Psychometric Properties of Full and Shortened Persian-version of Western Ontario Rotator Cuff Index Questionnaires in Persian-speaking Patients with Shoulder Pain.
This study aimed to translate the shortened Western Ontario Rotator Cuff (Short-WORC) questionnaire into Persian and determine the psychometric features of WORC and Persian-Short-WORC in patients with shoulder pain. A total of 130 patients completed Persian-WORC and -Short-WORC, Shoulder Pain And Disability Index (SPADI), shortened Disability of Arm, Shoulder, and Hand (Quick-DASH), WORC, as well as Short-Form health survey (SF-36), in the evaluation and re-evaluation sessions with an interval of 5-7 days to assess reliability and validity. To determine responsiveness, all patients completed questionnaires and a global rating of change scale before and after the 4-week physiotherapy. Intra-class correlation coefficient (ICC) was used for assessing reliability, two-tailed Pearson (r) for validity, as well as longitudinal validity, and receiver operating characteristics (ROC) curve analysis for responsiveness. The ICC was 0.95 (confidence interval: 0.93-0.96) for Short-WORC. A strong correlation was found between Short-WORC, SPADI (r=-0.82), Quick-DASH (r=-0.79), WORC (r=0.92), SF-36 physical (r=0.76), and SF-36 mental (r=0.71). Floor and ceiling effects were not detected. The responsiveness of Short-WORC and WORC was proven with an area under the curve of >0.90, and their minimal important change was 28.56 and 26.28 points, respectively. The Persian version of WORC has good psychometric properties to measure disability and health-related quality of life in patients with shoulder pain.


Elective switching from infliximab to adalimumab in stable Crohn's disease.
Elective switching of biological therapy in patients with Crohn's disease (CD) in remission is generally discouraged, given the theoretical risk of antibody formation and loss of response. The aim of this study was to assess efficacy and tolerability of adalimumab (ADA) therapy after an elective switch from infliximab (IFX) in patients with stable CD. Patients with CD with stable disease for >6 months (Harvey-Bradshaw Index ≤ 8) on IFX were eligible for this prospective, open-label single-center study. The primary endpoint was termination of ADA therapy. Disease activity (Harvey-Bradshaw Index, laboratory results) and adverse events were documented during the follow-up. We enrolled 29 patients with CD (19 women, mean age, 39 years; interquartile range, 23-58 years) who switched from IFX to ADA. At the end of the 54-week follow-up period, 72% of patients continued ADA therapy. Eight patients discontinued ADA therapy due to disease activity (n = 3), side effects (n = 4), or general symptoms (n = 1). After discontinuation of ADA, 4 patients switched back to IFX, and no infusion reactions occurred. No significant changes were observed in Harvey-Bradshaw Index scores, C-reactive protein, and leukocyte counts at 0 versus 54 weeks. Half of the patients who discontinued ADA showed an elevated baseline C-reactive protein. The majority of patients with CD (72%) continued therapy and maintained remission after an elective switch from IFX to ADA, although switching back to IFX, if required, was well tolerated. However, elective switching of anti-tumor necrosis factor therapy in stable CD should be carefully considered, given the risk of loss of response and the limited options for alternative maintenance therapies.


Tachycardia caused by an accessory nodoventricular tract: a clinico-pathologic correlation.
Paroxysmal tachycardia with widened QRS complexes was recorded in an eleven-year old boy who had suffered from brain damage, which had resulted from an episode of ventricular fibrillation. Atrial stimulation produced an increased AV conduction, sudden disappearance of the His bundle deflection and a complete left bundle branch block pattern. Tachycardias of this morphology were initiated by early atrial and ventricular premature beats. The findings suggested the presence of a macro re-entry circuit, utilizing a slow AV node- nodoventricular bypass tract as the anterograde limb and the His-Purkinje system--fast AV node as the retrograde limb. This supposition found further support by serial sectioning of the AV junctional area of the heart, which revealed a nodoventricular tract, which originated from the posterior extension of the compact part of the atrioventricular node and inserted into the crest of the ventricular septum.


Wavefunctions of macroscopic electron systems.
Wavefunctions for large electron numbers N are plagued by the Exponential Wall Problem (EWP), i.e., an exponential increase in the dimensions of Hilbert space with N. Therefore, they lose their meaning for macroscopic systems, a point stressed, in particular, by Kohn. The EWP has to be resolved in order to provide a solid basis for wavefunction based electronic structure calculations of macroscopic systems, e.g., solids. The origin of the EWP is the multiplicative property of wavefunctions when independent subsystems are considered. Therefore, it can only be avoided when wavefunctions are formulated so that they are additive instead, in particular, when matrix elements involving them are calculated. We describe how this is done for the ground state of a macroscopic electron system. Going over from a multiplicative to an additive quantity requires taking a logarithm. Here it implies going over from Hilbert space to the operator- or Liouville space with a metric based on cumulants. The operators which define the ground-state wavefunction generate fluctuations from a mean-field state. The latter does not suffer from an EWP and therefore may serve as a vacuum state. The fluctuations have to be connected like the ones caused by pair interactions in a classical gas when the free energy is calculated (Meyer's cluster expansion). This fixes the metric in Liouville space. The scheme presented here provides a solid basis for electronic structure calculations for the ground state of solids. In fact, its applicability has already been proven. We discuss also matrix product states, which have been applied to one-dimensional systems with results of high precision. Although these states are formulated in Hilbert space, they are processed by using operators in Liouville space. We show that they fit into the general formalism described above.


Pheochromocytoma and Neurofibromatosis Type 1 in a Patient with Hypertension.
Neurofibromatosis type 1 is an autosomal dominant condition that has a variety of clinical manifestations. Essential or secondary hypertension may be associated with neurofibromatosis. A rare finding is hypertension due to pheochromocytoma in patient with neurofibromatosis type 1. We present a case with a 7-year medical history of hypertension which was poorly controlled and with wide variations of blood pressure before the examination. Investigations did not reveal a secondary cause of hypertension. After the physical examination and establishing the diagnosis of neurofibromatosis, as well as the history of symptomes suggestive of catecholamine discharge, diagnostic procedures for pheochromocytoma were undertaken. Abdominal CT and MRI have proven the presence of a right adrenal tumor mass which was suspected to be a pheochromocytoma. Patient was preoperatively treated for two weeks with alpha and beta blokers and right adrenalectomy was performed. Perioperatively and on a longer term, blood pressure remained well controlled with less antihypertensive therapy. Diagnosis and management of pheochromocytoma in neurofibromatosis involves a dermatologist, endocrinologist, nephrologist and an urologist and requires a well-coordinated multidisciplinary approach. Pheochromocytoma, although a rare condition in patients with neurofibromatosis, may be a cause for uncontrolled hypertension, as well as other cardiovascular complications and the clinician should do all available clinical investigations to confirm it or exclude it on time.


Minimally invasive transventricular implantation of pulmonary xenograft.
Minimally invasive valve replacement is now a clinical reality. A number of ingenious techniques have been described for percutaneous aortic and pulmonary valve replacement as well as transventricular aortic valve replacement. We describe a technique for transventricular pulmonary valve replacement utilizing off-the-shelf bovine tissue valve, vascular stents, and simplified delivery system. After median sternotomy with limited exposure of the right ventricle, Contegra 200 pulmonary valve (Medtronic, Inc., Minneapolis, MN, USA) is transfixed inside a CP stent (NuMed, Inc., Hopkinton, NY, USA) using multiple 5/0 prolene sutures. The valve/stent composite is crimped on a Cristal balloon catheter (Balt, Montmorency, France). The valve/stent and the balloon are then introduced via a small purse-string placed at the RVOT. The stent/valve composite is then expanded in the pulmonary valve position.


Unintended consequences of eliminating medicare payments for consultations.
Prior to 2010, Medicare payments for consultations (commonly billed by specialists) were substantially higher than for office visits of similar complexity (commonly billed by primary care physicians). In January 2010, Medicare eliminated consultation payments from the Part B Physician Fee Schedule and increased fees for office visits. This change was intended to be budget neutral and to decrease payments to specialists while increasing payments to primary care physicians. We assessed the impact of this policy on spending, volume, and complexity for outpatient office encounters in 2010. We examined outpatient claims from 2007 through 2010 for 2 247 810 Medicare beneficiaries with Medicare Supplemental (Medigap) coverage through large employers in the Thomson Reuters MarketScan Database. We used segmented regression analysis to study changes in spending, volume, and complexity of office encounters adjusted for age, sex, health status, secular trends, seasonality, and hospital referral region. "New" office visits largely replaced consultations in 2010. An average of $10.20 more was spent per beneficiary per quarter on physician encounters after the policy (6.5% increase). The total volume of physician encounters did not change significantly. The increase in spending was largely explained by higher office-visit fees from the policy and a shift toward higher-complexity visits to both specialists and primary care physicians. The elimination of consultations led to a net increase in spending on visits to both primary care physicians and specialists. Higher prices, partially owing to the subjectivity of codes in the physician fee schedule, explained the spending increase, rather than higher volumes.


Genetic Diversity and Pathogenic Features in Klebsiella pneumoniae Isolates from Patients with Pyogenic Liver Abscess and Pneumonia.
While Klebsiella pneumoniae is a common cause of nosocomial and community-acquired infections, including pneumonia and pyogenic liver abscess, little is known about the population structure of this bacterium. In this study, we investigated the prevalence and molecular characteristics of K. pneumoniae isolates from carriers, pyogenic liver abscess patients, and pneumonia patients, and genomic and phenotypic assays were used to determine the differences among the isolates. A total of 232 K. pneumoniae isolates were subtyped into 74 sequence types (STs). The isolates from different sources had their own STs, and the predominant subtypes in liver abscess and pneumonia patients were ST23 and ST11, respectively. Pangenome analysis also distinguished three phylogroups that were consistent with the isolate sources. The isolates collected from liver abscess patients carried significantly more virulence factors, and those from pneumonia patients harbored significantly more resistance genes and replicons. Almost all isolate STs (93/97 [95.88%]) from liver abscesses strongly correlated with the virulence factor salmochelin, while most pneumonia isolate STs (52/53 [98.11%]) from pneumonia did not correlate with salmochelin. The isolates collected from liver abscesses showed higher virulence in the cytotoxicity and mouse models. These data provide genomic support for the proposal that isolates collected from carriers, liver abscess patients, and pneumonia patients have distinct genomic features. Isolates from the different sources are largely nonoverlapping, suggesting that different patients may be infected via different sources. Further studies on the pathogenic mechanisms of salmochelin and other virulence factors will be required. IMPORTANCE While Klebsiella pneumoniae is a common cause of nosocomial and community-acquired infections, including pneumonia and pyogenic liver abscess, little is known about the population structure of this bacterium. We collected 232 isolates from carriers, pyogenic liver abscess patients, and pneumonia patients, and the isolates from different sources had their own sequence types. Pangenome analysis also distinguished three phylogroups that were consistent with the isolate sources. The isolates collected from liver abscess patients carried significantly more virulence factors, and those from pneumonia patients harbored significantly more resistance genes and replicons. Besides, there was a strong link between salmochelin and liver abscess. The isolates collected from liver abscesses also showed higher virulence in the cytotoxicity and mouse models. Isolates collected from different sources have distinct genomic features, suggesting that different patients may be infected via different sources.


The Prevalence of von Willebrand Disease and Significance of in Vitro Bleeding Time (PFA-100) in von Willebrand Disease Screening in the İzmir Region.
von Willebrand disease (vWD) is the most common hereditary bleeding disorder. The purpose of this investigation was to determine the prevalence of vWD among adolescents in İzmir and to assess the sensitivity and specificity of PFA-100 as a screening method in detecting this disease. Our study was conducted on adolescents in the city of İzmir between October 2006 and March 2007. A total of approximately 1500 high school students between 14 and 19 years of age were planned to be included in the investigation. Survey forms prepared for assessing hemorrhagic diathesis were completed by 1339 individuals (512 males, 827 females). The necessary laboratory tests were performed after having obtained written informed consent from 40 individuals suspected to have hemorrhagic diathesis. Based on the von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (vWF:RCo) levels and bleeding symptoms, vWD type-1 was diagnosed in 14 individuals (4 males, 10 females; prevalence: 1.04%). The most common bleeding symptom in these patients was found to be epistaxis (10/14). Screening with PFA-100 revealed prolongation in both cartridges (Col/ADP and Col/Epi) in 3 of the 14 patients. PFA-100 was determined to exhibit 21.4% sensitivity and 100% specificity in the diagnosis of vWD. The PFA-100 device was found to have high specificity but to have exhibited low sensitivity. Therefore, its utilization as a screening test may be problematic in patients with mild type-1 vWD. Specific tests (vWF:RCo, vWF:Ag) are required for the definite diagnosis of vWD. However, further studies with a large number of patients are needed. None declared.


Polarized distribution and cell type-specific localization of telencephalin, an intercellular adhesion molecule.
Telencephalin is an intercellular adhesion molecule (ICAM) restricted to the telencephalon. This study demonstrates that immunolabeled telencephalin is targeted to the somatodendritic domain of cultured hippocampal pyramidal neurons beginning with the first stages of dendritic differentiation. In contrast, it is entirely excluded from all gamma-aminobutyric acid (GABA)ergic inhibitory interneurons at all stages of development. Prior to the stage at which nearly all pyramidal neurons express telencephalin, labeled neurons possess more extensive dendritic arbors than unlabeled pyramidal neurons. More synaptic boutons form with the larger, more elaborate telencephalin-expressing dendritic trees, but bouton number per unit length is similar between neurons with and without telencephalin. These findings suggest that telencephalin identifies pyramidal neurons, it may identify plasma membrane as dendritic, and it may be generally adhesive or stabilize dendritic membranes, but it is probably not specifically synaptic. Such characteristics would be expected to be important for the formation of cell type-specific dendritic arbors.


Spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type.
We describe the clinical and radiological features of spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type (OMIM 271665) in a 7-year-old boy from Pakistan. The key clinical features of this condition include disproportionate short stature with short limbs, a narrow chest with pectus excavatum, brachydactyly in the hands and feet, a characteristic craniofacial appearance and developmental delay in some but not all patients. The radiological findings are distinctive and comprise short long bones throughout the skeleton with striking epiphyses that are stippled, flattened and fragmented and flared, irregular metaphyses. Platyspondyly in the spine with wide intervertebral spaces is observed and some vertebral bodies are pear-shaped with central humps, anterior protrusions and posterior scalloping. In the patient, we describe that the pelvic sacroiliac notch was narrow, several acetabular spurs were seen and there were several ossification defects in the pelvic bones. This form of spondylo-meta-epiphyseal dysplasia has been reported in 14 patients previously. The occurrence of affected siblings with normal parents in three families and consanguinity on three occasions indicates autosomal recessive inheritance.


FBXW7 modulates malignant potential and cisplatin-induced apoptosis in cholangiocarcinoma through NOTCH1 and MCL1.
The ubiquitin ligase F-box and WD repeat domain-containing 7 (FBXW7) is responsible for degrading diverse oncoproteins and is considered a tumor suppressor in many human cancers. Inhibiting FBXW7 enhances the malignant potential of several cancers. In this study, we aimed to investigate the role of FBXW7 in cholangiocarcinoma. We found that FBXW7 expression was associated with clinicopathological outcomes in cholangiocarcinoma patients. Both disease-free and overall survival were significantly worse in the low-FBXW7 group than in the high-FBXW7 group (P = .001 and P < .001, respectively). Multivariate analysis with the Cox proportional hazards model indicated that FBXW7 was the most important independent prognostic factor for disease-free (P = .006) and overall (P = .0004) survival. We also showed that the two FBXW7 substrates, NOTCH1 and myeloid cell leukemia sequence 1 (MCL1), regulate cholangiocarcinoma progression. Depletion of FBXW7 resulted in NOTCH1 accumulation and increased cholangiocarcinoma cell migration and self-renewal. Interestingly, when cells were stimulated with cis-diamminedichloridoplatinum(II) (cisplatin), FBXW7 suppression induced MCL1 upregulation, which reduced the sensitivity of cholangiocarcinoma cells to apoptosis, indicating that FBXW7-mediated ubiquitylation is context-dependent. These results indicate that FBXW7 modulates the malignant potential of cholangiocarcinoma through independent regulation of NOTCH1 and MCL1.


Role of vertical segregation in semitransparent organic photovoltaics.
In this work, the efficiency of semitransparent organic photovoltaic (OPV) devices for low intensity applications is investigated as a function of the processing conditions. It is observed that a thermal treatment of the organic layer induces fullerene migration toward the active layer/air interface. This physical process gives rise to different vertical segregation profiles of donor and acceptor molecules. Once the back contact is deposited, the amount of fullerene covering the surface will determine the contact selectivity and leakage current of the device. Control of this leakage current may not be essential for devices fabricated for high illumination condition applications. However, devices to be used under low illumination conditions may be highly influenced by the presence of this parasitic dark current which flows in the opposite direction to photogenerated current. At the proximity of the contacts, the vertical segregation profile is inferred from optical and electrical measurements. In particular, external quantum efficiency (EQE) measurements carried out from a relatively opaque back contact provide local information on the materials spatially close to the light source. Alternatively, capacitance-voltage measurements enable calculation of the percentage of fullerene molecules covering the cathode contact. Overall, a versatile method that can be used in regular and inverted configuration is presented that explains the different behavior observed for devices to be used under low illumination conditions.


Estimating pediatric doses of drugs metabolized by cytochrome P450 (CYP) isozymes, based on physiological liver development and serum protein levels.
We established a method for estimating pediatric doses of drugs metabolized by cytochrome P450 (CYP) isozymes, using the free fraction of drug in plasma (fu), serum protein level (P), liver volume (LV), and CYP activity (Vmax/Km) as indices of physiological and biochemical development in children up to 15 years old. This method allows the child/adult dose ratio (D(C)/D(A))=child/adult oral clearance ratio (CL((PO)(C))/CL((PO)(A))) of drugs mainly metabolized in the liver to be estimated by the following equation: [formula: see text]. Major metabolism of drugs was ascribed to CYP1A2 for theophylline and caffeine, and CYP1A2 and CYP2D6 for propranolol and mexiletine. For theophylline and caffeine, CL((PO)(C))/CL((PO)(A)) calculated from the child/adult body surface area ratio (BSA ratio) and the value calculated by our method were compared, using CL((PO)(C))/CL((PO)(A)) calculated from the clearance ratio based on population pharmacokinetics (PPK ratio) as a reference. For all drugs, pediatric doses calculated from the Crawford equation and our equation were compared, with predetermined doses as the reference. For theophylline and caffeine, the relative accuracy of our method was significantly higher than that of BSA-based estimation when the PPK ratio was used for reference. For theophylline, caffeine, and propranolol, the relative accuracy of our method was significantly higher than that of BSA-based estimation when predetermined doses were used for reference. These findings indicate the validity of our method which considers the physiological and biochemical development (i.e., fu, P, LV, and CYP activity) for pediatric dose estimation.


Clusterin enhances proliferation of primary astrocytes through extracellular signal-regulated kinase activation.
Clusterin, a secretory glycoprotein, has been shown to be up-regulated in the reactive astrocytes in response to brain injury and neurodegenerative diseases, but its function has not been clearly elucidated. In this study, we investigate whether clusterin has growth-stimulatory activity in astrocytes. Suppression of clusterin with antisense oligonucleotide induced growth arrest, whereas transient overexpression of clusterin by cDNA transfection or exogenous treatment with purified clusterin promoted proliferation of the primary astrocytes in culture. This clusterin-stimulated proliferation was abrogated by PD98059, an inhibitor of mitogen-activated protein kinase kinase. These results suggest that clusterin might play an important role in astrogliosis by stimulating the proliferation of astrocytes through activation of the extracellular signal-regulated kinase 1/2 signaling pathway.


An atypical presentation of malaria in a 19-year-old woman.
We describe an atypical presentation of malaria in a 19-year-old female who emigrated from Nigeria to the United States one year prior to presentation. Her primary complaint was fever and occipital headache radiating down to the neck. Rapid antigen testing was positive for Plasmodium vivax/ovale and microscopy demonstrated the same. She received treatment with atovaquone-proguanil with improvement in symptoms but was lost to outpatient follow up. This case is unusual in several aspects: the 12-month latency in disease manifestation after her last epidemiologic exposure and the recovery of P. vivax/ovale which is uncommon in Nigeria. Appropriate identification of travel history, clinical presentation and disease epidemiology are necessary to guide pharmacologic treatment.


A device for sorting soft capsules in a microchannel flow.
The sorting of deforming capsules of varying stiffnesses is a challenging problem that finds applications in areas such as the pharmaceutical and food industries. Recent studies have shown that various flow configurations can be used to segregate the capsules. A lack of inertia in the microchannels makes the design of such devices extremely challenging. In this context, we propose a sorting device, which consists of capsules going through a tapered slit section. Using numerical simulations, we show that the proposed device is able to achieve significant levels of sorting with a compact setup. The design parameters can be conveniently adjusted, thus making it easier to extend the use of the device to a large range of stiffnesses.


mPSQed: a software for the design of multiplex pyrosequencing assays.
Molecular-based diagnostic assays are the gold standard for infectious diseases today, since they allow a rapid and sensitive identification and typing of various pathogens. While PCR can be designed to be specific for a certain pathogen, a subsequent sequence analysis is frequently required for confirmation or typing. The design of appropriate PCR-based assays is a complex task, especially when conserved discriminating polymorphisms are rare or if the number of types which need to be differentiated is high. One extremely useful but underused method for this purpose is the multiplex pyrosequencing technique. Unfortunately there is no software available to aid researchers in designing multiplex pyrosequencing assays. Here, we present mPSQed (Multiplex PyroSeQuencing EDitor), a program targeted at closing this gap. We also present the design of an exemplarily theoretical assay for the differentiation of human adenovirus types A-F using two pyrosequencing primers on two distinct PCR products, designed quickly and easily using our software.


Alcohol Consumption and Risky Drinking Patterns among College Students from Selected Countries of the Carpathian Euroregion.
Reduction of excessive alcohol consumption still remains a significant challenge to the actions in the scope of public health of European citizens. The aim of this study is to present the prevalence of alcohol consumption and to estimate the occurrence of risky drinking among college students from the Polish, Slovak, Romanian, and Ukrainian parts of the Carpathian Euroregion, taking social contexts into account. The consumption of alcohol was estimated on the basis of the respondents' statements regarding the quantity and frequency of their consumption of beer, wine, and vodka. The study included people from the first year of undergraduate studies. The analysis used the Chi-square independence test and odds ratios (ORs). There were significant differences in the frequency of alcohol consumption, as well as the individual types consumed, among the respondents from the analyzed countries. Of the examined college students, 70% admit to occasional drinking. The pattern of dangerous alcohol consumption occurs in the case of approximately every seventh person. Risky drinking occurs with much greater frequency among male students rather than their female counterparts. In Romania, a very small percentage of female students engage in risky drinking. The analysis did not show statistically significant differences in the frequency of risky drinking between countries. The coexistence of other adverse health behaviors, such as smoking and alcohol abuse, was confirmed.


Phorbol ester-mediated re-expression of endogenous LAT adapter in J.CaM2 cells: a model for dissecting drivers and blockers of LAT transcription.
Linker for activation of T cells (LAT) is a raft-associated, transmembrane adapter protein critical for T-cell development and function. LAT expression is transiently upregulated upon T-cell receptor (TCR) engagement, but molecular mechanisms conveying TCR signaling to enhanced LAT transcription are not fully understood. Here we found that a Jurkat subline J.CaM2, initially characterized as LAT deficient, conditionally re-expressed LAT upon the treatment with a protein kinase C activator, phorbol 12-myristate 13-acetate (PMA). We took advantage of the above observation for studying cis-elements and trans-acting factors contributing to the activation-induced expression of LAT. We identified a LAT gene region spanning nucleotide position -14 to +357 relative to the ATG start codon as containing novel cis-regulatory elements that were able to promote PMA-induced reporter transcription in the absence of the core LAT promoter. Interestingly, a point mutation in LAT intron 1, identified in J.CaM2 cells, downmodulated LAT promoter activity by 50%. Mithramycin A, a selective Sp1 DNA-binding inhibitor, abolished LAT expression upon PMA treatment as did calcium ionophore ionomycin (Iono) and valproic acid (VPA), widely used as an anti-epileptic drug. Our data introduce J.CaM2 cells as a model for dissecting drivers and blockers of activation induced expression of LAT.


ERPs and oscillations during encoding predict retrieval of digit memory in superior mnemonists.
Previous studies have consistently demonstrated that superior mnemonists (SMs) outperform normal individuals in domain-specific memory tasks. However, the neural correlates of memory-related processes remain unclear. In the current EEG study, SMs and control participants performed a digit memory task during which their brain activity was recorded. Chinese SMs used a digit-image mnemonic for encoding digits, in which they associated 2-digit groups with images immediately after the presentation of each even-position digit in sequences. Behaviorally, SMs' memory of digit sequences was better than the controls'. During encoding in the study phase, SMs showed an increased right central P2 (150-250ms post onset) and a larger right posterior high-alpha (10-14Hz, 500-1720ms) oscillation on digits at even-positions compared with digits at odd-positions. Both P2 and high-alpha oscillations in the study phase co-varied with performance in the recall phase, but only in SMs, indicating that neural dynamics during encoding could predict successful retrieval of digit memory in SMs. Our findings suggest that representation of a digit sequence in SMs using mnemonics may recruit both the early-stage attention allocation process and the sustained information preservation process. This study provides evidence for the role of dynamic and efficient neural encoding processes in mnemonists.


[Social environment and morpho-physiological status of young males in the fall groups of great gerbil (Rhombomys opimus Licht). Effect of adults' presence].
The dependence of stress and sex hormone levels, size of mid-ventral skin gland, and body mass of young males on the presence in social groups of adult gerbils (>1 year old) were studied during the fall of 1999 in the non-breeding high density population of the great gerbil (Rhombomys opimus Licht; Bukhara region, Uzbekistan). Contents of corticosterone and testosterone in fecal samples collected from young males in the field were analyzed by non-invasive radioimmunoassay. The fall gerbil groups with adults were of larger size than those without adults. The total number of individuals in a group is positively correlated with concentration of corticosterone in feces of young males. Presence of adult male and especially of adult female suppresses maturation of juvenile males indicated by size of the androgene-dependent mid-ventral gland, but accelerates their total growth. Thus, the social environment influences morpho-physiological characters of young males, effecting rate of their maturation directly or indirectly through the density dependent stress.


Effect of surface degradation on optical performance of potassium dihydrogen phosphate optics.
We have measured scatter produced by roughening of bare potassium dihydrogen phosphate (KDP) surfaces and by surface degradation (etch pits) that develop beneath a porous solgel coating on KDP after exposure to ambient relative humidity. The etch pits that form on coated KDP scatter incident light into strongly anisotropic angular distributions characteristic of the defect size and shape. The total integrated scatter (TIS) can be as high as 9% for a crystal with etch pits as compared with 0.05% for the as-manufactured crystal. The amount of TIS correlates with the area obscured by defects as measured by optical microscopy.


Improvement of diagnostic efficiency in distinguishing the benign and malignant thyroid nodules via conventional ultrasound combined with ultrasound contrast and elastography.
We aimed to evaluate the diagnostic values of conventional ultrasound (US), ultrasound contrast (UC) and ultrasound elastography (UE) in distinguishing the benign and malignant thyroid nodules. A total of 100 patients with thyroid nodules receiving operative treatment were selected; they underwent the conventional US, UE and UC examinations before operation, respectively. The nodules received pathological examination after operation to distinguish benign from malignant lesions. The sensitivity, specificity and diagnostic accordance rate of each diagnostic method was evaluated by receiver operating characteristic (ROC) curve, and the area under the curve (AUC) of ROC was calculated. The manifestations of malignant thyroid nodules in conventional US examination were mostly the hypoecho, heterogeneous echo, irregular shape, unclear boundary, aspect ratio <1, microcalcification and irregular peripheral echo halo, and there were statistically significant differences compared with the benign nodules (P<0.05). UE showed that the differences between benign and malignant nodules in 2, 3 and 4 points were statistically significant (P<0.05). The manifestations of malignant nodules in UC were mostly the irregular shape, obscure boundary, no obvious enhancement, heterogeneous enhancement and visible perfusion defects, and there were statistically significant differences compared with the benign nodules (P<0.05). ROC curve showed that both sensitivity and specificity of UE and UC were superior to those of conventional US. AUC was the largest (AUC = 0.908) and the diagnostic value was the highest in the conventional US combined with UE and UC. Conventional US combined with elastography and UC can significantly improve the sensitivity, specificity and accuracy of diagnosis of benign and malignant thyroid nodules.


Heterozygous antithrombin deficiency improves in vivo haemostasis in factor VIII-deficient mice.
Decreased levels of factor VIII (FVIII) limit the amount of thrombin generated at the site of injury, but not the rate that thrombin is neutralised by antithrombin (AT). We hypothesised that FVIII-deficient mice with heterozygous AT deficiency will demonstrate increased thrombin generation and therefore less in vivo bleeding compared to FVIII-deficient mice with normal AT levels. Therefore, we performed tail bleeding experiments in wild-type (WT), heterozygous AT deficient (AT(+/-)) mice, FVIII-deficient (FVIII(-/-)) mice, and FVIII-deficient mice with heterozygous AT deficiency (FVIII(-/-)/AT(+/-)). Amount of bleeding was assessed by measuring absorbance of haemoglobin released from lysed red blood cells collected after tail transection. In addition, we measured thrombin generation, activated partial thromboplastin time (aPTT), and AT activity in plasma from the different mice groups. Tail bleeding was significantly reduced in FVIII(-/-)/AT(+/-) mice compared to FVIII(-/-) mice. On the other hand, there was no difference in tail bleeding between AT(+/-) and wild-type mice. Thrombin generation was dependent on the mice genotype, and increased in the following order: FVIII(-/-) < FVIII(-/-)/AT(+/-) < WT < AT(+/-). The aPTT was not influenced by reduced AT activity (i.e. AT(+/-) genotype), but was significantly prolonged in FVIII(-/-) and FVIII(-/-)/AT(+/-) mice. Using FVIII-deficient mice as an in vivo murine model of reduced thrombin generation, we demonstrated that moderately reduced AT levels increase thrombin generation and decrease bleeding after traumatic tail vessel injury. In agreement with congenital thrombotic conditions, our data elucidate that bleeding phenotypes can be modulated by the balance between procoagulant and anticoagulant proteins.


Critical Illness-induced Corticosteroid Insufficiency: What It Is Not and What It Could Be.
Critical illnesses are hallmarked by increased systemic cortisol availability, a vital part of the stress response. Acute stress may trigger a life-threatening adrenal crisis when a disease of the hypothalamic-pituitary-adrenal (HPA) axis is present and not adequately treated with stress doses of hydrocortisone. Stress doses of hydrocortisone are also used to reduce high vasopressor need in patients suffering from septic shock, in the absence of adrenal insufficiency. Research performed over the last 10 years focusing on the HPA axis during critical illness has led to the insight that neither of these conditions can be labeled "critical illness-induced corticosteroid insufficiency" or CIRCI. Instead, these data suggested using the term CIRCI for a condition that may develop in prolonged critically ill patients. Indeed, when patients remain dependent on vital organ support for weeks, they are at risk of acquiring central adrenal insufficiency. The sustained increase in systemic glucocorticoid availability, mainly brought about by suppressed circulating cortisol-binding proteins and suppressed hepatic/renal cortisol metabolism, exerts negative feedback inhibition at the hypothalamus/pituitary, while high levels of other glucocorticoid receptor ligands, such as bile acids, and drugs, such as opioids, may further suppress adrenocorticotropic hormone (ACTH) secretion. The adrenal cortex, depleted from ACTH-mediated trophic signaling for weeks, may become structurally and functionally impaired, resulting in insufficient cortisol production. Such a central HPA axis suppression may be maladaptive by contributing to lingering vasopressor need and encephalopathy, hence preventing recovery. Here, we review this concept of CIRCI and we advise on how to recognize and treat this poorly understood condition.


Failure of feedback as a putative common mechanism of spreading depolarizations in migraine and stroke.
The stability of cortical function depends critically on proper regulation. Under conditions of migraine and stroke a breakdown of transmembrane chemical gradients can spread through cortical tissue. A concomitant component of this emergent spatio-temporal pattern is a depolarization of cells detected as slow voltage variations. The propagation velocity of approximately 3 mm/min indicates a contribution of diffusion. We propose a mechanism for spreading depolarizations (SD) that rests upon a nonlocal or noninstantaneous feedback in a reaction-diffusion system. Depending upon the characteristic space and time scales of the feedback, the propagation of cortical SD can be suppressed by shifting the bifurcation line, which separates the parameter regime of pulse propagation from the regime where a local disturbance dies out. The optimization of this feedback is elaborated for different control schemes and ranges of control parameters.


Miniaturized Antenna Array-Based Novel Metamaterial Technology for Reconfigurable MIMO Systems.
In this work, a highly miniaturized microstrip antenna array based on two elements is proposed for multiple inputs multiple outputs (MIMO) application systems at sub-6 GHz frequency bands. The antenna is structured from a meander line in conjugate with an interdigital capacitor when excited through the monopole basic antenna. The proposed antenna elements are separated with a Minkowski factor-shaped metamaterial (MTM) column to achieve a separation distance (D) of 0.08λ at 3 GHz when printed on an FR-4 substrate. Later on, the antenna performance in terms of bandwidth and gain is controlled using a photonic process based on optical active switches based on light-dependent resistances (LDR). Therefore, the reconfiguration complexity with such a technique can be eliminated significantly without the need for a biasing circuit. The antenna design was conducted through several parametric studies to arrive at the optimal design that realizes the frequency bandwidth between 3 and 5.5 GHz with a maximum gain of about 4.5 dBi when all LDR terminals are off. For a wireless channel performance study-based massive MIMO environment, the proposed antenna is suitable to be configured in arrays of 64 × 64 elements. From this study, it was found the maximum bit error rate (BER) does not exceed 0.15 with a channel capacity (CC) of 2 Gbps. For validation, the antenna was fabricated based on two elements and tested experimentally. Finally, it was revealed that the measured results agree very well with simulations after comparing the theoretical calculations with the measured data.


Targeted chemical disruption of clathrin function in living cells.
The accurate assignment of molecular roles in membrane traffic is frequently complicated by the lack of specific inhibitors that can work on rapid time scales. Such inhibition schemes would potentially avoid the complications arising from either compensatory gene expression or the complex downstream consequences of inhibition of an important protein over long periods (>12 h). Here, we developed a novel chemical tool to disrupt clathrin function in living cells. We engineered a cross-linkable form of clathrin by using an FK506-binding protein 12 (FKBP)-clathrin fusion protein that is specifically oligomerized upon addition of the cell-permeant cross-linker FK1012-A. This approach interrupts the normal assembly-disassembly cycle of clathrin lattices and results in a specific, rapid, and reversible approximately 70% inhibition of clathrin function. This approach should be applicable to a number of proteins that must go through an assembly-disassembly cycle for normal function.


Differentiation of autoimmune pancreatitis from pancreatic adenocarcinoma using CT characteristics: a systematic review and meta-analysis.
To determine informational CT findings for distinguishing autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC) and to review their diagnostic accuracy. A systematic and detailed literature review was performed through PubMed, EMBASE, and the Cochrane library. Similar descriptors to embody the identical image finding were labeled as a single CT characteristic. We calculated the pooled diagnostic odds ratios (DORs) of each CT characteristic using a bivariate random-effects model. A total of 145 various descriptors from 15 studies (including 562 AIP and 869 PDAC patients) were categorized into 16 CT characteristics. According to the pooled DOR, 16 CT characteristics were classified into three groups (suggesting AIP, suggesting PDAC, and not informational). Seven characteristics suggesting AIP were diffuse pancreatic enlargement (DOR, 48), delayed homogeneous enhancement (DOR, 46), capsule-like rim (DOR, 34), multiple pancreatic masses (DOR, 16), renal involvement (DOR, 15), retroperitoneal fibrosis (DOR, 13), and bile duct involvement (DOR, 8). Delayed homogeneous enhancement showed a pooled sensitivity of 83% and specificity of 85%. The other six characteristics showed relatively low sensitivity (12-63%) but high specificity (93-99%). Four characteristics suggesting PDAC were discrete pancreatic mass (DOR, 23), pancreatic duct cutoff (DOR, 16), upstream main pancreatic duct dilatation (DOR, 8), and upstream parenchymal atrophy (DOR, 7). Eleven CT characteristics were informational to distinguish AIP from PDAC. Diffuse pancreatic enlargement, delayed homogeneous enhancement, and capsule-like rim suggested AIP with the highest DORs, whereas discrete pancreatic mass suggested PDAC. However, pooled sensitivities of informational CT characteristics were moderate. This meta-analysis underscores eleven distinctive CT characteristics that aid in differentiating autoimmune pancreatitis from pancreatic adenocarcinoma, potentially preventing misdiagnoses in patients presenting with focal/diffuse pancreatic enlargement. • Diffuse pancreatic enlargement (pooled diagnostic odds ratio [DOR], 48), delayed homogeneous enhancement (46), and capsule-like rim (34) were CT characteristics suggesting autoimmune pancreatitis. • The CT characteristics suggesting autoimmune pancreatitis, except delayed homogeneous enhancement, had a general tendency to show relatively low sensitivity (12-63%) but high specificity (93-99%). • Discrete pancreatic mass (pooled diagnostic odds ratio, 23) was the CT characteristic suggesting pancreatic ductal adenocarcinoma with the highest pooled DORs.


The role of potassium channels in the endothelial dysfunction induced by periodontitis.
Periodontitis is associated with endothelial dysfunction, which is clinically characterized by a reduction in endothelium-dependent relaxation. However, we have previously shown that impairment in endothelium-dependent relaxation is transient. Therefore, we evaluated which mediators are involved in endothelium-dependent relaxation recovery. Rats were subjected to ligature-induced experimental periodontitis. Twenty-one days after the procedure, the animals were prepared for blood pressure recording, and the responses to acetylcholine or sodium nitroprusside were obtained before and 30 minutes after injection of a nitric oxide synthase inhibitor (L-NAME), cyclooxygenase inhibitor (Indomethacin, SC-550 and NS- 398), or calcium-dependent potassium channel blockers (apamin plus TRAM- 34). The maxilla and mandible were removed for bone loss analysis. Blood and gingivae were obtained for C-reactive protein (CRP) and myeloperoxidase (MPO) measurement, respectively. Experimental periodontitis induces bone loss and an increase in the gingival MPO and plasmatic CRP. Periodontitis also reduced endothelium-dependent vasodilation, a hallmark of endothelial dysfunction, 14 days after the procedure. However, the response was restored at day 21. We found that endothelium-dependent vasodilation at day 21 in ligature animals was mediated, at least in part, by the activation of endothelial calcium-activated potassium channels. Periodontitis induces impairment in endothelial-dependent relaxation; this impairment recovers, even in the presence of periodontitis. The recovery is mediated by the activation of endothelial calcium-activated potassium channels in ligature animals. Although important for maintenance of vascular homeostasis, this effect could mask the lack of NO, which has other beneficial properties.


Permeability Loss of Bituminous Coal Induced by Water and Salinity Sensitivities: Implications of Minerals' Occurrence and Pore Structure Complexity.
Water sensitivity (WS) and salinity sensitivity (SS) are key issues to be investigated for instructing coalbed methane (CBM) production. This work studied the influences of minerals and pores on WS and SS of medium-volatile bituminous coal (MVBC) and highly volatile bituminous coal (HVBC) deposited in northwestern China by detecting and observing minerals using the TESCAN Integrated Mineral Analyzer, simulating WS and SS, and characterizing pore structural complexities using rate-controlled mercury penetration. The results show that (1) kaolinite is mainly distributed as irregular particles or fragile aggregates attaching on the bedding surface or filling in meso-pores or transition pores, showing a high potential for detachment; (2) MVBC and HVBC in this study are characterized as medium to weak WS and weak SS, respectively; (3) for HVBC during the WS or SS process, kaolinite distributed in meso-pores or transition pores first detaches and then migrates to the narrow throat of macro-pores and super macro-pores, leading to volume decreases of macro-pores and super macro-pores and loss of permeability; and (4) kaolinite filling in macro-pores of MVBC detaches, then migrates, and finally deposits in super macro-pores after WS and SS, leading to losses of super macro-pore volume and permeability. Results of this study can enhance the scientific knowledge on WS and SS of coal during CBM development.


Folate-modified, indocyanine green-loaded lipid-polymer hybrid nanoparticles for targeted delivery of cisplatin.
Cisplatin is a potent antitumor drug, which is widely applied in clinical cancer treatment. However, cisplatin can hardly distinguish between healthy tissue and tumor tissue, resulting in serious toxic side effects. Indocyanine green (ICG) is a FDA-approved near-infrared (NIR) fluorescence dye which has been used in photothermal therapy and optically mediated diagnostic, but the application of ICG is limited by its concentration-dependent aggregation, poor aqueous stability in vitro, lack of target specificity and rapid elimination from the body. Herein, to overcome these limitations of cisplatin and ICG, we fabricated folate-modified, cisplatin, ICG-loaded lipid-polymer hybrid nanoparticles (FCINPs) using a single-step sonication method. The FCINPs exhibited well-defined monodispersity, significant stability and excellent NIR penetration ability. The intracellular uptake experiment showed that the targeting efficacy of the FCINPs was more effective in folate receptors (FRs) over-expressing MCF-7 cells than FRs negative A549 cells. In addition, compared with chemo or photothermal treatment alone, the treatment of FCINPs in combination with 808 nm NIR laser irradiation can significantly induce the apoptosis and necrosis of MCF-7 cells. These findings indicated that the FCINPs would be a promising nanosized drug formulation for tumor-targeted therapy in the future.


Synthesis and antihypertensive activity of some thienylethanolamines.
Synthesis of a series of thienylethanolamines having varying substituents on the thiophene ring and on the nitrogen atom is described using the general procedure reported earlier. In the determination of their pharmacological profile, some of the derivatives showed marked antihypertensive activity in the spontaneously hypertensive rat model. Tests are also reported which demonstrated that some of these derivatives antagonized alpha- and/or beta-adrenoreceptor activities. The ability of this class of compounds to inhibit catecholamine-induced release of free fatty acids by adipose tissue was demonstrated. Structure-activity relationships in different tests were also determined.


Mass forming chronic pancreatitis mimicking pancreatic cystic neoplasm: A case report.
Mass forming chronic pancreatitis is very rare. Diagnosis could be done by the pathologic findings of focal inflammatory fibrosis without evidence of tumor in pancreas. A 34-year-old man presented with right upper abdominal pain for a few weeks and slightly elevated bilirubin level on clinical findings. Radiological findings of multidetector-row computed tomography, magnetic resonance (MR) imaging with MR cholangiopancreatography and endoscopic ultrasonography revealed focal branch pancreatic duct dilatation with surrounding delayed enhancing solid component at uncinate process and head of pancreas, suggesting branch duct type intraductal papillary mucinous neoplasm. Surgery was done and pathology revealed the focal chronic inflammation, fibrosis, and branch duct dilatation. Herein, I would like to report the first case report of mass forming chronic pancreatitis mimicking pancreatic cystic neoplasm.


Effect of cancer/testis antigen NY-SAR-35 on the proliferation, migration and invasion of cancer cells.
NY-SAR-35 is a cancer/testis (CT) antigen that was identified by serological analysis of recombinant complementary DNA expression libraries. The gene encoding NY-SAR-35 is located on the × chromosome and is aberrantly expressed in a number of cancer types and germ cells, such as those in the testes, but not in normal tissue. It has been reported that treatment with a demethylating agent induced the expression of NY-SAR-35 in several types of cancer cells. However, the function of NY-SAR-35 in cancer remains undetermined. In present study, the role of NY-SAR-35 in human lung adenocarcinoma (SK-LC-14) and hepatocellular carcinoma (SNU-449) cells was investigated following stable transfection of the NY-SAR-35 gene. NY-SAR-35 was observed to be expressed in the cytoplasm of the cells. In addition, the bromodeoxyuridine incorporation assay and immunofluorescence staining for proliferating cell nuclear antigen and Ki-67 demonstrated that proliferation was increased in cells transfected with NY-SAR-35. In addition, the trypan blue exclusion assay indicated that NY-SAR-35 increased cancer cell viability. Furthermore, NY-SAR-35 increased the migration and invasion of the cells. These results indicate that NY-SAR-35 increases cancer cell viability, proliferation, migration and invasion.


Colicin E1 in planar lipid bilayers.
The channel formed by the C-terminal domain of colicin E1 in planar lipid bilayers has proven to be more complex than one might have guessed for such a simple system. The protein undergoes a pH-dependent rearrangement which transforms it from a water soluble form to a much different membrane bound form. There are at least two bound states which don't form a channel. The process by which the channel opens and closes is regulated by the pH and the transmembrane voltage. The voltage is probably sensed by at least 3 (and more likely 4 or more) lysine residues which must be driven through the field to open the channel. The process appears to be hindered by particular carboxyl groups when they are in the unprotonated state. The open channel has several substates and several superstates. Very large positive voltage catalyzes a transition of the open channel to an inactivated state, and may be able to drive the channel-forming region of the protein across the membrane. Little is known about the structure of any of these states, but the open channel is large enough to allow NAD to traverse the membrane and appears to be formed by one colicin molecule. This single polypeptide mimics many of the properties found in channels of mammalian cell membranes, but it may prove more relevant as a model for the transport of proteins across membranes. The comparative ease with which the protein can be manipulated chemically and genetically, along with the complexity of its behavior, promises to keep several laboratories busy for some time.


Genetic diversity, population structure, and relationships of apricot (Prunus) based on restriction site-associated DNA sequencing.
Single-nucleotide polymorphisms (SNPs) are the most abundant form of genomic polymorphisms and are widely used in population genetics research. Here, high-throughput sequencing was used to examine the genome-level diversity, population structure, and relationships of apricot, which are important for germplasm conservation and molecular breeding. Restriction site-associated DNA sequencing (RAD-seq) was adopted to sequence 168 Prunus spp. accessions distributed in five ecological groups, including 74 accessions of cultivated Prunus armeniaca L. and 94 accessions of wild apricots (P. armeniaca L. and Prunus sibirica L.), which generated 417,961 high-quality SNPs. We used cluster, genetic structure, and principal component analyses to examine the genetic diversities and genetic relationships of the 168 accessions. The Dzhungar-Ili ecological group accessions showed the highest genetic diversity in terms of private allele number, observed heterozygosity, and nucleotide diversity. We speculate that the Central Asian ecological group accessions were domesticated from the Dzhungar-Ili ecological group accessions. The population structure and gene flow of the North China and European ecological group accessions suggested a genetic background of P. sibirica. We argue that the two groups should be considered hybrid swarms connected to P. sibirica by continuous and extensive gene flow. P. armeniaca originated in Northwest China (Ili Valley), subsequently spread throughout Central Asia, and eventually spread to Europe. In addition, selective sweep signatures in P. armeniaca during domestication from wild to cultivated apricots, combined with differentially expressed genes, underlie distinct fruit traits, including sugars, aromas, organic acids, and carotenoids. This study provides substantive and valuable genomic resources that will significantly advance apricot improvement and effective utilization.


Effectiveness of Corticosteroid Monotherapy for Dyspnea Relief in Patients with Terminal Cancer.
Dyspnea is a common symptom in patients with cancer, particularly those with late-stage terminal disease. It markedly affects terminal cancer patients, reducing their quality of life. Reduced quality of life also affects survival; therefore, dyspnea is a prognostic factor. However, the role of corticosteroids, which often are used to alleviate dyspnea, has not been sufficiently validated. In this study, we retrospectively investigated whether corticosteroid monotherapy was effective for dyspnea palliation. The effectiveness rate of corticosteroid therapy was 45% in nine male and two female study subjects (mean age: 74.5 years; range: 64-86 years). No significant differences were found between responders and nonresponders in the first-day corticosteroid doses (25.5 ± 10.86 vs. 36.1 ± 16.39 mg, P = .29) or doses administered on 2 days (47.7 ± 25.99 vs. 72.2 ± 32.78 mg, P = .25). The mean ± standard error assessment score changed significantly from 2.7 ± 0.14 at the beginning of corticosteroid administration to 1.5 ± 0.37 at the time of maximum effect (P = .028); however, the decrease to 2.1 ± 0.25 at the final administration was not significant (P = .068). This indicates that corticosteroid therapy relieved dyspnea and could provide an early-stage treatment option.


The influence of sulfur and hair growth on stable isotope diet estimates for grizzly bears.
Stable isotope ratios of grizzly bear (Ursus arctos) guard hair collected from bears on the lower Stikine River, British Columbia (BC) were analyzed to: 1) test whether measuring δ34S values improved the precision of the salmon (Oncorhynchus spp.) diet fraction estimate relative to δ15N as is conventionally done, 2) investigate whether measuring δ34S values improves the separation of diet contributions of moose (Alces alces), marmot (Marmota caligata), and mountain goat (Oreamnos americanus) and, 3) examine the relationship between collection date and length of hair and stable isotope values. Variation in isotope signatures among hair samples from the same bear and year were not trivial. The addition of δ34S values to mixing models used to estimate diet fractions generated small improvement in the precision of salmon and terrestrial prey diet fractions. Although the δ34S value for salmon is precise and appears general among species and areas, sulfur ratios were strongly correlated with nitrogen ratios and therefore added little new information to the mixing model regarding the consumption of salmon. Mean δ34S values for the three terrestrial herbivores of interest were similar and imprecise, so these data also added little new information to the mixing model. The addition of sulfur data did confirm that at least some bears in this system ate marmots during summer and fall. We show that there are bears with short hair that assimilate >20% salmon in their diet and bears with longer hair that eat no salmon living within a few kilometers of one another in a coastal ecosystem. Grizzly bears are thought to re-grow hair between June and October however our analysis of sectioned hair suggested at least some hairs begin growing in July or August, not June and, that hair of wild bears may grow faster than observed in captive bears. Our hair samples may have been from the year of sampling or the previous year because samples were collected in summer when bears were growing new hair. The salmon diet fraction increased with later hair collection dates, as expected if samples were from the year of sampling because salmon began to arrive in mid-summer. Bears that ate salmon had shorter hair and δ15N and δ34S values declined with hair length, also suggesting some hair samples were grown the year of sampling. To be sure to capture an entire hair growth period, samples must be collected in late fall. Early spring samples are also likely to be from the previous year but the date when hair begins to grow appears to vary. Choosing the longest hair available should increase the chance the hair was grown during the previous year and, maximize the period for which diet is measured.


A comparison of anticryptosporidial activity of paromomycin with that of other aminoglycosides and azithromycin in immunosuppressed rats.
Of six evaluated aminoglycosides, paromomycin was the only one that showed activity against Cryptosporidium parvum in immunosuppressed rats. Oral dosages > or = 200 mg/kg/day reduced the severity of ileal infections; however, paromomycin was ineffective against cecal and biliary tract infections at 400 mg/kg/day orally and 50 mg/kg/day intraperitoneally. Oral paromomycin (400 mg/kg/day) was also less effective than azithromycin (400 mg/kg/day) against Cryptosporidium infection involving the ileum, cecum, or biliary tract of immunosuppressed rats. The data suggest that paromomycin may be an effective treatment for acute cryptosporidiosis of the small intestine but is probably ineffective against large intestine or biliary tract infections in the immunosuppressed host.


Hematospermia.
During a 15-year period, 200 patients with hematospermia were seen at the Mayo Clinic. General physical examination, including digital rectal palpation and urinalysis, was performed on all 200 patients. Of these, 26 had no additional urologic evaluation. In the remaining 174 patients, cystoscopy and K.U.B. roentgenography were done. The results of urologic evaluation in the 174 patients revealed various minor abnormalities in 64; however, in no instance was there significant urologic disease. During follow-up of five to 23 years in 150 of the 174 patients, 106 had no further hematospermia whereas 44 had recurring hematospermia, which persisted in some for more than ten years. None of these patients developed any significant disease related to the hematospermia. In our experience, the occurrence of hematospermia in an otherwise asymptomatic man with normal findings on physical examination, including digital rectal examination, seems not to be associated with the presence of, and does not lead to future development of, significant urologic disease.


The efficacy of preoperative versus postoperative rofecoxib for preventing acute postoperative dental pain: a prospective randomized crossover study using bilateral symmetrical oral surgery.
Previous data have demonstrated that rofecoxib has good analgesic efficacy for acute postoperative dental pain. However, up to half of these patients require rescue analgesics within the first 24 hours. As the timing of analgesic interventions may be an important factor in pain control, the present study tested the hypothesis that rofecoxib administered preoperatively would improve the analgesic efficacy and reduce rescue analgesic requirements within the first 24 hours compared with postoperative administration. This was a double-blind, randomized, crossover study where 45 patients had each of their identical impacted mandibular third molars removed under local anesthesia on 2 separate occasions. Patients acted as their own control; one side was pretreated with rofecoxib 50 mg, 2 hours before surgery, followed by placebo 15 minutes after surgery, and the contralateral side was pretreated with placebo 2 hours before surgery and posttreated with rofecoxib 50 mg 15 minutes after surgery. The difference in postoperative pain between 2 sides was assessed by 4 primary end-points: pain intensity as measured by a 100-mm visual analogue scale hourly for 12 hours, time to rescue analgesic, postoperative analgesic consumption, and patient's global assessment. Patients reported significantly lower pain scores (P = 0.04), longer time to rescue analgesic (P = 0.02), lesser postoperative analgesic consumption (P = 0.008), and better global assessment (P = 0.01) in the pretreated compared with the posttreated sides. There were significantly more patients in the pretreated group who did not required rescue analgesic within the first 24 hours (80% vs. 58%, P = 0.01), and the pain scores were extremely low in both groups during the 12 hours postoperative period (9.8 +/- 5.0 mm vs. 14.3 +/- 7.4 mm). Rofecoxib is an excellent analgesic for preventing postoperative dental pain and when given 2 hours preoperatively rendered most patients relatively pain free, requiring no rescue analgesics on the first postoperative day.


Intercorrelated In-Plane and Out-of-Plane Ferroelectricity in Ultrathin Two-Dimensional Layered Semiconductor In2Se3.
Enriching the functionality of ferroelectric materials with visible-light sensitivity and multiaxial switching capability would open up new opportunities for their applications in advanced information storage with diverse signal manipulation functions. We report experimental observations of robust intralayer ferroelectricity in two-dimensional (2D) van der Waals layered α-In2Se3 ultrathin flakes at room temperature. Distinct from other 2D and conventional ferroelectrics, In2Se3 exhibits intrinsically intercorrelated out-of-plane and in-plane polarization, where the reversal of the out-of-plane polarization by a vertical electric field also induces the rotation of the in-plane polarization. On the basis of the in-plane switchable diode effect and the narrow bandgap (∼1.3 eV) of ferroelectric In2Se3, a prototypical nonvolatile memory device, which can be manipulated both by electric field and visible light illumination, is demonstrated for advancing data storage technologies.


Analysis of the horizontal corneal diameter, central corneal thickness, and axial length in premature infants.
To determine the horizontal corneal diameter, central corneal thickness, and axial length in premature infants. Infants with a birth weight of less than 2,500 g or with a gestation period of less than 36 weeks were included in the study. Infants with retinopathy of prematurity (ROP) were allocated to Group 1 (n=138), while those without ROP were allocated to Group 2 (n=236). All infants underwent a complete ophthalmologic examination, including corneal diameter measurements, pachymetry, biometry, and fundoscopy. Between-group comparisons of horizontal corneal diameter, central corneal thickness, and axial lengths were performed. Independent sample t-tests were used for statistical analysis. Data was obtained from 374 eyes of 187 infants (102 female, 85 male). The mean gestational age at birth was 30.7 ± 2.7 weeks (range 25-36 weeks), the mean birth weight was 1,514 ± 533.3 g (range 750-1,970 g), and the mean postmenstrual age at examination was 40.0 ± 4.8 weeks. The mean gestational age and the mean birth weight of Group 1 were statistically lower than Group 2 (p<0.05). There were no significant differences in horizontal corneal diameter, central corneal thickness, and axial length between the two groups (p>0.05). The presence of ROP in premature infants does not alter the horizontal corneal diameter, central corneal thickness, or axial length.


Characterization of polycyclic aromatic compounds in historically contaminated soil by targeted and non-targeted chemical analysis combined with in vitro bioassay.
Soil samples from a contaminated site in Sweden were analyzed to identify the presence of 78 polycyclic aromatic compounds (PACs) using gas chromatography coupled with mass spectrometry (GC-MS). The target analysis revealed large contributions not only from polycyclic aromatic hydrocarbons (PAHs), but also from alkylated- and oxygenated-PAHs (alkyl- and oxy-PAHs, respectively), and N-heterocyclics (NPACs). PAC profiles indicated primarily pyrogenic sources, although contribution of petrogenic sources was also observed in one sample as indicated by a high ratio of alkylated naphthalene compared to naphthalene. The aryl hydrocarbon receptor (AhR)-activity of the soil extracts was assessed using the H4IIe-pGudluc 1.1 cells bioassay. When compared with the calculated total AhR-activity of the PACs in the target list, 35-97% of the observed bioassay activity could be explained by 62 PACs with relative potency factors (REPs). The samples were further screened using GC coupled with Orbitrap™ high resolution MS (GC-HRMS) to investigate the presence of other PACs that could potentially contribute to the AhR-activity of the extracts. 114 unique candidate compounds were tentatively identified and divided into four groups based on their AhR-activity and environmental occurrence. Twelve substances satisfied all the criteria, and these compounds are suggested to be included in regular screening in future studies, although their identities were not confirmed by standards in this study. High unexplained bio-TEQ fractions in three of the samples may be explained by tentatively identified compounds (n = 35) with high potential of being toxic. This study demonstrates the benefit of combining targeted and non-targeted chemical analysis with bioassay analysis to assess the diversity and effects of PACs at contaminated sites. The applied prioritization strategy revealed a number of tentatively identified compounds, which likely contributed to the overall bioactivity of the soil extracts.


[Indications for special rehabilitation programs for cerebrovascular strokes].
The rehabilitation of patients with stroke was a long time a neglected problem. Meanwhile there are several hospitals with comprehensive rehabilitation services with physical, occupational, speech, psychological and social assessments. The effectiveness were investigated in 296 stroke patients. 195 patients from two internal hospitals were compared with 101 patients from a hospital rehabilitation unit. Both groups were very similar according of age, sex, nature of stroke and the most of other factors. The effect were evaluated on the basic of ADL-classes (activities of daily living) at the time of discharge. The success of the special rehabilitation was better in patients with aphasia, flaccid and strong spastic hemiparesis, complicated diseases, lower motivation and mild or moderate psychoorganic syndromes. Absent of ability to cooperate limited the rehabilitation outcomes. In mild and severe followings of stroke were found same results in both groups. High age of life alone are not decreased the prognosis.


Investigating the Sources of Urban Air Pollution Using Low-Cost Air Quality Sensors at an Urban Atlanta Site.
Advances in low-cost sensors (LCS) for monitoring air quality have opened new opportunities to characterize air quality in finer spatial and temporal resolutions. In this study, we deployed LCS that measure both gas (CO, NO, NO2, and O3) and particle concentrations and co-located research-grade instruments in Atlanta, GA, to investigate the capability of LCS in resolving air pollutant sources using non-negative matrix factorization (NMF) in a moderately polluted urban area. We provide a comparison of applying the NMF technique to both normalized and non-normalized data sets. We identify four factors with different temporal trends and properties for both normalized and non-normalized data sets. Both normalized and non-normalized LCS data sets can resolve primary organic aerosol (POA) factors identified from research-grade instruments. However, applying normalization provides factors with more diverse compositions and can resolve secondary organic aerosol (SOA). Results from this study demonstrate that LCS not only can be used to provide basic mass concentration information but also can be used for in-depth source apportionment studies even in an urban setting with complex pollution mixtures and relatively low aerosol loadings.


[A Cloward-type bone-harvesting technic in the management of pseudarthrosis of the navicular bone].
Authors present an apparatus resembling the Cloward instrument, that can be however used more simply and safely for gaining a good quality cortico-spongious cylinder from the iliac wing. The functioning of the bone gaining instrument and the process of bone gaining is described. The apparatus was used in more than 100 cases for filling up with spongious bone chips the cavity arising after the cleaning of the pseudarthrosis of the navicular bone. Three different cases are presented to demonstrate the alternative applications of the apparatus. It is supported by literary data that the autologous bone gained from the iliac wing is the most suitable for transplantation.


Mefloquine and new related compounds target the F(0) complex of the F(0)F(1) H(+)-ATPase of Streptococcus pneumoniae.
The activities of mefloquine (MFL) and related compounds against previously characterized Streptococcus pneumoniae strains carrying defined amino acid substitutions in the c subunit of the F(0)F(1) H(+)-ATPase were studied. In addition, a series of MFL-resistant (Mfl(r)) strains were isolated and characterized. A good correlation was observed between inhibition of growth and inhibition of the membrane-associated F(0)F(1) H(+)-ATPase activity. MFL was about 10-fold more active than optochin and about 200-fold more active than quinine in inhibiting both the growth and the ATPase activities of laboratory pneumococcal strain R6. Mutant strains were inhibited by the different compounds to different degrees, depending on their specific mutations in the c subunit. The resistant strains studied had point mutations that changed amino acid residues in either the c subunit or the a subunit of the F(0) complex. Changes in the c subunit were located in one of the two transmembrane alpha helices: residues M13, G14, G20, M23, and N24 of helix 1 and residues M44, G47, V48, A49, and V57 of helix 2. Changes in the a subunit were also found in either of the transmembrane alpha helices, helix 5 or 6: residue L186 of helix 5 and residues W206, F209, and S214 of helix 6. These results suggest that the transmembrane helices of the c and a subunits interact and that the mutated residues are important for the structure of the F(0) complex and proton translocation.


Immediate-type latex hypersensitivity in a hairdresser.
Hairdressers commonly develop contact dermatitis caused by either skin irritants or allergens to which they are exposed. Those using latex gloves are also at risk of developing immediate hypersensitivity reactions to latex. We present a hairdresser with hand dermatitis, primarily as a result of immediate-type hypersensitivity to latex causing contact urticaria, diagnosed with radioallergosorbent testing. Only three previous studies have reported latex allergy in hairdressers. This condition needs to be considered as a differential diagnosis in hairdressers presenting with hand dermatitis and a history of wearing either rubber or disposable latex gloves.


Identification of optimal reference genes in Bombyx mori (Lepidoptera) for normalization of stress-responsive genes after challenge with pesticides.
Pesticides are frequently used to control pests in agriculture due to their ease of use and effectiveness, but their use causes serious economic losses to sericulture when their production overlaps with agriculture. However, no suitable internal reference genes (RGs) have been reported in the study of silkworms in response to pesticides. In this study, a standard curve was established to detect the expression levels of seven RGs in different tissues of different silkworm strains after feeding with pesticides using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), including BmGAPDH, BmActin3, BmTBP, BmRPL3, Bm28sRNA, Bmα-tubulin, and BmUBC, and the stability of them was evaluated by using NormFinder, geNorm, Delta CT, BestKeeper, and RefFinder. The results showed that BmGAPDH and Bmα-tubulin were relatively stable in the midgut after feeding with fenvalerate, BmGAPDH and Bmactin3 were relatively stable in the fat body, and Bmα-tubulin and Bmactin3 were relatively stable in the hemolymph, indicating that Bmactin3 was the most suitable RG when evaluating fenvalerate, followed by BmGAPDH and Bmα-tubulin. Besides, BmGAPDH and Bmactin3 were relatively stable in the midgut after treatment with DDVP, BmGAPDH and Bmα-tubulin were relatively stable in the fat body, and BmGAPDH and Bmα-tubulin were relatively stable in the hemolymph, indicating that Bmα-tubulin was the most stable RG when evaluating DDVP, followed by BmGAPDH and Bmactin3. Of note, BmGAPDH was shared by the two pesticides. The results will be valuable for RG selection in studying the pesticide response mechanism of silkworms and other lepidopteran insects.


Thymoquinone‑induced autophagy mitigates doxorubicin‑induced H9c2 cell apoptosis.
Doxorubicin (Dox)-induced myocardiopathy is a massive obstacle in administering chemotherapeutic drugs in cancer patients. In the present study, the effects of thymoquinone (TQ) on Dox-induced cardiotoxicity were investigated in vitro. H9c2 cardiomyocytes were pre-treated with TQ followed by Dox, and cell viability and cell death were subsequently measured. Flow cytometry was conducted to evaluate the apoptosis of H9c2 cells. Autophagy was assessed by immunofluorescence LC3 staining. Western blot analysis was performed to determine autophagy-, apoptosis- and LKB1/AMPK-related proteins. Dox-induced H9c2 cell death and apoptosis were decreased after pretreatment with TQ in vitro. The number of autophagosomes and autophagic markers was further increased by TQ in the Dox-treated H9c2 cells, which mediated LKB1/AMPK activation and the deactivation of mTOR. Suppression of autophagosomes abolished the TQ-induced antiapoptotic effect. In conclusion, TQ reduces Dox-induced apoptosis of cardiomyocytes by upregulating autophagy through activation of the LKB1/AMPK pathways. These novel results highlight the therapeutic potential of TQ to prevent Dox cardiotoxicity.


Effects of high but nontoxic dietary manganese and iron on their metabolism by calves.
Sixteen male Holstein calves were fed one of four diets for 18 days in an experiment consisting of 0 and 1000 ppm supplemental manganese and 0 and 1000 ppm added iron as manganese carbonate and ferrous carbonate. The control diet contained 55 ppm manganese and 220 ppm iron. All calves were dosed orally 48 h prior to sacrifice with 500 muCi of manganese-54. Small intestinal iron was less in calves fed a high manganese diet, a possible interaction of these two elements at the absorption site. Feeding a high manganese diet tended to decrease iron (total) concentrations in liver and pancreas. When the high manganese diet was supplemented with additional iron, antagonistic effects of manganese on iron were eliminated. Neither iron nor manganese concentrations in tissues were affected by an increase of dietary iron. Manganese-54 content of tissue was reduced by the high manganese diet but was not affected by dietary iron. Total manganese and iron in feces fairly closely reflected dietary intake of each element with no evidence of interaction. Calves fed the high iron diet excreted less manganese-54 in their feces over 2 days. Total iron in blood serum was not affected significantly by the dietary treatments.


Towards optimization of time modulated chemical vapour deposition for nanostructured diamond films on Ti6Al4V.
In this paper, we report the use of the TMCVD technique for the optimisation of deposited diamond films onto Ti6Al4V substrates. A number of samples were made varying the experimental parameters. The specimen surfaces were characterised using micro Raman spectra and SEM analyses. Results show that very different surface finish (from micro to nanostructures) and film characteristics can be obtained from the experimental parameters used. The quality of deposited diamond is very dependant on the experimental settings and process. It was found that lower residual stresses are developed using the TMCVD technique than with conventional CVD but depend on the structural diamond growth during the process. The quality of the deposited film was evaluated as a function of diamond to amorphous carbon ratio but showed no direct relation with the surface finish since it characterises the quality of the deposited diamond but not the quality of the film surface.


Leukocyte chemotaxis.
Monocyte chemotaxis is a function of mononuclear phagocytic system cells that enables migration toward the focus of infection and inhibition of microorganism growth and proliferation. In this paper we review the chemotactic phenomena following Becker's scheme that distinguishes three phases: recognition, transduction and the effector phase. The recognition phase is comprised of the interaction of a chemotactic agent with a receptor located on the cell surface. We cite the multiple chemoattractant presently known, and the mechanisms that regulate this phase, "up-regulation" and "down-regulation" phenomena, and the presence of receptors in low and high-affinity states. The transduction phase comprises all biochemical events produced after internalization of the attractant-receptor complex, whose purpose is triggering the cell motor apparatus. The key event in beginning movement is the increase of cytosol calcium. Alterations in membrane phosphoinositols constitute the initial transductor mechanism in chemotaxis, inositol-triphosphate and diacylglycerol behaving as second messengers. We review the diverse functions of these phospholipids, as well as we do a graphic representation of these (fig 1). Motor phase comprises the movement of the cell toward the chemotactic gradient through activation of the motor cell apparatus. We describe the intervening elements, actin and its regulatory proteins acumentin and gelsolin, actin-fixing protein, myosin and microtubuli, and the four phases of locomotion mechanism: reversible adherence, pseudopode emission, cell polarity and movement that results from an alternance between gel and sol states.


Coping patterns in special school staff: demographic and organizational factors.
Teachers' mental health is commonly discussed in organizational health studies, but studies in special schools are rare. Work-related coping and experience patterns (WCEPs) have been shown to be associated with mental health and intentions to leave. The influence of organizational factors on coping patterns has not been examined. To assess the distribution of WCEPs in special school staff and to identify potential influencing factors. We surveyed a sample of teachers and educational staff in 13 German special schools using the WCEP questionnaire and COPSOQ (Copenhagen Psychosocial Questionnaire). Of 245 teachers and 417 educational staff contacted, 114 teachers (47%) and 252 educational staff (60%) responded, an overall response rate of 55% (366/662). Coping patterns of special school staff were classified as unambitious (30%), excessively ambitious (7%), resigned (17%), healthy-ambitious (12%) or unclassifiable (34%). Furthermore we found several significant relations with demographic and organizational factors. For example, the resigned pattern is associated with age [Exp(B) 1.12; 95% CI 1.05-1.19], emotional demands [Exp(B) 1.07; 95% CI 1.01-1.12], work-family conflict [Exp(B) 1.07; 95% CI 1.03-1.10] and bullying [Exp(B) 1.04; 95% CI 1.00-1.08]. Since emotional and social factors are associated with risky (excessively ambitious or resigned) and unambitious coping patterns in special school teachers and educational staff, interventions should focus on them. Further research could explore causal relations and observe the development of coping styles over time.


Magnetic properties of very-high-spin organic pi-conjugated polymers based on Green's function theory.
Magnetic properties of two very-high-spin organic pi-conjugated polymers have been investigated theoretically by means of the many-body Green's function method with random phase approximation. The polymers are designed with a large density of cross-links and alternating connectivity of radical modules with unequal spin quantum numbers (S), macrocyclic S=2 or 3, and cross-linking S=1/2 modules, which permit large net S values for either antiferromagnetic or ferromagnetic exchange coupling between the modules. The numerical results reveal that, ascribing to the zero-temperature spin fluctuations, the sublattice magnetizations of the two polymers are both smaller than their classical spin values and the ground-state magnetizations of them are also smaller than their predicted values in the antiferromagnetic exchange coupling case. However, these magnetic behaviors do not occur in the ferromagnetic exchange coupling case. On the basis of our synthesis of the temperature dependence of the magnetic susceptibility multiplied by temperature, and through comparing the theoretical results with the experimental measurements, it is concluded that the magnetic exchange couplings between the modules within the two high-spin polymers should be ferromagnetic exchange couplings, which are consistent with other theoretical results drawn from the investigations into the ground-state properties of the two organic polymers.


Digital subtraction angiography with an Isocon camera system: clinical applications.
A new imaging system for digital subtraction angiography (DSA) was evaluated in 30 clinical studies. The image receptor is a 25 X 25 cm, 12 par gadolinium oxysulfate rare-earth screen whose light output is focused to a low-light-level Isocon camera. The video signal is digitized and processed by an image-array processor containing 31 512 X 512 memories 8 bits deep. In most patients, intraarterial DSA studies were done in conjunction with conventional arteriography. In these arterial studies, images adequate to make a specific diagnosis were obtained using half the radiation dose and half the amount of contrast material needed for conventional angiography. In eight intravenous studies performed either to identify renal artery stenosis or for evaluation of congenital heart anomalies, the images were diagnostic but objectionably noisy.


A national study of eHealth standardization in Finland--goals and recommendations.
The role of standards is constantly increasing in health services, electronic health records, and eHealth applications. There are many areas of standardization which affect the healthcare work and health information systems. On a national level, the organization of the development and support for standardization should be a key priority. This paper summarizes a national study in Finland which reviewed the current status of eHealth standardization and made recommendations for the national standardization and the use of standards. The recommendations are related to the organization model and balanced participation, international and cross-domain collaboration and quality assurance of standards-related activities. In addition, education and support services and support for introductions and pilots are recommended to improve the know-how of standards in system acquisitions.


Replication and serial passage of a singly enveloped baculovirus of Orgyia leucostigma in homologous cell lines.
A singly enveloped nuclear polyhedrosis virus (SNPV) of the white-marked tussock moth, Orgyia leucostigma, was successfully grown in four continuous cell lines developed from minced neonate larvae of this insect. Level of infection in two cell lines, IPRI-OL-12 and IPRI-OL-13, was 65-90%, but in the other two, IPRI-OL-4 and IPRI-OL-9, it was about 3%. Polyhedral inclusion bodies (PIBs) appeared in the nuclei of cells within 24 h postinoculation. Cytopathological changes and morphogenesis of the virus, as revealed by light and electron microscopy, were in general typical of an SNPV. However, some of the PIBs contained very few virions, and some were fractured. Rate zonal centrifugation of alkali-released occluded virions further confirmed the singly enveloped characteristics of the virus. The SNPV was serially passaged 60 times each in OL-12 and OL-13 cells. Percentage infected cells and PIB production stayed generally high throughout serial passaging in OL-13 cells, but declined sharply after the 41st passage in OL-12 cells. PIBs from the 4th passage of the virus in OL-12 cells were tested and found to be pathogenic to O. leucostigma larvae.


[Addictive behavior in the elderly].
Alcohol and drug abuse are the two main addictions in the elderly subject. Prevalence of alcohol dependency is 14% in those over 65 years of age and 17% in elderly psychiatric patients. The distribution of alcoholism between the sexes becomes equal with age. After 65 years of age, the sex-ratio is 1 female to 1.3 male subjects. The elderly alcoholic population consists of both subjects having become alcoholics at a young age and those in whom alcoholic behaviour appeared at a late age. In one third of elderly alcoholics such dependency appeared after 60 years of age. The main risk factors for alcoholism in the elderly subject are lonliness, death of the spouse and the presence of an invalid or bedridden spouse. In the elderly, tolerance to and dependence on alcohol are rare and appear late. Somatic complications are particularly severe (cirrhosis, liver cancer, gastritis, acute pancreatitis and myocardial involvement). Psychiatric complications include anxiety, depression and especially suicide. Alcoholism is the third most frequent cause of organic cerebral dementia, following Alzheimer disease and vascular dementia. Drug dependency is very often linked to alcoholism and consists of tranquillizers and less often of antalgics.


[Etiology of community-acquired pneumonia in immunocompetent adults].
In an ideal clinical setting, empiric antimicrobial treatment prescribed in adult community acquired pneumonia (CAP) should be based on national etiological surveillance and in vitro susceptibility assays. Available information about etiology in ambulatory patients and intensive care unit (ICU) patients is scarce, compared to information obtained in hospitalized patients. In studies designed to explore the etiology of pneumonia, no microorganism is detected in 40-50% of patients, a fact that represents limited yields in diagnostic methods. In all settings, Streptococcus pneumoniae is the main respiratory pathogen recovered in adults CAP, being responsible of about 16% of cases among ambulatory patients and about 22% of those admitted to hospital and ICU. About one third of cases are caused by a small group of microorganisms: Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae, respiratory viruses, Staphylococcus aureus, gramnegative bacillus, Legionella sp; each one is isolated in less than 10% of cases. In general, microorganism distribution varies scarcely in the following attending settings: ambulatory patients, common wards and ICU. An exception is represented by a higher frequency of gram negative bacillus, S. aureus and Legionella sp in ICU, and of C. pneumoniae in the ambulatory setting. In Chile, CAP etiology in hospitalized adult patients is similar to foreign reports; no systematic information has been collected about the etiology in neither ambulatory patients nor in severe CAP.


Myelin-associated mRNA and protein expression deficits in the anterior cingulate cortex and hippocampus in elderly schizophrenia patients.
Microarray and other studies have reported oligodendrocyte and myelin-related (OMR) deficits in schizophrenia. Here, we employed a quantitative approach to determine the magnitude of OMR gene expression deficits and their brain-region specificity. In addition, we examined how expression levels among the studied OMR genes are interrelated. mRNA of MAG, CNP, SOX10, CLDN11, and PMP22, but not MBP and MOBP, was reduced in the hippocampus and anterior cingulate cortex but not in the putamen of patients with schizophrenia. Expression of the only protein examined (CNP) was decreased in the hippocampus but not in the putamen. Correlation and factor analyses revealed that mRNA levels for genes that did exhibit differential expression in schizophrenia (MAG, CNP, SOX10, CLDN11, and PMP2), as opposed to those that did not (MOBP and MBP), loaded on separate factors. Thus, OMR gene and protein expression deficits in schizophrenia are brain-region specific, and the affected components may share regulatory elements.


The yolk syncytial layer regulates myocardial migration by influencing extracellular matrix assembly in zebrafish.
The roles of extra-embryonic tissues in early vertebrate body patterning have been extensively studied, yet we know little about their function during later developmental events. Here, we analyze the function of the zebrafish extra-embryonic yolk syncytial layer (YSL) specific transcription factor, Mtx1, and find that it plays an essential role in myocardial migration. Downregulating the function of Mtx1 in the YSL leads to cardia bifida, a phenotype in which the myocardial cells fail to migrate to the midline. Mtx1 in the extra-embryonic YSL appears to regulate the embryonic expression of fibronectin, a gene previously implicated in myocardial migration. We further show dosage-sensitive genetic interactions between mtx1 and fibronectin. Based on these data, we propose that the extra-embryonic YSL regulates myocardial migration, at least in part by influencing fibronectin expression and subsequent assembly of the extracellular matrix in embryonic tissues.


ADAPTIVE REAL-TIME CARDIAC MRI USING PARADISE: VALIDATION BY THE PHYSIOLOGICALLY IMPROVED NCAT PHANTOM.
Patient-Adaptive Reconstruction and Acquisition Dynamic Imaging with Sensitivity Encoding (PARADISE) is a dynamic MR imaging scheme that optimally combines parallel imaging and model-based adaptive acquisition. In this work, we propose the application of PARADISE to real-time cardiac MRI. We introduce a physiologically improved version of a realistic four-dimensional cardiac-torso (NCAT) phantom, which incorporates natural beat-to-beat heart rate and motion variations. Cardiac cine imaging using PARADISE is simulated and its performance is analyzed by virtue of the improved phantom. Results verify the effectiveness of PARADISE for high resolution un-gated real-time cardiac MRI and its superiority over conventional acquisition methods.


Vestibular deepening by periosteal fenestration and its use as a periosteal pedicle flap for root coverage.
Gingival recession along with reduced width of attached gingiva and inadequate vestibular depth is a very common finding. Multiple techniques have been developed to obtain predictable root coverage and to increase the width of attached gingiva. Usually, the width of gingiva is first increased and then the second surgery is caried out for root coverage. The newer methods of root coverage are needed, not only to reconstruct the lost periodontal tissues but also to increase predictability, reduce the number of surgical sites, reduce the number of surgeries and improve patient comfort. Hence, this paper describes a single stage technique for increasing the width of attached gingiva and root coverage by using the periosteal pedicle flap.


ER stress in temozolomide-treated glioblastomas interferes with DNA repair and induces apoptosis.
Glioblastoma multiforme (GBM) is a deadly grade IV brain tumor. Radiation in combination with temozolomide (TMZ), the current chemotherapeutic for GBMs, only provides 12-14 months survival post diagnosis. Because GBMs are dependent on both activation of the DNA damage pathway and the endoplasmic reticulum (ER) stress response, we asked if a novel ER stress inducing agent, JLK1486, increases the efficacy of TMZ.We found that the combination of TMZ+JLK1486 resulted in decreased proliferation in a panel of adherent GBM cells lines and reduced secondary sphere formation in non-adherent and primary lines. Decreased proliferation correlated with increased cell death due to apoptosis. We found prolonged ER stress in TMZ+JLK1486 treated cells that resulted in sustained activation of the unfolded protein response (UPR) through increased levels of BiP, ATF4, and CHOP. In addition, TMZ+JLK1486 treatment caused decreased RAD51 levels, impairing DNA damage repair. Furthermore, we found delayed time to tumor doubling in TMZ+JLK1486 treated mice.Our data shows that the addition of JLK1486 to TMZ increases the efficaciousness of the treatment by decreasing proliferation and inducing cell death. We propose increased cell death is due to two factors. One, prolonged ER stress driving the expression of the pro-apoptotic transcription factor CHOP, and, second, unresolved DNA double strand breaks, due to decreased RAD51 levels. The combination of TMZ+JLK1486 is a potential novel therapeutic combination and suggests an inverse relationship between unresolved ER stress and the DNA damage response pathway.


Design of a highly sensitive and specific nucleotide sensor based on photon upconverting particles.
We have designed and developed a novel sensor that reports the presence of specific nucleic acids in solutions, based on photon upconverting particles. The significantly high signal-to-noise ratio of photon upconverting particles leads to high sensitivity of the sensor. The sensor does not suffer from photobleaching. It also displays high specificity and self-calibrating capability. We expect nucleotide sensors of this type to be effective for applications in both DNA/RNA detection and protein-DNA/RNA interaction studies.