiodinase messenger ribonucleic acid, and vasoactive intestinal polypeptide-immunoreactive cells in hypothalamus in the heat stress-induced or chemically induced hypothyroid laying hen.
Heat stress (HS) effects on reproductive and thyroid hormones have been well documented; however, mechanisms of action are not well understood. Two studies were conducted to determine whether HS-induced and hypothyroid-induced effects are similar in the laying hen, with regard to reproductive hormones and vasoactive intestinal polypeptide (VIP)-immunoreactive cells in the hypothalamus. In study 1, thirty 32-wk-old Hy-Line W-36 laying hens, housed at 22 degrees C, were cannulated. On d 0 and then on d 1 to 5 of HS (35 degrees C, 50% RH), a daily blood sample was obtained and assayed for triiodothyronine (T(3)), thyroxine (T(4)), 17beta-estradiol (E(2)), progesterone (P(4)), prolactin (PRL), and VIP, and T(3):T(4)was calculated. On d 0, 1, 3, and 5, livers were obtained for hepatic type I deiodinase mRNA (cDI-1) determination. In study 2, eighty 32-wk-old hens were randomly assigned to 4 treatments of 20 birds each: 1) HS (36.5 degrees C, 50% RH), 2) thiouracil-induced hypothyroidism (HY), 3) HY + T(4) administration, and 4) control (22 degrees C). Beginning on d 1 of the 5-d study, daily blood samples (3.0 mL) were removed and assayed as in study 1. On d 5, brains were removed from 3 hens/treatment and immunoreactivity of VIP cells was determined. In study 1, HS reduced E(2), P(4), T(3) (P = 0.0001), T(3):T(4) ratio (P = 0.0078), and hepatic type I deiodinase mRNA (P = 0.0204) and increased T(4) (P = 0.0013); there was no effect on VIP or PRL. In study 2, HS and HY reduced T(3), T(3):T(4) ratio, and E(2) (P = 0.0001) and increased PRL (P = 0.0045); HS alone decreased P(4) (P = 0.0001). In HY + T(4), plasma E(2) and PRL were similar to control. Vasoactive intestinal polypeptide increased in plasma of HY birds, but there was no effect of HS or HY + T(4). Immunoreactive VIP cells increased (P = 0.0036) in nucleus inferior hypothalami of HS and HY brains. In HY + T(4), VIP immunoreactive cell numbers were similar to control. It appears that HY induced chemically or by HS exerts similar effects on reproductive hormones in the hen; the results suggest involvement of the VIP-PRL pathway even though peripheral blood concentrations were not consistent between studies.


[Comparative data on biogenic amines and GABA in three Rodents Filariae].
Detection and quantification of biogenic amines and GABA were carried out on three adult Filariae Litomosoides carinii, Acantocheilonema viteae and Molinema dessetae obtained from Rodents. Catecholamines were under the level of detection. Indolamines and GABA levels depend on species and sex. Results are discussed in relation to the parasitism and localization in the host.


Nutritional programming in the rat is linked to long-lasting changes in nutrient sensing and energy homeostasis in the hypothalamus.
Nutrient deficiency during perinatal development is associated with an increased risk to develop obesity, diabetes and hypertension in the adulthood. However, the molecular mechanisms underlying the developmental programming of the metabolic syndrome remain largely unknown. Given the essential role of the hypothalamus in the integration of nutritional, endocrine and neuronal cues, here we have analyzed the profile of the hypothalamus transcriptome in 180 days-old rats born to dams fed either a control (200 g/kg) or a low-protein (80 g/kg) diet through pregnancy and lactation. From a total of 26 209 examined genes, 688 were up-regulated and 309 down-regulated (P<0.003) by early protein restriction. Further bioinformatic analysis of the data revealed that perinatal protein restriction permanently alters the expression of two gene clusters regulating common cellular processes. The first one includes several gate keeper genes regulating insulin signaling and nutrient sensing. The second cluster encompasses a functional network of nuclear receptors and co-regulators of transcription involved in the detection and use of lipid nutrients as fuel which, in addition, link temporal and nutritional cues to metabolism through their tight interaction with the circadian clock. Collectively, these results indicate that the programming of the hypothalamic circuits regulating energy homeostasis is a key step in the development of obesity associated with malnutrition in early life and provide a valuable resource for further investigating the role of the hypothalamus in the programming of the metabolic syndrome.


Approaches to patients with variants in RAG genes: from diagnosis to timely treatment.
Introduction: Patients with primary immunodeficiency secondary to abnormal recombinase activating genes (RAG) can present with broad clinical phenotypes ranging from early severe infections to autoimmune complications and inflammation. Immunological phenotype may also vary from T-B- severe combined immunodeficiency to combined immunodeficiency or antibody deficiencies with near-normal T and B cell counts and even preserved specific antibody response to pathogens. It is not uncommon that RAG variants of uncertain significance are identified by serendipity during a broad genetic screening process and pathogenic RAG variants are increasingly recognized among all age groups, including adults. Establishing the pathogenicity and clinical relevance of novel RAG variants can be challenging since RAG genes are highly polymorphic. This review paper aims to summarize clinical phenotypes of RAG deficiencies and provide practical guidance for confirming the direct link between specific RAG variants and clinical disease. Lastly, we will review the current understanding of treatment option for patients with varying severity of RAG deficiencies. Area covered: This review discusses the different phenotypes and immunological aspects of RAG deficiencies, the diagnosis dilemma facing clinicians, and an overview of current and advancement in treatments. Expert opinion: A careful analysis of immunological and clinical data and their correlation with genetic findings helps to determine the significance of the genetic polymorphism. Advances in functional assays, as well as anti-cytokine antibodies, make it easier to resolve the diagnostic dilemma.