Utility of indocyanine green fluorescence lymphography in identifying the source of persistent groin lymphorrhea.
Surgical manipulation of the groin can result in lymphatic injury in a significant number of patients leading to poor wound healing or infectious complications. Surgical repair of lymphatic injury is greatly aided by the precise and prompt intraoperative localization of the injured lymphatic vessels. We assessed and identified lymphatic leaks in 2 cases of surgical wound lymphorrhea occurring after instrumentation of the groin using laser-assisted indocyanine green lymphography paired with isosulfan blue injection. Both cases healed without complication, and no lymphatic leak recurrence was observed during postoperative follow-up. Laser-assisted indocyanine green lymphography is a useful adjunct in the management of lymphatic leaks after surgery of the groin and may have potential for prophylactic evaluation of high-risk groin wounds.


[Determination of sensitivity of biofilm-positive forms of microorganisms to antibiotics].
Nosocomial infections caused by biofilm-positive microorganisms are a serious therapeutic problem. In the biofilm, microorganisms are protected against adverse effects of the external environment, including the action of antibiotics. It is well known that the values of minimum inhibitory concentrations (MIC) determined for planktonic forms do not correspond to the actual concentrations of antibiotics necessary for the eradication of bacteria in a biofilm. The purpose of the study was to propose a method of determining minimum biofilm inhibitory concentrations (MBIC) and minimum biofilm eradication concentrations (MBEC) and to compare these values with MIC values. Biofilm-positive strains of Staphylococcus epidermidis were cultured so as to form a biofilm layer on polystyrene pegs. The biofilm on the pegs was then exposed to the action of antibiotics and after 18 hours we determined the minimum biofilm inhibitory concentration (MBIC). The evaluation of minimum biofilm eradication concentrations was done colorimetrically from the metabolic activity of surviving cells. MBIC and MBEC values were many times higher than MIC values. We selected such a duration of the biofilms cultivation on the pegs of the plate, which ensured that the number of bacterial cells corresponded to standard MIC assessment. The MBEC values established in our study indicate that the currently used concentrations of tested antibiotics cannot be used in monotherapy for an efficacious eradication of a biofilm. The MBEC determination is a far more laborious and time-consuming method than the determination of MIC, but the use of plates with pegs facilitates the handling of biofilms. The advantage of our method is the possibility of standardization of the size of the inoculum and thus of the whole MBEC assessment.


USG-guided continuous erector spinae block as a primary mode of perioperative analgesia in open posterolateral thoracotomy: A report of two cases.
The postoperative pain management in open thoracotomy is very crucial as the effective analgesia can prevent respiratory and thrombotic complications and lead to early mobilization and discharge. The thoracic epidural analgesia is the gold standard in such surgeries; however, there are few adverse effects such as hypotension, dural puncture, and contralateral block that always warrants safer alternative. Recently, with the advent of ultrasound, the regional anesthetic techniques are getting more popular to avoid such complications. Erector spinae plane (ESP) block is one of the novel techniques that has been described as a safe thoracic paravertebral block. We are reporting here the continuous ESP block as a primary mode of postoperative analgesia which was continued for 48 h. The intraoperative opioid requirement was very less, and the maximum NRS score in postoperative period was 4 at 12 h, which was well managed with multimodal analgesic regimen along with rescue doses of opioid.


Micro-wear patterns on UHMWPE tibial inserts in total knee joint simulation.
The objective of this study was to examine both simulator and retrieved total knee replacement polyethylene inserts to confirm, using scanning electron microscopy, whether similar micro-wear patterns to those seen on retrieved inserts were reproduced on simulator specimens. The simulator specimens consisted of samples subjected to sliding and rolling movement (Experiment 1) and to sliding movement only (Experiment 2). Samples from Experiment 1 demonstrated longitudinal patterns in the middle of the wear track and transverse patterns in the anterior and posterior ends, whereas in Experiment 2, only transverse patterns were observed. In the retrieved specimens, both longitudinal and transverse patterns were observed. The results showed that the simulator study reproduced similar patterns of micro-damage on polyethylene, and that the longitudinal micro-wear pattern was related to the rolling movement that is distinctive in knee kinematics.


[Synthesis and biological activity of 1-(4-acylamino)benzyl-1,2,3,4-tetrahydroisoquinolines].
For searching more effective antiarrhythmic agents, on the basis of integration of the structural feature of certain potassium channel blockers available, various acylamino groups were introduced to the position 4 of the benzyl ring of this series of compounds. Thus, eight 1-(4-acylamino)benzyl-1,2,3,4-tetrahydroisoquinolines were designed and synthesized, which had not been reported in the literatures. Compounds V1, V2 and V6 at concentration 10(-6) mol.L-1 depressed rat aortia contraction induced by high KCl (80 mmol.L-1). The effect was similar to that of tetrandrine. Compound V6 showed potent antiarrhythmic activity at the dosage of 1 mg.kg-1.


Intermittent antegrade/selective cerebral perfusion during circulatory arrest for repair of the aortic arch.
If the aortic arch requires repair or replacement due to an aneurysm or dissection, conventional cardiopulmonary bypass (CPB) is not possible during the period in which the aortic arch is excluded from the circulation. This creates a situation in which there is no cerebral circulation. The brain needs adequate protection from this ischaemic insult. Hypothermic circulatory arrest (HCA), antegrade/selective cerebral perfusion (ASCP) and retrograde cerebral perfusion (RCP) are reported to exhibit their cerebral protective capabilities during procedures involving the aortic arch. HCA can provide adequate protection in procedures of short duration and avoids the complications associated with cerebral perfusion techniques. The main disadvantage of HCA is that the 'safe' duration of circulatory arrest is not clearly defined. Topical cooling of the head may enhance cerebral hypothermia and provide additional protection. If longer periods of circulatory arrest are anticipated or occur unexpectedly, we suggest that ASCP can offer improved cerebral protection by providing adequate brain perfusion and improved cerebral cooling. By using a coronary sinus perfusion catheter as a carotid artery cannula, it is not necessary to snare or clamp the carotid arteries. This technique minimizes the chance of damaging the carotid arteries. In this report, we describe our set-up and ASCP perfusion protocol for the surgical repair of an aortic arch aneurysm.


Autologous stem cell transplantation with in vivo purged progenitor cells shows long-term efficacy in relapsed/refractory follicular lymphoma.
High-dose chemotherapy with autologous stem cell transplantation (ASCT) has been shown effective in the control of relapsed/refractory follicular lymphoma. We evaluate the long-term outcome of patients with relapsed or refractory follicular lymphoma treated with ASCT with in vivo purged progenitors cells. We report the long-term results of a prospective multicenter phase 2 trial on 124 relapsed/refractory follicular lymphoma patients treated with a program of anthracycline-based debulking chemotherapy, immunochemotherapy, mobilization of in vivo purged PBSC followed by ASCT. Median age was 52 years; 14% of patients had grade 3A histology. Debulking chemotherapy produced CR in 16% and PR in 71%, while 13% of patients progressed. After rituximab, cyclophosphamide, vincristine, prednisone (R-COP), CR was obtained in 60% and PR in 35%; 118 patients successfully mobilized PBSC and 117 proceeded to ASCT. The harvest in all the 32 molecularly informative patients was bcl-2 negative. TRM was 0%. The 5-year PFS was 54% and the 5-year OS was 83%. After a median f-up of 6.7 years (range 1.5-13.6), 54% are still in CR. These data show that prolonged PFS is achievable in relapsed/refractory patients with high dose autologous transplantation of in vivo purged progenitor cells.


Dietary cholesterol modulates delta6 and delta9 desaturase mRNAs and enzymatic activity in rats fed a low-eFA diet.
The effects of a 1% addition of cholesterol to a diet low in EFA on FA desaturases were examined. The administration of cholesterol markedly increased the esterified cholesterol content in microsomes and total liver lipids from the first day, whereas the proportion of free cholesterol remained unaltered throughout the treatment. An excellent homeostasis in the free cholesterol content was apparently evoked by the acyl-CoA cholesterol acyltransferase. The cholesterol esters were mainly oleate, palmitate, and stearate, and the addition of cholesterol increased the relative proportions of cholesterol palmitoleate and oleate. The addition of cholesterol to a low-EFA diet induced, as in animals fed a high-EFA diet, a marked increase in liver stearoyl-CoA desaturase-1 mRNA and enzyme activity. This increased activity apparently evoked a similar enhancement of palmitoleic and oleic acids in total and microsomal liver lipids. The cholesterol-rich diet depressed the liver A6 and delta5 desaturase activity. However, the abundance of delta6 desaturase mRNA was not modified throughout the treatment. This indicates that the depressive effect is evoked at a step beyond that controlled by the mRNA level. The depression of both enzymatic activities was consistent with the decrease in the percentages of arachidonic acid and DHA in total and microsomal liver lipids. Taken together, these results indicate that through its modulating effect on the desaturases, dietary cholesterol may lead an animal or human fed low-EFA diet to a true deficiency by the decreased synthesis of the highly polyunsaturated acids derived from linoleic and alpha-linolenic acids.


Compression of 3D Point Clouds Using a Region-Adaptive Hierarchical Transform.
In free-viewpoint video, there is a recent trend to represent scene objects as solids rather than using multiple depth maps. Point clouds have been used in computer graphics for a long time, and with the recent possibility of real-time capturing and rendering, point clouds have been favored over meshes in order to save computation. Each point in the cloud is associated with its 3D position and its color. We devise a method to compress the colors in point clouds, which is based on a hierarchical transform and arithmetic coding. The transform is a hierarchical sub-band transform that resembles an adaptive variation of a Haar wavelet. The arithmetic encoding of the coefficients assumes Laplace distributions, one per sub-band. The Laplace parameter for each distribution is transmitted to the decoder using a custom method. The geometry of the point cloud is encoded using the well-established octtree scanning. Results show that the proposed solution performs comparably with the current state-of-the-art, while being much more computationally efficient. We believe this paper represents the state of the art in intra-frame compression of point clouds for real-time 3D video.


The Immune Signatures data resource, a compendium of systems vaccinology datasets.
Vaccines are among the most cost-effective public health interventions for preventing infection-induced morbidity and mortality, yet much remains to be learned regarding the mechanisms by which vaccines protect. Systems immunology combines traditional immunology with modern 'omic profiling techniques and computational modeling to promote rapid and transformative advances in vaccinology and vaccine discovery. The NIH/NIAID Human Immunology Project Consortium (HIPC) has leveraged systems immunology approaches to identify molecular signatures associated with the immunogenicity of many vaccines. However, comparative analyses have been limited by the distributed nature of some data, potential batch effects across studies, and the absence of multiple relevant studies from non-HIPC groups in ImmPort. To support comparative analyses across different vaccines, we have created the Immune Signatures Data Resource, a compendium of standardized systems vaccinology datasets. This data resource is available through ImmuneSpace, along with code to reproduce the processing and batch normalization starting from the underlying study data in ImmPort and the Gene Expression Omnibus (GEO). The current release comprises 1405 participants from 53 cohorts profiling the response to 24 different vaccines. This novel systems vaccinology data release represents a valuable resource for comparative and meta-analyses that will accelerate our understanding of mechanisms underlying vaccine responses.


Salvage of silicone-treated facial deformities using autogenous free tissue transfer.
Silicone, in the form of injectable liquid and prosthetic blocks, has been used to correct facial contour defects. However, silicone also has been associated with many complications including malposition, dyschromia, dysesthesia, contractures, infection, and fistula. Complications related to injectable-liquid and prosthetic-block silicone use in treatment of facial deformities pose a challenging surgical dilemma. Over a 15-year period, microvascular free flap technique has been used successfully as a surgical tool to correct severe soft-tissue complications of the face resulting from silicone treatment of facial contour deformities. Surgical treatment guidelines, methods, and results for treating this difficult problem with free tissue transfer are presented. In 23 patients, 24 free tissue transfers (22 inframammary extended circumflex scapular free flaps and two superficial inferior epigastric free flaps) were performed. Flap survival was 100 percent. Both hematoma and skin necrosis were encountered in three of 24 cases (12.5 percent). Revisional surgery combined with aesthetic surgical procedures was required in 20 of 24 cases (83 percent). We recommend the following surgical treatment guidelines for this unique subset of patients: silicone excision with immediate microvascular free flap reconstructive procedure when the skin and soft tissue are mildly to moderately affected, or silicone excision with delayed reconstructive procedure when the skin and soft tissue are severely affected. Free tissue transfer is a useful surgical tool for salvaging severe facial skin and soft-tissue deformities caused by previous silicone treatment.


Predictive factors for bleeding during percutaneous nephrolithotomy.
Although percutaneous nephrolithotomy (PCNL) has been accepted as a standard method for the management of large renal stones, the incidence of renal hemorrhage is relatively high. This study investigated the variables that affect bleeding during PCNL. The medical records of 370 patients who underwent PCNL by a single surgeon from January 2005 to December 2010 were reviewed retrospectively. All patients were divided into two groups according to median blood loss (lesser bleeding group and higher bleeding group). Various clinical and perioperative factors including age, sex, stone size and position, degree of hydronephrosis, operative time, underlying disease, history of anticoagulant medication, presence of previous nephrostomy catheter, stone composition, and thickness of the renal cortex were assessed. For statistical assessment, univariate and multivariate logistic regression analyses were used. The mean patient age was 48.8 years (range, 22 to 75 years). Forty-three patients (11.6%) received a transfusion and 9 patients (2.4%) underwent angioembolization after surgery. The mean blood loss was 511.8±341.3 mL. Body mass index (BMI), stone size, stone position, operation time, and degree of preoperative hydronephrosis were predictive factors for severe bleeding during PCNL. On the basis of the results achieved by a single surgeon, staghorn stones, high BMI, large stones, prolonged operation time, and absence of hydronephrosis were significantly associated with the risk of severe bleeding during PCNL.


Painting the rye genome with genome-specific sequences.
We used rye-specific repetitive DNA sequences in fluorescence in situ hybridization (FISH) to paint the rye genome and to identify rye DNA in a wheat background. A 592 bp fragment from the rye-specific dispersed repetitive family R173 (named UCM600) was cloned and used as a FISH probe. UCM600 is dispersed over the seven rye chromosomes, being absent from the pericentromeric and subtelomeric regions. A similar pattern of distribution was also observed on the rye B chromosomes, but with weaker signals. The FISH hybridization patterns using UCM600 as probe were comparable with those obtained with the genomic in situ hybridization (GISH) procedure. There were, however, sharper signals and less background with FISH. UCM600 was combined with the rye-specific sequences Bilby and pSc200 to obtain a more complete painting. With these probes, the rye chromosomes were labeled with distinctive patterns; thus, allowing the rye cultivar 'Imperial' to be karyotyped. It was also possible to distinguish rye chromosomes in triticale and alien rye chromatin in wheat-rye addition and translocation lines. The distribution of UCM600 was similar in cultivated rye and in the wild Secale species Secale vavilovii Grossh., Secale sylvestre Host, and Secale africanum Stapf. Thus, UCM600 can be used to detect Secale DNA introgressed from wild species in a wheat background.


Immunohematological characteristics of Nigerian sickle cell disease patients with osteomyelitis.
We aimed in this paper to investigate some immunohematological characteristics of Nigerian sickle cell anemia (SCA) patients with osteomyelitis. Thirty SCA patients with osteomyelitis (SO) and 30 SCA patients without osteomyelitis (S) were investigated. The PCV, WBC and platelet count were done on automated counter, while the erytorocyte sedimentation rate (ESR) was determined by Westergren's technique. C3 activator, C1-INH, IgA, IgG and IgM were estimated by the single radial immunodiffusion method. The SO patients weighed less (z =1.943, p<0.055) and were shorter (z = -2.064, p<0.039). High serum levels of IgG, IgM, C1-INH and C3 activator were also found in the SO group. ESR correlated positively with hematocrit (r=0.371, p<0.04) and C3 activator (r=0.468, p<0.03) in SO. Similarly, WBC correlated positively with C1-INH (r=0.806, p<0.01), while we also noted positive correlation between C1-INH and C3 activator (r=0.525, p<0.02). In SO, ESR correlated positively with both IgM (r=0.531, p<0.02) and C3 activator (r=0.449, p<0.05). This study suggests some derangement in immune status in Nigerian SCA patients with osteomyelitis and that C1-INH and C3 activator may be useful markers of immune status in SCA patients.


Diabetes and hypertension prevalence in homeless adults in the United States: a systematic review and meta-analysis.
We estimated hypertension and diabetes prevalence among US homeless adults compared with the general population, and investigated prevalence trends. We systematically searched 5 databases for published studies (1980-2014) that included hypertension or diabetes prevalence for US homeless adults, pooled disease prevalence, and explored heterogeneity sources. We used the National Health Interview Survey for comparison. We included data from 97366 homeless adults. The pooled prevalence of self-reported hypertension was 27.0% (95% confidence interval=23.8%, 29.9%; n=43 studies) and of diabetes was 8.0% (95% confidence interval=6.8%, 9.2%; n=39 studies). We found no difference in hypertension or diabetes prevalence between the homeless and general population. Additional health care and housing resources are needed to meet the significant, growing burden of chronic disease in the homeless population.


The advanced photon source: performance and results from early operation.
The Advanced Photon Source at Argonne National Laboratory is now providing researchers with high-brilliance undulator radiation from below 1 keV to beyond 100 keV. All technical facilities and components are operational and have met design specifications. Fourteen research teams, with responsibility for 40 beamlines on the APS experiment hall floor, are currently installing beamline instrumentation or actively taking data. An overview is presented for the first operational year of the Advanced Photon Source. Emphasis is on the performance of accelerators and insertion devices, as well as early scientific results and future plans.


A comparison of the myocardial depressant effects of several aminoglycoside antibiotics.
The myocardial depressant action of aminoglycosides has been known for a number of years but there was no available data on newer derivatives. We have thus studied the contractile responses of isolated guinea pig left atria to increasing concentrations of gentamicin, tobramycin, lividomycin and amikacin (0.02, 0.04, 0.08, 0.13, 0.17 and 0.22 mM). Our results are consistent with those of previous workers and show that newer aminoglycosides do exert a similar depressant action. As gentamicin and tobramycin are more depressant than lividomycin, then amikacin at similar concentrations, no clear-cut difference was obtained when respecting a relative range of concentrations mimicking that of clinical situations. However, these depressant effects were attained using concentrations far exceeding those reached in man.


A novel urinary biomarker protein panel to identify children with ureteropelvic junction obstruction - A pilot study.
Reliable urinary biomarker proteins would be invaluable in identifying children with ureteropelvic junction obstruction (UPJO) as the existing biomarker proteins are inconsistent in their predictive ability. Therefore, the aim of this study was to identify consistent and reliable urinary biomarker proteins in children with UPJO. To identify candidate biomarker proteins, total protein from age-restricted (<2 years) and sex-matched (males) control (n = 22) and UPJO (n = 21) urine samples was analyzed by mass spectrometry. Proteins that were preferentially identified in UPJO samples were selected (2-step process) and ranked according to their diagnostic odds ratio value. The top ten proteins with highest odds ratio values were selected and tested individually by ELISA. The total amount of each protein was normalized to urine creatinine and the median with interquartile ranges for control and UPJO samples was determined. Additionally, fold change (UPJO/Control) of medians of the final panel of 5 proteins was also determined. Finally, we calculated the average + 3(SD) and average + 4(SD) values of each of the 5 proteins in the control samples and used it as an arbitrary cutoff to classify individual control and UPJO samples. In the first step of our selection process, we identified 171 proteins in UPJO samples that were not detected in the majority of the control samples (16/22 samples, or 72.7%). Of the 171 proteins, only 50 proteins were detected in at least 11/21 (52.4%) of the UPJO samples and hence were selected in the second step. Subsequently, these 50 proteins were ranked according to the odds ratio value and the top 10 ranked proteins were validated by ELISA. Five of the 10 proteins - prostaglandin-reductase-1, ficolin-2, nicotinate-nucleotide pyrophosphorylase [carboxylating], immunoglobulin superfamily-containing leucine-rich-repeat-protein and vascular cell adhesion molecule-1 were present at higher levels in the UPJO samples (fold-change of the median protein concentrations ranging from 2.9 to 9.4) and emerged as a panel of biomarkers to identify obstructive uropathy. Finally, the order of prevalence of the 5 proteins in UPJO samples is PTGR1>FCN2>QPRT>ISLR>VCAM1. In summary, this unique screening strategy led to the identification of previously unknown biomarker proteins that when screened collectively, may reliably distinguish between obstructed vs. non-obstructed infants and may prove useful in identifying informative biomarker panels for biological samples from many diseases.


Explaining the association between music training and reading in adults.
We sought to clarify whether the positive association between music lessons and reading ability is explained better by shared resources for processing pitch and temporal information, or by general cognitive abilities. Participants were native and nonnative speakers of English with varying levels of music training. We measured reading ability (comprehension and speed), music-perception skills (melody and rhythm), general cognitive ability (nonverbal intelligence, short-term memory, and working memory), and socioeconomic status (SES; family income, parents' education). Reading ability was associated positively with music training, English as a native language, and general cognitive ability. The association between reading and music training was significant after SES, native language, and music-perception skills were controlled. After general cognitive abilities were held constant, however, there was no longer an association between reading and music training. These findings suggest that the association between reading ability and music training is a consequence of general cognitive abilities. (PsycINFO Database Record


Acylpeptide hydrolase is a novel regulator of KRAS plasma membrane localization and function.
The primary site for KRAS signaling is the inner leaflet of the plasma membrane (PM). We previously reported that oxanthroquinone G01 (G01) inhibited KRAS PM localization and blocked KRAS signaling. In this study, we identified acylpeptide hydrolase (APEH) as a molecular target of G01. APEH formed a stable complex with biotinylated G01, and the enzymatic activity of APEH was inhibited by G01. APEH knockdown caused profound mislocalization of KRAS and reduced clustering of KRAS that remained PM localized. APEH knockdown also disrupted the PM localization of phosphatidylserine (PtdSer), a lipid critical for KRAS PM binding and clustering. The mislocalization of KRAS was fully rescued by ectopic expression of APEH in knockdown cells. APEH knockdown disrupted the endocytic recycling of epidermal growth factor receptor and transferrin receptor, suggesting that abrogation of recycling endosome function was mechanistically linked to the loss of KRAS and PtdSer from the PM. APEH knockdown abrogated RAS-RAF-MAPK signaling in cells expressing the constitutively active (oncogenic) mutant of KRAS (KRASG12V), and selectively inhibited the proliferation of KRAS-transformed pancreatic cancer cells. Taken together, these results identify APEH as a novel drug target for a potential anti-KRAS therapeutic.


Comparison of range of motion after standard and high-flexion posterior stabilised total knee replacement.
The purpose of this study was to compare the range of motion after standard version posterior stabilised TKR and high-flexion version TKR in patients receiving bilateral total knee replacement. Thirty-five patients were recruited. The range of motion of the knees was measured clinically with a goniometer in both the pre-operative period and the most recent follow-up. It was found that the pre-operative range of motion was comparable in the two groups. The average post-operative flexion was 105 degrees +/- 13 degrees in the standard version group and 106 degrees +/- 14 degrees in the high-flexion design group (p = 0.201, paired t-test; beta error = 0.073). A slight loss in flexion was observed in the standard version group (0.5 degrees ) as opposed to a slight gain in the high-flexion design group (2 degrees ). However, this was not statistically significant (p = 0.251, paired t-test; beta error = 0.105).


Detection of molecular binding via charge-induced mechanical response of optical fibers.
We report a charge sensitive optical detection technique for label-free study of molecular interactions. Traditional label-free optical detection techniques largely rely on the detection of the mass of a molecule, which are insensitive to small molecules. In contrast, the present technique detects the charge of a molecule, where the signal does not diminish with the size of the molecule, thus capable for studying small molecules. In addition, the technique is compatible with the standard microplate platform, making it suitable for high-throughput screening of drug candidates. Using the technique, we have detected 0.2 nM anti-BSA and 15 μM anti-cancer drug (imatinib) with an enzyme modified surface. The achieved effective charge detection limit is ~0.25 electron charge/μm2, corresponding to ~0.3 fg/mm2 for imatinib, which is orders of magnitude better than traditional label-free optical detection methods.


Dynamic-clamp analysis of the effects of convergence on spike timing. II. Few synaptic inputs.
Sensory pathways in the nervous system possess mechanisms for decreasing spike-timing variability ("jitter"), probably to increase acuity. Most studies of jitter reduction have focused on convergence of many subthreshold inputs. However, many neurons receive only a few active inputs at any given time, and jitter reduction under these conditions is not well understood. We examined this issue using dynamic-clamp recordings in slices from mouse auditory brain stem. Significant jitter reduction was possible with as few as two inputs, provided the inputs had several features. First, jitter reduction was greatest and most reliable for supra-threshold inputs. Second, significant jitter reduction occurred when the distribution of input times had a rapid onset, i.e., for alpha- but not for Gaussian-distributed inputs. Third, jitter reduction was compromised unless late inputs were suppressed by the refractory period of the cell. These results contrast with the finding in the previous paper in which many subthreshold inputs contribute to jitter reduction, whether alpha- or Gaussian-distributed. In addition, convergence of many subthreshold inputs could fail to elicit any postsynaptic response when the input distribution outlasted the refractory period of the cell. These significant differences indicate that each means of reducing jitter has advantages and disadvantages and may be more effective for different neurons depending on the properties of their inputs.


Needling after trabeculectomy - does augmentation by anti-metabolites provide better outcomes and is Mitomycin C better than 5-Fluoruracil? A systematic review with network meta-analyses.
Favourable outcome after glaucoma surgery depends on proper control of the inflammatory response. Failing filtration bleb and consequently increased intraocular pressure is an important cause of continuous visual field deterioration after uncomplicated glaucoma surgery. The present systematic review and meta-analysis aimed to compare the effects of employing either Mitomycin C (MMC), 5-Fluoruracil (5-FU) or no anti-metabolite in needling revision of trabeculectomies. We performed a systematic literature search in PubMed, Cochrane and EMBASE to identify randomized and non-randomized trials published between year 2000 and March 2019 comparing the efficacy of needling filtering blebs when using no anti-fibrotic agent, MMC or 5-FU in patients with glaucoma. Efficacy was defined as intraocular pressure at 12 months or latest follow-up, rate of complications, rates of success and the number of re-needling cases. Comparisons were made using network meta-analyses. We identified one randomized trial and five retrospective trials. Twelve months after needling revision of trabeculectomy, no significant difference was observed when comparing the effect of the use of MMC with 5-FU or without any use of anti-metabolite on intraocular pressure, complication rates, qualified success, complete success or number of re-needling cases. We found no significant difference in the efficacy of using either MMC, 5-FU or no anti-metabolite in needling revision of trabeculectomies. The number of studies meeting our inclusion criteria was limited. Considering the design of studies, only one was randomized leading to an overall low quality of evidence on the subject matter. Further research is warranted.


Insulin-like growth factors in breast cancer.
Insulin-like growth factor (IGF)-I is one of the most potent mitogens to many breast cancer cell lines in vitro. Effective growth inhibition in vitro may be achieved by antibodies to the type I IGF receptor (IGF-IR) or by using antisense strategies. Most human breast cancers express IGF-IR in vivo. Thus, different therapeutic strategies aimed at inhibiting ligand stimulation of the IGF-IR may be an attractive treatment option against breast cancer. Several drugs commonly used in breast cancer influence the IGF system both in vitro and in vivo. While antioestrogens such as tamoxifen and droloxifene reduce the expression of IGF-IR in vitro and suppress plasma levels of IGF-I but elevate IGF-binding protein-1 in vivo, megestrol acetate may reduce the delivery of IGFs to the tissues by inhibition of IGFBP-3 protease activity.


Stability and change in resolution of diagnosis among parents of children with autism spectrum disorder: Child and parental contributions.
The contribution of change over time in parent and child characteristics to parents' resolution of child's diagnosis was examined among 78 mothers and fathers of children with autism spectrum disorder. Children's characteristics (e.g., mental age and severity of symptoms), parental characteristics (e.g., attachment-related anxiety and stress level), and parents' resolution of their child's diagnosis (resolved vs. unresolved) were examined at Time 1, and reassessed 3 years later at Time 2. Results indicated a deferential contribution of change in parent and child characteristics among mothers and fathers. An increase in child symptom severity and in maternal attachment-related anxiety, as well as longer durations of time since receiving the diagnosis, significantly predicted maternal resolved status at Time 2. Conversely, none of the changes in children's or paternal characteristics predicted paternal resolved status at Time 2. Results are discussed in relation to child and parental contributions to resolution, the differences in the adjustment and well-being of mothers and fathers of children with autism spectrum disorder, parental growth following receiving the diagnosis, and the need for intervention components specific to parental resolution and attachment-related anxiety.


High-throughput cloning of Campylobacter jejuni ORfs by in vivo recombination in Escherichia coli.
A rate-limiting and costly step in many proteomics analyses is the cloning of all of the ORFs for an organism into technique-specific vectors. Here, we describe the generation of a Campylobacter jejuni expression clone set using a high-throughput cloning approach based on recombination in E. coli. The approach uses native E. coli recombination functions and requires no in vitro enzymatic steps or special strains. Our results indicate that this approach is an efficient and economical alternative for high-throughput cloning.


Hereditary pancreatic endocrine tumours.
The two main types of hereditary pancreatic neuroendocrine tumours are found in multiple endocrine neoplasia type 1 (MEN-1) and von Hippel-Lindau disease (VHL), but also in the rarer disorders of neurofibromatosis type 1 and tuberous sclerosis. This review considers the major advances that have been made in genetic diagnosis, tumour localization, medical and surgical treatment and palliation with systemic chemotherapy and radionuclides. With the exception of the insulinoma syndrome, all of the various hormone excess syndromes of MEN-1 can be treated medically. The role of surgery however remains controversial ranging from no intervention (except enucleation for insulinoma), intervening for tumours diagnosed only by biochemical criteria, intervening in those tumours only detected radiologically (1-2 cm in diameter) or intervening only if the tumour diameter is > 3 cm in diameter. The extent of surgery is also controversial, although radical lymphadenectomy is generally recommended. Pancreatic tumours associated with VHL are usually non-functioning and tumours of at least 2 cm in diameter should be resected. Practice guidelines recommend that screening in patients with MEN-1 should commence at the age of 5 years for insulinoma and at the age of 20 years for other pancreatic neuroendocrine tumours and variously at 10-20 years of age for pancreatic tumours in patients with VHL. The evidence is increasing that the life span of patients may be significantly improved with surgical intervention, mandating the widespread use of tumour surveillance and multidisciplinary team management.


An open-label pilot study of homeopathic treatment of attention deficit hyperactivity disorder in children and youth.
An open-label pilot study of individualized homeopathy for attention deficit hyperactivity disorder (ADHD) was conducted to assess the potential for future studies with a focus on the feasibility of the recruitment plan and outcome measure schedules; identification of any group characteristics of participants who respond significantly to the therapy; and establishing the length of time required for an improvement in ADHD symptoms. Participants (aged 6-16) were recruited through community advertisement and outreach. Participants completed 1 screening and 9 individualized homeopathic follow-up consultations. ADHD symptoms were assessed using the Conners 3 - Parent Questionnaire administered at each consultation. The pre- and post-study difference in Conners Global Index - Parent (CGI-P) T-score was evaluated for each participant. Baseline data of those who showed a statistically significant improvement (responders) were compared to those who did not (non-responders). 35 participants were enrolled over 11 months. 80% completed all 10 consultations in a median of 12.1 months. 63% had a statistically significant improvement in the primary outcome, first occurring after a mean of 4.5 visits. Overall scores for participants completing at least 2 data points decreased from a baseline median of 85.5 to 74.0 (p < 0.001, CI 95%). There were no significant baseline differences between responders and non-responders. No serious adverse events related to the therapy were reported. The change in the median CGI-P T-score from baseline to the end of this open-label pilot study was statistically significant. The research methods are feasible. Future studies are warranted. NCT01141634.


The Moral Construct of Caring in Nursing as Communicative Action: the theory and practice of a caring science.
This article presents an instrument and data testing a theory of the Moral Construct of Caring in Nursing as Communicative Action. Pilot testing involved 185 items administered to 82 nurses in 3 countries. The instrument includes 7 subscales addressing the nurse's personal and professional selves, the patient's personal and illness selves, the bidirectional interaction, the moral maturity of both, and the current state of nursing practice. Results suggest that the theory provides predictive control of the phenomena, drawing attention to the founding of evidence-based practice on practical, workable theory. Research continues, focusing on refining construct definitions and improving reliabilities.


Localization and characterization of prolipoprotein diacylglyceryl transferase (Lgt) critical in bacterial lipoprotein biosynthesis.
Lipid modification of proteins is an essential post-translational event that can be targeted for protein engineering and pharmaceutical applications. In this regard, the unique and ubiquitous bacterial N-terminal lipid modification (N-acyl S-diacylglyceryl modification of N-terminal cysteine) is particularly attractive. It is initiated by phosphatidylglycerol:prolipoprotein diacylglyceryl transferase (Lgt) and therefore its properties, which remain uninvestigated, largely define the specifics of the modification. A synthetic peptide-substrate (MKATKSAVGSTLAGCSSHHHHHH) with a short hydrophilic h-region, unlike that of the prototypical substrate used so far, demonstrated lack of enzyme's substrate preference based on hydrophobicity, perhaps accounting for a significant number of lipoproteins possessing hydrophilic signal peptides. Solubilization experiments revealed a peripheral and possibly reversible hydrophobic association of Lgt with the inner-membrane on the cytosolic side contradicting its deduced transmembrane topology. Except for heat stability, the soluble enzyme was indistinguishable from the membrane-bound enzyme in kinetic behaviour, indicating that the committed first step of bacterial lipid modification may be aqueous compatible. The direct, more accurate, precise and easier paper electrophoretic assay, designed anew, and Lgt's ready extraction with water or low ionic strength solutions from inverted vesicles could aid better understanding and exploitation of the enzyme and bacterial lipid modification.


The system chief nurse executive: more than the sum of the parts.
The role of the healthcare system chief nurse executive is complex, daunting, risk-laden, and exciting, and provides unprecedented opportunities to influence the care of patients in a very broad context. Creating a unified vision, mission, and culture is a challenging task that can be personally and professionally rewarding. At first glance, the role can appear impersonal and distant, with little opportunity for meaningful interaction with staff. However, with thoughtful consideration, the system chief nurse executive can establish effective relationships that have far-reaching outcomes.


Atezolizumab Plus PEGPH20 Versus Chemotherapy in Advanced Pancreatic Ductal Adenocarcinoma and Gastric Cancer: MORPHEUS Phase Ib/II Umbrella Randomized Study Platform.
The MORPHEUS platform comprises multiple open-label, randomized, phase Ib/II trials designed to identify early efficacy and safety signals of treatment combinations across cancers. Atezolizumab (anti-programmed cell death 1 ligand 1 [PD-L1]) was evaluated in combination with PEGylated recombinant human hyaluronidase (PEGPH20). In 2 randomized MORPHEUS trials, eligible patients with advanced, previously treated pancreatic ductal adenocarcinoma (PDAC) or gastric cancer (GC) received atezolizumab plus PEGPH20, or control treatment (mFOLFOX6 or gemcitabine plus nab-paclitaxel [MORPHEUS-PDAC]; ramucirumab plus paclitaxel [MORPHEUS-GC]). Primary endpoints were objective response rates (ORR) per RECIST 1.1 and safety. In MORPHEUS-PDAC, ORRs with atezolizumab plus PEGPH20 (n = 66) were 6.1% (95% CI, 1.68%-14.80%) vs. 2.4% (95% CI, 0.06%-12.57%) with chemotherapy (n = 42). In the respective arms, 65.2% and 61.9% had grade 3/4 adverse events (AEs); 4.5% and 2.4% had grade 5 AEs. In MORPHEUS-GC, confirmed ORRs with atezolizumab plus PEGPH20 (n = 13) were 0% (95% CI, 0%-24.7%) vs. 16.7% (95% CI, 2.1%-48.4%) with control (n = 12). Grade 3/4 AEs occurred in 30.8% and 75.0% of patients, respectively; no grade 5 AEs occurred. Atezolizumab plus PEGPH20 showed limited clinical activity in patients with PDAC and none in patients with GC. The safety of atezolizumab plus PEGPH20 was consistent with each agent's known safety profile. (ClinicalTrials.gov Identifier: NCT03193190 and NCT03281369).


Long-term results of the anterior cervical spondylodesis.
From 1974 to 1992, anterior cervical spondylodesis was performed in 163 patients of cervical spondylotic myelopathy, cervical spondylotic radiculopathy, traumatic spinal injury, ossification of the posterior longitudinal ligament, or cervical spondylitis. Forty-five of these patients were followed for more than 4 years. To analyze the long-term results of anterior cervical spondylodesis, a radiological examination was performed in these 45 patients and magnetic resonance imaging was conducted in 41 of them. Postoperative spondylotic changes were observed radiologically in 23 (51.1%) of the 45 patients. Anterior bony spur was more frequently observed than posterior bony spur in these postoperative spondylotic changes. Postoperative canal stenosis caused by the bulging of the discs and the ligamentum flavum was frequently demonstrated with hypo- or isointense signal on T2-weighted images by magnetic resonance imaging in patients followed long term after surgery and in patients with malalignment of the cervical spine due to kyphosis of the fused vertebrae and multisegmental fusion. Neurological improvement was less in patients with bulge of the discs and the ligamentum flavum seen in magnetic resonance imaging than in patients without it. The bulge of the ligamentum flavum was histopathologically defined as hypertrophy of the ligament.


Interdependence needs and nursing care of the new family.
A pilot study based on the interdependence mode of the Roy adaptation model was conducted to evaluate interdependence needs in the new family. The interdependence mode consists of giving and receiving behaviors in the categories of significant other, support systems (friendships), support systems (extended family), and a person's experience of feeling alone. A questionnaire addressing these categories was administered to 10 newly delivered mothers on a family-centered maternity unit. The lower mean scores for the categories of extended family and feeling alone suggest the need for further evaluation in these categories. A foundation was laid for further study of interdependence needs and family nursing, but more research using larger, random samples is needed.


Cord blood dendritic cell subsets in African newborns exposed to Plasmodium falciparum in utero.
Placental Plasmodium falciparum infection affects birth outcomes and sensitizes fetal lymphocytes to parasite antigens. We assessed the influence of maternal P. falciparum infection on fetal myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC), analyzing the cord blood of offspring of Gabonese mothers with different infection histories. Cord blood from newborns of mothers with malarial infection at delivery had significantly more mDC than that from nonexposed newborns (P = 0.028) but mDC and pDC HLA-DR expression was unrelated to maternal infection history. Independently of these findings, cord blood mDC and pDC numbers declined significantly as a function of increasing maternal age (P = 0.029 and P = 0.033, respectively). The inducible antigen-specific interleukin-10-producing regulatory-type T-cell population that we have previously detected in cord blood of newborns with prolonged in utero exposure to P. falciparum may directly reflect the altered DC numbers in such neonates, while the maintenance of cord blood DC HLA-DR expression contrasts with that of DC from P. falciparum malaria patients.


Efficacy of Epratuzumab, an Anti-CD22 Monoclonal IgG Antibody, in Systemic Lupus Erythematosus Patients With Associated Sjögren's Syndrome: Post Hoc Analyses From the EMBODY Trials.
EMBODY 1 (ClinicalTrials.gov identifier: NCT01262365) and EMBODY 2 (ClinicalTrials.gov identifier: NCT01261793) investigated the efficacy and safety of epratuzumab, a CD22-targeted humanized monoclonal IgG antibody, in patients with systemic lupus erythematosus (SLE). The studies showed no significant difference from placebo in primary or secondary clinical outcome measures but did demonstrate B cell-specific immunologic activity. The aim of this post hoc analysis was to determine whether epratuzumab had a different clinical efficacy profile in SLE patients with versus those without an associated diagnosis of Sjögren's syndrome (SS). The efficacy and safety of epratuzumab were compared between 2 patient subpopulations randomized in EMBODY 1 and 2: SLE patients with and those without a diagnosis of associated SS. British Isles Lupus Assessment Group (BILAG) total score, BILAG-based Combined Lupus Assessment (BICLA) clinical response to treatment, biologic markers (including B cells, IgG, IgM, and IgA), and safety were assessed. A total of 1,584 patients were randomized in the EMBODY 1 and EMBODY 2 trials; 113 patients were anti-SSA positive and had a diagnosis of associated SS, and 1,375 patients (86.8%) had no diagnosis of associated SS (918 patients were randomized to receive epratuzumab and 457 to receive placebo). For patients with associated SS, but not those without associated SS, a higher proportion of patients receiving epratuzumab achieved a BICLA response and a reduction from baseline in BILAG total score. B cell reduction was faster in patients with associated SS. The sensitivity of B cells to epratuzumab as measured by the mean concentration producing 50% of the maximum B cell count depletion was lower for patients with associated SS (9.5 μg/ml) versus the total EMBODY population (87.1 μg/ml). No difference in the frequency of adverse events in those receiving placebo was reported. Patients with SLE and associated SS treated with epratuzumab showed improvement in SLE disease activity, which was associated with bioactivity, such as decreases in B cell number and IgM level.


[Personalized patient-oriented approach to the treatment of musculoskeletal pain syndrome using over-the-counter medications. Resolution of the Expert Council (May 28, 2023)].
Diseases of the musculoskeletal system in Russia affect 19.2 million people. Untimely diagnosis and inadequate therapy of pain syndrome negatively affect the daily functioning and quality of life of patients, and create significant socioeconomic problems. The most common variants of musculoskeletal pain (MSP) are osteoarthritis (OA) and low back pain (LBP). OA is seen in 57.6% of individuals over 65 years of age. It should be noted that chronic pain syndrome, rather than anatomical and degenerative changes detected by imaging studies, determines to a greater extent the quality of life of patients with OA and prognosis during the course of the disease. The global burden of disability associated with LBPD increased in all age groups between 1990 and 2019 and was highest in the 50-54 age group.


P061 Impact of Inflammatory Bowel Disease on sleep quality in a Mexican population attended in a referral center.
Sleep disorders occur recurrently in patients with inflammatory bowel disease (IBD). The relationship between poor sleep quality and IBD activity has been subject to scarce attention. Poor sleep quality could be considered a relevant extraintestinal manifestation and a potential marker of subclinical inflammation, which could increase the severity of inflammation and the risk of relapse, however, we do not have enough information to confirm this hypothesis. Objective: Describe the impact of IBD on the quality of sleep, in patients treated in a referral hospital. Observational, analytical, and cross-sectional study. Patients with diagnosis of IBD treated at Centro Médico Nacional "20 de Noviembre" were evaluated. The Pittsburgh Sleep Quality Index (PSQI) was used to measure sleep quality. IBD activity was measured using the Harvey-Bradshaw index for Crohn's disease (CD) and the Mayo scale for Ulcerative Colitis (UC). A total of 51 patients were included, the Pittsburgh Sleep Index Questionnaire (PSQI) was performed, after informed consent was signed. Patients had a mean age of 52. Fifty five percent were female, 65% had UC. Biological therapy was administered to 70.5%. In CD 89% were in remission and 11% in moderate activity. In UC 48.5% were in remission, 45.5% had mild activity and 6% had moderate activity. Eighty percent of the patients did not use hypnotic drugs. Patients with UC in remission had a bad perception of sleep quality in 68%, quite good sleep quality in 18% and very good sleep quality in 12% with a PSQI of 10.5 ± 3.2. In patients with mild activity, the perception of sleep quality was very good in 6%, quite good in 46%, quite bad in 40% and very bad in 6%, with a PSQI of 8 ± 3.7. In patients with moderate activity, 100% had a rather bad perception of sleep quality with a PSQI of 11 ± 1.4. For CD in remission the perception of sleep was quite bad in 43%, quite good in 43%, very bad in 6% and very good in 6% with a PSQI of 9 ± 4.3. In patients with moderate activity 50% had a very bad sleep quality perception and 50% a fairly good sleep quality perception with a PSQI of 14 ± 4.2. In this study a statistically significant association was obtained between PSQI and the perception of sleep reported by the patients, with a p < 0.005. Further research is still needed to better characterize sleep disturbances in this population. Due to the sample size, a prospective, randomized study is required to confirm these findings. The present analysis has no conflict of interest.


[The effect of xantham gum on satiety status of obese patients after test meal].
Investigation of soluble fiber-xantham gum on hunger, satiety and epigastric fullness in obese subjects. 21 obese women: age 40.7 +/- 17, BMI 35.4 +/- 5.7 otherwise healthy, actually non dieting. Eating behavior was assessed by Three Factor Eating Behavior Questionnaire (TFEBQ) by evaluating eating restrain, dysinhibition and hunger. Satiety, hunger and epigastric fullness were assessed by visual analogue scale (VAS) and 7-point ratings scale before ingestion of test meal (ham sandwich--90 kcal) and in 20 min intervals during 2-hour observation. The study was done twice: with fiber and with placebo. Ingestion of test meal with drug and placebo causes statistical significant reduction in hunger and increase in satiety feelings in both groups. Afterwards during 2-hour observation the significant increase in hunger was observed. There were no differences in hunger, satiety and epigastric feelings between both groups. The significant positive correlation between third factor of TFEBQ (hunger) and BMI index was found. (r = 48, p < 0.05). 0.5 g of xanthan fiber with test meal didn't cause significant change of satiety. It is probably the effect of too low dose of xantham gum.


Screening for Type 2 diabetes: an exploration of subjects' perceptions regarding diagnosis and procedure.
To explore the psychological impact of a stepwise population-screening project for Type 2 diabetes. As part of a stepwise population screening project for Type 2 diabetes in the Hoorn region, The Netherlands, an explorative interview study was conducted. The psychological impact of screening was studied using semistructured interviews in 40 subjects: 20 who were diagnosed with Type 2 diabetes, and 20 subjects who were at increased risk of having diabetes but who did not meet criteria for diabetes. Transcripts were analysed using techniques of content analysis. Newly diagnosed subjects reported limited understanding of their elevated blood glucose levels. None, with the exception of one, was alarmed by the diagnosis. Having Type 2 diabetes was not experienced as severe and no concerns were expressed. Adjusting diet was perceived as a major change by some. All newly diagnosed subjects had informed close relatives and friends of the diabetes, who were in general not alarmed by the news. Both groups positively judged the screening procedure. In general the screening procedure was considered as useful and not experienced as burdensome. This explorative study suggests that the psychological impact of screening in newly diagnosed subjects is limited. Both those who were and those who were not diagnosed with Type 2 diabetes judged the screening procedure positively.


RflM functions as a transcriptional repressor in the autogenous control of the Salmonella Flagellar master operon flhDC.
Motility of bacteria like Salmonella enterica is a highly regulated process that responds to a variety of internal and external stimuli. A hierarchy of three promoter classes characterizes the Salmonella flagellar system, and the onset of flagellar gene expression depends on the oligomeric regulatory complex and class 1 gene product FlhD(4)C(2). The flhDC promoter is a target for a broad range of transcriptional regulators that bind within the flhDC promoter region and either negatively or positively regulate flhDC operon transcription. In this work, we demonstrate that the RflM protein is a key component of flhDC regulation. Transposon mutagenesis was performed to investigate a previously described autoinhibitory effect of the flagellar master regulatory complex FlhD(4)C(2). RflM is a LuxR homolog that functions as a flagellar class 1 transcriptional repressor. RflM was found to be the negative regulator of flhDC expression that is responsible for the formerly described autoinhibitory effect of the FlhD(4)C(2) complex on flhDC operon transcription (K. Kutsukake, Mol. Gen. Genet. 254:440-448, 1997). We conclude that upon commencement of flagellar gene expression, the FlhD(4)C(2) complex initiates a regulatory feedback loop by activating rflM gene expression. rflM encodes a transcriptional repressor, RflM, which fine-tunes flhDC expression levels.


Evaluation of the broiler's ability to adapt to an early moderate deficiency of phosphorus and calcium.
We studied the ability of broiler chickens to adapt to early moderate P and Ca deficiencies by evaluating the impact of feeding different concentrations of P and Ca, from 1 to 18 d, on performance, bone characteristics, and nutrient absorption in the grower (Gr) period (18 to 32 d). Two starter (St) diets were fed from 1 to 18 d: a control (C) diet [0.45% nonphytate P (nPP) and 0.9% Ca] and a low (L) diet (0.30% nPP and 0.6% Ca). On d 19, half of the birds fed the St C diet were switched to a Gr C diet (0.40% nPP and 0.8% Ca), and the other half were switched to a Gr L diet (0.30% nPP and 0.6% Ca), whereas those fed the L diet in the St phase were fed the L diet in the Gr phase, resulting in a total of 3 treatments. Broiler chickens fed the St L diet weighed less (P < 0.05) than those fed the St C diet at 18 d; however, by 23 d they had they caught up to the C-C birds, and no BW differences (P > 0.05) were observed at 28 and 32 d. Feeding the St L diet resulted in decreased (P < 0.05) tibia ash at 18 d, but by 32 d their tibia ash was not different from that of birds fed the St C and Gr L diets. Broilers subjected to P and Ca restriction from hatch to 18 d absorbed more P and Ca during all times sampled than birds fed the St C and Gr C diets or those fed the St C and the Gr L diet. These results demonstrated that modern broilers exhibited a high adaptive capacity when they were exposed to early dietary P or Ca restrictions.


Ligand-based chemoinformatic discovery of a novel small molecule inhibitor targeting CDC25 dual specificity phosphatases and displaying in vitro efficacy against melanoma cells.
CDC25 phosphatases are important regulators of the cell cycle and represent promising targets for anticancer drug discovery. We recently identified NSC 119915 as a new quinonoid CDC25 inhibitor with potent anticancer activity. In order to discover more active analogs of NSC 119915, we performed a range of ligand-based chemoinformatic methods against the full ZINC drug-like subset and the NCI lead-like set. Nine compounds (3, 5-9, 21, 24, and 25) were identified with Ki values for CDC25A, -B and -C ranging from 0.01 to 4.4 μM. One of these analogs, 7, showed a high antiproliferative effect on human melanoma cell lines, A2058 and SAN. Compound 7 arrested melanoma cells in G2/M, causing a reduction of the protein levels of CDC25A and, more consistently, of CDC25C. Furthermore, an intrinsic apoptotic pathway was induced, which was mediated by ROS, because it was reverted in the presence of antioxidant N-acetyl-cysteine (NAC). Finally, 7 decreased the protein levels of phosphorylated Akt and increased those of p53, thus contributing to the regulation of chemosensitivity through the control of downstream Akt pathways in melanoma cells. Taken together, our data emphasize that CDC25 could be considered as a possible oncotarget in melanoma cells and that compound 7 is a small molecule CDC25 inhibitor that merits to be further evaluated as a chemotherapeutic agent for melanoma, likely in combination with other therapeutic compounds.


A basic introduction to the thermodynamics of the Earth system far from equilibrium and maximum entropy production.
The Earth system is remarkably different from its planetary neighbours in that it shows pronounced, strong global cycling of matter. These global cycles result in the maintenance of a unique thermodynamic state of the Earth's atmosphere which is far from thermodynamic equilibrium (TE). Here, I provide a simple introduction of the thermodynamic basis to understand why Earth system processes operate so far away from TE. I use a simple toy model to illustrate the application of non-equilibrium thermodynamics and to classify applications of the proposed principle of maximum entropy production (MEP) to such processes into three different cases of contrasting flexibility in the boundary conditions. I then provide a brief overview of the different processes within the Earth system that produce entropy, review actual examples of MEP in environmental and ecological systems, and discuss the role of interactions among dissipative processes in making boundary conditions more flexible. I close with a brief summary and conclusion.


Versatile Clinical Application of the Spike Screw: Direct Anchorage Versus Indirect Anchorage.
This article represents clinical application of spike screw, novel design of miniscrew, for direct anchorage and indirect anchorage in orthodontic treatment. Accompanied by easy placement and removal, the spike screw provides good stability for the orthodontic anchorage. The spike screw consists of 6 spikes attached to a washer with laser welded stainless-steel hook that is placed by self-drilling fixation miniscrew. The spike screws were applied to correct malocclusions in patients as follows: traction of impacted canines and protraction of posterior teeth as a direct anchorage and correction of midline discrepancy as an indirect anchorage. For orthodontic traction of impacted canines, spike screws were placed in the mandibular labial mucosal area to create extrusive forces. Afterward, it was utilized for the protraction of posterior teeth. In the second case of the indirect anchorage, spike screw was applied on the midpalatal area to correct midline discrepancy that occurred during orthodontic treatment. The extended hook of a washer was prebended along the curvature of the palate and then secured with a mini screw. The extended hook was bonded to maxillary left first molar. In the first case, the spike screw provided adequate anchorage for the vertical traction of horizontally impacted canine. Since the spike screws were placed in the mandibular anterior lesion, the vertical traction force was applied simply with orthodontic elastics. Also, enough distance was achieved for up-down elastics to work by placing the spike screw in the opposite arch. The force of vertical traction was adjusted with selection of size and force of up-down elastics. Later, it was used to provide anchorage for protraction of mandibular molars without changing orientation of the spike screws. In the second case, the spike screw placed in the midpalatal area was attached to the left first molar and worked as an indirect anchorage. The midline discrepancy was resolved by consolidating the spaces to the left with securing the left first molar location. The novel design of the spike screw permits clinicians to have minimum invasive and easy placement and removal of the appliance while maintaining a good control over tooth movement with improved stability in various clinical cases.


Properties of an acid phosphatase in pulmonary surfactant.
Lung surfactant, a lipid-protein complex purified from dog lungs, contains a highly active phosphomonoesterase associated with it. This phosphatase is quite specific for the hydrolysis of phosphatidic acid and 1-acyl-2-lysophosphatidic acid. The enzyme possesses many of the characteristics of the microsomal enzyme, phosphatidate phosphohydrolase (EC 22.214.171.124). In addition, we have shown that this enzyme will also convert phosphatidylglycerol phosphate [1-(3-sn-phosphatidyl)-sn-glycerol-1-P] to phosphatidylglycerol [1-(3-sn-phosphatidyl)-sn-glycerol] and Pi. The phosphatidylglycerol phosphate was made available to the surfactant enzyme in a coupled assay by hydrolysis of cardiolipin [1-(3-sn-phosphatidyl)-3-(3-sn-phosphatidyl)-sn-glycerol] by stereospecific cleavage with phospholipase C (phosphatidylcholine cholinephosphohydrolase, EC 220.127.116.11) from Bacillus cereus. This enzyme has been previously shown to generate the naturally occurring isomer of phosphatidylglycerol phosphate because it has specificity for the 3-(3-sn-phosphatidyl) group of cardiolipin. Other properties of the surfactant enzyme are discussed in relation to its presence in lung surface active material.


An autoantibody inhibitory to glutamic acid decarboxylase in the neurodegenerative disorder Batten disease.
Mutations in the CLN3 gene are responsible for the neurodegenerative disorder Batten disease; however, the molecular basis of this disease remains unknown. In studying a mouse model for Batten disease, we report the presence of an autoantibody to glutamic acid decarboxylase (GAD65) in cln3-knockout mice serum that associates with brain tissue but is not present in sera or brain of normal mice. The autoantibody to GAD65 has the ability to inhibit the activity of glutamic acid decarboxylase. Furthermore, brains from cln3-knockout mice have decreased activity of glutamic acid decarboxylase as a result of the inhibition of this enzyme by the autoantibody, resulting in brain samples from cln3-knockout mice having elevated levels of glutamate as compared with normal. This elevated glutamate in the brain of cln3-knockout mice co-localizes with presynaptic markers. The decreased activity of GAD65 and increased levels of glutamate may have a causative role in astrocytic hypertrophy evident in cln3-knockout mice, and in altered expression of genes involved in the synthesis and utilization of glutamate that underlie a shift from synthesis to utilization of glutamate. An autoantibody to GAD65 is also present in sera of 20 out of 20 individuals tested who have Batten disease. Postmortem tissue shows decreased reactivity to an anti-GAD65 antibody that may be due to loss of GAD65-positive neurons or due to the reactive epitope being blocked by the presence of the autoantibody. We propose that an autoimmune response to GAD65 may contribute to a preferential loss of GABAergic neurons associated with Batten disease.


In vivo splicing of the premRNAs from early region 3 of adenovirus-2: association of precursors, intermediates and products with hnRNP.
To elucidate the function of hnRNP in the splicing of premRNA, we studied the distribution of the transcripts from the early region 3 of adenovirus-2 in hnRNP from infected HeLa cells. In addition to premRNAs and mRNAs, we detected excised IVS 1 and the products of cleavage of premRNA at the 5' splice site of IVS 1 (free leader 1 and IVS 1-exon 2). All these molecules were present in hnRNP and persisted in the salt-resistant complexes after a 400 mM KCl treatment. None of them was exclusively part of the salt dissociable monoparticles. The precursors, intermediates and products of the splicing reaction were associated with both monoparticles and salt resistant complexes. This eliminates the possibility that one of the classes of RNP is exclusively involved in one of the steps of RNA processing. Whereas the size of hnRNP was related to that of its RNA for most molecules, the small molecules free leader 1 and excised IVS 1 were found in the large hnRNP containing premRNA as well as in small size hnRNP. A probable interpretation of these results is that the cleavage products are associated with the premRNP complex immediately after cleavage and are then released in the form of an individual RNP.


Maternal Health of Undocumented Women With and Without Medicaid Access in Nebraska, 2007-2011.
Four million infants are born in the United States to undocumented mothers. Nebraska granted Medicaid access to undocumented pregnant women from 1996 to 2010 and then discontinued access from 2010 to 2012. However, little is known about the maternal health of these undocumented women. The purpose of this study was to compare maternal health of undocumented women with and without access to Medicaid in Nebraska from 2007 to 2011. A retrospective, longitudinal cohort design was conducted with 2007 to 2011 Nebraska birth certificate data. Study participants were 6,262 undocumented women. Groups of measures were created for demographics, prenatal, pregnancy, and delivery characteristics. Descriptive statistics were calculated and comparisons were conducted between women with and without access to Medicaid using chi-square and Student t tests. More than 60% of undocumented women had access to Medicaid, while 32% had no access to Medicaid. Undocumented women were predominately Hispanic (73.32%) and did not have a high school education (68.77%). The comparison of undocumented women with and without Medicaid revealed that women with Medicaid access had more than adequate prenatal care (17.86% vs. 14.80%) and a higher frequency of infant born with abnormal conditions (6.26% vs. 8.03%). Women without access to Medicaid more often had inadequate prenatal care (10.28% vs. 6.94%) and were obese prior to pregnancy (19.37% vs. 17.37%). Undocumented women who are prenatally obese and lack access to prenatal care may be at increased risk for poor maternal outcomes.


GSK-3β Contributes to Parkinsonian Dopaminergic Neuron Death: Evidence From Conditional Knockout Mice and Tideglusib.
Glycogen synthase kinase-3 (GSK-3) dysregulation has been implicated in nigral dopaminergic neurodegeneration, one of the main pathological features of Parkinson's disease (PD). The two isoforms, GSK-3α and GSK-3β, have both been suggested to play a detrimental role in neuronal death. To date, several studies have focused on the role of GSK-3β on PD pathogenesis, while the role of GSK-3α has been largely overlooked. Here, we report in situ observations that both GSK-3α and GSK-3β are dephosphorylated at a negatively acting regulatory serine, indicating kinase activation, selectively in nigral dopaminergic neurons following exposure of mice to 1-methyl-4-pheny-1,2,3,6-tetrahydropyridine (MPTP). To identify whether GSK-3α and GSK-3β display functional redundancy in regulating parkinsonian dopaminergic cell death, we analysed dopaminergic neuron-specific Gsk3a null (Gsk3a ΔDat ) and Gsk3b null (Gsk3b ΔDat ) mice, respectively. We found that Gsk3b ΔDat , but not Gsk3a ΔDat , showed significant resistance to MPTP insult, revealing non-redundancy of GSK-3α and GSK-3β in PD pathogenesis. In addition, we tested the neuroprotective effect of tideglusib, the most clinically advanced inhibitor of GSK-3, in the MPTP model of PD. Administration of higher doses (200 mg/kg and 500 mg/kg) of tideglusib exhibited significant neuroprotection, whereas 50 mg/kg tideglusib failed to prevent dopaminergic neurodegeneration from MPTP toxicity. Administration of 200 mg/kg tideglusib improved motor symptoms of MPTP-treated mice. Together, these data demonstrate GSK-3β and not GSK-3α is critical for parkinsonian neurodegeneration. Our data support the view that GSK-3β acts as a potential therapeutic target in PD and tideglusib would be a candidate drug for PD neuroprotective therapy.


Co-expression of Fas and Fas ligand in malignant glial tumors and cell lines.
Fas ligand (FasL) is involved in tumor evasion from the immune system. We analyzed 22 human gliomas for expression of FasL and its receptor, Fas. Positive FasL and Fas immunoreactivity was detected in 13 out of 22 tumors by Western blotting and in 15 out of 22 tumors by immunohistochemistry. Immunohistochemistry also showed that Fas and FasL expression was confined to tumor cells. Co-expression of these molecules was confirmed by Western blotting and immunohistochemistry in 4 of 7 glioma cell lines. Co-expression of FasL and Fas within tumor cells suggests that their contribution in vivo to the process of immune system evasion and tumor cell apoptosis is complex and probably involves additional factors.


Pre-replication assembly of E. coli replisome components.
The localization of SeqA, thymidylate synthase, DnaB (helicase) and the DNA polymerase components alpha and tau, has been studied by immunofluorescence microscopy. The origin has been labelled through GFP-LacI bound near oriC. SeqA was located in the cell centre for one replication factory (RF) and at 1/4 and 3/4 positions in pre-divisional cells harbouring two RFs. The transition of central to 1/4 and 3/4 positions of SeqA appeared abrupt. Labelled thymidylate synthetase was found all over the cell, thus not supporting the notion of a dNTP-synthesizing complex exclusively localized near the RF. More DnaB, alpha and tau foci were found than expected. We have hypothesized that extra foci arise at pre-replication assembly sites, where the number of sites equals the number of origins, i.e. the number of future RFs. A reasonable agreement was found between predicted and found foci. In the case of multifork replication the number of foci appeared consistent with the assumption that three RFs are grouped into a higher-order structure. The RF is probably separate from the foci containing SeqA and the hemi-methylated SeqA binding sites because these foci did not coincide significantly with DnaB as marker of the RF. Co-labelling of DnaB and oriC revealed limited colocalization, indicating that DnaB did not yet become associated with oriC at a pre-replication assembly site. DnaB and tau co-labelled in the cell centre, though not at presumed pre-replication assembly sites. By contrast, alpha and tau co-labelled consistently suggesting that they are already associated before replication starts.


A case of human brucellosis in Hong Kong.
Brucellosis is an infectious disease of humans and animals caused by Brucella species. We report on a 34-year-old housewife who presented with recurrent headache, fever, and malaise. Blood cultures yielded slow-growing gram-negative coccobacilli that were later identified as Brucella melitensis. The patient recalled handling goat placenta in China. She was prescribed a 6-week course of doxycycline and rifampicin. Laboratory staff who had been exposed to the isolate remained asymptomatic. The epidemiology, diagnosis, and treatment of brucellosis are discussed.


Cardiac survival in anoxia-tolerant vertebrates: An electrophysiological perspective.
Certain vertebrates, such as freshwater turtles of the genus Chrysemys and Trachemys and crucian carp (Carassius carassius), have anoxia-tolerant hearts that continue to function throughout prolonged periods of anoxia (up to many months) due to successful balancing of cellular ATP supply and demand. In the present review, we summarize the current and limited understanding of the cellular mechanisms underlying this cardiac anoxia tolerance. What emerges is that cold temperature substantially modifies cardiac electrophysiology to precondition the heart for winter anoxia. Intrinsic heart rate is slowed and density of sarcolemmal ion currents substantially modified to alter cardiac action potential (AP) characteristics. These changes depress cardiac activity and reduce the energetic costs associated with ion pumping. In contrast, anoxia per se results in limited changes to cardiac AP shape or ion current densities in turtle and crucian carp, suggesting that anoxic modifications of cardiac electrophysiology to reduce ATP demand are not extensive. Additionally, as knowledge of cellular physiology in non-mammalian vertebrates is still in its infancy, we briefly discuss the cellular defense mechanisms towards the acidosis that accompanies anoxia as well as mammalian cardiac models of hypoxia/ischemia tolerance. By examining if fundamental cellular mechanisms have been conserved during the evolution of anoxia tolerance we hope to have provided a framework for the design of future experiments investigating cardiac cellular mechanisms of anoxia survival.


Antiproliferative activity of standardized phytopreparations from Ibervillea sonorae (S. Watson) Greene.
Ibervillea sonorae (Cucurbitaceae) is a medicinal plant utilized in Northwest Mexico against Diabetes and cancer. This natural product is taken orally, its presentation is capsules containing the plant's dried and powdered caudices. There is no regulation or standardized dosage that allows reproducibility of its pharmacological effects. Cucurbitacins are the main group of compounds found in I. sonorae and are known for their antiproliferative activity in cancer cells. Cucurbitacin IIb (CIIb), one of the compounds present in I. sonorae, has demonstrated in experimental models with HeLa cervical cancer cells an apoptotic and anti-tumoral activity. The objective of this study is to obtain and standardize two phytopreparations of I. sonorae based on their CIIb content, evaluate their antiproliferative activity in cancer cell lines, and compare the results with those obtained with CIIb; expecting to find phytopreparations with anti-cancer potential. APCI-IT-MSn is utilized for the identification of cucurbitacins, FT-ICR-MS/MS for the quantification of CIIb, and the MTT assay for the evaluation of the antiproliferative activity. The CIIb content was 0.67% for Fito-Ison-EtOH and 1.84% for Fito-Ison-EtOAc. In both phytopreparations, six cucurbitacins have been identified, and a seventh one not previously identified. Phytopreparations were more effective against HeLa, with IC50 of 30.0 and 18.6 µg/mL for Fito-Ison-EtOH and Fito-Ison-EtOAc, respectively. This effect is lower than observed on CIIb in HeLa (5.8 µg/mL). There are no significant differences (p > 0.05) in the antiproliferative activity between Fito-Ison-EtOAc and CIIb in A549, LS180, and MDA-MB-231 cells. Phytopreparations of I. sonorae have potential for the development of anti-cancer products.


A comparison of corneal biomechanical properties in patients with psoriasis and healthy subjects.
To evaluate the differences in corneal biomechanical properties between healthy subjects and patients with psoriasis using the ocular response analyzer (ORA). Fifty-nine eyes of 59 psoriasis patients and 66 healthy individuals were included in the study. Corneal biomechanical parameters were obtained using ORA. Ultrasound pachymetry was used to measure central corneal thickness (CCT). The main parameters assessed were corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg) measurement and corneal-compensated IOP (IOPcc) through ORA. The dry eye evaluation was performed with tear break-up time (TBUT) and Shirmer test. The mean CH values in psoriasis and healthy subject eyes were 10.75±2.9 mm Hg, 11.97±3.6 mm Hg, respectively (P=0.047). The mean CRF values were 10.14±3.1 mm Hg and 11.61±3.3 mm Hg, respectively (P=0.012). The mean CCT were 539.1±36 μm and 536.3±28 μm, respectively (P=0.643). Mean TBUT values were 8.2±2.9 sec in psoriasis group and 10.4±3.6 sec in healthy subjects (P<0.001). Shirmer test values were less (8.9±3.8 mm/5 min) in psoriasis than in healthy subjects (13.1±3.6 mm) (P<0.001). Psoriasis can influence the corneal biomechanical properties. Patients with psoriasis had lower CH and CRF, but higher IOPg and IOPcc values than healthy controls. These corneal biomechanical changes should be considered when determining IOP values.


The body size and temperature dependence of organismal locomotion.
The speed and maneuverability of organisms are central to their fitness, determining the strength and outcome of many species interactions that drive population and community-level processes. While locomotion is influenced by many internal and external factors, body size and temperature are two key factors governing organismal locomotion. Biologists have been measuring locomotor performance, particularly maximum speed, for over a century. Studies have tended to focus on single species or groups of species that are either phylogenetically related, functionally similar, or use the same habitat. Few studies compare locomotor performance across a diverse range of taxa or locomotor modes, very few have incorporated locomotor traits other than maximum speed, and the data are not accessible in a single database with standardized units. Here, we present a data set we compiled from the literature that contains 2,951 measurements of locomotor performance for five traits (exploratory speed, maximum speed, maximum acceleration, minimum powered turn radius, and maximum angular speed) that are important in the daily lives of many organisms. This represents the most diverse and comprehensive database on animal locomotion yet published and includes 884 species spanning 23 orders of magnitude of body size. Together with body size (mass and length) and temperature (body and ambient), we also provide data on trophic group and habitat (aerial, terrestrial, aquatic). In publishing our data set, we hope to encourage others to contribute to a continued effort to build this locomotion database and to analyze these data for underlying patterns. Interspecific analyses can help elucidate how organismal locomotion varies with important morphological and physiological traits and environmental conditions, revealing generalities and deviations in organismal locomotion. Additionally, intraspecific analyses, which are possible for a number of species in our data set, can help corroborate these patterns and deviations and explore potential mechanisms that could underlie these patterns. Insights from these analyses should uncover drivers of locomotor performance and contribute to an understanding about how locomotion shapes ecological processes across scales. There are no copyright or proprietary restrictions, except this data paper should be cited when data are used for publication. In addition, we would appreciate hearing for which research projects or teaching exercises these data are used.


[Peripheral arterial disease and diabetes mellitus(author's transl)].
Among a group of 286 patients with atherosclerotic arterial disease 35.3% had normal carbohydrate tolerance, 28% asymptomatic (biochemical or latent), and 36.7% overt diabetes mellitus. There was a tendency towards peripheral artery involvement and a greater incidence of coronary heart disease (myocardial infarction, changes in ST-T segment) among patients with asymptomatic or overt diabetes, figures being comparable for men and women. Most of the patients with atherosclerotic arterial disease without diabetes mellitus were in stage II, while in diabetics there was a shift towards stages I and IV. There was no significant correlation between incidence, symptoms, and location of atherosclerotic arterial disease, on the one hand, and duration of overt diabetes, on the other.


Fn14 receptor appears as a modulator of ovarian steroid-related regulation of goat endometrial epithelial cell IL-18 expression.
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) interactions affect the regulation of cytotoxic/immunotrophic pathways that are themselves under control of IL-18. The effect of Fn14 on regulation of endometrium IL-18 expression, however, remains unclear. The aim was to determine the mode of ovarian steroid action in regulating Fn14 expression by goat endometrial epithelial cells (EECs) in the presence and absence of endometrial stromal cells (ESCs). The possible role of Fn14 on the expression of IL-18 by EECs was also evaluated. Opposite effects of E2 and/or P4 on the regulation of both Fn14 mRNA and protein expression by EECs were observed in the presence and absence of ESCs. Fn14 knockdown by blocking antibody or siRNA resulted in a decrease of IL-18 mRNA and protein levels in EECs cocultured with ESCs, and no significant difference of the IL-18 mRNA and protein levels in the EECs was observed between steroid treatment group and control group. These findings confirm the importance of steroids in controlling Fn14 expression in goat EECs. Furthermore, Fn14 appears as a novel modulator of the steroid-related IL-18 expression in EECs in the presence of ESCs.


Measurement of Pro-Islet Amyloid Polypeptide (1-48) in Diabetes and Islet Transplants.
Islet amyloid is a feature of β-cell failure in type 2 diabetes (T2D) and type 1 diabetes (T1D) recipients of islet transplants. Islet amyloid contains islet amyloid polypeptide (IAPP; amylin), a circulating peptide that is produced in β cells by processing of its precursor, proIAPP1-67, via an intermediate form, proIAPP1-48. Elevated proinsulin to C-peptide ratios in the plasma of persons with diabetes suggest defects in β-cell prohormone processing. Determine whether plasma levels of precursor forms of IAPP are elevated in diabetes. We developed an immunoassay to detect proIAPP1-48 in human plasma, and we determined the ratio of proIAPP1-48 to mature IAPP in subjects with T1D, T2D, recipients of islet transplants, and healthy controls. The proIAPP1-48 immunoassay had a limit of detection of 0.18 ± 0.06 pM and cross-reactivity with intact proIAPP1-67 <15%. Healthy individuals had plasma concentrations of proIAPP1-48 immunoreactivity of 1.5 ± 0.2 pM and a proIAPP1-48 to total IAPP ratio of 0.28 ± 0.03. Plasma concentrations of proIAPP1-48 immunoreactivity were not significantly different in subjects with T2D but were markedly increased in T1D recipients of islet transplants. Children and adults with T1D had reduced mature IAPP levels relative to age-matched controls but an elevated ratio of proIAPP1-48 to total IAPP. The β cells in T1D and islet transplants have impaired processing of the proIAPP1-48 intermediate. The ratio of proIAPP1-48-to-IAPP immunoreactivity may have value as a biomarker of β-cell stress and dysfunction.


Overexpression of Sly-miR398b Compromises Disease Resistance against Botrytis cinerea through Regulating ROS Homeostasis and JA-Related Defense Genes in Tomato.
MicroRNAs (miRNAs) have been shown to be critical components in plant immunity. MicroRNA398 (miR398) is a highly conserved miRNA in all land plants and plays crucial roles in diverse biotic stress responses. However, the role of miR398 has not yet been characterized in tomato resistance against Botrytis cinerea. In this report, the transcript levels of sly-miR398b were strongly decreased in B. cinerea-infected leaves and the overexpression of sly-miR398b resulted in enhanced susceptibility. The attenuated expression of cytosol Cu/Zn-SOD (CSD1), chloroplast Cu/Zn-SOD (CSD2), and guaiacol peroxidase (GPOD), as well as the decreased activities of superoxide dismutase (SOD) and GPOD, collectively led to increased hydrogen peroxide (H2O2) accumulation in sly-miR398b overexpressing plants. Furthermore, sly-miR398b was induced by methyl jasmonate (MeJA) treatment. The overexpression of sly-miR398b suppressed the expression of TomLoxD, LapA, and PR-STH2 in response to B. cinerea and MeJA treatment. Our data demonstrate that sly-miR398b overexpression negatively regulates the resistance to B. cinerea in tomato by inducing the accumulation of reactive oxygen species (ROS) and downregulating the expression of MeJA-responsive defense genes.


Problems of tuberculosis treatment in Thailand.
Problems of tuberculosis treatment in Thailand are an obstacle in the national tuberculosis control programme. Reasons concerning the problems on the health provider side being the most important are the budget and the health personnel attitude and behavior, convenience of service, distance of service, health provider-consumer social relation, social support and health service quality. On the health consumer side are patient attitude and behavior and patient economy. The most important understanding to the problems is the socio-economic status of the nation and health providers are responsible for the problems.


Concomitant preterm birth and severe small-for-gestational age birth weight among infants of immigrant mothers in Ontario originating from the Philippines and East Asia: a population-based study.
Women from the Philippines form one of the largest immigrant groups to North America. Their newborns experience higher rates of preterm birth (PTB), and separately, small-for-gestational age (SGA) birth weight, compared with other East Asians. It is not known if Filipino women are at elevated risk of concomitant PTB and severe SGA (PTB-SGA), a pathological state likely reflective of placental dysfunction and neonatal morbidity. We conducted a population-based study of all singleton or twin live births in Ontario, from 2002 to 2011, among immigrant mothers from the Philippines (n=27 946), Vietnam (n=15 297), Hong Kong (n=5618), South Korea (n=5148) and China (n=42 517). We used modified Poisson regression to generate relative risks (RR) of PTB-SGA, defined as a birth <37 weeks' gestation and a birth weight <5th percentile. RRs were adjusted for maternal age, parity, marital status, income quintile, infant sex and twin births. Relative to mothers from China (2.3 per 1000), the rate of PTB-SGA was significantly higher among infants of mothers from the Philippines (6.5 per 1000; RR 2.91, 95% CI 2.27 to 3.73), and those from Vietnam (3.7 per 1000; RR 1.68, 95% CI 1.21 to 2.34). The RR of PTB-SGA was not higher for infants of mothers from Hong Kong or South Korea. Among infants born to immigrant women from five East Asian birthplaces, the risk of PTB-SGA was highest among those from the Philippines. These women and their fetuses may require additional monitoring and interventions.


Waste activated sludge fermentation for hydrogen production enhanced by anaerobic process improvement and acetobacteria inhibition: the role of fermentation pH.
In this study an efficient strategy, i.e., controlling the fermentation pH at constant pH 10, for significantly increasing hydrogen yield from waste activated sludge (WAS) via the improvement of anaerobic process (sludge solubilization, hydrolysis, and acidification) and inhibition of hydrogen consumption by acetobacteria was reported. Without addition of pure hydrogen producer and nutrient source, the effect of different constant pH in the range of pH 4-11 on hydrogen production from WAS was compared with that of different initial pH. The maximal hydrogen yield was observed respectively at constant pH 10 and initial pH 10, but the former was 47.8% higher than the latter (26.9 versus 18.2 mL per gram volatile suspended solids) and much greater than that reported in literature. Then, the mechanisms for constant pH 10 resulting in remarkably higher hydrogen production than initial pH 10 were investigated. It was observed that constant pH 10 fermentation showed much higher solubilization of sludge main particulate organic matters, hydrolysis of solubilized organic materials and acidification of hydrolyzed products, which were of benefit to the hydrogen production. Also, there was more acetic but less propionic acid in the constant pH 10 test, which was in correspondence with the theory of fermentation type affecting hydrogen production. Moreover, in the reactor of initial pH 10 the produced hydrogen was readily converted to acetic acid, but no obvious hydrogen consumption was observed in constant pH 10 reactor. Further investigation of microorganisms with enzymes analysis and fluorescence in situ hybridization (FISH) indicated that the activity and growth of acetobacteria in the reactor of constant pH 10 was much lower than those in initial pH 10 reactor.


Immediate transcatheter embolization of Swan-Ganz catheter-induced pulmonary artery pseudoaneurysm.
Digital subtraction angiography is an indispensable complement to cut film studies for the detection of pulmonary artery injury. Immediate transcatheter embolization of catheter-induced pulmonary artery pseudoaneurysm is a safe, minimally invasive, fast, and cost-effective alternative to surgical treatment.


Fold combinations in multi-domain proteins.
Domain-domain interactions in multi-domain proteins play an important role in the combined function of individual domains for the overall biological activity of the protein. The functions of the tethered domains are often coupled and hence, limited numbers of domain architectures with defined folds are known in nature. Therefore, it is of interest to document the available fold-fold combinations and their preference in multi-domain proteins. Hence, we analyzed all multi-domain proteins with known structures in the protein databank and observed that only about 860 fold-fold combinations are present among them. Analyses of multi-domain proteins represented in sequence database result in recognition of 29,860 fold-fold combinations and it accounts for only 2.8% of the theoretically possible 1,036,080 (1439C2) fold-fold combinations. The observed preference for fold-fold combinations in multi-domain proteins is interesting in the context of multiple functions through structural adaptation by gene fusion.


Acute neck tendonitis with dyspnea: A case report.
Longus colli tendinitis (LCT) with dyspnea is a relatively less-reported condition in the literature, and physicians should be aware of its existence. Misdiagnosis of this condition may cause unnecessary treatment for dyspnea. Herein, we report the case of a 40-year-old man with acute neck tendonitis. The patient presented to the pneumology department clinic with a complaint of acute neck tendonitis with dyspnea. An emergency cervical magnetic resonance examination was performed, and the preliminary diagnosis was "acute longus cervicalis tendinitis." After aggressive medical treatment, the symptoms obviously improved. LCT is a self-limiting disease that usually improves after three to seven days of conservative treatment following a definite diagnosis. However, owing to its insidious onset and complex clinical manifestations, most relevant personnel are not fully understood. The definite diagnosis of LCT is based on a comprehensive understanding of the triad, rare symptoms, and the clear identification of cervical 1 and 2 levels calcification and prevertebral edema by medical imaging examination, especially magnetic resonance imaging and computed tomography.


Persistence of fetal cardiopulmonary circulation: one manifestation of transient tachypnea of the newborn.
Five cyanotic newborn infants underwent cardiac catheterization between 8 and 36 hours of age with a tentative diagnosis of cyanotic congenital heart disease. All had normal cardiovascular anatomy. Cyanosis was the result of persistence of fetal cardiopulmonary circulation with right-to-left shunting across the ductus arteriosus. In all infants, cyanosis resolved spontaneously and the infants survived without sequelae. Admission chest roentgenograms of all infants showed marked hyperinflation of the lungs. Except for severe hypoxemia, the clinical presentation, chest films, and course of illness of these infants were consistent with transient tachypnea of the newborn. It is proposed that an increase in pulmonary vascular resistance, due to hyperinflation of the lungs, was the mechanism which reopened the fetal cardiopulmonary circulatory channels and produced hypoxemia, and that these infants suffered from a rare manifestation of a usually benign newborn respiratory condition. Further, given these pathophysiologic mechanisms, the use of continuous transpulmonary pressure gradients in the management of such infants would be contraindicated.


Genetic susceptibility to age-related macular degeneration: a paradigm for dissecting complex disease traits.
Age-related macular degeneration (AMD) is a progressive neurodegenerative disease, which affects quality of life for millions of elderly individuals worldwide. AMD is associated with a diverse spectrum of clinical phenotypes, all of which include the death of photoreceptors in the central part of the human retina (called the macula). Tremendous progress has been made in identifying genetic susceptibility variants for AMD. Variants at chromosome 1q32 (in the region of CFH) and 10q26 (LOC387715/ARMS2) account for a large part of the genetic risk to AMD and have been validated in numerous studies. In addition, susceptibility variants at other loci, several as yet unidentified, make substantial cumulative contribution to genetic risk for AMD; among these, multiple studies support the role of variants in APOE and C2/BF genes. Genome-wide association and re-sequencing projects, together with gene-environment interaction studies, are expected to further define the causal relationships that connect genetic variants to AMD pathogenesis and should assist in better design of prevention and intervention.


Muscle strength and regional lean body mass influence on mineral bone health in young male adults.
The relationship between muscle strength and bone mineral content (BMC) and bone mineral density (BMD) is supposed from the assumption of the mechanical stress influence on bone tissue metabolism. However, the direct relationship is not well established in younger men, since the enhancement of force able to produce effective changes in bone health, still needs to be further studied. This study aimed to analyze the influence of muscle strength on BMC and BMD in undergraduate students. Thirty six men (24.9 ± 8.6 y/o) were evaluated for regional and whole-body composition by dual energy X-ray absorptiometry (DXA). One repetition maximum tests (1RM) were assessed on flat bench-press (BP), lat-pull down (LPD), leg-curl (LC), knee extension (KE), and leg-press 45° (LP45) exercises. Linear regression modelled the relationships of BMD and BMC to the regional body composition and 1RM values. Measurements of dispersion and error (R2adj and standard error of estimate (SEE)) were tested, setting ρ at ≤0.05. The BMD mean value for whole-body was 1.12±0.09 g/cm2 and BMC attained 2477.9 ± 379.2 g. The regional lean mass (LM) in upper-limbs (UL) (= 6.80±1.21 kg) was related to BMC and BMD for UL (R2adj = 0.74, p<0.01, SEE = 31.0 g and R2adj = 0.63, SEE = 0.08 g/cm2), and LM in lower-limbs (LL) (= 19.13±2.50 kg) related to BMC and BMD for LL (R2adj = 0.68, p<0,01, SEE = 99.3 g and R2adj = 0.50, SEE = 0.20 g/cm2). The 1RM in BP was related to BMD (R2adj = 0.51, SEE = 0.09 g/cm2), which was the strongest relationship among values of 1RM for men; but, 1RM on LPD was related to BMC (R2adj = 0.47, p<0.01, SEE = 44.6 g), and LC was related to both BMC (R2adj = 0.36, p<0.01, SEE = 142.0 g) and BMD (R2adj = 0.29, p<0.01, SEE = 0.23 g/cm2). Hence, 1RM for multi-joint exercises is relevant to BMC and BMD in young men, strengthening the relationship between force and LM, and suggesting both to parametrizes bone mineral health.