Topical timolol administration reduces the incidence of glaucomatous damage in ocular hypertensive individuals. A randomized, double-masked, long-term clinical trial (1).
A randomized, double-masked, 5-year clinical trial was conducted to determine whether topical timolol therapy was more effective than placebo in delaying or preventing the onset of glaucomatous damage in moderate-risk ocular hypertensive subjects. One eye was chosen randomly to receive timolol therapy twice daily; the fellow eye received placebo (timolol vehicle). The primary end point of the study was reproducible visual field loss detected on three consecutive tests. Automated static threshold visual fields were added to the protocol as the study proceeded, and criteria for reproducible defects for the automated fields were developed. The secondary end point was progressive optic disc cupping confirmed by examination of stereoscopic disc photographs. Intraocular pressure was not used as an end point (i.e., eyes were not withdrawn from the study because they reached a predetermined level of intraocular pressure).


Sarcoidosis: an update on current pharmacotherapy options and future directions.
Sarcoidosis is a systemic disease of unknown etiology characterized by the development of non-caseating epitheloid granulomas. The lungs are the most commonly involved organ (>90% of cases), followed by the lymph nodes, the skin, and the eyes. Areas covered: This review summarizes current pharmacotherapy options and future directions for the development of new therapies. Glucocorticoids are the first-line therapy for sarcoidosis. For patients with the most severe forms of sarcoidosis (who will need glucocorticoids for long periods) and for those intolerant or refractory, immunosuppressive drugs are used as sparing agents. The management of extrathoracic sarcoidosis must be tailored to the specific organ or organs involved; however, there is limited data from controlled trials to guide the treatment of these patients. The emergence of biological therapies has increased the therapeutic armamentarium available to treat sarcoidosis, with monoclonal anti-TNF agents being the most promising, but their use is still limited by a lack of licensing and costs. Expert commentary: The treatment of sarcoidosis is still not totally standardized. New effective therapies are urgently needed to enable the reduction or replacement of long-term therapy with glucocorticoids in patients with sarcoidosis.


Chimeric RHDV Virus-Like Particles Displaying Foot-and-Mouth Disease Virus Epitopes Elicit Neutralizing Antibodies and Confer Partial Protection in Pigs.
Currently there is a clear trend towards the establishment of virus-like particles (VLPs) as a powerful tool for vaccine development. VLPs are tunable nanoparticles that can be engineered to be used as platforms for multimeric display of foreign antigens. We have previously reported that VLPs derived from rabbit hemorrhagic disease virus (RHDV) constitute an excellent vaccine vector, capable of inducing specific protective immune responses against inserted heterologous T-cytotoxic and B-cell epitopes. Here, we evaluate the ability of chimeric RHDV VLPs to elicit immune response and protection against Foot-and-Mouth disease virus (FMDV), one of the most devastating livestock diseases. For this purpose, we generated a set of chimeric VLPs containing two FMDV-derived epitopes: a neutralizing B-cell epitope (VP1 (140-158)) and a T-cell epitope [3A (21-35)]. The epitopes were inserted joined or individually at two different locations within the RHDV capsid protein. The immunogenicity and protection potential of the chimeric VLPs were analyzed in the mouse and pig models. Herein we show that the RHDV engineered VLPs displaying FMDV-derived epitopes elicit a robust neutralizing immune response in mice and pigs, affording partial clinical protection against an FMDV challenge in pigs.


Cardioprotective effects of adenosine transport inhibition during reversible ischaemia in patients with coronary artery disease.
BACKGROUND: Adenosine plays a major role in protecting ischaemic myocardium and may potentiate ischaemic preconditioning. Nucleosine transport inhibition may enhance these favourable effects. DESIGN: Randomized, double blind, placebo controlled study, to investigate the haemodynamic and cardioprotective effects of nucleoside transport inhibition during ischaemia in patients with coronary artery disease. PATIENTS AND METHODS: Elective left anterior descending (LAD) coronary angioplasty was used to produce reversible ischaemia in 24 patients with stable angina and a single LAD lesion. They were randomized to receive either the nucleoside transport inhibitor draflazine or placebo. The study medication was infused between the 2nd and 3rd balloon inflation. The primary endpoint was ischaemia-induced wall motion abnormalities as measured by left septal echo amplitude, which was plotted against time to produce an area under the curve. RESULTS: No differences were observed in the systemic haemodynamics or the myocardial collateral circulation of the two groups. The ischaemia-induced regional wall motion abnormalities improved significantly after draflazine, while no difference was observed in the placebo group. This improvement was even more pronounced in patients with low caffeine levels compared with those with high caffeine levels. CONCLUSIONS: Draflazine, in the dose and route used, is associated with a significant improvement in regional myocardial function of the ischaemic area, without affecting systemic or collateral circulation, when compared with placebo. This implies that draflazine has a cardio-protective effect in ischaemic myocardium. High caffeine blood levels reduce these effects.


The identification of alcohol intoxication by police.
The identification of alcohol intoxication by police, bartenders, social hosts, and potential passengers is an important issue in the prevention of alcohol-related driving accidents. This study examines the ability of police officers to correctly identify and make ratings of the sobriety of target drinkers presented on video. Raters were asked to determine (1) whether the target drinker had been drinking alcohol, (2) whether it was "okay" to serve the target another drink, and (3) whether the target drinker was "okay" to drive. A rater confidence score for each target evaluated, as well as demographic characteristics about the raters, was obtained. Drinkers were accurately targeted to low (0.08-0.09%), medium (0.11-0.13%), and high (0.15-0.16%) blood alcohol concentrations (BACs) by using a method previously described. At lower BACs, most police officers were unable to identify whether or not targets had been drinking. Raters were "pretty sure" that targets in the 0.15-0.16% range had been drinking and "not sure" whether or not they should be served another drink or drive a car. The ability of raters to reliably identify target drinkers who were too intoxicated to drive safely was not obtained until the BACs were relatively high. These results suggest that prevention measures must focus on improving behavioral observations made of potential drunk drivers. Implications for bartenders and social hosts are discussed.


Human-Specific Genes, Cortical Progenitor Cells, and Microcephaly.
Over the past few years, human-specific genes have received increasing attention as potential major contributors responsible for the 3-fold difference in brain size between human and chimpanzee. Accordingly, mutations affecting these genes may lead to a reduction in human brain size and therefore, may cause or contribute to microcephaly. In this review, we will concentrate, within the brain, on the cerebral cortex, the seat of our higher cognitive abilities, and focus on the human-specific gene ARHGAP11B and on the gene family comprising the three human-specific genes NOTCH2NLA, -B, and -C. These genes are thought to have significantly contributed to the expansion of the cerebral cortex during human evolution. We will summarize the evolution of these genes, as well as their expression and functional role during human cortical development, and discuss their potential relevance for microcephaly. Furthermore, we will give an overview of other human-specific genes that are expressed during fetal human cortical development. We will discuss the potential involvement of these genes in microcephaly and how these genes could be studied functionally to identify a possible role in microcephaly.


[Orphan drugs--medications for patients with rare diseases].
Orphan drugs (ODs) are products developed for the diagnosis and/or treatment of rare diseases and conditions. Patients with this group of disorders have historically been denied access to medical therapy because prescription drug manufacturers could rarely make a profit from marketing such drugs. This changed in 1983, when the U.S. Congress passed the Orphan Drug Act, creating financial incentives for manufacturers. Since 2000 the EU has had a similar regulation, resulting in more than 20 ODs being granted marketing authorisation in the EU.


The heritability of characteristics associated with dispositional empathy.
This investigation used data from Loehlin and Nichols's (1976) study of over 800 sets of twins to examine evidence for the heritability of three facets of empathy: empathic concern, personal distress, and perspective taking. Expert judges first identified sets of adjectives, included within Loehlin and Nichols's original data, which reflected each empathy construct; these items were then validated in an independent sample. Comparisons of the responses given to these items by identical and fraternal twins in the Loehlin and Nichols investigation revealed evidence of significant heritability for characteristics associated with the two affective facets of empathy--empathic concern and personal distress--but not for the nonaffective construct of perspective taking. This pattern is consistent with the view that temperamental emotionality may underlie the heritability of affective empathy.


[Laparoscopic very low anterior resection with coloanal anastomosis and intersphincteric resection].
The author present the laparoscopic coloanal anastomosis and intersphincteric resection technique to treat patients with very low rectal cancer. The operative steps are: 1 - Patient positioning; 2 - Instruments and equip positioning; 3 - Insertion of the ports; 4 - Preparation of the operative field; 5 - Difining and dividing the inferior mesenteric artery and vein by the medial approach; 6 - Mobilization of splenic flexure and sigmoid colon; 7 - rectal mobilization and total mesorectum excision by Rullier technique; 8 - Rectal division and coloanal anastomosis; 9 - intersphincteric resection and coloanal anastomosis by coloplasty, J pouch or latero-to-end techniques. The technique employed is safe and have presented low rate of complication and no mortality.


Use of Critical View of Safety and Proctored Preceptorship in Preventing Bile Duct Injury During Laparoscopic Cholecystectomy-Experience of 3726 Cases From a Tertiary Care Teaching Institute.
Bile duct injury (BDI) continues to occur despite technological advances and improvements in surgical training over the past 2 decades. This study was conducted to audit our data on laparoscopic cholecystectomies performed over the past 2 decades to determine the role of Critical View of Safety (CVS) and proctored preceptorship in preventing BDI and postoperative complications. All patients undergoing elective laparoscopic cholecystectomy were analyzed retrospectively. The data were obtained from a prospectively maintained database from January 2004 to December 2019. Proctored preceptorship was used in all cases. Intraoperative details included the number of patients where CVS was defined, number of BDI and conversions. Postoperative outcomes, including hospital stay, morbidity, and bile duct stricture, were noted. Three thousand seven hundred twenty-six patients were included in the final analysis. Trainee surgeons performed 31.6% of surgeries and 9.5% of these surgeries were taken over by the senior surgeon. A CVS could be delineated in 96.6% of patients. The major BDI rate was only 0.05%. This study reiterates the fact that following the basic tenets of safe laparoscopic cholecystectomy, defining and confirming CVS, and following proctored preceptorship are critical in preventing major BDI.


Compact full-color augmented reality near-eye display using freeform optics and a holographic optical combiner.
We develop a compact full-color augmented reality near-eye display system with a multicolor holographic optical combiner and a freeform relay system. The digital image is produced by a full-color micro organic light-emitting diode (Micro-OLED) display module. The freeform relay system includes four freeform optics and a holographic optical mirror, which are employed to correct both the monochromatic and chromatic aberrations caused by the holographic optical combiner. The two multicolor holographic mirrors have a three-layer laminated structure and are delicately fabricated to yield an improved diffractive efficiency and a reduced efficiency difference for red, green, and blue colors. The high degrees of freedom of freeform optics, and the thin and light nature of the holographic optical combiner yield a compact form factor near-eye display system with a diagonal field of view (FOV) of 20° and the eye-box of 5 mm × 5 mm. Two prototypes are built to demonstrate the feasibility of the proposed display system.


Tensile strained direct bandgap GeSn microbridges enabled in GeSn-on-insulator substrates with residual tensile strain.
Despite having achieved drastically improved lasing characteristics by harnessing tensile strain, the current methods of introducing a sizable tensile strain into GeSn lasers require complex fabrication processes, thus reducing the viability of the lasers for practical applications. The geometric strain amplification is a simple technique that can concentrate residual and small tensile strain into localized and large tensile strain. However, the technique is not suitable for GeSn due to the intrinsic compressive strain introduced during the conventional epitaxial growth. In this Letter, we demonstrate the geometrical strain amplification in GeSn by employing a tensile strained GeSn-on-insulator (GeSnOI) substrate. This work offers exciting opportunities in developing practical wavelength-tunable lasers for realizing fully integrated photonic circuits.


[Sports under the sun].
The outdoor sports during summer and winter are often performed under uncontrolled exposure to ultraviolet irradiation from sunlight. Dangers are not small for the skin, the eyes and the immune system. Adequate sun protection is recommended. Caution is important in young children. The daily UV index represents a standardized assessment having a regional predictive value for the intensity of the ultraviolet irradiation reaching the biosphere.


Transcriptional effects of transfection: the potential for misinterpretation of gene expression data generated from transiently transfected cells.
Transfection is used to introduce a gene of interest into a cell. To interpret the downstream results, understanding which effects are the true biological responses to the gene and which, if any, are off-target effects can be difficult. In order to discriminate true biological effects from off-target effects, we transfected a breast cancer cell line, MCF7, with a vector encoding either a reporter gene or the identical vector without the reporter gene insert. Both resulted in similar numbers of differentially expressed transcripts, suggesting that very few of the responses were directly due to the introduction of the reporter gene. We postulate that many differentially expressed transcripts are the result of the introduction of foreign DNA, as the biological processes associated with these genes are primarily associated with an immune response to a viral infection. Interestingly, different transfection reagents resulted in > 10-fold difference in the number of differentially expressed transcripts. This suggests the importance of testing multiple reagents and selecting the best transfection reagent along with the appropriate vector within the context of the experimental model system to ensure that the majority of the observed responses are biological effects of the gene of interest and not based on a particular transfection process used.


Hybrid treatment for complex aortic problems combining surgery and stenting in the integrated operating theater.
Conventional surgical treatment of complex aortic pathologies involving several thoracoabdominal aortic segments necessitates extended incisions or subsequent surgeries, resulting in significant mortality and morbidity rates. The combination of surgery and simultaneous stenting in the operating theater may reduce the surgical trauma. A total of nine patients (62 +/- 10 years, range 44-70) underwent a combined surgical and endovascular treatment of thoracic or thoracoabdominal aortic aneurysms or chronic dissection. Five patients were treated with viscero-renal artery translocation followed by transfemoral stenting of the entire thoracoabdominal aorta. Two patients underwent debranching of the supraaortic vessels followed by immediate transfemoral stenting of the aortic arch, and two patients with a history of an ascending aortic aneurysm repair were treated with open surgical debranching of the supraaortic trunks and repair of the ascending aorta and aortic arch with elephant trunk technique. Preoperatively, magnetic resonance imaging was used to check supraaortic and intracranial vessels as well as the completeness of the Circle of Willisi prior to arch stenting and/or supraaortic vessel surgery. Cerebrospinal fluid drainage and induced mild hypertension have been used for one-step thoracoabdominal aortic stenting. Thirty-day mortality rate and incidence of paraplegia was 0%. There was a single reversible perioperative stroke after aortic arch stenting. One patient required temporary renal replacement therapy using continuous arterio-venous hemofiltration. There was one early reoperation at the superior mesenteric artery after viscero-renal translocation. Four type I endoleaks occurred in three patients requiring two interventions. All patients have been discharged to home. The innovative combination of simultaneous conventional surgery and stenting reduces the operative burden for patients with complex aortic pathologies involving several segments of the thoracic and thoracoabdominal aorta. Arch debranching and viscero-renal artery translocation may avoid the use of thoracoabdominal incisions, cardiopulmonary bypass techniques, deep hypothermia, and circulatory arrest.


Transesophageal Echocardiography in Cardiogenic Embolic Cerebral Infarction.
To evaluate the diagnostic values of transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) in cardiogenic embolic cerebral infarction. Fifty patients with occult cerebral infarction who were admitted to the hospital between June 2015 and June 2016 were selected as research subjects. The patients were diagnosed by transesophageal echocardiography and transthoracic echocardiography. Diagnostic data were compared to analyze the values of the two diagnostic methods. Sixteen out of fifty patients were diagnosed as cardiogenic embolic cerebral infarction by TEE (32%), including two cases of aortic plaques, six cases of atrial septal defect, two cases of atrial septal aneurysm, two cases of patent foramen ovale, one case of left atrial spontaneous echo contrast, one case of mitral prolapse and two case of mitral stenosis. Four cases were diagnosed as cardiogenic embolic cerebral infarction by TTE (8.0%), including one case of patent foramen ovale, one case of left atrial spontaneous echo contrast, one case of mitral prolapse and one case of mitral stenosis. The difference was statistically significant (P<0.05). The main difference of TEE and TTE was detection of aorta atheromatous plaques and atrial septal lesions. Aortic atheromatous plaques of two cases and atrial septal lesions of eight cases were missed in the diagnosis by TTE. Detection and diagnosis of cardiac embolic cerebral infarction with TEE is highly accurate and advantageous. Therefore, TEE is worth promotion and application.


Characteristics of liquid product from the pyrolysis of waste plastic mixture at low and high temperatures: influence of lapse time of reaction.
Pyrolysis of a waste plastic mixture (high-density polyethylene: low-density polyethylene: polypropylene: polystyrene = 3:2:3:1) into a liquid product was carried out in a stirred semi-batch reactor at low (350 degrees C) and high (400 degrees C) temperatures. The effect of lapse time of reaction in the reactor and also degradation temperature on the characteristics of the liquid product from pyrolysis of the mixture was investigated. Liquid products were described by cumulative amount distribution, paraffin, olefin, naphthene and aromatic (PONA) distribution and molecular weight distribution. Their characteristic was quite differed with a lapse time of reaction and also at a low and high degradation temperatures, because of the different physicochemical properties of the plastic types in the mixture. With increase of lapse time of reaction, the order for the main products in PONA components obtained at 350 degrees C was firstly aromatic products and then olefin products, while at 400 degrees C the order was firstly aromatic products, then olefin products and finally paraffin products. The experiments also showed from the molecular weight distribution of liquid PONA components that the paraffin and olefin products had a wide distribution by mainly random scission of polymer, but in the case of olefin products were produced by an end-chain scission mechanism as well as random scission mechanism, as evidenced by much more light olefin products. This phenomenon was evident at a higher degradation temperature. Also, both the light olefin and naphthene products with a molecular weight of around 120, as a main product, showed a similar trend as a function of lapse time, which had a maximum fraction at 343 min (at 350 degrees C) and 83 min (at 400 degrees C). Among PONA components, the highest concentrations of aromatic products were obtained with a molecular weight of around 100 at the fastest lapse time of reaction, regardless of degradation temperature. It was concluded that the characteristics of liquid product on the pyrolysis of plastic mixtures were strongly influenced by lapse time of reaction and degradation temperature.


[Retracted] Activation of the δ‑opioid receptor inhibits serum deprivation‑induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway.
Following the publication of the above article, an interested reader drew to the authors' attention that the control western blots shown in Figs. 1K and 2D on p. 1080 and 1081 respectively were the same, even though the experiments shown in these figures were reportedly different. Moreover, data featured in the flow cytometric plots in Figs. 1 and 2 were strikingly similar to data which appeared in subsequent publications by different authors at different research institutes, and moreover, in comparing the data between Figs. 1A and 2B, the 'Fig. 1A, 24 h' and 'Fig. 2B, Control' panels appeared to share certain of the same data. After having considered the authors' request to publish a corrigendum, in view of the various issues that have come to light the Editor of International Journal of Molecular Medicine has decided that the more suitable course of action would be the retract the article from the publication, on the grounds of a lack of overall confidence in the present data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 28: 1077‑1085, 2011; DOI: 10.3892/ijmm.2011.784].


Cloning, purification, crystallization and preliminary X-ray diffraction analysis of nitrile hydratase from the themophilic Bacillus smithii SC-J05-1.
Nitrile hydratase (NHase) converts nitriles to the corresponding amides and is recognized as having important industrial applications. Purification, cloning, crystallization and initial crystallographic studies of the NHase from Bacillus smithii SC-J05-1 (Bs NHase) were conducted to analyze the activity, specificity and thermal stability of this hydrolytic enzyme. Bs NHase was purified to homogeneity from microbial cells of B. smithii SC-J05-1 and the nucleotide sequences of both the alpha- and beta-subunits were determined. Purified Bs NHase was used for crystallization and several crystal forms were obtained by the vapour-diffusion method. Microseeding and the addition of magnesium ions were essential components to obtain crystals suitable for X-ray diffraction analysis.


Are the acid-labile interferon alpha and interferon omega-1 identical?
The interferon (IFN) activity found in human leukocyte IFN alpha preparations, autoimmune and AIDS sera, and others was reported to have distinct antigenic and deviating biological properties. This led to its vague designation as acid-labile and thermolabile IFN alpha. However, using specific monoclonal antibodies, the acid-labile component of IFN alpha (not exposed to pH 2) and recombinant IFN omega 1 showed significant relatedness. Monoclonal antibody T19, generated with virus-induced leukocyte IFN alpha that had not been exposed to pH 2, neutralized both the antiviral and antiproliferative activities of IFN omega-1, and vice versa; monoclonal antibody OMG 5, specific for recombinant IFN omega-1, cross-neutralized the antiviral and antiproliferative effects of the acid-labile component of leukocyte IFN alpha. When these two IFN preparations were incubated at pH 2 for 72 hr, their biological activity significantly decreased.


Evaluation by quantitative magnetic resonance imaging of trabecular bone quality in mandible and cervical vertebrae.
The purpose of this study was to make a comparison between mandibular and cervical vertebral bone quality (BQ) using quantitative magnetic resonance imaging (MRI). The cervical MRI images included in this study belonged to 36 patients (23 women, 13 men; mean age 54 years) who had various clinical symptoms (e.g., headache, vertigo, imbalance). The mandible and cervical vertebrae BQ measurements were performed by the same investigator on these sections. Mandibular and cervical vertebral T2(*) axial cross sections were performed following receipt of consent from each patient. T2(*) relaxation time values were determined in the trabecular area. The relationship between cervical vertebral and mandibular BQ was revealed by regression and correlation analysis. The correlation coefficient was r=0.04, r(2)=0.002, and P=0.818, which is not statistically significant. The relation between age and mandible BQ was very weak (r=0.001, r(2)=0.000001, and P=0.995), and the relation between age and cervical vertebrae BQ was correlated (r=-0.585, r(2)=0.342, and P<0.001). There is a low correlation between the BQ measurements of cervical vertebrae and the mandible. Precise mandibular BQ measurement does not provide information that correlates with BQ in the other sites of the skeleton. Although an age-dependent decrease occurs in vertebral BQ, no significant alteration occurs in mandibular BQ.


A new approach for cleansing geographical dataset using Levenshtein distance, prior knowledge and contextual information.
Epidemiological studies are necessary to take public health decisions. Their relevance depends on the quality of data. Doctors in continuous care collect a big amount of data that can be used for epidemiological purpose, but spatial data may be dirty; based on city names, the localization is imprecise, even more if it is misspelled. The only way to identify a city without ambiguity is to use its identifier, which can be retrieved by cleansing geographical textual data. In France, cities are organized in administrative zones called departments and some city names are shared by several cities in several departments. The clear identification of the department and the city name allows to deduce the city unique identifier and to make some spatial analysis such as epidemiological studies. In this paper, we propose a method to cleanse such data, using several steps. After having standardized the text to cleanse, we use the Levenshtein distance to generate a first set of propositions. Finally, the propositions are filtered, by removing the less likely candidates, so that it remains only one, which becomes the chosen city. Tested on a dataset of 9818 entries, we obtained 89.1% of concordance, whereas the standard Levenshtein distance obtained 70.5%. This demonstrates that our method has better results.


The hook effect in calcitonin immunoradiometric assay: a case report.
The hook effect, which has long been detected and documented for immunoradiometric assays (IRMA) such as those measuring prolactin or thyroglobulin, occurs when the serum antigen level is extremely high, thus inducing a bias in the methodology of measurement. We report the case of an 80-year-old man with confirmed medullary thyroid carcinoma (MTC). In the case reported here, the clinical status of the patient contrasts with his tumor antigen, serum calcitonin (CT), concentrations. The measured increased CT concentrations revealed the presence of a hook effect. This phenomenon occurs due to an excess of antigen during the one-step IRMA where the signal antibodies, bound to the non-captured antigens, are washed out during the measurement, inducing the loss of signal. Aiming to prevent the "hook effect", successive dilutions of the same sample of serum were done. Previous studies have shown when one-step IRMA reveals high concentrations of a tumor serum antigen (i.e. prolactin or thyroglobulin), a two-step IRMA or a systematic 1:10 dilution of the serum sample prevents the formation of the "hook effect". In our case report, the CT "hook effect" formation was prevented by performing serial dilutions of the serum sample.


FastEtch: A Fast Sketch-Based Assembler for Genomes.
De novo genome assembly describes the process of reconstructing an unknown genome from a large collection of short (or long) reads sequenced from the genome. A single run of a Next-Generation Sequencing (NGS) technology can produce billions of short reads, making genome assembly computationally demanding (both in terms of memory and time). One of the major computational steps in modern day short read assemblers involves the construction and use of a string data structure called the de Bruijn graph. In fact, a majority of short read assemblers build the complete de Bruijn graph for the set of input reads, and subsequently traverse and prune low-quality edges, in order to generate genomic "contigs"-the output of assembly. These steps of graph construction and traversal, contribute to well over 90 percent of the runtime and memory. In this paper, we present a fast algorithm, FastEtch, that uses sketching to build an approximate version of the de Bruijn graph for the purpose of generating an assembly. The algorithm uses Count-Min sketch, which is a probabilistic data structure for streaming data sets. The result is an approximate de Bruijn graph that stores information pertaining only to a selected subset of nodes that are most likely to contribute to the contig generation step. In addition, edges are not stored; instead that fraction which contribute to our contig generation are detected on-the-fly. This approximate approach is intended to significantly improve performance (both execution time and memory footprint) whilst possibly compromising on the output assembly quality. We present two main versions of the assembler-one that generates an assembly, where each contig represents a contiguous genomic region from one strand of the DNA, and another that generates an assembly, where the contigs can straddle either of the two strands of the DNA. For further scalability, we have implemented a multi-threaded parallel code. Experimental results using our algorithm conducted on E. coli, Yeast, C. elegans, and Human (Chr2 and Chr2+3) genomes show that our method yields one of the best time-memory-quality trade-offs, when compared against many state-of-the-art genome assemblers.


Comparison of monoclonal antibodies used for immunological monitoring of renal transplant recipients.
To investigate the comparability of the OKT and Leu monoclonal antibodies (mAbs) used for immunological monitoring, T cell subpopulations in 360 blood samples from 35 renal allograft recipients were studied by flow cytometry using both series of mAbs. To identify the activated cells in the different subpopulations, those labeled with the Leu mAbs were double-labeled with an anti-HLA-DR mAb. The percentages of T cells that stained with the Leu3a and Leu2a mAb using a direct immunofluorescence technique were significantly lower than the percentages of cells that stained with the OKT4 and OKT8 mAb using an indirect immunofluorescence technique (47.6 +/- 12.8% and 14.5 +/- 9.1% [mean +/- SD] versus 50.5 +/- 11.2% and 18.3 +/- 8.0%, respectively; P less than 0.0001). Since the difference between the Leu2a+ and OKT8+ cells was relatively greater (21%) than that between the Leu3a+ and OKT4+ cells (6%), the mean Leu3a/2a ratio was significantly higher than the mean OKT4/8 ratio (6.64 +/- 9.7 versus 3.60 +/- 2.82; P less than 0.0001). The difference between the Leu2a+ and OKT8+ cells were not attributable to a difference in the sensitivity of the direct and indirect immunofluorescence technique. A large difference between the Leu2a+ and OKT8+ cells correlated with a high percentage of DR+ cells within the Leu2a population (P less than 0.001). No correlation was found for the difference between the OKT4+ and Leu3a+ cells and the DR expression in the Leu3a+ cell population. These observations suggest that activation of some T cells of the "cytotoxic-suppressor" phenotype leads to antigen modulation in which the OKT8 epitope is not affected but the Leu2a epitope disappears or cannot be detected with the present method.


Accuracy of prenatal diagnosis of congenital heart disease with fetal echocardiography.
To study the diagnostic value of fetal echocardiography in detecting congenital heart disease (CHD) during the prenatal period. One hundred and ninety-seven pregnant women with a high risk of prenatal CHD of their fetuses were included in this study. The fetal heart was scanned with echocardiography, performing complete evaluation of the cardiac system. The prenatal echocardiographic findings were correlated with postnatal echocardiography results or autopsy findings, if the pregnancy was terminated or the fetus died in utero. 10 of the 197 fetuses showed CHD by fetal echocardiography, whereas postnatal echocardiography and postmortem examination revealed cardiac abnormalities in 21 patients. Of those, 7 (41.1%) had the most common referral indication, i.e., cardiac abnormality, found on routine ultrasound examination. Specificity and sensitivity of fetal echocardiography for cardiac abnormalities were found to be 98 and 42%, respectively. The positive predictive value of echocardiography was 90% and the negative predictive value 93%. We conclude that fetal echocardiography is a reliable tool for prenatal diagnosis in experienced hands. Pediatric cardiologists should be more aware while performing fetal echocardiography in patients referred by obstetricians for CHD.


The effect of methylphenidate on neurofibromatosis type 1: a randomised, double-blind, placebo-controlled, crossover trial.
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with an estimated prevalence of about 1/3000, independent of ethnicity, race, or gender. Attention Deficit Hyperactivity like Disorder (ADHD)-like characteristics are often reported in patients with NF1. We hypothesised that learning disabilities in NF1 children were related to ADHD symptoms. Treatment with methylphenidate (MPD) has improved learning disabilities in ADHD by acting on neurotransmitters. Our objective was to evaluate its efficacy on ADHD-like symptoms in neurofibromatosis type 1 children (7-12 years). This was a randomised, double blind, placebo controlled, and crossover trial comparing 0.5 to 0.8 mg/kg/d of MPD as it is indicated for ADHD to placebo in NF1 children with ADHD-like symptoms. Children aged 7 to 12 years were eligible when their IQ was between 80 and 120. The total follow-up was 9 weeks including 4 weeks for each period and 1 week wash out. Fifty subjects (25 for each period) were required for testing the primary study hypothesis. The main outcome was an improvement in scores on the simplified Conners' Parent Rating Scale. Thirty-nine patients were included between April 2004 and December 2010. Twenty participants received MPD and 19 placebo during the first period. They all completed the trial. MPD decreased the simplified Conners by 3.9 points (±1.1, p = 0. 0003). This is the first randomised controlled trial showing the short-term benefit of MPD on simplified Conners scores in NF1 children. ClinicalTrials.gov NCT00169611.


Conservation and evolution of gene coexpression networks in human and chimpanzee brains.
Comparisons of gene expression between human and non-human primate brains have identified hundreds of differentially expressed genes, yet translating these lists into key functional distinctions between species has proved difficult. Here we provide a more integrated view of human brain evolution by examining the large-scale organization of gene coexpression networks in human and chimpanzee brains. We identify modules of coexpressed genes that correspond to discrete brain regions and quantify their conservation between the species. Module conservation in cerebral cortex is significantly weaker than module conservation in subcortical brain regions, revealing a striking gradient that parallels known evolutionary hierarchies. We introduce a method for identifying species-specific network connections and demonstrate how differential network connectivity can be used to identify key drivers of evolutionary change. By integrating our results with comparative genomic sequence data and estimates of protein sequence divergence rates, we confirm a number of network predictions and validate these findings. Our results provide insights into the molecular bases of primate brain organization and demonstrate the general utility of weighted gene coexpression network analysis.


Economic evaluation of three surgical interventions for menorrhagia.
The study was carried out to compare the overall effectiveness and direct economic costs of vaginal hysterectomy (VH), endometrial ablation (EA) and thermo-coagulation (TC) for the treatment menorrhagia. We treated 50, 50 and 47 women with menorrhagia (>150 points on the Higham pictorial chart) by VH, EA and TC respectively. The patients were treated consecutively by the same surgeon and the choice between the three procedures depended on the desire of the patients. Resource utilization for the interventions was collected retrospectively from the hospital charts. A study questionnaire was mailed to the patients 24-36 months after the primary surgery. Patients who reported that they had undergone a second procedure or who were still menorrhagic were considered as treatment failures. As expected, the failure rate was lowest for VH. The total cost (without re-intervention for persistent menorrhagia) was 5315 Euros for VH, 1098 Euros for EA and 921 Euros for TC. The total cost with re-intervention was calculated based on therapeutic strategies used in 2001 and estimated at 5321 Euros for VH, 1263 Euros for EA and 1320 Euros for TC. The two out-patient procedures are very comparable in terms of success rates and costs. Choices will depend on budgeting considerations, surgeon skill and patient preference. The results may give guidance to investment decisions.


Sorting out the competing effects of acculturation, immigrant stress, and social support on depression: a report on Korean women in California.
This research identifies stressors that correlate with depression, focusing on acculturation, among female Korean immigrants in California. Telephone interviews were conducted with female adults of Korean descent (N = 592) from a probability sample from 2006 to 2007. Sixty-five percent of attempted interviews were completed, of which over 90% were conducted in Korean. Analyses include descriptive reports, bivariate correlations, and structural equation modeling. Findings suggest that acculturation did not have a direct impact on depression and was not associated with social support. However, acculturation was associated with reduced immigrant stress which, in turn, was related to decreased levels of depression. Immigrant stress and social support were the principal direct influences on depression, mediating the effect for most other predictors. Stressful experiences associated with immigration may induce depressive feelings. Interventions should facilitate acculturation thereby reducing immigrant stress and expand peer networks to increase social support to assuage depression.


Diffuse metabolic changes in the brain of patients with familial amyloid polyneuropathy. A proton MRSI study.
To assess brain metabolic abnormalities in patients with familial amyloid polyneuropathy (FAP) due to the transthyretin (TTR) gene mutations. The TTR-FAP has variable phenotypic expression, which includes abnormalities of the central nervous system (CNS). Several conventional MRI studies have shown brain abnormalities, probably secondary to amyloid accumulation in leptomeningeal and subarachnoid vessels. However, TTR-related amyloid deposits do not seem to significantly affect the brain parenchyma and a prominent CNS impairment is considered to be rare in TTR amyloidosis. We performed proton MR spectroscopic imaging (1H-MRSI) in the central brain of four unrelated TTR-FAP patients with either minimal or no signs of neurological involvement and eight age- and sex-matched normal controls (NC). Metabolic changes were assessed in the entire volume of interest (VOI) and in the frontal, periventricular and posterior white matter (WM). Conventional MRI was normal in 2 patients and showed minimal WM lesions in the remaining 2 patients. 1H-MRSI showed N-acetylaspartate to creatine ratio (NAA/Cr) decreases in the central brain VOI in all TTR-FAP patients (p < 0.005). These NAA/Cr decreases were homogeneous in all WM regions (p < 0.05 for all). 1H-MRSI findings suggest that diffuse metabolic changes, probably related to axonal damage, are present in brains of TTR-FAP patients even when they have no or minimal clinical and MRI signs of CNS involvement. The mechanism leading to sub-clinical metabolic brain changes needs to be identified.


Fast removal of toxic hexavalent chromium from an aqueous solution by high-density Geobacter sulfurreducens.
Hexavalent chromium (Cr(VI)) is a carcinogenic compound that can be removed from contaminated sites by the activity of metal-reducing bacteria. The model bacterium Geobacter sulfurreducens reduces Cr(VI) to less toxic Cr(III) and accumulates Cr ions intracellularly. However, this process is usually slow with small concentrations of Cr(VI) removed in a matter of days. Here, high-density G. sulfurreducens cultures were tested for the capacity to remove Cr(VI) readily. With an initial G. sulfurreducens density of 5.8 × 108 cells ml-1, 99.0 ± 0.8% of 100 mg l-1 Cr(VI) was removed after 20 min. With a higher starting Cr(VI) concentration of 200 mg l-1, G. sulfurreducens with a density of 11.4 × 108 cells ml-1 removed 99.0 ± 0.4% Cr(VI) after 2 h. Experiments performed with cell-free spent medium indicate that extracellular proteins are major contributors for the reduction of Cr(VI) to Cr(III). Furthermore, results show that most Cr(III) ions ultimately end up inside the bacterial cells where they are less susceptible to re-oxidation. The fast Cr(VI) removal rates observed with high-density G. sulfurreducens demonstrate the potential of this bacterium for bioremediation applications such as the cleaning of industrial wastewaters.


Recovery of Mixtures of Construction Waste, PET and Sugarcane Bagasse for the Manufacture of Partition Blocks.
The building industry generates millions of tons of construction and demolition waste annually (12 million tons/year are generated in Mexico, of which only 4% is reused or recycled). Concomitantly, the demand for goods and services by the building industry causes significant environmental impacts. On the other hand, plastic waste is also difficult to assimilate into the environment in the short term, and its recovery is of special interest. Therefore, this research focuses on the feasibility of the manufacture of Partition Blocks (essential building element) through the combination of construction and demolition waste (CDW), polyethylene terephthalate (PET) plastic flakes, dust from tire shredding, and residue from the sugar industry (bagasse). The results of this study show that the Partition Blocks made with CDW and PET reach an average compressive strength of 115.003 kgf/cm2 (11.278 MPa) (suitable for structural use according to Mexican regulations); the use of lime enhances the consistency of the mixture of CDW and PET (increases its cohesion and homogeneity); and finally, these Partition Blocks have a cost comparable to the current conventional Partition Blocks made with virgin material, thus, conferring them validity as a feasible recycling option for these residues.


Trainee Sex and Accreditation Council for Graduate Medical Education Milestone Assessments During General Surgery Residency.
In evaluating the effectiveness of general surgery (GS) training, an unbiased assessment of the progression of residents with attention to individual learner factors is imperative. To evaluate the role of trainee sex in milestone achievement over the course of GS residency using national data from the Accreditation Council for Graduate Medical Education (ACGME). This cross-sectional study evaluated female and male GS residents enrolled in ACGME-accredited programs in the US from 2014 to 2018 with reported variation in milestones performance across years in training and representation. Data were analyzed from November 2019 to June 2021. Mean reported milestone score at initial and final assessment, and predicted time-to-attainment of equivalent performance by sex. Among 4476 GS residents from 250 programs who had milestone assessments at any point in their clinical training, 1735 were female (38.8%). Initially, female and male residents received similar mean (SD) milestone scores (1.95 [0.50] vs 1.94 [0.50]; P = .69). At the final assessment, female trainees received overall lower mean milestone scores than male trainees (4.25 vs 4.31; P < .001). Significantly lower mean milestone scores were reported for female residents at the final assessment for several subcompetencies in both univariate and multivariate analyses, with only medical knowledge 1 (pathophysiology, diagnosis, and initial management) common to both. Multilevel mixed-effects linear modeling demonstrated that female trainees had significantly lower rates of monthly milestone attainment in the subcompetency of medical knowledge 1, which was associated with a significant difference in training time of approximately 1.8 months. Both female and male GS trainees achieved the competency scores necessary to transition to independence after residency as measured by the milestones assessment system. Initially, there were no sex differences in milestone score. By graduation, there were differences in the measured assessment of female and male trainees across several subcompetencies. Careful monitoring for sex bias in the evaluation of trainees and scrutiny of the training process is needed to ensure that surgical residency programs support the educational needs of both female and male trainees.


Peripheral neuropathy following nitrous oxide abuse.
Undifferentiated neurological presentations are not uncommon to the ED. Vitamin B (12) deficiency can lead to progressive demyelination and axonal lesions on the peripheral nerves and cervicothoracic spinal cord causing a peripheral neuropathy. Nitrous oxide is a common adjuvant to anaesthesia in the ED but it not often thought of as a drug of abuse. A case is reported of prolonged and intensive nitrous oxide abuse that resulted in the development of a peripheral neuropathy.


Hospital treatment of alcoholism: a profile of middle income Americans.
3,411 first admissions for alcoholism treatment to nine proprietary hospitals were studied with standardized questionnaire and diagnostic instruments. Despite the patients' relative economic and social stability, severe patterns of addictive alcohol use had developed and persisted for many years with a high incidence of alcohol-related and intercurrent medical disorders which required prompt medical intervention. Although most patients had a personal physician, less than 9% of referrals for hospital treatment for alcoholism were made by physicians; most patients responded to television outreach programs, recommendations by former patients or were self or family referred. This survey shows that persons who are neither socially disadvantaged nor economically deprived may have severe alcohol-related problems. Such patients constitute a significant challenge to the medical profession to develop strategies for early intervention and more efficacious treatment.


Mastering the antegrade femoral artery access in patients with symptomatic lower limb ischemia: learning curve, complications, and technical tips and tricks.
Antegrade femoral access is fraught by technical challenges and steeper learning curve, in comparison with retrograde contralateral femoral access. We appraised learning curve, complications, and technical aspects inherent in the adoption of antegrade approach. Consecutive cases in which antegrade access was attempted by a cardiologist experienced in retrograde access, but inexperienced in antegrade, under supervision of an operator with anterograde expertise, were collected. The primary end-point was the occurrence of antegrade access failure or local complications. Major complications were defined as those life-threatening, requiring transfusion, percutaneous, or surgical repair. Anterograde access was attempted in 120 patients. The primary end-point occurred in 14 (11.6%) cases, but according to the learning curve, in 12 (20%) for first 60 cases vs 2 (3.3%) for the last 60 cases (P = 0.008). Access failure in the hands of the in-training operator was similarly found in all cases but one during the first 60 cases. No major complications occurred, while minor complications were found in 9 (7.5%) patients, again with all but two of them occurring in the first 60 cases. These included peri-adventitial extravasation in 8 patients (6.7%), and perforation of a small branch in one (0.8%); all these complications were conservatively and successfully managed. Obesity was the only significant predictor of access failure/complication (P = 0.004). This work, the first to report on the learning curve of the antegrade approach, supports the feasibility and safety of this access site even for an in-training operator, if supervised. A minimum caseload of 60 procedures is likely needed to master this technique.


Asthma onset prior to multiple sclerosis and the contribution of sibling exposure in early life.
Higher sibling exposure is associated with a reduced risk of asthma and other T helper 2 (Th2)-type disorders, possibly through a beneficial effect of higher infection load. The effect on Th1 disorders such as multiple sclerosis (MS) is less clear. Here we examine the association between asthma and MS, taking into account early life sibling exposure. A population-based case-control study in Tasmania, Australia based on 136 cases of magnetic resonance imaging (MRI)-confirmed MS and 272 community controls, matched on sex and year of birth. Study measures include cumulative exposure to total, older or younger siblings by age 6 years, history of doctor-diagnosed asthma and serological IgG responses to herpes viruses. MS cases were more likely (P = 0.02) than controls to have asthma which began before age of onset of MS symptoms compared to the corresponding age for controls. The absence of younger sibling exposure by age 6 years potentiated (P = 0.04) the association between asthma and MS. Compared to those with younger sibling exposure and no asthma, the adjusted odds ratio for MS for those with asthma and no younger sibling exposure was 7.22 (95% CI: 2.52, 20.65). Early life sibling exposure was associated with altered IgG serological responses to Epstein-Barr virus (EBV) and herpes simplex virus 1 (HSV1) in adulthood. Reduced early life sibling exposure appeared to contribute to the excess of asthma among MS cases by the time of MS onset. MS development may reflect factors that relate to a general immuno-inflammatory up-regulation of immune activity as well as disease specific factors. The link between early life sibling exposure and the immune response to herpes group viral antigens is consistent with a protective role for early life infections.


Phosphatidylinositol 3-kinase: a molecule mediating BDNF-dependent spatial memory formation.
Brain-derived neurotrophic factor (BDNF) plays a critical role in synaptic plasticity such as long-term potentiation (LTP), a form of synaptic correlate of learning and memory. BDNF is also implicated in learning and memory. We have demonstrated that radial arm maze training in rats for spatial learning and memory results in a significant increase in the BDNF mRNA expression in the hippocampus. Moreover, antisense BDNF oligonucleotide treatment impaired not only acquisition, but also maintenance and/or recall of spatial memory in the maze. Although these results suggest a role of BDNF for spatial memory processes, the signal transduction mechanisms that mediate the actions of BDNF remain unknown. Here we show that phosphorylation of BDNF receptor tyrosine kinase B (TrkB), phosphatidylinositol 3-kinase (PI3-K) and Akt, a target of PI3-K, in the hippocampus increased in parallel with spatial memory formation. Moreover, an activation of translational processes was suggested in the hippocampus after the maze training. When spatial learning was inhibited by antisense BDNF oligodeoxynucleotide, the activation was diminished. Chronic treatment with PI3-K inhibitor wortmannin impaired spatial learning. Our findings suggested that activation of TrkB/PI3-K and protein synthesis signaling pathway by BDNF in the hippocampus is important for spatial memory.


[Role of Helicobacter pylori eradication in the prevention of peptic ulcer in NSAID users].
Helicobacter pylori (H. pylori) and non-steroidal anti-inflammatory drug (NSAID) are independent risk factors for peptic ulcers and ulcer complications and they have additive or synergistic effects. A meta-analysis showed that the OR for the incidence of peptic ulcer was 61.1 in patients infected with H. pylori and also taking NSAID when compared to patients uninfected with H. pylori and not taking NSAID. H. pylori eradication may prevent NSAID-induced ulcers in NSAID naive patients. In patients receiving long-term NSAID, proton pump inhibitor(PPI) is more effective in the prevention of ulcer recurrence and bleeding. However, H. pylori eradication should be considered in patients receiving long -term PPI maintenance treatment to prevent the development of corpus gastritis and gastric atrophy.


Validity of the CES-D for depression screening in military service members with a history of mild traumatic brain injury.
Primary Objective: To advance knowledge about the value of the Center for Epidemiologic Studies - Depression scale (CES-D) for depression screening in military service members with a history of mild traumatic brain injury (mTBI). Research Design: Retrospective data from 336 military service members with a history of mTBI were extracted from a TBI Repository at a large military medical center. Participants included in this study screened positive for mTBI in a primary care clinic or soldier readiness processing center and were enrolled in the TBI repository from November 6, 2014 to May 31, 2017. At the time of enrollment, participants completed the CES-D and their electronic medical records (EMR) were searched for diagnoses of depressive disorders. Methods and Procedures: Receiver-operating characteristic (ROC) analysis of the CES-D was used to discriminate cases with and without depression diagnoses. Main Outcomes and Results: Area under the ROC curve (AUC) was .897. Sensitivity (.824) and specificity (.826) were maximized at a cut score of 18 or greater, slightly higher than the standard cut of 16 established for civilian samples. Conclusions: Results suggest that the CES-D is a valid screening instrument for depressive disorders in military samples with a history of mTBI.


Hematuria in children due to schistosomiasis in a nonendemic setting.
Infection with Schistosoma hematobium is common in immigrants from tropical Africa and commonly presents with painless hematuria. Since chronic, heavy infection can lead to significant morbidity, it is imperative for clinicians who serve the immigrant and refugee population to become familiar with this traditionally exotic disease. Increased awareness will allow earlier diagnosis and treatment of infection, avoiding complications and minimizing expensive and invasive diagnostic procedures.


Tarsal tunnel surgery secondary to a tarsal ganglion: be prepared before performing this complicated operation.
Tarsal tunnel surgery complicated with ganglia or any other type of cystic mass can be a very challenging operation. Preoperative planning before any tarsal tunnel surgery involving a soft-tissue mass is imperative. Plans to reconstruct the posterior tibial nerve and/or artery should be in place. The authors will present a case study that involved tarsal tunnel syndrome with an associated ganglion in the tarsal canal. They will review what microsurgical techniques and equipment should be on hand prior to performing this complicated surgical procedure.


Authentic leadership and employee resilience during the COVID-19: The role of flow, organizational identification, and trust.
The present work investigated fundamental mediating mechanisms (i.e., flow experience, organizational identification, and trust), underlining the impact of authentic leadership on employee resilience during the turbulent COVID-19 pandemic. A total of 901 frontline employees working in a construction engineering company in China participated in this study. They were asked to respond to a battery of questionnaires comprising Trust Scale (affective-based, cognitive-based, and competence-based), Flow Proneness Questionnaire (FPQ), Organizational Identification Scale, Authentic Leadership Questionnaire, and Employee Resilience Scale. Results of structural equation modeling indicated that: (1) Authentic leadership positively predicted employee resilience in the COVID-19 pandemic, directly and indirectly. (2) As for the indirect relationship, two parallel mediation effects and one chain mediation were detected: employees' flow at work and organizational identification respectively and dependently mediated the relationship between authentic leadership and employee resilience; trust and organizational identification played as a chain mediation role within authentic leadership-employee resilience association. The study provides empirical evidence for organizations' resilience-building and leadership training programs. Findings also contribute to the literature by facilitating flow intervention, promoting organizational identification and trust to enhance the effect of authentic leadership in promoting positive psychological functioning of employee resilience. Limitations with respect to future research directions were also outlined.


Sentinel node staging in colon carcinoma: value of sentinel lymph node biopsy with radiocolloid and blue staining.
Nodal staging accuracy is important in the prognosis and selection of patients for chemotherapy. This prospective study aims to assess the feasibility and accuracy of the sentinel lymph node procedure (SNP) using radiocolloid and blue dye in colon carcinoma. In 56 patients, lymphatic mapping was accomplished by means of intraoperatively injecting patent blue and nanocoll subserosally around the tumour. Sentinel nodes (SNs) were harvested ex-vivo. Nodes were stained with H&E. If lymph nodes were interpreted as negative for metastatic tumour, serial sectioning and immunohistochemical staining were performed. At least one SN was detected in 49 of 53 patients (92.5%). Three patients were excluded because of preoperatively detected metastases. Overall, 121 SN were harvested with a mean of 2.2 SN/patients. Eighteen patients had tumour positive nodes. In four patients, pathological nodes were palpable during operation and were excluded. The SN was histologically negative in 2 of 14 patients with positive nodes (false-negative rate 14.3%). In 5 of 14 patients with positive nodes, the SN was the exclusive site of regional nodal metastasis. Four patients were upstaged by immunohistochemical staining (28.6%). The negative predictive value was 93.9% and the overall accuracy 95.6%. Scintigraphy was done in 17 patients. In three patients the SN was detected only by this modality. The SN biopsy with the combined technique proved a feasible technique with a steep learning curve. It can change the initial staging from stage II to stage III colon carcinoma. Scintigraphy can improve the success rate of the technique.


Efficient gene transfer into differentiated human trophoblast cells with adenovirus vector containing RGD motif in the fiber protein.
Previously we reported fiber-modified adenovirus (Ad) vectors containing the Arg-Gly-Asp (RGD) motif on the HI loop of the fiber knob (Ad-RGD vectors) have high gene transfer efficacy into some human trophoblast cell lines. In the current study, we investigate transgene activity of Ad-RGD during differentiation of human cytotrophoblast BeWo cells into syncytiotrophoblast-like cells. Although cellular differentiation into syncytiotrophoblast cells was followed by a decrease in the coxsackievirus and adenovirus receptor levels on the cell membrane, the alphaVbeta3 and alphaVbeta5 integrin levels did not change. Conventional adenovirus vector had lower transduction activity in the differentiated cells than non-differentiated cells. In contrast, Ad-RGD vector had no influence on differentiation and had a ca. 2-5 fold higher transduction activity than that of the conventional Ad vector. Thus, Ad-RGD vector can be a powerful tool for gene transfer experiments in syncytiotrophoblast cells.


The enigmatic genome of Chara australis virus.
Most of the genomic sequence of Chara australis virus (CAV), previously called Chara corallina virus, has been determined. It is a ssRNA molecule of 9065 nt with at least four ORFs. At its 5' end is an ORF encoding a protein of 227 kDa, distantly homologous to the multifunctional replicases of benyviruses and rubiviruses. Next is an ORF encoding a protein of 44 kDa, homologous to the helicases of pestiviruses. The third ORF encodes an unmatched protein of 38 kDa that is probably a movement protein. The fourth and 3'-terminal ORF encodes a protein of 17.7 kDa homologous to the coat proteins of tobamoviruses. The short methyltransferase region of the CAV replicase matches only the C-terminal motif of benyvirus methyltransferases. This and other clues indicate that approximately 11% and 2% of the 5' and 3' termini of the complete CAV genome, respectively, are missing from the sequence. The aligned amino acid sequences of the CAV proteins and their nearest homologues contain many gaps but relationships inferred from them were little affected by removal of these gaps. Sequence comparisons show that three of the CAV genes may have diverged from the most closely related genes of other viruses 250-450 million years ago, and the sister relationship between the genes of CAV and those of benyviruses and tobamoviruses, mirroring the ancient sister relationship between charophytes (i.e. the algal host of CAV) and embryophytes (i.e. the plant hosts of tobamoviruses and benyviruses), is congruent with this possibility.


[Use of D-dimer to exclude upper extremity deep venous thrombosis].
D-dimer is often used to exclude deep venous thrombosis, primarily in the lower extremities. We describe a 38-year-old man who had deep venous thrombosis in the left vena subclavia in spite of a normal D-dimer. Only one inconclusive survey compares the value of D-dimer and upper extremity deep venous thrombosis. We conclude that where deep venous thrombosis of the upper extremities is suspected, you cannot rely on the D-dimer value, but should examine the patient using other modalities such as colour Doppler ultrasound.


[Kidney disease and insulin resistance--clinical impact of thiazolidinedione compounds for kidney disease].
The thiazolidinedione compounds are well known hypoglycemic agents via increasing insulin-sensitivity. Herein, we provide the possibility that thiazolidinedione compounds could be useful for renal dysfunction through mechanism dependent or independent of its insulin-sensitizing action. In type 2 diabetes, troglitazone could reduce urinary albumin-creatinine ratio compared to metformin. Furthermore, we have shown that troglitazone was able to prevent diabetic glomerular dysfunction through inhibition of diacylglycerol-protein kinase C-extracellular signal-regulated kinase pathway in type 1 diabetic rats. Thus, thiazolidinediones might be effective agents for treating insulin-resistant diabetes as well as diabetes-induced kidney disease.


Maximum likelihood estimation of marginal pairwise associations with multiple source predictors.
Researchers interested in the association of a predictor with an outcome will often collect information about that predictor from more than one source. Standard multiple regression methods allow estimation of the effect of each predictor on the outcome while controlling for the remaining predictors. The resulting regression coefficient for each predictor has an interpretation that is conditional on all other predictors. In settings in which interest is in comparison of the marginal pairwise relationships between each predictor and the outcome separately (e.g., studies in psychiatry with multiple informants or comparison of the predictive values of diagnostic tests), standard regression methods are not appropriate. Instead, the generalized estimating equations (GEE) approach can be used to simultaneously estimate, and make comparisons among, the separate pairwise marginal associations. In this paper, we consider maximum likelihood (ML) estimation of these marginal relationships when the outcome is binary. ML enjoys benefits over GEE methods in that it is asymptotically efficient, can accommodate missing data that are ignorable, and allows likelihood-based inferences about the pairwise marginal relationships. We also explore the asymptotic relative efficiency of ML and GEE methods in this setting.


Synthesis and Analysis of Bacterial Folate Metabolism Intermediates and Antifolates.
The mechanism of action of para-aminosalicylic acid (PAS), a drug used to treat drug-resistant tuberculosis (TB), has been confirmed through the first synthesis and biochemical characterization of its active metabolite 7. The synthesis features the coupling of N2-acetyl-6-formylpterin obtained from the degradation of folic acid and appropriately functionalized arylamines to form Schiff bases. The sequential chemoselective reduction of the imine and pterin ring led to the formation of dihydrofolate analogue 7 and two other dihydropteroate species.


Perceived risk of occupational injury: control over pace of work and blue-collar versus white-collar work.
Factors influencing the perception of risk of work-related accidental injury were investigated for 244 full-time employed men and women. Autonomy and freedom in one's work were the strongest predictors of perceived risk, with those respondents exercising the greatest control over their work perceiving the least risk of accidental injury. Two other dimensions of control over work-task repetitiveness and speed of pace-had weaker effects. Respondents using primarily blue collar kinds of equipment felt more at risk than those using white collar equipment or no equipment. This result is interpreted in terms of the impact of 'sudden harm' on perceptions. Present working conditions, represented by the number of hazards identified in the workplace, predicted perceived risk more strongly than previous accident history.


Modulating Resonance Energy Transfer with Supramolecular Control in a Layered Hybrid Perovskite and Chromium Photosensitizer Assembly.
Recently, the low-dimensional organic-inorganic halide perovskites (OIHP) have been exploited heavily for their favorable exciton dynamics, broad-band emission, remarkable stability, and tunable band-edge excited-state energy compared to their 3D counterparts for potential optoelectronic applications. Low-dimensional perovskites are generally good candidates for utilization as room-temperature photoluminescence (PL) materials. Further, doping divalent transition metals like Mn2+ into OIHP is expected to introduce a 4T1-6A1-based low-energy luminescence emission around 600 nm; an optical property that is favorable for biomedical optoelectronics. Doping Mn2+ in the perovskite lattice is also expected to induce the generation of cytotoxic singlet oxygen species (1O2), a ROS that is being exploited for various therapeutic applications. To integrate these optical and therapeutic properties of a 2D (PEA)2PbBr4 (Pb PeV; PEA = phenylethylammonium cation) perovskite alloyed with Mn2+ ions (Mn:PbPeV) and the option for a photoinduced energy transfer process involving a Cr(III)-based 1O2 generating photosensitizer (CrPS), we designed a unique purpose-built nanoassembly (Mn:PbPeV@PCD) using the encapsulation properties of a water-soluble polymer derived from β-cyclodextrin (PCD). Here the PCD is observed to modulate the classical internal energy transfer of Pb2+ exciton to alloyed Mn2+ orange emission, resulting in the emergence of a new blue emission. The addition of CrPS into the Mn:PbPeV@PCD to generate the CrPS@Mn:PbPeV@PCD assembly results in restoring perovskite luminescence followed by the external energy transfer to CrPS. We have elucidated the mechanism of these cascade energy transfer processes between multiple components using steady-state and time-resolved luminescence techniques. Efficient ROS generation and its potential to induce an oxidation reaction of a biomolecule are realized using guanine as the target molecule. Further photoinduced cleavage studies with biomolecules confirmed the efficacy of the nanoassembly in inducing the cleavage of guanine-rich DNA. The study opens up a new direction in the field of perovskite for biomedical applications.


Prognostic Value of Electrocardiographic Left Ventricular Hypertrophy on Cardiovascular Risk in a Non-Hypertensive Community-Based Population.
The appearance of left ventricular hypertrophy on 12-lead electrocardiography (ECG-LVH) has been clarified to be associated with the risk of incidence of cardiovascular events (CVEs) in hypertensive individuals and the general population, but not enough in non-hypertensive individuals. A total of 4,927 non-hypertensive individuals ≥40 years of age who were free of CVE in the general population were followed for the incidence of CVE. ECG-LVH was defined according to criteria of the Sokolow-Lyon (SL) voltage, Cornell voltage (CV), or Cornell voltage product (CP). During the average 9.8 ± 2.0 years of follow-up, 267 individuals (5.4%) had their first CVE. The hazard ratio (HR) for the incidence of CVE after full adjustment by potential confounders significantly increased in the individuals with ECG-LVH by any criteria of the SL voltage, CV, and CP (HR = 1.77, P < 0.001) compared to those with no ECG-LVH. This association was also significant in individuals without any of obesity, dyslipidemia, and diabetes mellitus or those with systolic blood pressure (BP) <120 mm Hg and diastolic BP <80 mm Hg. Furthermore, ECG-LVH by each criteria provided the reclassification improvement for the CVE risk prediction model by the Framingham 10-year risk score (the net reclassification improvement = 0.17-0.22, each P value < 0.010). In the absence of hypertension, ECG-LVH parameters are associated with the increased risk of developed CVEs independent of the established risk factors and provide the additional prognostic value in an assessment of the CVE risk using the traditional risk factors.


Dumbbell-like Au-Fe3O4 nanoparticles: a new nanostructure for supercapacitors.
Monodispersed dumbbell-like Au-Fe3O4 nanoparticles (NPs) were synthesized and studied for use in supercapacitors. These dumbbell NPs show Au/Fe3O4-size dependent capacitive behaviors and the 7-14 nm Au-Fe3O4 NPs have the best specific capacitance of 464 F g(-1) at 1 A g(-1) and capacity retention of 86.4% after 1000 cycles, much larger than pure Fe3O4 NPs (160 F g(-1) and 72.8% retention). This capacitive enhancement is believed to arise from the Au-induced increase in electron transfer across the dumbbell-like NPs. Thise report demonstrates a new strategy to enhance oxide NP capacitance for applications in high performance supercapacitors.


Structure-Activity Relationship Studies of Small Molecule Modulators of the Staphylococcal Accessory Gene Regulator.
The accessory gene regulator (agr) quorum-sensing system is arguably the most important regulator of Staphylococcus virulence. The agr-system serves a crucial role in pathogenesis by triggering substantive gene expression alterations to up-regulate the production of a wide variety of virulence determinants such as exoenzymes (proteases, lipases, nucleases) and downregulate the expression of surface binding proteins. Accordingly, the agr-system represents a compelling target for the development of antivirulence therapeutics as potential adjuncts, or alternatives, to conventional bactericidal and bacteriostatic antibiotics. Despite this potential, to date, no agr-system inhibitors have progressed to the clinic; however, several promising lead compounds have been identified through screens of synthetic and natural product libraries. On the basis of the molecular components within the agr-system, the current contingent of regulating compounds can be clustered into three broad groups, AgrA-P3 activation inhibitors, AgrB-AgrD processing inhibitors, and AgrC-AIP interaction inhibitors. This review aims to provide an overview of the development, structure-activity-relationships, and limitations of compounds within each of these groups in addition to the current opportunities for developing next-generation anologs.


Health Characteristics of Patients with Cystic Fibrosis whose Genotype Includes a Variant of the Nucleotide Sequence c.3140-16T>A and Functional Analysis of this Variant.
Cystic fibrosis (CF) is the most common monogenic autosomal recessive disease, associated with pathogenic variants in the CFTR gene. The splicing variant c.3140-16T>A (3272-16T>A) has been described previously and, according to the Russian CF Patients Registry, occurs with a frequency of 0.34%. The phenotypic features of CF patients with the c.3140-16T>A variant were compared with those of patients with the genotype F508del/F508del. Patients with the allele c.3140-16T>A had higher average age and age at diagnosis, and the allele was present in a greater proportion of adults. Patients carrying the c.3140-16T>A allele were characterised by better physical development indicators, both in adults and in children, had preserved pancreatic function, as well as the absence of a number of complications, and required pancreatic enzyme replacement therapy less often than patients with the F508del/F508del genotype. Sweat test values also were lower in patients with the c.3140-16T>A genotype. According to the results of clinical and laboratory studies, the phenotype of patients with the genetic variant c.3140-16T>A can be considered "mild". Functional CFTR protein activity in the presence of c.3140-16T>A was evaluated using intestinal current measurements (ICM) and the forskolin-induced swelling assay on organoids obtained from patients' rectal biopsies. c.3140-16T>A had high residual CFTR channel activity and was amenable to effective pharmacological correction with thea VX-770 potentiator. To evaluate the effect of the variant on CFTR pre-mRNA splicing we performed a minigene assay, as well as RT-PCR analysis of RNA isolated from the nasal epithelium and rectal biopsy of patients. We showed that the c.3140-16T>A variant creates a novel acceptor AG dinucleotide within CFTR intron 19, resulting in a 14-nucleotide extension of exon 20. This frameshift produces a premature termination codon and triggers mRNA degradation by the nonsense-mediated decay (NMD) mechanism. Moreover, we observed that the c.3140-16T>A allele could produce a residual amount of normally spliced transcript, thus explaining the patient's mild phenotype.


A Stepwise Approach Using Metastatic Lymph Node Ratio-Combined Thyroglobulin for Customization of [18F]FDG-PET/CT Indication to Detect Persistent Disease in Patients with Papillary Thyroid Cancer.
We investigated whether an indication for [18F]FDG-PET/CT to detect FDG-avid persistent disease (PD) could be identified precisely using the extent of metastatic lymph nodes (MLNs) and serum thyroglobulin (Tg) in papillary thyroid cancer (PTC) patients. This retrospective study included 429 PTC patients who underwent surgery and radioactive iodine (RAI) therapy. [18F]FDG-PET/CT and serum Tg were evaluated just before RAI therapy. The MLN ratio (LNR) was defined as the ratio of the number of MLNs to the number of removed LNs. To derive the LNR-combined criteria, different Tg cut-off values for identifying the PET/CT-indicated group for PD detection were applied individually to subgroups initially classified based on LNR cut-off values. The cut-off values for serum Tg, the number of MLNs, and LNR for a PET/CT indication were 6.0 ng/mL, 5, and 0.51, respectively. Compared to a single parameter (serum Tg, total number of MLNs, and LNR), the LNR-combined criteria showed significantly superior diagnostic performance in detecting FDG-avid PD (p < 0.001). The diagnostic performance of PET/CT in detecting FDG-avid PD was significantly improved when the PET/CT-indicated group was identified through the LNR-combined criteria in a stepwise manner; this can contribute to a customized PET/CT indication in PTC patients.


Monoclonal antibodies to the carboxy-terminal Ea sequence of pro-insulin-like growth factor-IA (proIGF-IA) recognize proIGF-IA secreted by IM9 B-lymphocytes.
Insulin-like growth factor-I (IGF-I) circulates in human serum as a 7 kDa peptide but analysis of IGF-I cDNAs predicts two pro-hormone precursors (proIGF-IA and proIGF-IB) with distinct C-terminal E domains. The function of these precursors, and the E peptides generated on cleavage to mature IGF-I, is unknown, largely because of a lack of tools for distinguishing precursors from constituent peptides. We used a synthetic Ea peptide to develop monoclonal antibodies (MAbs) which can recognize the carboxy-terminal sequence of proIGF-IA. These were characterized using proIGF-IA generated by transfected HEK293 cells. The anti-proIGF-IA MAbs immunoprecipitated two peptides (19--21 and 14 kDa) which were also recognized by MAbs to mature IGF-I. The proIGF-IA MAbs could also detect peptides of 9 and 4 kDa predicted to be Ea peptides. Treatment with N -glycosidase proved the 19--21 kDa and 9 kDa bands to be glycosylated proIGF-IA and Ea peptide respectively. Using these antibodies, we have identified proIGF-IA secreted from the IM9 B-lymphocyte cell line. This work paves the way for studies on proIGF-IA and Ea peptide regulation and function.


[When a season means depression].
Although becoming more and more recognized among physicians and psychiatrists the etiology of seasonal affective disorder (SAD) remains unclear. Indeed, the only incontestable fact is the close link between the decrease in sunlight occurring during fall and winter and the onset of depressive symptoms. But why does this seasonal decrease in the amount of light trigger a depression in some individuals while not affecting others? Why and how has sun exposure such an impact on brain-mood regulation? This review intends to shed some light on the main neurochemical hypotheses that have been advanced for the past 25 years. While several hypotheses have been advanced to explain SAD, the present review will focus on three major suspects which are: (1) melatonin due to its crucial role in circadian rhythms (2) serotonin which has been linked with depressive disorders in general and atypical symptoms and (3) catecholamine because as for serotonin, many data reported an implication of these neurotransmitter family in depressive disorders. However, similarly to other reviews about SAD, we conclude that none of those could explain the pathophysiology of this northern disease on its own.


Study on the Mechanism of Elastic Instability Caused by Natural Growth in Orthotropic Material.
Compared to synthetic materials, naturally grown biological materials have more specific behavioral patterns and life connotations in their morphological evolution over millions of years of environmental evolution on Earth. In this paper, we investigate the physical mechanisms and manifestations of out-of-plane deformation instability. Firstly, the origin of the instability phenomenon caused by the growth of the leaf is introduced. Leaf instability problems are modeled using rectangular thin plates. Secondly, the variation in the critical intrinsic strain with the principal shear modulus is obtained by numerical solution. The post-buckling behavior of the growth instability is further analyzed by general static analysis, and we obtain the phase diagram of morphogenesis of thin plant organs as functions of the principal shear modulus and off-axis angle. The research results enhance the understanding of the mechanism of elastic instability caused by natural growth in orthotropic materials.


Cancer stem cell and embryonic development-associated molecules contribute to prognostic significance in ovarian cancer.
Embryonic molecules and cancer stem cell signaling resemble each other, and they organize cancer modality. We hypothesized that similar immunohistochemical expressions between tumor spheroids and patients' samples compared with clinical relevance would give an important clue in patients' prognosis. Immunohistochemical expression of c-kit, Notch1, Jagged1, and Delta1 in 50 cases of primary ovarian tumors (10 endometrioid, 10 serous, 10 mucinous adenocarcinoma, 10 borderline serous, and 10 borderline mucinous tumors) and MDAH-2774 spheroids were investigated. Results were compared in both spheroids and tumor samples with morphologic parameters (histological grade) and clinical data (age, stage, tumor size, and metastasis). High c-kit and Notch1 immunoreactivity was shown in spheroids, but interestingly immunoreactivity of these molecules in tumor samples was different from patients' clinicopathological characteristics. In serous carcinoma, metastasis correlated with Notch1 immunoexpression; in mucinous carcinoma, Jagged1 immunohistochemistry correlated with grade, stage, and metastasis of tumor; in borderline serous and mucinous tumors, Jagged1 correlated with high grade. Moreover, Jagged1 correlated with stage and Notch1 with size in borderline mucinous tumor. Endometrioid carcinoma statistics showed that there was a correlation between age and Notch1 expression. Notch1, Jagged1, and Delta1 expressions might be useful markers for clinical prognosis of ovarian carcinomas; and Notch pathway, one of the most intensively studied putative therapeutic targets, may be a useful marker for cancer. Consequently, Jagged1 could be a marker for tumor grades and Notch1 as a marker for metastases.


Education Research: The current state of neurophysiology education in selected neurology residency programs.
Prior research has illustrated there is a knowledge gap in neurology residents' neurophysiology education (EEG and EMG), and we sought to understand whether this is still an issue and to recognize the barriers in order to create solutions and improve education. Surveys were developed for adult neurology residents and one for program directors asking about confidence in neurophysiology knowledge, percent of graduates reaching level 4 ACGME (American Council of Graduate Medical Education) milestones in EEG and EMG, methods of learning used, interest in the subjects, and suggestions for improvements. Twenty-six program directors (19% responder rate) and 55 residents (from at least 16 different programs) completed the survey. Program directors thought that 85% of graduating residents met level 4 milestones in EEG and only 75% in EMG. Structured rotations and more time allocated to education of these topics were frequent barriers mentioned. Postgraduate year 4 residents were 60% and 67% confident in EEG and 64%, 59%, and 62.3% in EMG level 4 milestones. Learning to read EEGs was considered important throughout residents' training; however, this interest and value decreased over time with EMG. In our study, program directors suspect up to a quarter of residents may graduate not meeting level 4 ACGME milestones, and residents expressed lack of confidence in these areas. The educational methods used to instruct residents in EEG and EMG were similar as were the barriers they face across programs. This information hopefully will help fuel curriculum design and interest in these important neurology techniques.


The synthesis and characterization of zinc-containing electrospun chitosan/gelatin derivatives with antibacterial properties.
Homogenous allocation of inorganic particles in a polymeric matrix is a challenge. In this work, we discuss electrospinning of chitosan /gelatin using CS-Si (chitosan silicone hybrids) as well as the formation of homogeneously distributed Zn elements inside chitosan nanofiber through chitosan -GPTMS hybrids. Chitosan -GPTMS hybrids can be synthesized by acid catalyzed amino-oxirane addition reaction. The proposed mechanism was approved by using spectral and elemental analyses. The chitosan derivative Si-Cs was mixed with gelatin and their solution were applied to electrospinning. Optimization of spinning process is reached. A homogeneous spinnable solution with desirable properties is obtained by addition of Zinc acetate. The characterizations of the spinnable solution in term of electrical conductivity and viscosity were studied. Characterization of the nanofiber formed by SEM show that there is no Zn accumulated on the nanofiber surfaces which is one of the advantages of introducing GPTMS to Cs chain. The superior antibacterial activity of the produced zinc-containing electrospun fibers of Gelatin-Si-Cs nominate it to be applied for medical purpose.


The Potential Link between Episodes of Diverticulitis or Hemorrhoidal Proctitis and Diets with Selected Plant Foods: A Case-Control Study.
Diverticulitis and hemorrhoidal proctitis in the population are significant public health problems. We studied the potential association between the intake of certain plant foods and diverticulitis or hemorrhoidal episodes through a case-control study including 410 cases and 401 controls. We used a semiquantitative food frequency questionnaire. The intake was additionally quantified according to a 24 h recall. The plant foods or derived food products were categorized by their main chemical components into ethanol, caffeine/theine/theobromine, capsaicin, alliin, acids, eugenol, and miscellaneous foods such as curcumin. The mean score for overall intake of plant foods under consideration was 6.3 points, and this was significantly higher in cases (8.5) than in controls (4.1). Overall intake was similar in cases presenting with diverticulitis or hemorrhoidal proctitis. Cases had 13 times the odds of being in the upper quartile for overall intake (>7 points), compared to controls. Explanatory logistic regression models showed that the strongest association with diverticulitis and hemorrhoidal proctitis was shown by the chemical food group of capsaicin, followed by ethanol, eugenol, caffeine/theine/theobromine, and acids. Neither alliin nor miscellaneous food groups showed any association. High, frequent consumption of capsaicin, followed by ethanol, eugenol, caffeine/theine/theobromine, and acids increase the risk of diverticulitis and hemorrhoidal proctitis.


Online recognition of music is influenced by relative and absolute pitch information.
Three experiments explored online recognition in a nonspeech domain, using a novel experimental paradigm. Adults learned to associate abstract shapes with particular melodies, and at test they identified a played melody's associated shape. To implicitly measure recognition, visual fixations to the associated shape versus a distractor shape were measured as the melody played. Degree of similarity between associated melodies was varied to assess what types of pitch information adults use in recognition. Fixation and error data suggest that adults naturally recognize music, like language, incrementally, computing matches to representations before melody offset, despite the fact that music, unlike language, provides no pressure to execute recognition rapidly. Further, adults use both absolute and relative pitch information in recognition. The implicit nature of the dependent measure should permit use with a range of populations to evaluate postulated developmental and evolutionary changes in pitch encoding.


Silver Diamine Fluoride (SDF) Efficacy in Arresting Cavitated Caries Lesions in Primary Molars: A Systematic Review and Metanalysis.
A systematic review and meta-analysis were carried out to evaluate the efficacy of silver diamine fluoride (SDF) in controlling caries progression in cavitated primary molars. A search for randomized and non-randomized trials with follow-up > 6 months was performed using PubMed, Scopus and Embase. The Cochrane risk of bias tools were used for the quality assessment. The success rate and odds ratios were chosen to calculate the effect size for the meta-analysis. A total of 792 papers were identified and 9 were selected. A high variability regarding SDF application protocol was found; otherwise, caries arrest was always recorded using visual/tactile methods. Two studies were judged at low risk of bias, six at moderate risk and one at high risk. Data from five studies were aggregated for meta-analysis. Heterogeneity was found moderate (I2 = 35.69%, p = 0.18). SDF application was found to be overall effective (fixed effect model) in arresting caries progression (ES = 0.35, p < 0.01). In a total of 622 arrested lesions, out of 1205 considered, the caries arrest rate was 51.62% ± 27.40% (Confidence = 1.55) using SDF ≥ 38% applied annually or biannually. In conclusion, when applied to active cavitated caries lesions in primary molars, SDF appears to be effective in arresting dental caries progression, especially if applied biannually.


[Decreased antioxidant-defence mechanisms in cerebrospinal fluid (CSF) in patients with tick-borne encephalitis (TBE)].
14 patients with Tick-borne Encephalitis (TBE) aged 21-64 (mean = 42.3) were analysed. The activity of superoxide dismutase (SOD), glutathione reductase (GSSG-R), glutathione peroxidase (GSH-Px), concentrations of malondialdehyde (MDA) and total sulphydryl groups (-SH) were measured in cerebrospinal fluid (CSF). Control group consisted of 10 patients whose CSF parameters remained in normal range. The CSF examination was performed twice: before and 3 weeks after treatment. The analysed activity of SOD, GSH-Px, GSSG-R, MDA and total sulphydryl groups (-SH) during the acute stage of the disease was significantly lower comparing to the control group. Despite the treatment, GSSG-R activity, MDA concentration and total sulphydryl groups--SH further lowered significantly. Although the SOD activity in CSF was higher in the second examination, it remained significantly lower comparing to the control group. We showed that the GSH-Px and GSSG-R activity in CSF after the acute stage of the TBE remained significantly lower than in the control group. Our examinations prove that during the TBE an increased generation of oxygen-derived free radicals occurs what shows decreased activity of the antioxidant parameters (SOD, GSH-Px, GSSG-R) and decreased concentration of total sulphydryl groups--SH in CSF. Our results suggest that during TBE, molecular structures injury of enzymes and antioxidative reactive cofactors may occur.


[Ectopic osteogenesis of stromal cell-derived factor 1 combined with simvastatin-loaded collagen scaffold in vivo].
To construct and evaluate a novel tissue-engineered bone composed of murine stromal cell-derived factor 1(mSDF-1), simvastatin (SIM) and collagen scaffold (Bio-Oss®), serving as a cell-homing approach for bone formation. In the study, 32 ICR mice were randomly divided into 4 groups,each group including 8 mice. The drug-loaded collagen scaffolds were implanted subcutaneously onto the cranium of each mouse according to the groups: (1) 1:50 (volume ratio) dimethyl sulfoxide (DMSO)/phosphate-buffered saline (PBS) solution + collagen scaffold (blank control group); (2) 10⁻³ mol/L SIM solution + collagen scaffold (SIM group); (3) 200 mg/L mSDF-1 solution + collagen scaffold (mSDF-1 group); and (4) 10® mol/L SIM +200 mg/L mSDF-1 solution + collagen scaffold (SIM + mSDF-1 group). One week after implantation, the mice were treated by injecting the same drug solution mentioned above around the scaffold once a day for two days. The specimens were harvested 6 weeks after implantation and the bone formation was evaluated by soft X-ray analysis, HE staining and immunohistochemical staining. Angiogenesis of each group was checked by calculation of vessels in each tissue section. Six weeks after implantation, the collagen scaffolds were retrieved. The value of gray scale for the SIM+mSDF-1 group [(421 836.5 ± 65 425.7)pixels] was significantly higher than that of the blank control group[(153 345.6 ± 45 222.2) pixels, P<0.01], the SIM group [(158 119.2 ± 100 284.2)pixels, P<0.01], and the mSDF-1 group[(255 529.5 ± 152 142.4)pixels, P<0.05]; HE staining analysis revealed that significant bone formation was achieved in the SIM + mSDF-1 group; The immunohistochemical staining showed the existence of osteopontin and osteocalcin in the SIM + mSDF-1 group; There were more vessels in the SIM+mSDF-1 group[(46 ± 8)vessels/mm²] than in the blank control group [(23 ± 7) vessels/mm2, P<0.01], and the SIM group[(24 ± 6) vessels/mm2, P<0.01]. The novel tissue-engineered bone composed of mSDF-1, SIM and collagen scaffolds has the potential to form bone subcutaneously in vivo. It represents a novel method of in vivo bone re-generation without seed cell delivery.


Leucine125Valine (Leu125Val) Gene Polymorphism of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) and Myocardial Infarction in Indian Population.
Platelet-endothelial cell adhesion molecule-1 (PECAM-1) has role in atherosclerotic plaque development as well as in thrombosis leading to myocardial infarction (MI). Present study was aimed to analyse the association of PECAM-1 Leu125Val gene polymorphism with MI in Indian population. Subjects included healthy individuals as control (N = 116) and MI patients (N = 100) divided into two groups; MI patients at presentation of the acute event (MI-Group-1, N = 46) and patients with recent event of MI stabilized with treatment 4.5 days from their symptoms (MI-Group-2, N = 54). The difference in the distribution of Leu125Val genotype frequencies of controls and patients did not reach statistical significance. However Leu allele frequency (0.57) was more associated with MI patients as compared to control (0.504). sPECAM-1 levels were significantly elevated in patients at acute event of MI (MI-Group-1) by 44.1% (P = 0.009) as compared to controls and by 95.2% (P = 0.001) as compared to stabilized MI patients (MI-Group-2).