Rac1 and Rac2 control distinct events during antigen-stimulated mast cell exocytosis.
The release of preformed mediators from immune cells is through a process described as exocytosis. In mast cells, exocytosis is regulated by several coordinated intracellular signaling pathways. Here, we investigated the role of the hematopoietic-specific Rho GTPase, Rac2, and the ubiquitously expressed Rac1, in controlling mast cell exocytosis. These two isoforms showed equivalent levels of expression in mouse BMMCs. Although Rac1 and Rac2 share 92% sequence identity, they were not functionally redundant, as Rac2-/- BMMCs were defective in exocytosis, even though Rac1 levels were unaffected. Antigen-stimulated WT mast cells underwent a series of morphological transitions: initial flattening, followed by actin-mediated peripheral membrane ruffling and calcium influx, which preceded exocytosis. Whereas membrane ruffling was unaffected in Rac2-/- BMMCs, calcium influx was decreased significantly. Calcium influx was studied further by examining SOCE. In Rac2-/- BMMCs, the activation of PLCγ1 and calcium release from intracellular stores occurred normally; however, activation of plasma membrane calcium channels was defective, shown by the lack of extracellular calcium influx and a reduction of YFP-STIM1 puncta at the plasma membrane. Additionally, we used the small molecule Rac inhibitor, EHT 1864, to target Rac signaling acutely in WT BMMCs. EHT 1864 blocked exocytosis and membrane ruffling completely in conjunction with exocytosis. Our findings suggest that antigen-stimulated membrane ruffling in mast cells is a Rac1-mediated process, as this persisted in the absence of Rac2. Therefore, we define distinct modes of Rac-regulated mast cell exocytosis: Rac2-mediated calcium influx and Rac1-mediated membrane ruffling.


Factors influencing rates and products in the transformation of trichloroethylene by iron sulfide and iron metal.
Batch experiments were performed to assess (i) the influence of pH, solution amendments, and mineral aging on the rates and products of trichloroethylene (TCE) transformation by iron sulfide (FeS) and (ii) the influence of pretreatment of iron metal with NaHS on TCE transformation rates. The relative rates of FeS-mediated transformation of TCE to different products were quantified by branching ratios. Both pseudo-first-order rate constants and branching ratios for TCE transformation by FeS were significantly influenced by pH, possibly due to a decrease in the reduction potential of reactive surface species with increasing pH. Neither Mn2+, expected to adsorb to FeS surface S atoms, nor 2,2'-bipyridine, expected to adsorb to surface Fe atoms, significantly influenced rate constants or branching ratios. FeS that had been aged at 76 degrees C for 3 days was completely unreactive with respect to TCE over 6.5 months, yet this aged FeS transformed hexachloroethane to tetrachloroethylene with a rate constant only slightly lower than that for nonaged FeS. This finding suggests that the oxidation state of iron sulfide minerals in the environment will strongly influence the potential for intrinsic remediation of pollutants such as TCE. Treatment of iron metal with bisulfide significantly increased the pseudo-first-order rate constant for TCE transformation at pH 8.3. This effect was attributed to formation of a reactive FeS coating or precipitate on the iron surface.


Role of aldehydes in fructose induced hypertension.
Aldehydes are formed in tissues of humans and animals as intermediates of glucose and fructose metabolism and due to lipid peroxidation. N-acetyl cysteine (NAC), an analogue of the dietary amino acid cysteine, binds aldehydes thus preventing their damaging effect on physiological proteins. We measured systolic blood pressure (SBP), platelet cytosolic free calcium [Ca2+]i and tissue aldehyde conjugates in fructose induced hypertensive Wistar-Kyoto (WKY) rats and examined the effect of NAC in the diet on these parameters. Animals age 7 weeks were divided into three groups of 6 animals each and were treated as follows: WKY-control (chow diet and normal drinking water); WKY-Fructose (chow diet and 4% fructose in drinking water); WKY-Fructose+NAC (1.5% NAC in chow diet and 4% fructose in drinking water). After 11 weeks, systolic blood pressure, platelet [Ca2+]i and kidney aldehyde conjugates were all significantly higher in fructose treated rats. NAC treatment prevented these changes. These results suggest that aldehydes may be the cause of fructose induced hypertension and elevated cytosolic free calcium.


Highly sensitive two-dimensional MoS2 gas sensor decorated with Pt nanoparticles.
A two-dimensional molybdenum disulfide (MoS2)-based gas sensor was decorated with Pt nanoparticles (NPs) for high sensitivity and low limit of detection (LOD) for specific gases (NH3 and H2S). The two-dimensional MoS2 film was grown at 400°C using metal organic gas vapour deposition. To fabricate the MoS2 gas sensor, an interdigitated Au/Ti electrode was deposited using the electron beam (e-beam) evaporation method with a stencil mask. The MoS2 gas sensor without metal decoration sensitively detects NH3 and H2S gas down to 2.5 and 30 ppm, respectively, at room temperature (RT). However, for improved detection of NH3 and H2S gas, we investigated the functionalization strategy using metal decoration. Pt NP decoration modulated the electronic properties of MoS2, significantly improving the sensitivity of NH3 and H2S gas by 5.58× and 4.25×, respectively, compared with the undecorated MoS2 gas sensor under concentrations of 70 ppm. Furthermore, the Pt NP-decorated MoS2 sensor had lower LODs for NH3 and H2S gas of 130 ppb and 5 ppm, respectively, at RT.


[Women pioneers: first female cardiothoracic surgeons in the USA and in Israel].
At the beginning of the 1960's, three female doctors managed to break the glass ceiling and become the first female cardiothoracic surgeons in the USA. Since then, the number of certified female cardiothoracic surgeons has steadily increased. Nevertheless, females stilt only account for a minority of cardiothoracic surgeons in the USA. In Israel, three women have become specialists in cardiothoracic surgery over the last two decades, aLthough these surgeons are working as general thoracic surgery consultants, without any representative females in cardiac surgery.


Predictive factor of androgen deprivation therapy for patients with advanced stage prostate cancer.
The purpose of this study was to identify the predictive factors for the efficacy of androgen deprivation therapy (ADT) in men with hormone-sensitive prostate cancer (PC) with or without distant metastasis. A retrospective review of PC patients was conducted of the medical records. We enrolled 246 patients who received primary ADT. PC patients treated with ADT for presumed nonlocalized PC were evaluated on the efficacy of ADT using prostate-specific antigen (PSA) time to progression (TTP) and compared factors associated with TTP in patients with distant metastasis and patients without distant metastasis. A total of 246 patients were treated primarily with ADT. The median follow-up period was 20.2 months. One hundred and ninety-one patients had metastatic disease. The median TTP on ADT for the distant metastasis group was 14.8 months versus 60.1 months in the without distant metastasis group (P < 0.0001). In the univariate analysis only, PSA nadir after ADT was associated with longer TTP (hazard ratio, 10.69; 95% confidence interval, 5.56-20.57). In the multivariate analysis, high grade tumor and PSA nadir were independent factors associated with a shorter TTP. In this study of hormone-sensitive PC patients treated with ADT for nonlocalized PC, high grade tumor and PSA nadir were predicting factors of this treatment.


Temporal prediction errors modulate cingulate-insular coupling.
Prediction error (i.e., the difference between the expected and the actual event's outcome) mediates adaptive behavior. Activity in the anterior mid-cingulate cortex (aMCC) and in the anterior insula (aINS) is associated with the commission of prediction errors under uncertainty. We propose a dynamic causal model of effective connectivity (i.e., neuronal coupling) between the aMCC, the aINS, and the striatum in which the task context drives activity in the aINS and the temporal prediction errors modulate extrinsic cingulate-insular connections. With functional magnetic resonance imaging, we scanned 15 participants when they performed a temporal prediction task. They observed visual animations and predicted when a stationary ball began moving after being contacted by another moving ball. To induced uncertainty-driven prediction errors, we introduced spatial gaps and temporal delays between the balls. Classical and Bayesian fMRI analyses provided evidence to support that the aMCC-aINS system along with the striatum not only responds when humans predict whether a dynamic event occurs but also when it occurs. Our results reveal that the insula is the entry port of a three-region pathway involved in the processing of temporal predictions. Moreover, prediction errors rather than attentional demands, task difficulty, or task duration exert an influence in the aMCC-aINS system. Prediction errors debilitate the effect of the aMCC on the aINS. Finally, our computational model provides a way forward to characterize the physiological parallel of temporal prediction errors elicited in dynamic tasks.


Directional hearing in aging rats.
The loss of the ability to localize sounds was discovered to occur in rats as a consequence of aging. Subjects were trained in a two-alternative forced-choice paradigm to press the left bar if a sound was presented from the left side and to press the right bar if sound was presented from the right side. Testing was conducted with a brief 200 msec pink noise signal. The accuracy of sound localization was measured in rats from 10 to 21 months of age. By 21 months of age the accuracy of localization had declined from greater than 90% correct to less than 69% correct. The loss of the ability to localize sounds may be involved with the onset of spatial disorientation observed in some subjects at advanced ages.


Low dose continuous infusion doxorubicin in children and young adults.
Ten patients (age range 3.2-26.3 yrs) with relapsed or resistant malignancies received a total of 20 courses of low dose continuous infusion doxorubicin (3 mg/m2/day for 28 days) delivered by portable Graseby infusion pumps via central venous catheters. Each patient received a median dose of 144 mg/m2 (range 87-261). Four patients responded to treatment (1 complete response (CR) and 3 partial response (PR)) and performance status improved in seven patients. Overall toxicity was minimal: WHO Grade 4 anaemia in 2/18 courses, Grade 4 neutropenia in 1/18, Grade 3-4 thrombocytopenia in 3/18, nausea and vomiting of Grades 2 and 4 in 4/20 and 1/20 respectively, and mucositis of Grades 2 and 4 in 2/20 courses each. Cardiac toxicity was assessed using echocardiography, and fractional shortening remained within normal limits in all patients. Low dose continuous infusion doxorubicin is a feasible, well tolerated, ambulatory therapy in children and may be an effective way of delivering doxorubicin with less toxicity, thus enabling the development of more dose intensive regimens.


Hepatocellular carcinoma directly invading the duodenum.
Recurrent gastrointestinal bleeding from hepatocellular carcinoma HCC invading the duodenum is very rare. We present a case of 50-year-old male who was admitted with a history of recurrent upper gastrointestinal tract UGIT bleeding, weight loss and anemia. The patient was known to have a chronic hepatitis C. Endoscopic examination showed grade-2 non-bleeding esophageal varices, and a large ulcerated duodenal mass partially obstructing the duodenal bulb outlet and causing recurrent UGIT bleeding. Pathological evaluation of the mass revealed HCC.


[Pulmonary toxicity associated with sirolimus therapy in liver transplantation].
Sirolimus is a potent immunosuppressive drug that began to be used in the last few years. This drug was initially used in renal transplantation but its use in other solid organ transplantations such as liver, heart, lung and pancreas, has been increasing. Sirolimus is indicated in rescue therapies and to reduce the secondary toxic effects of calcineurin inhibitors. However, this drug has been associated with infrequent but severe pulmonary toxicity and cases of interstitial pneumonitis, bronchiolitis obliterans with organizing pneumonia, and alveolar proteinosis have been described. We present the case of a male liver transplant recipient who developed interstitial pneumonitis associated with sirolimus use.


[IL-10 inhibits inducible expression pattern of beta-defensin-2 in human peripheral blood cells].
To investigate the effect of IL-10 on the inducibility of human beta-defensin 2 (hBD-2) in human peripheral blood cells. Peripheral blood samples were collected from 22 healthy individuals and co-cultured with 0 ng/ml lipopolysaccharide (LPS), 100 ng/ml LPS, 10 ng/ml IL-10, or 100 ng/ml LPS plus 10 ng/ml IL-10 at 37 degree for 6 h. Total RNA was extracted from peripheral blood cells and the mRNA level of hBD-2 was detected by relative quantitative real-time PCR.. No detectable level of hBD-2 mRNA was found in normal peripheral blood cells with stimulation of 0 ng/ml LPS or 10 ng/ml IL-10. The mRNA level of hBD-2 was increased to 166.9 +/- 35.14 after 100 ng/ml LPS challenge, while the mRNA level of hBD-2 was decreased to 30.40 +/- 9.18 after the co-stimulation of 100 ng/ml LPS plus 10 ng/ml IL-10; which was significantly lower than that with LPS alone (P<0.05). The expression of hBD-2 gene can be induced by LPS.IL-10 inhibits the inducible expression of hBD-2.


[The current state and prospect of Chinese medicine gastroenterology].
The progress and existent problems of Chinese medicine (CM) gastroenterology since the National Eleventh Five-Year Plan were discussed in this article in terms of theory innovation, formulation of clinical pathway and diagnosis-treatment consensus, efficacy assessment, formulation of efficacy assessment scale, advantage diseases, and exploration of the syndrome standardization, progress in science research, academic exchange, and the construction of study platform, and so on. Meanwhile, the development of CM gastroenterology was prospected in the following five aspects: to enhance the theory inheritance and innovation, the construction of discipline standardization; to establish scientific clinical efficacy assessment methods and the standard system; to expend treatment technologies and feature therapies; and to clarify the modern scientific connotation of CM theory and treatment.


Skin peptide tyrosine-tyrosine, a member of the pancreatic polypeptide family: isolation, structure, synthesis, and endocrine activity.
Pancreatic polypeptide, peptide tyrosine-tyrosine (PYY), and neuropeptide tyrosine (NPY), three members of a family of structurally related peptides, are mainly expressed in the endocrine pancreas, in endocrine cells of the gut, and in the brain, respectively. In the present study, we have isolated a peptide of the pancreatic polypeptide family from the skin of the South American arboreal frog Phyllomedusa bicolor. The primary structure of the peptide was established as Tyr-Pro-Pro-Lys-Pro-Glu-Ser-Pro-Gly-Glu10-Asp-Ala-Ser-Pro-Glu-Glu- Met-Asn- Lys-Tyr20-Leu-Thr-Ala-Leu-Arg-His-Tyr-Ile-Asn-Leu30-Val-Thr- Arg-Gln-Arg-Tyr-NH2 . This unusual peptide, named skin peptide tyrosine-tyrosine (SPYY), exhibits 94% similarity with PYY from the frog Rana ridibunda. A synthetic replicate of SPYY inhibits melanotropin release from perifused frog neurointermediate lobes in very much the same way as NPY. These results demonstrate the occurrence of a PYY-like peptide in frog skin. Our data also suggest the existence of a pituitary-skin regulatory loop in amphibians.


Controversy in amblyopia management.
Much has been written about amblyopia treatment. However, there is no consensus on the most efficacious therapeutic modality for amblyopia. The intensity of therapy needed to maximize visual acuity is also widely debated. The diversity of opinions emphasizes that the optimum treatment for amblyopia is unknown. Part of the uncertainty stems from the lack of standardization in the management of amblyopia. The objective of this paper is to conduct an in-depth review of the literature in an attempt to clarify the amblyopia treatment conundrum. The treatment of amblyopia in children is frequently discussed in the literature. It is obvious from the literature that there is the need for prospective studies with consistent controls, clear definitions of what constitutes successful therapy endpoints, and standardization of testing procedures.


Selecting transpositions using phage P1 headful packaging: new markerless transposons for functionally mapping long-range regulatory sequences in bacterial artificial chromosomes and P1-derived artificial chromosomes.
New Tn10 minitransposons were constructed to functionally map long-range transcription regulatory sequences in bacterial artificial chromosomes (BACs) and P1-derived artificial chromosomes (PACs). Each contained a wild-type loxP site but, significantly, contained no mammalian or bacterial genes and/or promoter elements within the transposed portion of DNA. In contrast to loxP transposons described previously, the new ones do not introduce transcription regulatory elements capable of interfering with those endogenous to the BAC clone in functional mapping studies. Progressive deletions from the loxP end of genomic DNA were efficiently generated using these transposons, and a series of truncations generated in a green fluorescence protein (GFP)-BAC fusion clone unambiguously identified three new long-range enhancer sequences functionally in the Nkx2-5 gene in transgenic mice. Insertions of these new transposons lacking antibiotic resistance genes into a BAC or PAC were indirectly selected by their ability to delete enough DNA from the clone so as to enable its packaging within a P1 phage head with both loxP sites intact for subsequent recovery of the large plasmid. The outcome of such an indirect mode of selection is both desirable and undesirable. First, because the screen is not antibiotic resistance marker dependent, the same transposon can be used to generate nested deletions efficiently in both BACs and PACs. Second, deletions through intrainsert recombinations unrelated to loxP/Cre also get packaged and recovered, and size analyses of the BAC/PAC vector band after NotI digestion is indispensable to identify authentic loxP/Cre deletions. The procedure nevertheless offers a potential approach to map recombinogenic sequences in BACs and PACs.


Why portal hypertensive varices bleed and bleed: a hypothesis.
Continued bleeding or early rebleeding is associated with a poor prognosis in patients with variceal haemorrhage. It is not clear why bleeding stops in some patients and continues or restarts in others. It is suggested that secondary haemodynamic changes in the splanchnic circulation after a bleed may contribute to the risk of further bleeding. These changes include the effects of hypotension on portocollateral resistance, the effects of blood in the gut on splanchnic blood flow, and the effects of blood volume expansion on portal venous pressure during resuscitation. These factors, working in concert, cause a secondary rise in portal venous pressure, which may precipitate further bleeding. Treatment aimed at preventing these secondary haemodynamic changes may be beneficial. It is probable that somatostatin and octreotide could act in this way, which may explain their therapeutic efficacy.


Degree of throat deposition can explain the variability in lung deposition of inhaled drugs.
Inhalation is a mainstay for treatment of asthma, and lung deposition can be seen as a surrogate marker for the ensuing clinical effects. Not only absolute lung deposition, but also its variability is of interest, as it indicates the range of expected lung deposition in an individual patient when prescribing the drug and the expected day-to-day variability when using it. A literature survey found 71 studies with relevant information on lung deposition and its variability. Further characteristics of the studies, such as if the subjects were healthy or asthmatics, adults or children, and what device that was used, were noted. In all, 187 data points were included. Variability in lung deposition was depicted as a function of mean lung deposition; for the entire data set and for subsets thereof. Independent of device type or subject category high lung deposition was associated with low relative variability and vice versa. Using a published throat deposition model, the observed correlation of lung deposition variability to mean lung deposition could be explained as being determined largely by the extent of and variability in throat deposition. We hypothesize that throat deposition is the major determinant for lung deposition of an inhaled aerosol, and its absolute variability will largely be determined by the absolute variability in throat deposition. The relative variability in lung deposition will therefore tend to be high for low lung deposition and low for high lung deposition. Consequently, low relative variability in lung deposition can only be attained if high lung deposition is achieved.


The magnet system of the Space Plasma Environment Research Facility (SPERF): Parameter design and electromagnetic analysis.
A magnet system is used in the SPERF to create the magnetic field configuration for simulating the space plasma environment. In this paper, the parameters of the system are designed to achieve the target fields needed by the scaling laws, and the electromagnetic analysis has been performed to validate the results. A procedure to obtain the parameters is proposed based on the investigation into the physical and technological constraints. The vacuum magnetic fields for studying the 3D magnetic reconnection at the magnetopause, Earth's magnetosphere, and 3D magnetic reconnection driven by a plasma gun are computed. In addition, the engineering complexity is reviewed in brief. This research is crucial to the construction of the SPERF, and it is valuable to designing the magnets applied in other fields.


Carotenoid intake and adipose tissue carotenoid levels in relation to prostate cancer aggressiveness among African-American and European-American men in the North Carolina-Louisiana prostate cancer project (PCaP).
Associations between carotenoid intake and prostate cancer (CaP) incidence have varied across studies. This may result from combining indolent with aggressive disease in most studies. This study examined whether carotenoid intake and adipose tissue carotenoid levels were inversely associated with CaP aggressiveness. Data on African-American (AA, n = 1,023) and European-American (EA, n = 1,079) men with incident CaP from North Carolina and Louisiana were analyzed. Dietary carotenoid intake was assessed using a detailed-food frequency questionnaire (FFQ), and abdominal adipose tissue samples were analyzed for carotenoid concentrations using high-performance liquid chromatography. Multivariable logistic regression was used in race-stratified analyses to calculate odds ratios (ORs) and 95% confidence intervals (95%CI) comparing high aggressive CaP with low/intermediate aggressive CaP. Carotenoid intake differed significantly between AAs and EAs, which included higher intake of lycopene among EAs and higher β-cryptoxanthin intake among AAs. Comparing the highest and lowest tertiles, dietary lycopene was associated inversely with high aggressive CaP among EAs (OR = 0.55, 95%CI: 0.34-0.89, Ptrend = 0.02), while an inverse association was observed between dietary β-cryptoxanthin intake and high aggressive CaP among AAs (OR = 0.56, 95%CI: 0.36-0.87, Ptrend = 0.01). Adipose tissue α-carotene and lycopene (cis + trans) concentrations were higher among EAs than AAs, and marginally significant inverse linear trends were observed for adipose α-carotene (Ptrend = 0.07) and lycopene (Ptrend = 0.11), and CaP aggressiveness among EAs only. These results suggest that diets high in lycopene and β-cryptoxanthin may protect against aggressive CaP among EAs and AAs, respectively. Differences in dietary behaviors may explain the observed racial differences in associations. Prostate 76:1053-1066, 2016. © 2016 Wiley Periodicals, Inc.


Prevention of preterm delivery. The important role of early recognition.
Perinatal deaths can be decreased most effectively by reducing the incidence of preterm delivery. Therapy with a tocolytic agent, such as ritodrine ( Yutopar ), can be of significant benefit if applied to patients in whom preterm labor is correctly diagnosed and has not advanced beyond the early stages. Identification of the patient at risk, intensive education and surveillance of such patients, and education of hospital and clinic staff can extend the application and success of labor-inhibiting therapy.


A Systematic Review and Content Analysis of Classroom Teacher Professional Development in Nutrition Education Programs.
Many nutrition programs include classroom-based education. Schoolteachers are relied upon to deliver these programs despite gaps in nutrition education motivation, knowledge, and self-efficacy. Teacher professional development (PD) for these nutrition education programs has been identified as a strategy for improving program effectiveness, yet many interventions do not include a PD component and still fewer describe it. A literature search was conducted between January and February 2017; articles were collected from PubMed, ERIC, and EBSCOhost. Article inclusion criteria were as follows: 1) published in an English-language peer-reviewed or scholarly journal, 2) published after 2000, 3) empirical research, 4) research conducted in a K-12 classroom, 5) research included nutrition education component, and 6) program delivered by a classroom teacher. Twenty-seven interventions were identified. A team of 2 researchers performed content analysis based on an evidence-based set of 7 PD components to assess if and how these components were incorporated before, during, or after program implementation. Little information was provided that described the role of teacher PD in the course of delivering nutrition education in classroom-based programs. The most common elements of PD described in the literature were the time spent in PD and follow-up with instructors during or after program implementation. There was a notable lack of methodologic description of teacher PD, and this limited reporting may decrease researchers' ability to work with teachers in a consistent and effective manner.


Interlocking screw configuration influences distal tibial fracture stability in torsional loading after intramedullary nailing.
This study evaluated the influence of fracture obliquity and locking screw configuration on interfragmentary motion during torsional loading of distal metaphyseal tibial fractures fixed by intramedullary (IM) nailing. The stability of six IM nail locking screw configurations used to fix distal metaphyseal tibial fractures of various obliquities was evaluated. A coronal osteotomy from proximal lateral to distal medial was made in sawbone tibiae at different obliquities from 0° to 60°. After fixation, motion at the fracture was assessed during internal and external rotation tests to 7 Nm under two compressive loading conditions: 20 N and 500 N. With results organized by interlocking configuration, significant differences in interfragmentary rotation between fracture obliquities are observed when the number of interlocking screws is decreased to one distal static and one proximal dynamic during internal rotation. During external rotation testing, significant rotational differences between fracture obliquities are encountered with two distal static screws and one proximal dynamic. No significant differences were seen between different distal interlocking screw orientations (two parallel versus perpendicular distal screws) for all fracture obliquity patterns tested. Fracture obliquity influences rotational stability which can be mitigated by interlocking screw configurations when nailing distal tibia fractures. At least two distal and one proximal interlocking screw in a static mode is recommended to resist torsional loading of distal tibia fractures undergoing intramedullary nailing. The addition of more interlocking screws than this did not significantly alter control of torsional displacement with load.


Visualizing the dynamics of cerebral aneurysms with four-dimensional computed tomographic angiography.
This study was designed to assess cerebral aneurysm hemodynamics with four-dimensional (4-D) computed tomographic (CT) angiography. Multislice computed tomography with a retrospective electrocardiography-gated reconstruction algorithm was used. The motions of the aneurysmal wall, bleb, and dissecting cavity were rendered observable in a 4-D CT movie. The findings for 30 patients with 34 aneurysms who underwent 4-D CT angiography were analyzed. Twenty-three aneurysms were documented in the anterior circulation region, and the remaining 11 aneurysms were in the posterior circulation. The average aneurysm size was 6.4 mm, and there were five large aneurysms. There were 28 saccular, 4 dissecting, and 2 fusiform aneurysms. 4-D CT movies were obtained successfully in all aneurysms. The aneurysm wall motion of two growing aneurysms exhibited a highly irregular pulsation in the 4-D CT movie. Pulsating blebs were detected in nine (32.1%) of the saccular aneurysms. In two patients with subarachnoid hemorrhage, preoperative 4-D CT angiography revealed dangerous pulsating blebs that were confirmed as the ruptured points during the surgical procedure. Specifically, in the dissecting aneurysms, the 4-D CT movie revealed a pulsating line, which provided accurate and detailed information regarding the dissecting cavity and intimal flap. The dissecting cavity revealed by the 4-D CT movie could not be detected with conventional or three-dimensional digital subtraction angiography. The 4-D CT movie images were highly useful in making anatomic judgments for the endovascular surgery procedure. 4-D CT images are valuable in determining aneurysmal wall dynamics. Highly useful information was obtained regarding intracranial aneurysms with 4-D CT angiography compared with other modalities. Further studies will be necessary to elucidate the optimal application of this new technology to both the pathological characteristics and therapeutic amelioration of aneurysmal features such as dome pulsation, blebs, and growing aneurysms.


Immunological Approach for Full NURBS Reconstruction of Outline Curves from Noisy Data Points in Medical Imaging.
Curve reconstruction from data points is an important issue for advanced medical imaging techniques, such as computer tomography (CT) and magnetic resonance imaging (MRI). The most powerful fitting functions for this purpose are the NURBS (non-uniform rational B-splines). Solving the general reconstruction problem with NURBS requires computing all free variables of the problem (data parameters, breakpoints, control points, and their weights). This leads to a very difficult non-convex, nonlinear, high-dimensional, multimodal, and continuous optimization problem. Previous methods simplify the problem by guessing the values for some variables and computing only the remaining ones. As a result, unavoidable approximations errors are introduced. In this paper, we describe the first method in the literature to solve the full NURBS curve reconstruction problem in all its generality. Our method is based on a combination of two techniques: an immunological approach to perform data parameterization, breakpoint placement, and weight calculation, and least squares minimization to compute the control points. This procedure is repeated iteratively (until no further improvement is achieved) for higher accuracy. The method has been applied to reconstruct some outline curves from MRI brain images with satisfactory results. Comparative work shows that our method outperforms the previous related approaches in the literature for all instances in our benchmark.


Recurrent Dislocation of the Proximal Interphalangeal Joint of the Finger: A Rare Issue in Hand Surgery.
Recurrent dislocation is not common in small joints. This report presents a recurrent dislocation of the proximal interphalangeal joint of the ring finger in a 23-years-old man. Recurrent dislocation was addressed successfully by repairing the avulsed volar plate to the base of the middle phalanx, followed by 6 weeks of splint immobilization.


A novel cysteine protease HeLa DUB-1 responsible for cleaving the ubiquitin in human ovarian cancer cells.
The regulation of ubiquitin-mediated protein degradation is becoming important for a number of cellular processes. Human HeLa DUB-1 cDNA, encoding a novel deubiquitinating enzyme, was isolated from ovarian cancer cells. It has 1,647 bp nucleotides and encodes a 548 amino acid polypeptide with the molecular weight of approximately 61 kDa. It contains the highly conserved Cys, Asp (I), His, and Asn/Asp (II) domains characteristic of the ubiquitin-specific processing proteases. Biochemical assay revealed that HeLa DUB-1 has deubiquitinating enzyme activity in vivo and in vitro. Northern blot analysis for HeLa DUB-1 showed the strong expression in human skeletal muscle and pancreas and to some extent in heart, placenta, lung, liver, and kidney. Interestingly, the expression was hardly seen in the brain. Localization study indicates that HeLa DUB-1 proteins are present in both the cytoplasm and nucleus.


Onset and progression of primary torsion dystonia in sporadic and familial cases.
Four hundred and sixty records of patients with primary torsion dystonia (296 women and 164 men) were evaluated. The mean age at disease onset was 48.3 +/- 17.7 years; 13 patients carried the DYT1 CAG deletion. The distribution of age at onset was represented by a bi-modal curve, with a nadir at 21 year separating early onset from late onset cases. In 15.9% of cases there was a positive family history of dystonia. Cranial, cervical or lower limb onset was more common amongst women (M:F ratios were 1:2.7, 1:1.9, and 1:3); by contrast, onset in the upper limb was more common in men (M:F ratio 2.2:1). As expected, disease progression was more pronounced in cases with early onset; it was reckoned that onset at or above 32 years was associated with a negligible likelihood to progress to a generalized form. The mean age at onset of familial cases was 44.8 +/- 11.2 years, significantly lower than the mean age at onset of sporadic cases (53.5 +/- 13.4 years). Familial cases were characterized by more sites involved throughout disease course. Familial cases had a higher tendency to progress to a segmental or generalized form than sporadic cases.


Association of renal function with cardiac reverse remodeling and long-term outcome in heart failure patients following cardiac resynchronization therapy.
Renal insufficiency (RI) is significantly associated with clinical prognosis in patients with heart failure (HF), but direct evidences on the relation between renal function and clinical outcome in patients receiving cardiac resynchronization therapy (CRT) are limited. The aim of the current study was to systematically evaluate the association of baseline and 6-month renal function with cardiac reverse remodeling and long-term outcome after CRT. We retrospectively evaluated 190 consecutive patients who underwent CRT at Fuwai Hospital from January 2008 to April 2013. Renal function tests, echocardiographic measurement, and clinical parameters at baseline and after 6 months of CRT were performed. Primary endpoint events included all-cause mortality, cardiac transplantation, and unplanned hospitalizations for HF. At baseline, compared with normal renal function or mild RI (estimated glomerular filtration rate (eGFR) ≥60 ml×min(-1)×1.73 m(-2)), moderate-to-severe RI (eGFR <60 ml×min(-1)×1.73 m(-2)) exerted a negative influence on cardiac reverse remodeling parameters. At 6-month follow-up, 114 (60.0%) patients were classified as responders and showed significant renal function improvement, whereas renal function deteriorated in non-responders and subsequently 41 (25.6%) patients developed worsening renal function (WRF). During the mean follow-up of (24.3±17.1) months, both patients with baseline eGFR <60 ml×min(-1)×1.73 m(-2) and those with WRF experienced worse event-free survival (P < 0.01, respectively). This analysis identified that baseline eGFR as well as WRF after CRT were found to be independent determinants of the combined endpoints of all-cause mortality and HF-related hospitalizations in CRT recipients.


Serum potassium and stroke risk among treated hypertensive adults.
In prospective studies, hypokalemia has been shown to be associated with a subsequent increase in stroke risk in treated hypertensive adults after 4 to 16 years of follow-up. Stroke risk associated with more recent assessments of hypokalemia has not been examined. We used data from an on-going, population-based, case-control study of incident stroke at Group Health Cooperative (GHC). Cases were treated hypertensive adults, 30 to 79 years old, who sustained an incident ischemic or hemorrhagic stroke between July 1989 and December 2000. Controls were GHC members without a history of stroke who met same inclusion criteria as cases. Serum potassium (K(+)) levels were collected from GHC laboratory database. Hypokalemia (< or =3.4 mM/L) was defined using the most recent serum K(+) measure in the year before the index date (event date for cases; random date within calendar year of identification for controls). Multivariate logistic regression estimated the relative risk of ischemic and hemorrhagic stroke. Among 593 ischemic and 125 hemorrhagic stroke cases, and 2397 controls, few subjects were hypokalemic: 3%, 6%, and 2%, respectively. Using the normal range of serum K(+) as a reference (3.5 to 5.0 mM/L), hypokalemia was associated with an elevated risk of ischemic (odds ratio [OR]: 2.04; 95% confidence interval [CI]: 1.14-3.64) and hemorrhagic stroke (OR: 3.29; 95% CI: 1.45-7.48) in adjusted analyses. Associations were not modified by diuretic use. In adults with treated hypertension, hypokalemia in the year before a stroke was associated with an increased risk of incident ischemic and hemorrhagic stroke independent of diuretic use when compared to normal serum K(+) levels.


VALD-3 inhibits proliferation and induces apoptosis of colorectal cancer cells via upregulating tumor suppressor activity of p53 to inhibit Wnt/β-catenin signal pathway.
Colorectal cancer is the third most common malignant tumor and a leading cause of cancer death. Currently lacks effective therapies available to improve the prognosis. In the present study, VALD-3, an important Schiff base ligand from o-vanillin derivatives was evaluated for its anti-cancer activity in vitro and in vivo against colorectal cancer. The effect of VALD-3 on colorectal cancer cells proliferation was assessed using MTT assay and the cell migration was evaluated using wound healing scratch assay. The appearance of apoptotic colorectal cancer cells was detected by flowcytometry analysis. Morphological changes caused by VALD-3 induced apoptosis were also observed by Hoechst 33258 staining. The flow cytometry assay was also used to measure cell cycle arrest. The expression levels of TP53 and Bad were analyzed using quantitative real-time PCR. Protein expression of P53, Wnt/β-catenin signaling pathway proteins, apoptosis proteins and cell cycle-related protein were viewed by Western blotting. In addition, HT-29 cells xenograft tumor model was used for the study in vivo. Immunohistochemistry (IHC) staining was employed to detect the P53 protein expression. The results showed that VALD-3 obviously inhibited the proliferation and migration for colorectal cancer cells. In addition, flow cytometry analysis demonstrated that VALD-3 markedly increased early and late apoptosis on colorectal cancer cells, respectively. VALD-3 induced cell cycle arrest at the G0/G1 phase. Most importantly, tumor growth in HT-29 xenograft mice was suppressed by VALD-3, but no significant change in body weight. As confirmed by IHC staining from tumor tissue, the P53 proteins expression increased. These results suggested that VALD-3 represses cell proliferation and induces apoptosis associated with upregulating tumor suppressor activity of p53 to inhibit Wnt/β-catenin signal pathway, and it is a potential anticancer agent for colorectal cancer.


Peer presence and the exploratory behavior of eighteen- and thirty-month-old children.
20 18- and 20 30-month-old children were observed in a situation requiring separation from the mother in order to play with attractive toys. An agemate was present for half the children but not the others. Peer presence facilitated leaving the mother and entering the playroom at both ages. Among 18-month-olds, the presence of the peer also shortened play bouts, increased unoccupied/self-solace behavior, and increased contact maintenance with the mother. Among 30-month-olds, however, the peer's presence did not have these effects. these children engaged in increased coordinate social interaction with the other child. Developmental changes occurring in the second and third year thus include the increased salience of agemates in supporting separation from the mother and exploration of the environment in the context of sustained social interaction.


Au(I)-Catalyzed Synthesis of Trisubstituted Indolizines from 2-Propargyloxypyridines and Methyl Ketones.
A new Au(I)-catalyzed method for the preparation of trisubstituted indolizines from easily accessible 2-propargyloxy-pyridines is reported. The reaction tolerates a wide range of functionality, allowing for diversity to be introduced in four distinct regions of the product (R, R1, R2, and Ar). The proposed mechanism proceeds via enol addition to an allenamide intermediate and explains the observed increase in yields when electron poor methyl ketones are utilized.


Potentiation of Cisplatin Cytotoxicity in Resistant Ovarian Cancer SKOV3/Cisplatin Cells by Quercetin Pre-Treatment.
Previously, we demonstrated that the overexpression of antioxidant enzymes (SOD-1, SOD-2, Gpx-1, CAT, and HO-1), transcription factor NFE2L2, and the signaling pathway (PI3K/Akt/mTOR) contribute to the cisplatin resistance of SKOV-3/CDDP ovarian cells, and treatment with quercetin (QU) alone has been shown to inhibit the expression of these genes. The aim of this study was to expand the previous data by examining the efficiency of reversing cisplatin resistance and investigating the underlying mechanism of pre-treatment with QU followed by cisplatin in the same ovarian cancer cells. The pre-incubation of SKOV-3/CDDP cells with quercetin at an optimum dose prior to treatment with cisplatin exhibited a significant cytotoxic effect. Furthermore, a long incubation with only QU for 48 h caused cell cycle arrest at the G1/S phase, while a QU pre-treatment induced sub-G1 phase cell accumulation (apoptosis) in a time-dependent manner. An in-depth study of the mechanism of the actions revealed that QU pre-treatment acted as a pro-oxidant that induced ROS production by inhibiting the thioredoxin antioxidant system Trx/TrxR. Moreover, QU pre-treatment showed activation of the mitochondrial apoptotic pathway (cleaved caspases 9, 7, and 3 and cleaved PARP) through downregulation of the signaling pathway (mTOR/STAT3) in SKOV-3/CDDP cells. This study provides further new data for the mechanism by which the QU pre-treatment re-sensitizes SKOV-3/CDDP cells to cisplatin.


A consensus for the development of a vector model to assess clinical complexity.
The progressive rise in multimorbidity has made management of complex patients one of the most topical and challenging issues in medicine, both in clinical practice and for healthcare organizations. To make this easier, a score of clinical complexity (CC) would be useful. A vector model to evaluate biological and extra-biological (socio-economic, cultural, behavioural, environmental) domains of CC was proposed a few years ago. However, given that the variables that grade each domain had never been defined, this model has never been used in clinical practice. To overcome these limits, a consensus meeting was organised to grade each domain of CC, and to establish the hierarchy of the domains. A one-day consensus meeting consisting of a multi-professional panel of 25 people was held at our Hospital. In a preliminary phase, the proponents selected seven variables as qualifiers for each of the five above-mentioned domains. In the course of the meeting, the panel voted for five variables considered to be the most representative for each domain. Consensus was established with 2/3 agreement, and all variables were dichotomised. Finally, the various domains were parametrized and ranked within a feasible vector model. A Clinical Complexity Index was set up using the chosen variables. All the domains were graphically represented through a vector model: the biological domain was chosen as the most significant (highest slope), followed by the behavioural and socio-economic domains (intermediate slope), and lastly by the cultural and environmental ones (lowest slope). A feasible and comprehensive tool to evaluate CC in clinical practice is proposed herein.


Peptidase N encoded by Salmonella enterica serovar Typhimurium modulates systemic infection in mice.
The cytosolic protein degradation pathway, involving ATP-dependent proteases and ATP-independent peptidases, is important for modulating several cellular responses. The involvement of pathogen-encoded ATP-dependent proteases is well established during infection. However, the roles of ATP-independent peptidases in this process are not well studied. The functional role of Peptidase N (PepN), an ATP-independent enzyme belonging to the M1 family, during systemic infection of mice by Salmonella enterica serovar Typhimurium (Salmonella typhimurium) was investigated. In a systemic model of infection, the number of CFU of S. typhimurium containing a targeted deletion in peptidase N (DeltapepN), compared with wild type, was significantly higher in the lymph node and spleen. In addition, S. typhimurium replicated in the thymus and greatly reduced the number of immature CD4(+)CD8(+) thymocytes in a dose- and time-dependent manner. Strains lacking or overexpressing pepN were used to show that the reduction in the number of thymocytes, but not lymph node cells, depends on a critical number of CFU. These findings establish a role for PepN in reducing the in vivo CFU of S. typhimurium during systemic infection. The implications of these results, in the context of the roles of proteases and peptidases, during host-pathogen interactions are discussed.


Human Representation Learning.
The central theme of this review is the dynamic interaction between information selection and learning. We pose a fundamental question about this interaction: How do we learn what features of our experiences are worth learning about? In humans, this process depends on attention and memory, two cognitive functions that together constrain representations of the world to features that are relevant for goal attainment. Recent evidence suggests that the representations shaped by attention and memory are themselves inferred from experience with each task. We review this evidence and place it in the context of work that has explicitly characterized representation learning as statistical inference. We discuss how inference can be scaled to real-world decisions by approximating beliefs based on a small number of experiences. Finally, we highlight some implications of this inference process for human decision-making in social environments.


The COVID Complex: A Review of Platelet Activation and Immune Complexes in COVID-19.
Coronavirus disease 2019 (COVID-19) is a highly prothrombotic viral infection that primarily manifests as an acute respiratory syndrome. However, critically ill COVID-19 patients will often develop venous thromboembolism with associated increases in morbidity and mortality. The cause for this prothrombotic state is unclear but is likely related to platelet hyperactivation. In this review, we summarize the current evidence surrounding COVID-19 thrombosis and platelet hyperactivation. We highlight the fact that several studies have identified a soluble factor in COVID-19 patient plasma that is capable of altering platelet phenotype in vitro. Furthermore, this soluble factor appears to be an immune complex, which may be composed of COVID-19 Spike protein and related antibodies. We suggest that these Spike-specific immune complexes contribute to COVID-19 platelet activation and thrombosis in a manner similar to heparin-induced thrombocytopenia. Understanding this underlying pathobiology will be critical for advancement of future research and therapeutic options.


Clinical presentation and management of congenital ptosis.
Congenital ptosis is a rare condition characterized by lower positioning of the upper eyelid that is present at birth and is a clinical condition that is persistent if not treated. It may be unilateral or bilateral and may be associated with other ocular disorders or systemic conditions, including Marcus Gunn, Horner, and Duane syndromes. It is a benign condition but causes functional, cosmetic, and psychological problems in children. However, not all patients need to undergo surgery, and usually only patients at risk of amblyopia need a prompt surgical correction, while in other cases, surgery can be postponed. The grade of ptosis, the eyelid function, and the amblyopic risk are the parameters that affect the ophthalmologist's decision on timing of surgery and the surgical technique to be used. In fact, there are several types of surgical techniques to correct a congenital ptosis, although very often more than one is needed to obtain an acceptable result. This paper reviews the causes of congenital ptosis and associated diseases. Particular emphasis is given to surgical management and different procedures available to correct the upper eyelid anomaly and avoid permanent damage to visual function.


Blastomycosis in Washington Parish, Louisiana, 1976-1985.
For the period 1976-1985, the authors attempted to identify all cases of blastomycosis in Louisiana and studied in detail one county (Washington Parish) suspected by local physicians of having an unusually high incidence of the disease. The mean annual incidence rates for Louisiana and for Washington Parish were 0.23 and 6.8 cases per 100,000 population, respectively. To the authors' knowledge, the rate for Washington Parish is the highest annual incidence rate documented for a population in a nonoutbreak setting. Among the 30 cases detected in Washington Parish, the age range was 3 weeks to 81 years. Five cases died; of these, one was an infant who may have been infected in utero, and another developed clinical symptoms compatible with adult respiratory distress syndrome. There was no geographic clustering among cases the authors investigated, and a case-control study failed to identify specific activities or host factors which may have predispose to infection. Washington Parish is probably a hyperendemic area for blastomycosis because environmental conditions are especially conducive to Blastomyces dermatitidis growth. The study suggests that most cases in Washington Parish were sporadically infected, and common-source exposures to B. dermatitidis with resultant clinical illness are rare even in hyperendemic settings.


An improved solid-phase method for peptide synthesis--the syntheses of oxytocin and vasopressin.
Peptide hormones are now widely used for both medicinal and veterinary purposes. It is, therefore, imminent to improve the process of peptide synthesis to meet the needs of production. This paper describes an improved method for the solid-phase synthesis of peptides. By reacting the potassium salt, instead of the triethyl ammonium salt, of the N-protected amino acid with the chloromethylated polystyrene-divinyl benzene (2%) support, esterification was found to attain higher levels, thus obviating or minimizing the formation of a quaternary anion exchanger which might cause side reactions during the subsequent steps of synthesis. The method has been applied to the syntheses of oxytocin and vasopressin and found to be quite satisfactory. A new method was introduced for the determination of free alpha-amino groups of the peptide polymer support through the formation of a Schiff's base with salicylaldehyde.


Multidecadal declines in particulate mercury and sediment export from Russian rivers in the pan-Arctic basin.
SignificanceRussian rivers are the predominant source of riverine mercury to the Arctic Ocean, where methylmercury biomagnifies to high levels in food webs. Pollution controls are thought to have decreased late-20th-century mercury loading to Arctic watersheds, but there are no published long-term observations on mercury in Russian rivers. Here, we present a unique hydrochemistry dataset to determine trends in Russian river particulate mercury concentrations and fluxes in recent decades. Using hydrologic and mercury deposition modeling together with multivariate time series analysis, we determine that 70 to 90% declines in particulate mercury fluxes were driven by pollution reductions and sedimentation in reservoirs. Results suggest that Russian rivers likely dominated over all other sources of mercury to the Arctic Ocean until recently.


Characteristics of a new repolarization descriptor substituted for T-wave morphology analysis in patients with cardiomyopathy and myocardial infarction.
Total cosine R-to-T (TCRT) is a descriptor of T-wave morphology analysis based on singular value decomposition of 12-lead electrocardiograms (ECGs), which is useful in risk stratification of patients with myocardial infarction (MI). A new marker of standard ECG substituted for TCRT is proposed and the aim of this study was to evaluate the correlation between the new index and TCRT in patients with cardiomyopathy and MI. Patients were divided into 2 groups: patients with cardiomyopathy (group CM, n=21, male =13), and patients with MI (group MI, n=36, male =28). TCRT was calculated using a custom software package. The ventricular gradient (VG)-index was defined as the total number of leads with opposite vectors for the QRS and T-wave. The value of TCRT was significantly lower in group CM than in group MI (-0.50+/-0.51 vs -0.04+/-0.65, p<0.01). The value for the VG-index was significantly greater in group CM than in group MI (5.9+/-3.4 vs 4.2+/-2.4, p<0.05). There was a significant correlation between TCRT and the VG-index in all of the patients (r(2)=0.47). The VG-index is significantly correlated with TCRT, and both descriptors distinguish patients with MI from those with cardiomyopathy.


A direct comparison of high-speed methods for the numerical Abel transform.
The Abel transform is a mathematical operation that transforms a cylindrically symmetric three-dimensional (3D) object into its two-dimensional (2D) projection. The inverse Abel transform reconstructs the 3D object from the 2D projection. Abel transforms have wide application across numerous fields of science, especially chemical physics, astronomy, and the study of laser-plasma plumes. Consequently, many numerical methods for the Abel transform have been developed, which makes it challenging to select the ideal method for a specific application. In this work, eight published transform methods have been incorporated into a single, open-source Python software package (PyAbel) to provide a direct comparison of the capabilities, advantages, and relative computational efficiency of each transform method. Most of the tested methods provide similar, high-quality results. However, the computational efficiency varies across several orders of magnitude. By optimizing the algorithms, we find that some transform methods are sufficiently fast to transform 1-megapixel images at more than 100 frames per second on a desktop personal computer. In addition, we demonstrate the transform of gigapixel images.


Professionalization of the older medical student.
While older applicants have traditionally had difficulty being admitted to medical schools, they slowly are gaining easier acceptance at some institutions. Little is known, however, about whether or not older medical students experience the same professionalization process as younger ones and whether or not the extensive literature developed over the past 40 years is useful in understanding older students' developmental processes. Structured interviews were conducted with 26 University of Cincinnati students who were 28 or older when they matriculated as freshmen in medical school. The findings indicated not only that these students experienced different stresses from their younger classmates but also that they cope with problems and view the professionalization process differently. These results are discussed in relation to the literature. Some suggestions for educational and counseling policies are offered.


[Factors influencing glucose metabolism in young obese subjects with obstructive sleep apnea hypopnea syndrome].
To explore the factors influencing glucose metabolism in young obese subjects with obstructive sleep apnea hypopnea syndrome (OSAHS). A total of 106 young obese subjects[18-44 years old, body mass index (BMI) ≥30 kg/m(2)]were enrolled and divided into two groups based on full-night polysomnography (PSG), OSAHS group[apnea hypopnea index (AHI) ≥5 events/h]and non-OSAHS group (AHI<5 events/h). Oral glucose tolerance-insulin releasing test (OGTT-IRT) was performed and serum glycosylated hemoglobin A1 (HbA1c) levels were measured after an overnight fast. Homeostasis model assessment-IR (HOMA-IR), Matsuda insulin sensitivity index (MI), homeostasis model assessment-β (HOMA-β), the early phase insulinogenic index (ΔI(30)/ΔG(30)), total area under the curve of insulin in 180 minutes (AUC-I180) and oral disposition index (DIo) were calculated to evaluate insulin resistance and pancreatic β cell function. Stepwise multiple linear regressions were conducted to determine the independent linear correlation of glucose measurements with PSG parameters. Prevalence of diabetes was higher in OSAHS than in non-OSAHS group (22.0% vs 4.3%, P=0.009). OGTT 0, 30, 60 min glucose and HbA1c levels were higher in OSAHS group than those in non-OASHS group (all P<0.05). DIo were lower in OSAHS group than those in non-OASHS group (P=0.024), HOMA-IR, MI, HOMA-β, ΔI(30)/ΔG(30), and AUC-I(180) were similar between two groups (all P>0.05). In stepwise multiple linear regressions, OGTT 0, 30 and 60 min glucose were positively correlated with oxygen desaturation index (ODI) (β=0.243, 0.273 and 0.371 respectively, all P<0.05). HOMA-β was negatively correlated with AHI (β=-0.243, P=0.011). DIo was negatively correlated with ODI (β=-0.234, P=0.031). OSAHS worsens glucose metabolism and compensatory pancreatic β-cell function in young obese subjects, which could probably be attributed to sleep apnea related oxygen desaturation during sleep.


[Study of human smooth muscle cells seeding in biologic blood vessel matrix].
To explore the human smooth muscle cells seeding in blood vessel of minor pig after trypsin treatment and provide data for xenotransplantation and for using pig vessel in tissue engineering. HE and silver stain were used for checking the smooth muscle cells seeding in acellular blood vessel. The results showed that the smooth muscle cells seeding succeeded and the smooth muscle cells were in normal morphological distribution. These demonstrate that the pig aorta can be used for smooth muscle cells seeding, and hence for constructing new vascular grafts.


The effect of Arabic gum on frozen dough properties and the sensory assessments of the bread produced.
The use of hydrocolloids in frozen dough has become frequent as bread improvers due to their anti-staling effect. Nevertheless, the impact of both different frozen storage and Arabic gum level in non-prefermented flat dough with following thawing procedure have not been studied. This work intended to study the effect of three different ratio of Arabic gum on rheological properties of 1, 7, and 30 days of frozen storage and the quality of the bread made from. In order to gain the least detrimental effects on gluten network, we used rapid rate freezing and microwave heating in thawing stage. Rheological results showed that the unfrozen samples to which Arabic gum had been added rendered the highest resistance to extension. The resistance of gum fortified samples were less than fresh dough, however the decline was not significant in 3.0% Arabic gum dough kept in a month storage (p > .05). The similar findings were obtained for extensibility and adhesiveness; in which the maximum incorporation of Arabic gum lessen the destructive impact of long freezing storage. Addition of 3% gum could be able to retard staling through an increment in hydrophilic bonds between water molecules and amylose during thawing (p < .05). The overall rating of Arabic gum enriched samples was similar with bread made from non-frozen dough, even after 30 days of storage as indicated by the sensory evaluation of breads. Producing a chapatti-like fermented bread without long fermentation period. Formulation a frozen dough without using chemical additives. Introducing a proper use of a new defrosting method with the aim of achieving a better texture. Improvement in retarding staling by the use of Gum Arabic after 7 days.


Multimodality Imaging Approaches for Evaluating Traumatic Extremity Injuries: Implications for Military Medicine.
Significance: Military service members are susceptible to traumatic extremity injuries that often result in limb loss. Tremendous efforts have been made to improve medical treatment that supports residual limb function and health. Despite recent improvements in treatment and novel prosthetic devices, many patients experience a wide range of clinical problems within residual limbs that can negatively impact the progress of rehabilitation programs while also impairing functional capacity and overall quality of life. Recent Advances: In addition to existing standard imaging modalities that are used for clinical evaluation of patients suffering from traumatic extremity injury, novel noninvasive imaging techniques are in development that may facilitate rapid and sensitive assessment of various aspects of traumatic extremity injuries and residual limb health. Critical Issues: Despite recent advances, there remains a clinical need for noninvasive quantitative imaging techniques that are capable of providing rapid objective assessments of residual limb health at the time of initial presentation as well as after various forms of medical treatment. Future Directions: Ongoing development of imaging techniques that allow for assessment of anatomical and physiological characteristics of extremities exposed to traumatic injury should greatly enhance the quality of patient care and assist in optimizing clinical outcomes.


Effects of neratinib and combination with irradiation and chemotherapy in head and neck cancer cells.
Prognosis of patients with head and neck squamous cell carcinoma (HNSCC) is still poor. Novel therapeutic approaches are of great interest to improve the effects of radiochemotherapy. We evaluated the effects of tyrosine kinase inhibitor neratinib on HNSCC cell lines CAL27, SCC25 and FaDu as a single agent and in combination with irradiation and chemotherapy. Effects of neratinib were evaluated in HNSCC cell lines CAL27, SCC25 and FaDu. Effect on cell viability of neratinib and combination with cisplatin and irradiation was measured using CCK-8 assays and clonogenic assays. Western blot analysis was performed to distinguish the effect on epithelial growth factor receptor and HER2 expression. Apoptosis was evaluated by flow cytometry analysis. Growth inhibition was achieved in all cell lines, whereas combination of cisplatin and neratinib showed greater inhibition than each agent alone. Apoptosis was induced in all cell lines. Combination of neratinib with irradiation or cisplatin showed significantly increased apoptosis. In clonogenic assays, significant growth inhibition was observed in all investigated cell lines. Neratinib, as a single agent or in combination with chemo-irradiation, may be a promising treatment option for patients with head and neck cancer.


Web app based patient education in psoriasis - a randomized controlled trial.
Patients report wanting more information about psoriasis and clear expectations from the onset of therapy. Dermatologists do not think patients receive or internalize adequate information. There isa need for further explanation of treatment regimens to increase knowledge, compliance, and patient satisfaction. Recent advancements in web technology have the potential to improve these psoriasis outcomes. A web based application was created to educate psoriasis patients using video, graphics, and textual information. An investigator blinded, randomized, controlled study evaluated the website's efficacy in 50 psoriasis patients at Wake Forest Baptist Health Dermatology. Patients were randomized into two groups: Group 1 received a link to the educational web app and a survey following their visit; Group 2 received a link to the survey with no educational web app. The survey assessed patient knowledge, self reported adherence to medication, and adequacy of addressing concerns. Twenty two patients completed the study. Patients in the web app group scored an average of 11/14 on the psoriasis knowledge quiz, whereas patients in the control group scored an average of 9/14 for an improvement of roughly 18% (p=0.008, n=22). Web app based education via DermPatientEd.Com is an efficient way to improve knowledge, but we did not demonstrate improvements in self-reported medication adherence or the ability to address concerns of psoriasis patients.


Allele-specific effects of PDF2 on floral morphology in Arabidopsis thaliana.
The class IV Homeodomain-leucine zipper (HD-ZIP IV) gene family includes several genes that are functionally significant in epidermal development. Our recent study revealed that double mutants of the epidermis-expressed HD-ZIP IV members, PROTODERMAL FACTOR2 (PDF2) in combination with some HOMEODOMAIN GLABROUS (HDG, pronounced "hedge") genes, affect stamen development and specification of petal and stamen identity, possibly in a non cell-autonomous manner. However, the effect of the pdf2 mutations on the floral development was largely different depending on T-DNA insertion locations: pdf2-1 hdg flowers exhibited homeotic conversion of petals and stamens, while pdf2-2 hdg flowers had only a reduced number of stamens. Here, we used 2 additional pdf2 alleles to make double mutants and found that their floral phenotypes were rather similar to those of pdf2-2 hdg. The allele-specific effect caused by pdf2-1, which carries a T-DNA in a steroidogenic acute regulatory protein-related lipid transfer (START) domain-encoding region, suggests the importance of the START domain in proper function of HD-ZIP IV proteins.


[A case of pulmonary thromboembolism due to idiopathic thrombosis of inferior vena cava, which was initially misdiagnosed as pneumonia].
We report a case of a 73-year-old man with pulmonary embolism due to idiopathic thrombosis of the inferior vena cava. He was referred to our hospital because of a fever and cough of 2 weeks' duration despite treatment with an oral antibiotic. Chest radiography on the first visit showed an infiltrate in the right middle lung field. He was diagnosed as having pneumonia and admitted to our hospital for treatment. Following administration of intravenous antibiotics, his symptoms disappeared and the chest radiography findings improved. The abdominal CT obtained in an attempt to visualize the cause of liver dysfunction serendipitously revealed thrombosis of the inferior vena cava, which was suspected to have caused the pulmonary embolism. A subsequent lung perfusion scan revealed marked perfusion defects in the right middle and lower lobes. Chest CT revealed an embolus located in the right pulmonary artery. Since thrombolytic therapy was not effective, the placement of a filter in the inferior vena cava was performed to prevent the recurrence of pulmonary embolism. The patient has been asymptomatic without recurrence of the disease since the filter insertion.


Estimation of nutrient excretion factors of broiler and layer chickens in Japan.
We estimated the nitrogen (N), phosphorus (P), potassium (K) and magnesium (Mg) excretion factors of broiler and layer chickens in Japan, using two approaches and the latest data available. In the top-down approach, we determined the nutrient amounts in the feeds and those in the products (i.e. the liveweight gain, eggs), and the national nutrient excretions were determined as the difference between these amounts. We then calculated the nutrient excretion factors by dividing the national excretions by the number of animals. In the bottom-up approach, we calculated the amounts of nutrients in the feed and product per head using productivity parameters (feed conversion ratio, etc.). The differences between these amounts were considered the nutrient excretion factors. The average nutrient excretion factors of broilers (g/day/head) estimated using the top-down and bottom-up approaches were: N, 1.40 and 1.87; P, 0.36, 0.50; K, 0.54, 0.77; Mg, 0.13, 0.18, respectively. The excretion factors obtained by the top-down approach can be used to calculate the national/regional excretions. The two approaches resulted in almost the same excretion factors for layers, and the average nutrient excretion factors of layers (g/day/head) estimated were: N, 2.20; P, 0.55; K, 0.68; Mg, 0.23. The estimated excretion factors for N (only) are smaller than the reported factors.


45,X/46,X,i(Yp): Importance of Assessment and Support during Puberty and Adolescence.
The Y-chromosome genes are primarily involved in sex determination, stature control, spermatogenesis, and fertility. Among structural rearrangements of the Y chromosome, the isochromosome of Yp, i(Yp), appears to be the most uncommon. We describe a detailed evolution of puberty in a boy with 45,X/46,X,i(Yp). Array CGH found 2 cell lines, one with i(Yp) and the other with monosomy X. Genetic analysis of currently known genes involved in Kallmann syndrome/normosomic central hypogonadotropic hypogonadism showed no abnormality. The patient presented with a pubertal course suggestive of a delayed puberty with gynecomastia, reduced growth rate, and infertility that need testosterone treatment to induce the appearance of the secondary sex characteristics. This patient shows the potential effects of i(Yp) and emphasizes the importance of appropriate management of puberty in people with 45,X/46,X,i(Yp). Early hormone treatment, concerns regarding fertility, emotional support, and a successful transition to adult care may help improve the physical and psychosocial well-being of affected patients.


Structural parameters associated with location of peaks of peripapillary retinal nerve fiber layer thickness in young healthy eyes.
The location of the peaks of the circumpapillary retinal nerve fiber layer (cpRNFL) thickness is affected by several ocular parameters. In this study, we have generated equations that can determine the peaks of the cpRNFL. This study was a prospective, observational, cross sectional study of 118 healthy right eyes. The axial length, optic disc tilt, superiortemporal (ST)- and inferiortemporal (IT)-peaks of the cpRNFL thickness, and angles of the ST and IT retinal arteries (RA) and veins (RV) were determined. The correlations between the location of the ST- and IT-peaks and ocular structural parameters and the sex, body height and weight were calculated. The best fit equations to generate the location of the ST/IT-peaks were determined using corrected-Akaike Information Criteria. The location of the ST-peak was 0.72+(0.40 x ST-RA)+(0.27 x ST-RV)+(0.14 x height)-(0.47 x papillo-macular-position)-(0.11 x disc tilt) with a coefficient of correlation of 0.61 (P<0.0001). The location of the IT-peak was 21.88+(0.53 x IT-RA)+(0.15 x IT-RV)+(0.041 x corneal thickness)-(1.00 x axial length) with a coefficient of correlation of 0.59 (P<0.0001). The location of ST/IT peaks is determined by different parameters of the ocular structure. These equations allow clinicians to obtain an accurate location of the peaks for a more accurate diagnosis of glaucoma.


Effects of GnRH and the dual regulatory actions of GnIH in the pituitary explants and brain slices of Astyanax altiparanae males.
The pituitary gonadotropins, Fsh (follicle-stimulating hormone) and Lh (luteinizing hormone), regulate testicular development and functions in all vertebrates. At the pituitary, different signaling systems regulate the synthesis and secretion of the gonadotropins, such as the hypothalamic neuropeptides GnRH (gonadotropin-releasing hormone) and GnIH (gonadotropin-inhibitory hormone). While GnRH exerts stimulatory roles, the actions of GnIH remain controversial for many teleost species. Therefore, the aim of this study was to evaluate the in vitro effects of chicken GnRH2 (cGnRH2) and zebrafish GnIH-3 (zGnIH-3) on the male gonadotropin and GnRH system expression using pituitary explants and brain slices from a neotropical species with economical and ecological relevance, Astyanax altiparanae. Our results showed that in males, cGnRH2 increased fshb and lhb mRNA levels in the pituitary explants. Interestingly, zGnIH-3 has no effect on basal gonadotropin expression, however zGnIH-3 decreased the cGnRH2-induced fshb and lhb transcripts in male pituitary explants. In the male brain slices, zGnIH-3 showed stimulatory effects, increasing gnrh2 mRNA levels. Overall, our results suggested that GnIH seems to have dual regulatory actions on gonadotropin and GnRH2 expression of A. altiparanae males. This study provided basic information on endocrine regulation of A. altiparanae reproduction, and the obtained results will expand our knowledge, improving the reproductive management of this economically important freshwater species.


Carcinogenic uterine risk of repeated abortions: hormone receptors tumoral expression.
The main objective of this study is to draw the attention that repeated induced abortions in the women's physiological history are very dangerous and could lead to developing uterine cancer. The legislation regarding this practice is variable in different countries. Relevant information in the field concerning the numerous risk factors that appear with abortions must be taught in schools before girls start their sexual life and can help avoiding the complications that may follow. Also, the abortion should be an extreme measure that must be used only in extreme cases that threaten the mother's life or imply the health of the future child. The study comprised 258 women diagnosed with endometrial carcinoma, without any risks factors for this type of cancer, which were questioned regarding the abortions in previous history. The results show that the age when the uterine carcinoma appears is even lower as the number of abortions is higher and the number of this type of cancer cases is directly proportional with the number of abortions suffered. In order to avoid this fact we have to pay more attention to the legislation and education of the patients. Also, we followed the expression of both estrogen and progesterone hormone receptors, in the case of uterine cancer that occurred in women who had abortions in history compared to the expression of hormone receptors in the case of patients who did not have abortions.


Imaging of spiking and subthreshold activity of mitral cells with voltage-sensitive dyes.
To obtain a more complete description of individual neurons, it is necessary to complement electrical measurements with technologies such as voltage imaging with intracellular dyes, which permit massive parallel recording from many sites on neuronal processes. Utilizing such an approach, we investigate the functional structure of the mitral cell, the principal output neuron in the rat olfactory bulb. These experiments were designed to determine the number, location, and the stability of spike trigger zones, the excitability of terminal dendritic branches, the pattern and nature of spike initiation and propagation in the primary dendrite, the basic characteristics of the evoked EPSPs at the site of origin (the glomerular tuft), and its attenuation along the primary dendrite. The images of spike trigger zones showed that an action potential can be initiated in three different compartments of the mitral cell: the soma-axon region, the primary dendrite trunk, and the terminal dendritic tuft, which appears to be fully excitable. The amplitude of the EPSPs evoked by olfactory nerve stimulation was determined at the site of origin (glomerular tuft) and its attenuation was monitored optically along the entire length of the primary dendrite.


Re-evaluating the TCLP's Role as the Regulatory Driver in the Management of Municipal Solid Waste Incinerator Ash.
Up to 30% of the municipal solid waste (MSW) that is incinerated for energy recovery ends up as MSW incinerator (MSWI) ash. In light of the large volume of MSWI ash and the expenses and regulatory burden if this ash were managed as a hazardous waste, U.S. MSWI facilities place great emphasis on ensuring MSWI ashes pass the toxicity characteristic leaching procedure (TCLP). The focus on passing the TCLP has the unintended consequence of making recycling more difficult and arguably making the ash less benign. This policy analysis examines current U.S. MSWI ash management practices in relation to the TCLP, and discusses the role of the TCLP as a regulatory driver in the management of MSWI ashes. A review of existing information, example data, and common MSWI ash management practices provide insight into potential issues with the current approach and opportunities for alternative directions.


Comparison of striatal 18F-dopa uptake in adult-onset dystonia-parkinsonism, Parkinson's disease, and dopa-responsive dystonia.
We studied six patients with adult-onset dystonia-parkinsonism (DYS-P) with 18F-6-fluoro-dopa (18F-dopa) positron emission tomography and compared their influx constants (Ki values) with those of six patients with classical childhood-onset dopa-responsive dystonia (DRD), 12 age-matched Parkinson's disease (PD) patients without dystonia, and 21 normal controls. The DYS-P group had significantly reduced mean caudate (67% of normal) and putamen (45% of normal) 18F-dopa uptake. These Ki values were similar to mean caudate and putamen Ki values obtained for the PD group. In contrast, the DRD group showed minor reductions in mean caudate (9%) and putamen (18%) 18F-dopa uptake when compared with normals. The mean caudate:putamen Ki ratio was 1.7 in the DYS-P group and 2.1 in the PD group. In the DRD and normal groups, the caudate:putamen ratios were close to unity. The findings of this study are that adult-onset DYS-P targets the nigrostriatal dopaminergic projections in a pattern similar to PD, with the putamen being more affected. This provides support for the hypothesis that DYS-P may be a phenotypic variant of Lewy body disease. DYS-P seems distinct from childhood-onset DRD, in which striatal 18F-dopa uptake is either normal or only mildly reduced.


PANRETINAL RITONAVIR-INDUCED RETINOPATHY: A REPORT OF LONG-TERM USE.
To report a case involving a patient with presumed panretinal ritonavir-induced retinopathy. A 52-year-old, HIV-positive patient, with no criteria for AIDS associated with the use of ritonavir for more than 10 years, underwent clinical examination, fundus photography, spectral domain optical coherence tomography, and fundus autofluorescence imaging. Fundus examination revealed areas of atrophy and hypertrophy in the retinal pigment epithelium throughout the retina. Laboratory tests for other diseases were all negative. HIV-positive patients undergoing ritonavir therapy should be carefully followed in the presence of low-acuity vision complaints and retinal changes.


Ndj1p, a meiotic telomere protein required for normal chromosome synapsis and segregation in yeast.
The Saccharomyces cerevisiae gene NDJ1 (nondisjunction) encodes a protein that accumulates at telomeres during meiotic prophase. Deletion of NDJ1 (ndj1Delta) caused nondisjunction, impaired distributive segregation of linear chromosomes, and disordered the distribution of telomeric Rap1p, but it did not affect distributive segregation of circular plasmids. Induction of meiotic recombination and the extent of crossing-over were largely normal in ndj1Delta cells, but formation of axial elements and synapsis were delayed. Thus, Ndj1p may stabilize homologous DNA interactions at telomeres, and possibly at other sites, and it is required for a telomere activity in distributive segregation.


The pathophysiology of inspiratory muscle fatigue.
The critical value of the rate of energy consumption of the inspiratory muscles above which fatigue occurs appears in some instances to be predictable from the relationship between energy demands and energy supplies rather than from the percentage of fatigue-resistant fibres in the inspiratory muscles. When this is the case the critical value of the external power produced by the inspiratory muscles is given by the product of muscular efficiency and the rate at which energy is supplied. Efficiency is reduced by hyperinflation and recruitment of the intercostal and accessory muscles of inspiration. The rate at which energy is supplied is decreased in states characterized by low cardiac output. The condition of low cardiac output, combined with the high oxygen cost of breathing against fatiguing loads, may be lethal in cardiogenic shock. Although the immediate cause of fatigue may not be related to reduced energy supplies, clinically useful predictions of conditions predisposing to fatigue result from an understanding of factors determining the balance between the energy demands and supplies of the inspiratory muscles. These predictions aid in the diagnosis of inspiratory muscle fatigue and have important therapeutic implications.


Alkene Transfer Hydrogenation with Alkaline-Earth Metal Catalysts.
The alkene transfer hydrogenation (TH) of a variety of alkenes has been achieved with simple AeN''2 catalysts [Ae=Ca, Sr, Ba; N''=N(SiMe3 )2 ] using 1,4-cyclohexadiene (1,4-CHD) as a H source. Reaction of 1,4-CHD with AeN''2 gave benzene, N''H, and the metal hydride species N''AeH (or aggregates thereof), which is a catalyst for alkene hydrogenation. BaN''2 is by far the most active catalyst. Hydrogenation of activated C=C bonds (e.g. styrene) proceeded at room temperature without polymer formation. Unactivated (isolated) C=C bonds (e.g. 1-hexene) needed a higher temperature (120 °C) but proceeded without double-bond isomerization. The ligands fully control the course of the catalytic reaction, which can be: 1) alkene TH, 2) 1,4-CHD dehydrogenation, or 3) alkene polymerization. DFT calculations support formation of a metal hydride species by deprotonation of 1,4-CHD followed by H transfer. Convenient access to larger quantities of BaN''2 , its high activity and selectivity, and the many advantages of TH make this a simple but attractive procedure for alkene hydrogenation.


Corrigendum.
Cavalli, E., Colé, P., Leloup, G., Poracchia-George, F., Sprenger-Charolles, L., & El Ahmadi, A. (2017). Screening for dyslexia in French-speaking university students: An evaluation of the detection accuracy of the Alouette test. Journal of Learning Disabilites. Advance online publication. (Original doi: 10.1177/0022219417704637 ) In the version of this article originally published OnlineFirst, the funding statement was incorrect. The correct funding statement is as follows: Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Labex BLRI (ANR-11-LABX-0036), managed by the French National Agency for Research (ANR), under the project title Investments of the Future A*MIDEX (ANR-11-IDEX-0001-02). Subsequent versions of the article will be corrected.


Stability of Hemoglobin Constant Spring Identified by Capillary Electrophoresis.
Hemoglobin Constant Spring (HbCS) is often missed by routine hemoglobin analysis. The aim of this research was to study HbCS stability as identified by capillary electrophoresis (CE) to determine the specimen storage time limit. The EDTA blood of 29 HbCS samples were kept at 4°C and analyzed every workday until CE could not detect HbCS or until 7 weeks after blood collection. The genotypes were confirmed by multiplex polymerase chain reaction. The median subject age was 27 years and 10 subjects were male. The HbCS levels were stable during the first 7 days but became undetectable in 5 cases (17.2%) after 1 week. All of them were heterozygous HbCS. Longer detection times were correlated with the higher baseline HbCS levels, with a correlation coefficient of 0.582 (P ≤ 0.001). Routine hemoglobin typing and quantitation should be performed within 1 week after blood collection to detect low HbCS levels, especially in heterozygous HbCS.


Neural damage in the guinea pig cochlea after noise exposure. A light microscopic study.
Neural damage produced by exposure to 8 kHz octave-band noise was studied by light microscopy in guinea pigs. Abnormal nerve endings were found beneath both inner and outer hair cells within 24 hours after exposure at either 118 or 120 dB SPL. In areas where the organ of Corti was destroyed degeneration of myelinated nerve fibers was seen immediately after 24-hour exposures. Nerve degeneration secondary to hair cell loss was observed. However, degeneration of myelinated fibers occurred in some cases without significant hair cell loss. At survival times as long as two months nerve fibers coursing near capillaries were still present in extensively damaged areas. In three animals nerve fibers which had apparently regenerated into regions where the sensory epithelium was destroyed were found distal to the habenula perforata. Evdence of regenerative activity was also noted in the osseous spiral lamina.


Miniaturized Continuous-Flow Digital PCR for Clinical-Level Serum Sample Based on the 3D Microfluidics and CMOS Imaging Device.
In recent years, the development of polymerase chain reaction (PCR) technology has focused on digital PCR, which depends on the microfluidics. Based on continuous-flow microfluidic technology, this paper designed a miniaturized digital PCR amplification system, and greatly reduced the area required for microdroplet generation and reaction. The core rod. made of polydimethylsiloxane (PDMS), was combined with the Teflon tube to form 3D microfluidics, which requires only one heating source to form the temperature difference required for gene amplification. Only two 34 g needles can form and transmit micro-droplets in a 4-fold tapered Teflon tube, which is the simplest method to generate digital PCR droplets as far as we know, which allows the microdroplet generation device to be free from dependence on expensive chips. A complementary metal oxide semiconductor (CMOS) camera was used as a detection tool to obtain fluorescence video for the entire loop area or a specified loop area. In addition, we developed a homebrew for automatic image acquisition and processing to realize the function of digital PCR. This technique realizes the analysis of clinical serum samples of hepatitis B virus (HBV) and obtained the same results as real-time quantitative PCR. This system has greatly reduced the size and cost of the entire system, while maintaining a stable response.


EPISTASIS AND THE EVOLUTION OF ADDITIVE GENETIC VARIANCE IN POPULATIONS THAT PASS THROUGH A BOTTLENECK.
Traditional models of genetic drift predict a linear decrease in additive genetic variance for populations passing through a bottleneck. This perceived lack of heritable variance limits the scope of founder-effect models of speciation. We produced 55 replicate bottleneck populations maintained at two male-female pairs through four generations of inbreeding (average F = 0.39). These populations were formed from an F2 intercross of the LG/J and SM/J inbred mouse strains. Two contemporaneous control strains maintained with more than 60 mating pairs per generation were formed from this same source population. The average level of within-strain additive genetic variance for adult body weight was compared between the control and experimental lines. Additive genetic variance for adult body weight within experimental bottleneck strains was significantly higher than expected under an additive genetic model This enhancement of additive genetic variance under inbreeding is likely to be due to epistasis, which retards or reverses the loss of additive genetic variance under inbreeding for adult body weight in this population. Therefore, founder-effect speciation processes may not be constrained by a loss of heritable variance due to population bottlenecks.


Immunopathology of periodontal disease. II. Immunofluorescent studies on the localized immune response in periodontitis and juvenile periodontitis.
Local immunologic responses were studied in eleven patients with periodontitis, ten patients with juvenile periodontitis, and ten control subjects by performing immunofluorescence on gingival biopsies. F(ab')2 monospecific conjugates to human IgG, IgM, IgA, IgD, and kappa and lambda light chains were used as well as monospecific conjugates to human IgE and properdin. Biopsies from patients with juvenile periodontitis displayed a more intensified immunologic response as evidenced by increases of (I) positive cells stained with a F(ab')2 antihuman immunoglobulin conjugate; (2) IgG, IgM, and kappa and lambda containing cells; (3) extracellular fluorescence of IgG, IgM, IgA, and kappa and lambda light chains; and (4) properdin deposition. Neither IgD nor IgE conjugates reacted significantly with biopsies from the three patient groups. These findings support our previous conclusion that immunologic responses in periodontitis and juvenile periodontitis appear qualitatively similar, but that patients with juvenile periodontitis exhibit a more intense immune response.


Topographic principles of cortical fluid-attenuated inversion recovery signal in temporal lobe epilepsy.
In drug-resistant temporal lobe epilepsy (TLE), relative to the large number of whole-brain morphological studies, neocortical T2 changes have not been systematically investigated. The aim of this study was to assess the anatomical principles that govern the distribution of neocortical T2-weighted fluid-attenuated inversion recovery (FLAIR) signal intensity and uncover its topographic principles. Using a surface-based sampling scheme, we mapped neocortical FLAIR intensity of 61 TLE patients relative to 38 healthy controls imaged at 3 T. To address topographic principles of the susceptibility to FLAIR signal changes in TLE, we assessed associations with normative data on tissue composition using 2 complementary approaches. First, we evaluated whether the degree of TLE-related FLAIR intensity changes differed across cytoarchitectonic classes as defined by Von Economo-Koskinas taxonomy. Second, as a proxy to map regions with similar intracortical composition, we carried out a FLAIR intensity covariance paradigm in controls by seeding systematically from all cortical regions, and identified those networks that were the best spatial predictors of the between-group FLAIR changes. Increased intensities were observed in bilateral limbic and paralimbic cortices (hippocampus, parahippocampus, cingulate, temporopolar, insular, orbitofrontal). Effect sizes were highest in periallocortical limbic and insular classes as defined by the Von Economo-Koskinas cytoarchitectonic taxonomy. Furthermore, systematic FLAIR intensity covariance analysis in healthy controls revealed that similarity patterns characteristic of limbic cortices, most notably the hippocampus, served as sensitive predictors for the topography of FLAIR hypersignal in patients. FLAIR intensity findings were robust against correction for morphological confounds. Patients with a history of febrile convulsions showed more marked signal changes in parahippocampal and retrosplenial cortices, known to be strongly connected to the hippocampus. FLAIR intensity mapping and covariance analysis provide a model of TLE gray matter pathology based on shared vulnerability of periallocortical and limbic cortices.


Prevention of post-spinal hypotension using crystalloid, colloid and ephedrine with three different combinations: A double blind randomized study.
The benefit of prophylactic combination therapy using crystalloid and colloid preload with ephedrine has not been cleared to prevent maternal hypotension after spinal anesthesia at cesarean delivery. This study evaluated the efficacy of three combinational methods to prevent hypotension following spinal anesthesia. In this prospective double blind trial, 150 candidates of elective cesarean delivery under spinal anesthesia were randomly allocated to three treatment groups; 1---Ringer's Lactate (RL) solution (15 ml/kg) plus Hemaxel (7 ml/kg) preload, 2---RL solution (15 ml/kg) preload plus ephedrine (15 mg, IV, bolus), 3---Hemaxel (7 ml/kg) preload plus ephedrine (15 mg, IV, bolus). Maternal hemodynamic changes during 60 min after spinal injection, nausea/vomiting, and neonatal condition were compared among the groups. The cumulative incidence of hypotension was 44%, 40%, and 46% in groups 1 to 3, respectively. There were not significant differences in supplementary ephedrine requirement among groups which received or among groups which did not receive prophylactic ephedrine. Groups were not different in the incidence of hypertension and nausea or vomiting. There were no significant differences among groups in Apgar scores at 1 or 5 min and umbilical artery PH. Combination of preventive methods decreased the occurrence of hypotension following spinal anesthesia to an acceptable level. Overall, the most effective method was a combination of crystalloid preload with ephedrine.


Validation of the LASA fall risk profile for recurrent falling in older recent fallers.
The fall risk profile developed in the Longitudinal Aging Study Amsterdam (LASA) identifies community-dwelling elderly at high risk for recurrent falling. This study assessed the predictive validity of this profile in older persons seeking care after a fall. The LASA fall risk profile was completed for 408 persons of 65 years and older who consulted the emergency department or general practitioner after a fall. Falls were prospectively reported with a calendar during 1 year. Recurrent falling was defined as ≥ 2 falls within a period of 6 months. During 1 year of followup, 76 (18.6%) participants became recurrent fallers. The area under the receiver operating characteristic curve was 0.65 (95% confidence interval [95% CI]: 0.58-0.72). At a cutoff value of 8, the sensitivity was 56.6% (CI: 51.8-61.4), the specificity was 71.4% (CI: 67.0-75.8), the positive predictive value was 34.1% (CI: 29.5-38.7), and the negative predictive value was 85.6% (CI: 82.2-89.0). The discriminative ability of the LASA fall risk profile was moderate. The predictive validity of the LASA fall risk profile to identify recurrent fallers is limited among older persons who consulted the emergency department or general practitioner after a fall.


The organization of visually mediated actions in a subject without eye movements.
We investigated the visual strategy of a subject without eye movements (AI), comparing her with normal subjects on the 'real-life' task of making a cup of tea. Differences in overall performance were surprisingly few. She took no more time than the controls to complete the tea-making task and the division of the task into object-related actions was essentially similar. However, the way AI took in visual information was very different from the normal subjects who used a typical 'saccade and fixate' strategy when moving between and scrutinizing objects. AI made saccades with the head, which were on average 1.5 times larger than the eye-head saccades of the controls and lasted four times as long, meaning that AI would have had impaired vision for more of the time than the controls. She also made only approximately one-third as many saccades as normals during the same task. However, she had another strategy, 'slow drift', in which she allowed her eyes to move smoothly across the scene at speeds of up to 30 degrees /s. Such movements were never seen in the controls, and we assume that AI used them to offset the cost in time of the slow head saccades, even though they had their own cost in terms of reduced resolution. We demonstrate that these differences have a minimal effect on the timings of events during an object-related action. We discuss supervisory checking operations within actions, and consider what information is needed for appropriate gaze control during object-related actions.