Comparison of DNA Microarray, Loop-Mediated Isothermal Amplification (LAMP) and Real-Time PCR with DNA Sequencing for Identification of Fusarium spp. Obtained from Patients with Hematologic Malignancies.
The performance of three molecular biology techniques, i.e., DNA microarray, loop-mediated isothermal amplification (LAMP), and real-time PCR were compared with DNA sequencing for properly identification of 20 isolates of Fusarium spp. obtained from blood stream as etiologic agent of invasive infections in patients with hematologic malignancies. DNA microarray, LAMP and real-time PCR identified 16 (80%) out of 20 samples as Fusarium solani species complex (FSSC) and four (20%) as Fusarium spp. The agreement among the techniques was 100%. LAMP exhibited 100% specificity, while DNA microarray, LAMP and real-time PCR showed 100% sensitivity. The three techniques had 100% agreement with DNA sequencing. Sixteen isolates were identified as FSSC by sequencing, being five Fusarium keratoplasticum, nine Fusarium petroliphilum and two Fusarium solani. On the other hand, sequencing identified four isolates as Fusarium non-solani species complex (FNSSC), being three isolates as Fusarium napiforme and one isolate as Fusarium oxysporum. Finally, LAMP proved to be faster and more accessible than DNA microarray and real-time PCR, since it does not require a thermocycler. Therefore, LAMP signalizes as emerging and promising methodology to be used in routine identification of Fusarium spp. among cases of invasive fungal infections.


Fat feeding stimulates only one of the two mRNAs encoding rat intestinal membranous and secreted alkaline phosphatase.
We have identified two mRNAs in rat intestinal mucosa by Northern blot analysis, using cloned cDNAs encoding human placental alkaline phosphatase (PLAP). Probes from both the NH2- and COOH-terminal ends of the human PLAP coding region identified, in rat intestine (especially duodenum), an mRNA of nearly identical size (3 kb) to that found in human placenta. A smaller mRNA (2.7 kb), detected only with the COOH-terminal probe, was more prevalent in jejunum. Following feeding of triacylglycerols, the prevalence of the 2.7 kb mRNA increased over 2-fold. The tissue distribution and response of the 2.7 kb mRNA to fat feeding corresponds exactly with the known behavior of the secreted alkaline phosphatase.


Clinical efficacy of thoracoscopic surgery by subxiphoid approach for thymoma and its influence on intraoperative blood loss and postoperative complications.
To evaluate the clinical efficacy of thoracoscopic surgery by subxiphoid approach for patients with thymoma and its influence on intraoperative blood loss and postoperative complications. From January 2019 to January 2020, 90 patients who underwent thoracoscopic surgery were enrolled and evenly divided into a control group receiving surgery by lateral thoracic approach and an experimental group adopting the subxiphoid approach according to different surgical approaches, and their clinical data were retrospectively analyzed. The clinical efficacy, perioperative indexes, postoperative complications, pulmonary function, and inflammatory factors were compared between the two groups. Generic Quality of Life Inventory-74 (GQOLI-74) was used to assess the quality of life of the patients before and after surgery, and Mini-Mental State Examination (MMSE) was used to assess their mental state. The Numerical Rating Scale (NRS) was used to evaluate the postoperative pain of the two groups. After treatment, the total clinical effectiveness rate of the experimental group was significantly higher than that of the control group (P<0.05). The experimental group obtained superior results in perioperative index and fewer postoperative complications compared with the control group (P<0.05). Better performance of FEV1 and FVC was observed in the experimental group than the control group (P<0.05). The experimental group had significantly higher postoperative GQOLI-74 scores (P<0.001) and MMSE scores (P<0.05) than the control group. Lower levels of C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α), and lower NRS scores at 12 h and 24 h after surgery were witnessed in the experimental group compared to the control group (P<0.05). For patients with thymoma, the thoracoscopic surgery by subxiphoid approach is safe and effective, and can reduce the intraoperative blood loss and postoperative complications.


Self-Efficacy and Postpartum Depression Teaching by Perinatal Nurses in a Rural Setting: A Replication Study.
Perinatal nurses in rural hospitals can play an important role in providing postpartum depression education to new mothers. Guided by Self-Efficacy Theory, this replication study used a self-report instrument to survey perinatal nurses' self-efficacy in postpartum depression teaching, self-esteem, stigma and attitudes toward seeking help for mental illness. Thirty-eight perinatal nurses employed in a rural hospital participated in the study. The results indicated perinatal nurses' postpartum depression teaching behaviors were associated with: self-efficacy related to postpartum depression teaching; social persuasion by a supervisor; prior mastery of teaching on other postpartum care topics; and vicarious experiences of observing peers teach about postpartum depression. Perinatal nurses with positive attitudes toward receiving psychological help were more likely to provide postpartum depression education.


Partial characterization of protein kinase C from an insect cell line.
The characteristics of protein kinase C (EC 184.108.40.206) from an insect cell line (Choristoneura fumiferana) have been described. DEAE-cellulose chromatography produced a major peak of activity which eluted at 0.04-0.055 M NaCl. The enzyme was sensitive to phosphatidylserine in the presence of calcium. Phorbol 12-myristate 13-acetate (PMA) in nanomolar concentrations stimulated protein kinase C activity 8-fold over basal levels and reduced the enzymes requirement for Ca2+. The enzyme had a Ka of 10 nM for PMA. Diacylglycerols tested included diolein, dilinolein, diarachidonin, oleoyl-acetyl-glycerol, dioctonoyl-sn-glycerol, dipalmitin and distearin. A 2.5- to 3-fold activation was obtained in the presence of 26 microM diolein, 40 microM oleoyl-acetyl-glycerol and 46 microM dioctonoyl-sn-glycerol. The enzyme activity was sensitive to the inhibitor H-7 and 50% inhibition was achieved at a concentration of 52 microM H-7. Phosphatidylinositol enhanced enzyme activity in the absence of phosphatidylserine but phosphatidylethanolamine had no effect.


Generation of Human iPSCs by Reprogramming with the Unmodified Synthetic mRNA.
Human-induced pluripotent stem cells (iPSCs) are showing great promise for both disease modeling and regenerative medicine. The choice of reprogramming methods have a significant effect on the outcomes of the experiments. Standard methods, such as Sendai viruses, episomes, and the base-modified mRNA have limitations. Here, I describe a method to reprogram human fibroblasts using a cocktail of mRNAs without any base modification that increases reprogramming efficiency, reduces the RNA-associated toxicity, and yields iPSCs ready for expansion and characterization in as short as 10-14 days.


Selective Dorsal Rhizotomy: Patient Demographics and Postoperative Physical Therapy.
Selective dorsal rhizotomy (SDR) is a surgical procedure that permanently alters lower extremity spasticity, common in children with spastic cerebral palsy (CP). Intensive postoperative physical therapy (PT) is recommended following SDR. The first purpose of this study is to describe and compare patient demographics between children who received SDR and the population of children with CP at one institution. The second purpose of this study is to compare the completed dose of postoperative PT with the clinically recommended dose for a subset of ambulatory children who underwent SDR. This retrospective, observational study included 60 children with spastic CP following SDR. A subset (n = 12 ambulatory children) was included to describe the dose of postoperative PT. Information gathered from electronic medical records included age at the time of SDR, sex, Gross Motor Function Classification System level, anatomic distribution, race, county-level habitancy, health insurance provider, timed current procedural terminology codes, and location for postoperative PT encounters within a single institution. Black or African American children (P = 0.002), children living in large central metro areas (P = 0.033), and children with public insurance (P ≤ 0.001) were significantly less likely to receive SDR. Children undergoing SDR do not achieve the recommended dose of PT after hospital discharge. SDR is not equally accessed by patient populations, and postoperative PT frequency is below current recommendations throughout the rehabilitation process. Future studies need to investigate why these disparities exist and what prevents children from meeting the clinically recommended dose of postoperative PT after SDR.


A pilot study of family-based management of behavioral excesses in young Iranian children with autism spectrum disorder.
Parent-mediated early behavioral interventions are considered as effective approaches in the treatment of children with Autism Spectrum Disorder (ASD). The majority of these interventions focus on social-communication deficits rather than behavioral excesses which severely irrupt child and family social life as well as the child's appearance behavior and learning processes. The study examines the effectiveness and feasibility of Family-based Management of Behavioral Excesses of Autism Program (FMBEAP) on Iranian families. This pre-post and follow-up intervention study involved 17 parents of children with DSM-5 diagnosis of ASD recruited from Tehran Autism Center. All parents conducted FMBEAP on their children while receiving 10-weekly group supervision on top of everyday on-line individual coaching. The study's measures were Repetitive Behavior Scale-R, video-monitoring of child-parent Interaction, Clinical Global Impression-Improvement Scale, Parental Self-Efficacy and Parenting Stress Index-short form. The measures were applied to the sample three times: pre and post-intervention and at one-month follow-up. The Results showed high and low order behavioral excesses significantly decreased at post-intervention and the follow-up. 15 out of 17 children reached to recovered or highly recovered at post-test. Parents showed significant improvements in self-efficacy and parenting stress scales. The intervention was highly accepted by them. FMBEAP is shown to be a feasible, acceptable and effective intervention to improve autistic behavioral. The parents should also benefit from the program in terms of self-efficacy and parenting stress. FMBEAP is highly recommended for overcoming behavioral excesses along with those interventions focus on behavioral deficits in ASD.


Identification of epitopes on the E glycoprotein of Saint Louis encephalitis virus using monoclonal antibodies.
Twenty-one hybridomas producing monoclonal antibodies specific for the E glycoprotein of St. Louis encephalitis (SLE) virus, strain MSI-7, have been isolated. Serologic reactivities were initially determined by cross-reactivity indirect immunofluorescence assays using 22 strains of SLE virus and 8 other related flaviviruses. Four groups demonstrating type-, subcomplex-, supercomplex-, and group-specific reactivity patterns were identified. Analysis of hemagglutination-inhibition (HI) and virus neutralization (N) subdivided the cross-reactivity groups into eight epitopes (E-1a,b,c,d, E-2, E-3, and E-4a,b). The antibodies could detect strain differences between SLE viruses isolated from various geographic areas. Analysis of the spatial arrangements of these epitopes using competitive binding assays with representative antibodies possessing similar binding avidities, indicated that the protein was a continuum of six overlapping domains.


Comparison between laparoscopic sleeve gastrectomy and laparoscopic adjustable gastric banding for morbid obesity: a meta-analysis.
Bariatric surgery is now widely accepted for treatment of morbid obesity. This study compared the effects of laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB) on excess weight loss (EWL) and type 2 diabetes mellitus (T2DM). PubMed and Embase were searched for publications concerning LAGB and LSG from 2000 to 2012, with the last search on August 17, 2012. EWL and T2DM improvement over 6 and 12 months were pooled and compared by meta-analysis. Odds ratios (ORs) and mean differences were calculated with 95 % confidence intervals (CIs). Eleven studies involving 1,004 patients met the inclusion criteria. Compared with LAGB, LSG achieved greater EWL. The mean percentage EWL for LAGB was 33.9 % after 6 months in six studies and 37.8 % after 12 months in four studies; for LSG, EWL was 50.6 % after 6 months and 51.8 % after 12 months in the same studies. LSG was also superior to LAGB in treating T2DM. In five studies, T2DM was improved in 42 of 68 (61.8 %) patients after LAGB and 66 of 80 (82.5 %) after LSG, representing a pooled OR of 0.34 (95 % CI 0.16-0.73) and pooled mean differences of -12.55 (95 % CI -15.66 to -9.43) and -4.97 (95 % CI -7.58 to -8.36), respectively. LSG is more effective than LAGB in morbid obesity, with higher percentage EWL and greater improvement in T2DM.


Decapping enzyme 1A breaks X-chromosome symmetry by controlling Tsix elongation and RNA turnover.
How allelic asymmetry is generated remains a major unsolved problem in epigenetics. Here we model the problem using X-chromosome inactivation by developing "BioRBP", an enzymatic RNA-proteomic method that enables probing of low-abundance interactions and an allelic RNA-depletion and -tagging system. We identify messenger RNA-decapping enzyme 1A (DCP1A) as a key regulator of Tsix, a noncoding RNA implicated in allelic choice through X-chromosome pairing. DCP1A controls Tsix half-life and transcription elongation. Depleting DCP1A causes accumulation of X-X pairs and perturbs the transition to monoallelic Tsix expression required for Xist upregulation. While ablating DCP1A causes hyperpairing, forcing Tsix degradation resolves pairing and enables Xist upregulation. We link pairing to allelic partitioning of CCCTC-binding factor (CTCF) and show that tethering DCP1A to one Tsix allele is sufficient to drive monoallelic Xist expression. Thus, DCP1A flips a bistable switch for the mutually exclusive determination of active and inactive Xs.


Gastric protein hydrolysis of raw and roasted almonds in the growing pig.
Gastric protein hydrolysis may influence gastric emptying rate and subsequent protein digestibility in the small intestine. This study examined the gastric hydrolysis of dietary protein from raw and roasted almonds in the growing pig as a model for the adult human. The gastric hydrolysis of almond proteins was quantified by performing tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subsequent image analysis. There was an interaction between digestion time, stomach region, and almond type for gastric protein hydrolysis (p<0.05). Gastric emptying rate of protein was a significant (p<0.05) covariate in the gastric protein hydrolysis. In general, greater gastric protein hydrolysis was observed in raw almonds (compared to roasted almonds), hypothesized to be related to structural changes in almond proteins during roasting. Greater gastric protein hydrolysis was observed in the distal stomach (compared to the proximal stomach), likely related to the lower pH in the distal stomach.


High-permeability layers for remediation of ground water; go wide, not deep.
A nitrate-reactive porous media layer comprising wood particles with very high hydraulic conductivity (K approximately 1 cm/s) was used to successfully treat nitrate in a shallow sand-and-gravel aquifer in southern Ontario. Nitrate concentrations of 1.3 to 14 mg/L as N in the aquifer were attenuated to <0.5 mg/L as N in the reactive layer. Borehole dilution testing indicated that ground water velocities in the reactive layer, although variable, averaged five times higher than in the surrounding aquifer, suggesting that the layer was capturing ground water flow from deeper in the aquifer. The use of high-K reactive media opens up the possibility of installing permeable reactive barriers as horizontal layers in the shallow water table zone that do not necessarily have to penetrate the full depth of a contaminant plume to be effective. Model simulations show that the depth of capture of a high-K layer increases as the layer width in the direction of flow increases. Shallower emplacement could decrease barrier costs at some sites.


In vitro enzymatic assays of protein tyrosine phosphatase 1B.
Many hormone or growth factor receptors signal via the activation of protein-tyrosine kinases and phosphatases. Alteration of the phosphorylation state of tyrosine residues in certain proteins can directly regulate enzyme activity or cause formation of protein complexes necessary for transducing intracellular signals. Genetic and biochemical evidence also implicates protein-tyrosine phosphatases in several disease processes, including negative regulation of insulin receptor signaling at the level of the insulin receptor and perhaps in signaling at the IRS-1 level. The expression of protein tyrosine phosphatase-1B (PTP1B) is elevated in muscle and adipose tissue in insulin-resistant states both in man and rodents suggesting that PTP1B may play a role in the insulin-resistant state associated with diabetes and obesity. As described in this unit, PTP1B activity can be determined with the small molecule substrate, p-nitrophenyl phosphate (pNPP), in which the cleavage of the phosphate results in production of p-nitrophenol (pNP) and an increase in absorbance at 405 nm. Alternatively, PTP1B activity can be measured as described using model phosphotyrosyl-containing peptide substrates in which the release of free phosphate from the peptide is determined using a malachite green colorimetric assay.


A Protocolized Management of Walled-Off Necrosis (WON) Reduces Time to WON Resolution and Improves Outcomes.
Patients with infected or symptomatic walled-off necrosis (WON) have high morbidity and health care utilization. Despite the recent adoption of nonsurgical treatment approaches, WON management remains nonalgorithmic. We investigated the impact of a protocolized early necrosectomy approach compared with a nonprotocolized, clinician-driven approach on important clinical outcomes. Records were reviewed for consecutive patients with WON who underwent a protocolized endoscopic drainage with a lumen-apposing metal stent (cases), and for patients with WON treated with a lumen-apposing metal stent at the same tertiary referral center who were not managed according to the protocol (control subjects). The protocol required repeat cross-sectional imaging within 14 days after lumen-apposing metal stent placement, with regularly scheduled endoscopic necrosectomy if WON diameter reduction was <50%. Control patients were treated according to their clinician's preference without an a priori strategy. Inverse probability of treatment weighting-adjusted analysis was used to evaluate the influence of being in the protocolized group on time to resolution. A total of 24 cases and 47 control subjects were included. There were no significant differences in baseline characteristics. Although numbers of endoscopies and necrosectomies were similar, cases had lower adverse event rates, shorter intensive care unit stay, and required nutritional support for fewer days. On matched multivariate Cox regression, cases had earlier WON resolution (hazard ratio, 5.73; 95% confidence interval, 2.62-12.5). This was confirmed in the inverse probability of treatment weighting-adjusted analysis (hazard ratio, 3.4; 95% confidence interval, 1.92-6.01). A protocolized strategy resulted in faster WON resolution compared with a discretionary approach without the need for additional therapeutic interventions, and with a better safety profile and decreased health care utilization.


The separation of [32P]inositol phosphates by ion-pair chromatography: optimization of the method and biological applications.
We have developed an ion-pair reverse-phase HPLC method to measure inositol phosphates in 32P-labeled cells. The different chromatographic parameters were analyzed to optimize the resolution of the 32P-labeled metabolites. Analysis of inositol phosphates in biological samples was improved by a single charcoal pretreatment which eliminated interfering nucleotides without removing inositol phosphates. The kinetics of production of inositol phosphates in calcium-activated erythrocytes, vasopressin-stimulated hepatocytes, and thrombin-activated platelets were analyzed. Original data on the activation of phosphoinositide phospholipase C were obtained in intact erythrocytes by direct measurement of inositol (1,4,5)P3. Data from agonist-stimulated hepatocytes and platelets were consistent with those from previous studies. In conclusion, this technique offers many advantages over the methodologies currently employed involving anion-exchange chromatography and [3H]inositol labeling: (i) 32P labeling is less expensive and more efficient than 3H labeling and can be used with all types of cells without permeabilization treatments and (ii) ion-pair HPLC gives good resolution of inositol phosphates from nucleotides with shorter retention times, and long reequilibration periods are not required.


[Modern approaches to the treatment of patients with a complicated form of gallstone disease in the Botkin hospital].
To determine the optimal timing of laparoscopic cholecystectomy in patients with gallstone disease complicated by cholelithiasis after endoscopic retrograde papillosphincterotomy with lithoextraction. We analyzed treatment outcomes in 229 patients with gallstone disease complicated by cholelithiasis between 2016 and 2020. Simultaneous surgery was performed in 31 patients, early cholecystectomy (after 1-3 days) - in 78 cases, delayed cholecystectomy (after 4-7 days) - in 35 cases and delayed cholecystectomy in 14-30 days after endoscopic retrograde papillosphincterotomy with lithoextraction in 85 cases. Simultaneous laparoscopic cholecystectomy and surgery in early period after endoscopic retrograde papillosphincterotomy with lithoextraction are followed by less surgery time, few postoperative complications and less hospital-stay. Simultaneous laparoscopic cholecystectomy and early surgery after endoscopic retrograde papillosphincterotomy with lithoextraction are preferred for patients with complicated gallstone disease. However, this requires adherence to strict criteria for patient selection.


Association Between Daily Dietary Eicosatetraenoic Acid Intake and the Lower Risk of Psoriasis in American Adults.
Unlike eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the relationship between eicosatetraenoic acid (ETA) and psoriasis remains unclear. Therefore, We performed a cross-sectional study in the general American population to investigate the association between daily dietary ETA, EPA, and DHA intake and the risk of psoriasis. This study applied data from the National Health and Nutrition Examination Survey (NHANES) 2003-2006 and 2009-2014. Dietary n3 polyunsaturated fatty acids (PUFA) were calculated based on two 24-hour dietary recall interviews. We defined psoriasis by responding to the question "Have you ever been told by a doctor or other health care professional that you had psoriasis?". Multivariable logistic regression analysis, trend tests, subgroup analysis, and interaction tests were used to evaluate the associations of ETA, EPA, and DHA intake with the risk of psoriasis, respectively. A total of 15,733 participants were included in this study. In our optimal multivariate-adjusted model, the odds ratio (OR) with 95% confidence interval (CI) of psoriasis were 0.30 (0.12, 0.88), 1.92 (0.78, 4.74), 1.28 (0.72, 2.27) for daily dietary ETA, EPA, and DHA intake, respectively. Trend tests showed a dose-effect relationship between daily dietary ETA intake and the lower risk of psoriasis. Subgroup analysis and tests for interaction showed that the association was stable in different subgroups. Our study revealed that there might be a dose-effect association of daily dietary ETA intake with the lower risk of psoriasis in American adults.


The distribution of events in the human menstrual cycle.
Daily reports of 85 married couples concerning their sexual behaviour for about 3 menstrual cycles per couple were organized according to menstrual events by using six techniques of aggregation. While there were some similarities among the different displays, including an apparent peak about 6 days before mid-cycle, different methods of aggregation produce widely different frequency curves. It is concluded that there is no single method of display of events of the menstrual cycle which will fit all investigations.


Risk analysis for dengue suitability in Africa using the ArcGIS predictive analysis tools (PA tools).
Risk maps identifying suitable locations for infection transmission are important for public health planning. Data on dengue infection rates are not readily available in most places where the disease is known to occur. A newly available add-in to Esri's ArcGIS software package, the ArcGIS Predictive Analysis Toolset (PA Tools), was used to identify locations within Africa with environmental characteristics likely to be suitable for transmission of dengue virus. A more accurate, robust, and localized (1 km × 1 km) dengue risk map for Africa was created based on bioclimatic layers, elevation data, high-resolution population data, and other environmental factors that a search of the peer-reviewed literature showed to be associated with dengue risk. Variables related to temperature, precipitation, elevation, and population density were identified as good predictors of dengue suitability. Areas of high dengue suitability occur primarily within West Africa and parts of Central Africa and East Africa, but even in these regions the suitability is not homogenous. This risk mapping technique for an infection transmitted by Aedes mosquitoes draws on entomological, epidemiological, and geographic data. The method could be applied to other infectious diseases (such as Zika) in order to provide new insights for public health officials and others making decisions about where to increase disease surveillance activities and implement infection prevention and control efforts. The ability to map threats to human and animal health is important for tracking vectorborne and other emerging infectious diseases and modeling the likely impacts of climate change.


[Dna organization in histone-free nuclei at various stages of rat spermatogenesis].
Electron microscopy analysis of DNA organization in histone-depleted nuclei of rat spermatogonial cells was performed. It was shown that the rosette-like structures are one of the forms of the loop organization of the meiotic cell nuclear DNA. Ions of bivalent metal play an important role in stabilizing the rosette-like structures of meiotic cells. A scheme for the restructuring of the mitotic organization of nuclear DNA into the meiotic one is suggested.


Balloon-assisted coiling of intracranial aneurysms is not associated with a higher complication rate.
Within the neurosurgical literature on intracranial aneurysms, balloon-assisted coiling (BAC) remains controversial when compared to conventional coiling (CC). The aim of this study was to compare our results with BAC and CC over a 4-year period. Daily interventional neuroradiology has been available since March 2004 in our institution. Between March 2004 and February 2008, 275 patients with 357 aneurysms were treated by an endovascular approach, including 174 patients/204 aneurysms treated by CC (group I) and 80 patients/92 aneurysms treated by BAC (group II). The remaining patients were treated with other endovascular techniques. Indications of BAC were as follow: aneurysms with an unfavourable neck/sac ratio and/or a branch arising from the neck (90.2%), unstable coiling catheter (6.5%), and anticipated aneurysm rupture (3.3%). The clinical charts, procedural data, and angiographic results of groups I and II were compared. BAC was used in 25.8% (92/357) of all embolized aneurysms and it was successful in 83/92 aneurysms (90%). There was no significant difference in the procedure-related morbidity and mortality rates between group I (2.3% and 1.15%, respectively) and group II (2.5% and 1.25%, respectively). Although retreatment was more frequent in group II (13%) than in group I (11%), the difference was not statistically significant (P = 0.8125). When BAC is used frequently, it is a safe and effective technique that is associated with complication rates comparable to those of CC. Although BAC is not associated with more stable anatomical results, it should be considered as an alternative therapeutic option for the treatment of broad-based intracranial aneurysms.


Invasion anomaly or neovascularization? A new surgical approach for cesarean delivery in pregnant women with invasive placenta accreta spectrum disorder accompanied by placenta previa.
The objective of study is to describe a new surgical approach to cesarean delivery in women with invasive placenta accreta spectrum (PAS) accompanied by placenta previa. Cesarean delivery was initiated with a transverse abdominal (Pfannenstiel) incision. A transverse incision was made above the vascular area in the lower uterine segment, and the fetus was delivered. The uterine fundus was removed from the abdomen and wrapped. Placental removal was started at posteriorly, continuing toward the anterior region. If dense adhesions were encountered, dissection was performed by inserting a finger between the adhesions to carefully separate them. It was recognized that two types of vessels develop to supply blood to the placenta. First, a perforating vessel emerges from adjacent tissues, entering the placental bed by perforating the uterine wall. Second, a superficial vessel runs along the uterine wall to enter the placental bed. The new emerging vessels were identified and ligated. Uterine sparing surgery was performed if the hemorrhage ceased. A cesarean hysterectomy was performed if hemorrhage did not cease. Eight cesarean deliveries were performed using this new surgical approach. Cesarean hysterectomy was performed in three patients in who want to sterilization diser and don't mind fertility preservation. Severe maternal morbidity, invasive procedures, intensive care unit admission, and relaparotomy were not required. The described new surgical approach provide surgeon to perform cesarean delivery without causing increase maternal morbidity and mortality. Although the approach is new and the study population is small, the results have acceptable rationality and applicability.


Isolating two sources of variability of subcortical stimulation to quantify fluctuations of corticospinal tract excitability.
Investigate the variability previously found with cortical stimulation and handheld transcranial magnetic stimulation (TMS) coils, criticized for its high potential of coil position fluctuations, bypassing the cortex using deep brain electrical stimulation (DBS) of the corticospinal tract with fixed electrodes where both latent variations of the coil position of TMS are eliminated and cortical excitation fluctuations should be absent. Ten input-output curves were recorded from five anesthetized cats with implanted DBS electrodes targeting the corticospinal tract. Goodness of fit of regressions with a conventional single variability source as well as a dual variability source model was quantified using a Schwarz Bayesian Information approach to avoid overfitting. Motor evoked potentials (MEPs) through DBS of the corticospinal tract revealed short-term fluctuations in excitability of the targeted neuron pathway reflecting endogenous input-side variability at similar magnitude as TMS despite bypassing cortical networks. Input-side variability, i.e., variability resulting in changing MEP amplitudes as if the stimulation strength was modulated, also emerges in electrical stimulation at a similar degree and is not primarily a result of varying stimulation, such as minor coil movements in TMS. More importantly, this variability component is present, although the cortex is bypassed. Thus, it may be of spinal origin, which can include cortical input from spinal projections. Further, the nonlinearity of the compound variability entails complex heteroscedastic non-Gaussian distributions and typically does not allow simple linear averages in statistical analysis of MEPs. As the average is dominated by outliers, it risks bias. With appropriate regression, the net effects of excitatory and inhibitory inputs to the targeted neuron pathways become noninvasively observable and quantifiable. The neural responses evoked by artificial stimulation in the cerebral cortex are variable. For example, MEPs in response to repeated presentations of the same stimulus can vary from no response to saturation across trials. Several sources of such variability have been suggested, and most of them may be technical in nature, but localization is missing.


Retracted: Rosiglitazone Alleviates Contrast-Induced Acute Kidney Injury in Rats via the PPARγ/NLRP3 Signaling Pathway.
[This retracts the article DOI: 10.1155/2022/4158692.].


Correction: The Good Food for Learning Universal Curriculum-Integrated Healthy School Lunch Intervention: Protocol for a Two-Year Matched Control Pre-Post and Case Study.
[This corrects the article DOI: 10.2196/30899.].


Mechanism of anchoring of OmpA protein to the cell wall peptidoglycan of the gram-negative bacterial outer membrane.
The outer membrane protein A (OmpA) plays important roles in anchoring of the outer membrane to the bacterial cell wall. The C-terminal periplasmic domain of OmpA (OmpA-like domain) associates with the peptidoglycan (PGN) layer noncovalently. However, there is a paucity of information on the structural aspects of the mechanism of PGN recognition by OmpA-like domains. To elucidate this molecular recognition process, we solved the high-resolution crystal structure of an OmpA-like domain from Acinetobacter baumannii bound to diaminopimelate (DAP), a unique bacterial amino acid from the PGN. The structure clearly illustrates that two absolutely conserved Asp271 and Arg286 residues are the key to the binding to DAP of PGN. Identification of DAP as the central anchoring site of PGN to OmpA is further supported by isothermal titration calorimetry and a pulldown assay with PGN. An NMR-based computational model for complexation between the PGN and OmpA emerged, and this model is validated by determining the crystal structure in complex with a synthetic PGN fragment. These structural data provide a detailed glimpse of how the anchoring of OmpA to the cell wall of gram-negative bacteria takes place in a DAP-dependent manner.


Arytenoid asymmetry in opera singers.
Otolaryngologists commonly observe asymmetrical movements of the arytenoid cartilages, but few authors have described the clinical implications of this asymmetry, especially in singers. The aim of this study was to determine the epidemiological and clinical characteristics of arytenoid asymmetry in adduction in a group of healthy opera singers and to evaluate the impact of this asymmetry on the voice. The medical charts and laryngeal video recordings of 245 healthy opera singers were retrospectively reviewed. Arytenoid asymmetry was defined in relation to the position of the corniculate cartilages, cuneiform cartilages and aryepiglottic angle. The subjects had a mean age of 38.54years (range: 18 to 85 years) and presented a male-to-female sex ratio of 1.02. About 5% of subjects had a history of smoking. The most common vocal symptoms were occasional dysphonia (4%), followed by vocal fatigue (2%) and pharyngeal dryness (2%). Arytenoid asymmetry was slightly more common in males (50.6%) and predominantly affected the right side (64.5%). The most common form of asymmetry was cuneiform asymmetry (37.5%), followed by aryepiglottic angle asymmetry in 33.1% of cases and corniculate asymmetry in 29.4% of cases. Mild asymmetry was observed in the majority of cases. No correlation was observed between arytenoid asymmetry and vocal symptoms. Almost one out of two singers was likely to present arytenoid asymmetry in adduction. The presence of this asymmetry does not appear to be correlated with any vocal symptoms.


Surgical treatment of a large emphysematous bulla complicated by accumulation of fluid and infection.
Emphysematous bulla complicated by infection is very rare. A case of a patient, who was a respiratory cripple, with an infected bulla is presented. Surgical resection was performed with excellent results. The treatment of choice is surgery by means of excision of bulla, partial pleurectomy, and decortication of the involved lung.


Minimally incisional stabilization of unstable L5 burst fracture.
Burst fractures of the L5 vertebral body are uncommon. Treatment options described include prolonged immobilization and surgical stabilization, most commonly with an instrumented fusion from L4 to the sacrum. We describe the use of a minimally incisional technique to provide temporary internal fixation in a patient with an L5 burst fracture who was not a candidate for prolonged immobilization. This technique resulted in an excellent outcome without the requirement for a fusion. Minimally incisional fixation procedures are a treatment option for select patients with L5 burst fractures.


The error in indirect blood pressure measurement with the incorrect size of cuff.
This paper shows the error to be expected when blood pressure is measured indirectly with a cuff that is too wide or too narrow for the member to which it is applied. A cuff that is too narrow overestimates and a cuff that is too wide underestimated blood pressure.


Investigation on removal of malachite green using EM based compost as adsorbent.
The discarded materials from different sources can be utilized as effective materials in wastewater remediation. This proposed study was aimed mainly to investigate the possibility of Effective Microorganisms based compost (EMKC), which is derived from the kitchen solid waste, as a non-conventional low cost adsorbent for the removal of malachite green from aqueous solution. Batch experiments were carried out to evaluate the optimum operating parameters like pH (2-9), initial dye concentration (50-1000mg/L), adsorbent particle size (0.6-2.36mm) and adsorbent dosage (2-12g/L). EMKC recorded maximum uptake of 136.6mg/g of MG at pH 8, initial dye concentration 1000mg/L, adsorbent particle size 1.18mm and adsorbent dosage 4g/L. Two and three parameter adsorption models were employed to describe experimental biosorption isotherm data. The results revealed that the Sips model resulted in better fit than other models. The pseudo-first and -second order models were applied to describe kinetic data, of which the pseudo-second order described experimental data better with high correlation coefficient. This investigation suggested that EMKC could be an effective and low cost material for the removal of malachite green dye from aqueous solution.


Stage-dependent processing and localization of a Plasmodium falciparum protein of 130,000 molecular weight.
A Plasmodium falciparum protein of 130,000 molecular weight (m.w.) has been identified, cloned in Escherichia coli, and completely sequenced (Kochan et al. 1986). The protein appeared to bind to soluble glycophorin, a host erythrocyte surface protein. In the present study, extracts of parasites from different intraerythrocytic stages were immunoblotted with antibodies, raised against a 30,000 m.w. fusion protein corresponding to the 3' end of the 130,000 m.w. protein. It was demonstrated that the protein is synthesized at the trophozoite stage, accumulates at the schizont stage, and is processed at the merozoite stage to a triplet of three polypeptides. The processed proteins are present in the culture supernatant at the time of merozoite burst from the red cell. Immunofluorescent staining of the parasite at different intracellular stages indicates that the protein is localized on the parasite at the trophozoite stage. At late trophozoite stage, it appears to be transported to the erythrocyte cytoplasm, where it is present in small vesicles or inclusions. In mature schizonts the protein accumulates around the plasma membrane of the erythrocyte. At the segmenter stage, just prior to merozoite release, it appears also to surround the intracellular merozoite, as well as the erythrocyte plasma membrane. The soluble 130,000 m.w. protein binds to erythrocytes but binds significantly greater to erythrocyte membranes, suggesting it binds to an internal domain of glycophorin rather than the domain exposed on the surface. The 130,000 m.w. protein is present in 11 different geographic isolates of P. falciparum from diverse geographic origins. Its molecular weight is similar in all isolates.


Synthesis of 4,5-dimethoxykynuramine and its in vivo conversion to 6,7-dimethoxy-4-quinolinol.
4,5-Dimethoxykynuramine was synthesized in a three-step sequence originating with veratrole. Indirect evidence indicates that the drug was converted in vivo to the hypotensive agent 6,7-dimethoxy-4-quinolinol by the action of monoamine oxidase.


Immunoglobulin subclasses in normal children.
The range, mean, and normal bounds of serum IgG 1--4 subclass concentrations in children 0--16 years old are given. Levels increase with age, plateauing at different ages. Definition of the normal range will permit better identification of individuals with either low or high levels.


PD-L1 expression in pancreatic ductal adenocarcinoma is a poor prognostic factor in patients with high CD8+ tumor-infiltrating lymphocytes: highly sensitive detection using phosphor-integrated dot staining.
Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. For the development of more effective immunotherapies, it is first necessary to elucidate the immunological escape mechanisms. In this study, we applied our recently developed highly sensitive immunostaining method employing fluorescent phosphor-integrated dot (PID) nanoparticles to evaluate the prevalence of programmed death ligand 1 (PD-L1) in patients with PDAC. This study included 42 patients with PDAC who underwent pancreatectomy. We evaluated PD-L1 expression in these patients using PID staining and correlated PD-L1 expression level with each patient's clinico-pathological features. PD-L1 expression was detected in 61.9% (26/42) of the patients with PDAC by PID staining. There was a significant difference in overall survival between PD-L1-positive and PD-L1-negative patients [hazard ratio (HR) 2.07, 95% confidence interval (CI) 1.00-4.54; P = 0.049]. Among CD8+-tumor-infiltrating lymphocyte-positive cases, the overall survival of PD-L1-positive patients was significantly poorer than that of PD-L1-negative patients (HR 3.84, 95% CI 1.59-10.35; P = 0.003). Univariate and multivariate analyses indicated that PD-L1 expression was an independent predictive poor prognostic factor in patients with PDAC. PD-L1 expression appears to be an important prognostic factor in patients with PDAC who underwent surgical resection.


ATM Localization and Heterochromatin Repair Depend on Direct Interaction of the 53BP1-BRCT2 Domain with γH2AX.
53BP1 plays multiple roles in mammalian DNA damage repair, mediating pathway choice and facilitating DNA double-strand break repair in heterochromatin. Although it possesses a C-terminal BRCT2 domain, commonly involved in phospho-peptide binding in other proteins, initial recruitment of 53BP1 to sites of DNA damage depends on interaction with histone post-translational modifications--H4K20me2 and H2AK13/K15ub--downstream of the early γH2AX phosphorylation mark of DNA damage. We now show that, contrary to current models, the 53BP1-BRCT2 domain binds γH2AX directly, providing a third post-translational mark regulating 53BP1 function. We find that the interaction of 53BP1 with γH2AX is required for sustaining the 53BP1-dependent focal concentration of activated ATM that facilitates repair of DNA double-strand breaks in heterochromatin in G1.


Cause of death after allogeneic haematopoietic stem cell transplantation (HSCT) in early leukaemias: an EBMT analysis of lethal infectious complications and changes over calendar time.
We analysed a large homogeneous group of 14,403 patients transplanted for early leukaemia from an HLA-identical sibling and reported to the EBMT in four time cohorts: 1980-1989 (24%), 1990-1994 (26%), 1995-1998 (30%) and 1999-2001 (20%). We focused on death from infection. End points were survival, death from relapse and transplant-related mortality (TRM), which was subdivided into death from graft-versus-host disease (GvHD) (1315 patients; 25% of deaths), infection (597 patients; 11% of deaths) or 'other' causes (1875 patients; 34% of deaths). Survival increased from 52% at 5 years in the first to 62% in the third cohort (P<0.05) and TRM decreased from 36 to 26% (P<0.05) due to a reduction in death from infection (P<0.001). GvHD, 'other' causes and relapse did not improve. The relative proportions of bacteria (217 patients; 36%), viruses (183 patients; 31%), fungi (166 patients; 28%) or parasites (32 patients; 5%) as cause of infectious death (cumulative incidence of death at 5 years 1.8, 1.6, 1.4 and > or = 0.3%, respectively) and median time to death from infections (3 months (range 0-158 months)) did not change. Death from infections has been reduced significantly, but it still represents an ongoing risk after HSCT and draws attention to the time beyond the initial period of neutropenia.


Myo-inositol dehydrogenase(s) from Acetomonas oxydans.
Experimental studies have been undertaken with a view of isolation of the enzyme(s) responsible for the stereospecific oxidation of myo-inositol. A partial fractionation has been achieved and the properties of this extract examined. Results show that the active enzyme may well have a cytochrome component and there is indication that the stereospecificity of Acetomonas oxydans results from permease as opposed to dehydrogenase activity. Kinetic experiments suggest that only one type of active enzyme site is involved in the dehydrogenation of myo-inositol.


An interdisciplinary approach to assess human health risk in an urban environment: A case study in temperate Argentina.
Unplanned urbanization increases the exposure of people to environmental hazards. Within a landscape ecology framework, this study is a diagnosis of human health risk in San Martín, an urban district of Buenos Aires, Argentina. Risk was estimated by combining four hazard indexes (water and air pollution, and mosquito and rodent infestation) and a vulnerability index. Each index was obtained by integrating environmental and socio-demographic layers in a Geographic Information System. Spatial autocorrelation was assessed for each hazard, vulnerability and risk indexes using Moran's tests. Also, spatial associations between pairs of variables were addressed by means of Geographically Weighted Regressions. The robustness of hazard and vulnerability indexes was checked by a sensitivity analysis. In General San Martín district, 83.3% of the population is exposed to relatively high levels of at least one hazard; 7.4% is exposed to relatively high levels of all hazards (11.5% of the total area) and only 16.7% lives in areas of relatively low levels of all hazards (15.4% of the total area). Areas where hazard intensity was relatively high corresponded to those areas where the most vulnerable population lives, enhancing human health risk. The models for hazards and vulnerability were reasonably robust to changes in the weights of the variables considered. Our results highlight the spatially heterogeneous nature of human health risk in an urban landscape, and reveal the location of critical risk hotspots where reduction or mitigation actions should be focused.


The genetic basis for mating-induced sex differences in starvation resistance in Drosophila melanogaster.
Multiple genetic and environmental factors interact to influence starvation resistance, which is an important determinant of fitness in many organisms, including Drosophila melanogaster. Recent studies have revealed that mating can alter starvation resistance in female D. melanogaster, but little is known about the behavioral and physiological mechanisms underlying such mating-mediated changes in starvation resistance. In the present study, we first investigated whether the effect of mating on starvation resistance is sex-specific in D. melanogaster. As indicated by a significant sex×mating status interaction, mating increased starvation resistance in females but not in males. In female D. melanogaster, post-mating increase in starvation resistance was mainly attributed to increases in food intake and in the level of lipid storage relative to lean body weight. We then performed quantitative genetic analysis to estimate the proportion of the total phenotypic variance attributable to genetic differences (i.e., heritability) for starvation resistance in mated male and female D. melanogaster. The narrow-sense heritability (h(2)) of starvation resistance was 0.235 and 0.155 for males and females, respectively. Mated females were more resistant to starvation than males in all genotypes, but the degree of such sexual dimorphism varied substantially among genotypes, as indicated by a significant sex×genotype interaction for starvation resistance. Cross-sex genetic correlation was greater than 0 but less than l for starvation resistance, implying that the genetic architecture of this trait was partially shared between the two sexes. For both sexes, starvation resistance was positively correlated with longevity and lipid storage at genetic level. The present study suggests that sex differences in starvation resistance depend on mating status and have a genetic basis in D. melanogaster.


Interpopulation, interindividual, intercycle, and intracycle natural variation in progesterone levels: a quantitative assessment and implications for population studies.
Methodological challenges in studying sex steroid hormones in premenopausal women result from the existence of variation at three levels: among women from the same population, among menstrual cycles recorded for women at different times of the year, and among days of the same cycle. We partitioned, for a Polish rural population, the natural, nonpathological, variation in salivary progesterone concentrations (measured during 14 days of the luteal phase) into the intracycle component (which accounts for 65% of the total variation) and the among-cycle component (the remaining 35% of the total variation). Out of the among-cycle variation in salivary progesterone, as much as 46% is expressed as differences among individual women (interindividual component); the remaining 54% of variation is due to differences among cycles of individual women (intercycle, within-women component). Such intercycle variation is probably caused by a seasonality of agricultural workload and is much higher than in nonseasonal, industrial populations. We also used bootstrap analyses to generate heuristic recommendations for choosing sample sizes of the number of subjects, number of cycles per woman, and number of days per cycle. Studies in populations with seasonal lifestyles should rely on measurements of at least three cycles per woman. Given the substantial intracycle amplitude in hormone levels to reliably assess biologically and medically relevant variation in ovarian function, at least 7-8 days/cycle should be measured.


Generation of a human urinary bladder smooth muscle cell line.
We report a cell line (hBSM) established from human urinary bladder wall smooth muscle that maintains most of the phenotypic characteristics of smooth muscle cells. Cells were dissociated from the muscular layer with collagenase (1 mg/ml) and collected and grown in M199 supplemented with 10% fetal calf serum and 1% antibiotic-antimycotic. Primary cultures were grown for 2 d and small colonies were isolated by placing glass rings around the colonies. These colonies were picked up with a fine-tipped Pasteur pipette and subcultured. This procedure was repeated several times until a culture with a uniform stable morphology was obtained. hBSM cells are elongated with tapered ends, and in high density cultures, they form swirls of cells arranged in parallel. These cells have a doubling time of approximately 72 h. Western blotting and immunofluorescence microscopy revealed stable expression of smooth muscle-specific proteins, including myosin isoforms (N-terminal isoforms SM-A/B and C-terminal isoforms SM1/2), SM22, α-smooth muscle actin, h-caldesmon, Ca(2+)-dependent myosin light chain kinase, and protein kinase G. These cells contract upon exposure to 10 μM bethanechol and this contraction is reversible by washing away the drug. Karyotyping showed tetraploidy with a modal chromosome number of 87, with multiple rearrangements. To our knowledge, the hBSM cell line is the first human cell line established from bladder wall smooth muscle that expresses both N- and C-terminal smooth muscle myosin isoforms. This cell line will provide a valuable tool for studying transcriptional regulation of smooth muscle myosin isoforms and effects of drugs on cellular function.


Insulin receptors on monocytes of young healthy persons correlated with glucose tolerance and insulin sensitivity.
We have studied in normal man the interrelationships between insulin binding to monocytes, glucose tolerance and insulin sensitivity. In 25 young healthy persons we found a significant positive correlation between insulin binding and glucose disappearance rate both after glucose (R = 0.68, p less than 0.001) and insulin (R = 0.49, p less than 0.02) given intravenously.


Hyper-stimulation of Pyrococcus furiosus CRISPR DNA uptake by a self-transmissible plasmid.
Pyrococcus furiosus is a hyperthermophilic archaeon with three effector CRISPR complexes (types I-A, I-B, and III-B) that each employ crRNAs derived from seven CRISPR arrays. Here, we investigate the CRISPR adaptation response to a newly discovered and self-transmissible plasmid, pT33.3. Transconjugant strains of Pyrococcus furiosus exhibited dramatically elevated levels of new spacer integration at CRISPR loci relative to the strain harboring a commonly employed, laboratory-constructed plasmid. High-throughput sequence analysis demonstrated that the vast majority of the newly acquired spacers were preferentially selected from DNA surrounding a particular region of the pT33.3 plasmid and exhibited a bi-directional pattern of strand bias that is a hallmark of primed adaptation by type I systems. We observed that one of the CRISPR arrays of our Pyrococcus furiosus laboratory strain encodes a spacer that closely matches the region of the conjugative plasmid that is targeted for adaptation. The hyper-adaptation phenotype was found to strictly depend both on the presence of this single matching spacer as well as the I-B effector complex, known to mediate primed adaptation. Our results indicate that Pyrococcus furiosus naturally encountered this conjugative plasmid or a related mobile genetic element in the past and responds to reinfection with robust primed adaptation.


Comparison of interaction, structure, and cell proliferation of α-lactalbumin-safflower yellow complex induced by microwave heating or conventional heating.
The protein-polyphenol interaction mechanism has always been a research hotspot, but their interaction is affected by heat treatment, which is widely applied in food processing. Moreover, the effects of microwave or water-bath heating on the protein-polyphenol interaction mechanism have been not clarified. The pasteurization condition (65 °C, 30 min) was selected to compare the effects of microwave or water bath on binding behavior, structure, and cell proliferation between α-lactalbumin (α-LA) and safflower yellow (SY), thus providing a guide for the selection of functional dairy processing conditions. Microwave heat treatment of α-LA-SY resulted in stronger fluorescence quenching than that of conventional heat treatment. Moreover, the binding constant Ka of all α-LA-SY samples was augmented significantly after microwave or water bath treatment, and microwave-heated α-LA-SY showed the maximum Ka . Fourier transform infrared spectroscopy showed that microwave heating resulted in more ordered structures of α-LA into its disordered structures than water bath heating. However, the ferric reducing antioxidant power and chroma value of α-LA-SY were more reduced by microwave heating than by water bath heating. Moreover, microwave heating facilitated the cell proliferation of α-LA-SY compared with water bath treatment. It was demonstrated that microwave heating promoted interaction between α-LA and SY more than water bath heating did. Microwave heat treatment was a safe and effective way to enhance the binding affinity of α-LA to SY, being a potential application in food industry. © 2022 Society of Chemical Industry.


Successful Breast Conservation After Neoadjuvant Chemotherapy in Lobular Breast Cancer: The Role of Menopausal Status in Response to Treatment.
While neoadjuvant chemotherapy (NAC) has been shown to increase rates of breast conservation surgery (BCS) for breast cancer, response rates in invasive lobular carcinoma (ILC) appear lower than other histologic subtypes. Some data suggest higher response rates to NAC in premenopausal versus postmenopausal patients, but this has not been studied in ILC. We evaluated the rates of successful BCS after NAC in patients with ILC stratified by menopausal status. We analyzed data from a single-institution cohort of 666 patients with stage I-III hormone receptor positive HER-2 negative ILC. We used t-tests, chi-squared tests, and multivariable logistic regression to investigate rates of NAC use, attempted BCS, and associations between NAC and successful BCS by menopausal status. In 217 premenopausal and 449 postmenopausal patients, NAC was used more often in the premenopausal group (15.2% vs. 9.8%, respectively, p = 0.041). Among those who attempted breast conservation (51.3% of pre- and 64.8% of postmenopausal cohorts), NAC was not associated with successful BCS in either group. Interestingly, for postmenopausal patients, receipt of NAC was significantly associated with increased rates of completion mastectomy in those who had positive margins at the first attempt at BCS. NAC was not associated with successful BCS in either premenopausal or postmenopausal patients with ILC. Although premenopausal patients were more likely to receive NAC, these data suggest that menopausal status may not be a good predictor of response to chemotherapy. Better predictors of response and more efficacious treatment for patients with ILC are needed.


Quantification of orthodontic loads on teeth in the correction of canine overeruption using different archwire designs.
This study quantifies the effects of material, size of the continuous archwires, and level of overeruption on the loads on teeth in the correction of overerupted canines. An orthodontic force test (OFT) was used to measure the 3-dimensional loads delivered by the archwires to the brackets attached to the maxillary right incisors, canine, and premolars. Dentoforms simulating canine overeruptions at the 0.5 mm and 1 mm levels were made from computerized tomography scans. Archwires with 2 types of material (stainless steel [SS] and nickel-titanium [NiTi]) and 2 sizes (0.014-in and 0.016-in) were tested, respectively, on the 0.022 × 0.028-in brackets through elastomeric ligatures. The forces were dominantly intrusive on the canines and extrusive on the first premolars and lateral incisors. The magnitudes of the extrusive forces were about 74% and 52% that of intrusive force on the canines, which range from -0.48 ± 0.01 N to -5.70 ± 0.14 N depending on the wire material, size, and severity of overeruption (P <0.01). The canine intrusive forces created by SS wires were about 3 times higher than that of NiTi wires with the same sizes, 0.016-in archwires were about twice higher than that of 0.014-in with the same materials, and 1 mm overeruption level doubled with respect to 0.5 mm. Significant second-order moment as coupled with the intrusive or extrusive forces. The intrusive and extrusive forces on teeth in the correction of canine overeruption can be quantified by the in vitro orthodontic force test, and the effects of the 3 factors significantly affect the loads on the teeth.


C. elegans dss-1 is functionally conserved and required for oogenesis and larval growth.
Dss1 (or Rpn15) is a recently identified subunit of the 26S proteasome regulatory particle. In addition to its function in the protein degradation machinery, it has been linked to BRCA2 (breast cancer susceptibility gene 2 product) and homologous DNA recombination, mRNA export, and exocytosis. While the fungal orthologues of Dss1 are not essential for viability, the significance of Dss1 in metazoans has remained unknown due to a lack of knockout animal models. In the current study deletion of dss-1 was studied in Caenorhabditis elegans with a dss-1 loss-of-function mutant and dss-1 directed RNAi. The analysis revealed an essential role for dss-1 in oogenesis. In addition, dss-1 RNAi caused embryonic lethality and larval arrest, presumably due to loss of the dss-1 mRNA maternal contribution. DSS-1::GFP fusion protein localised primarily in the nucleus. No apparent effect on proteasome function was found in dss-1 RNAi treated worms. However, expression of the C. elegans dss-1 in yeast cells deleted for its orthologue SEM1 rescued their temperature-sensitive growth phenotype, and partially rescued the accumulation of polyubiquitinated proteins in these cells. The first knockout animal model for the gene encoding the proteasome subunit DSS-1/Rpn15/Sem1 is characterised in this study. In contrast to unicellular eukaryotes, the C. elegans dss-1 encodes an essential protein, which is required for embryogenesis, larval growth, and oogenesis, and which is functionally conserved with its yeast and human homologues.


Associations of Food Intolerance with Irritable Bowel Syndrome, Psychological Symptoms, and Quality of Life.
The impact of different types of food intolerance on gastrointestinal symptoms and quality of life (QOL) is poorly understood. We aimed to investigate associations of food intolerance and type of intolerance with irritable bowel syndrome (IBS), health-related QOL, and psychological symptoms. We conducted an observational study of United States-based adults through an online survey. Demographics, culprit foods, symptoms, medical evaluation, Rome IV criteria for IBS, health-related QOL (Short-Form Health Survey 12), and anxiety and depression scores (Hospital Anxiety and Depression Scale) were collected in participants with self-reported food intolerance (lactose, non-lactose food, lactose plus food intolerance), and controls with no intolerance. Univariable associations of group with study endpoints were analyzed with the Kruskal-Wallis and Pearson χ2 or Fisher exact test. Multivariable comparisons were analyzed by logistic and linear regression. A total of 197 patients with (59 lactose, 61 non-lactose food, 77 lactose plus food intolerance) and 273 patients without intolerance participated. Lactose, wheat, and eggs were the most common food triggers. Gas (54.2%), abdominal pain (40.2%), and diarrhea (37.3%) were frequently reported symptoms of food intolerance. Reactions caused 57.8% to eliminate the food. Rates of IBS, abnormal anxiety scores, and abnormal depression scores were highest in lactose plus food intolerance; Short-Form Health Survey 12 scores were lowest in lactose plus food intolerance. Multivariable analyses revealed all intolerance subgroups were more likely to have IBS than controls. Food intolerance is associated with IBS, anxiety, depression, and decreased health-related QOL and frequently leads to food elimination. Adults with lactose and lactose plus food intolerance have higher rates of IBS, increased psychological symptoms, and poorer QOL.


Effects of in vitro incorporation of cholesterol and cholesterol analogues into rat platelets.
Cholesterol and analogues of cholesterol bearing shorter side chains were incorporated into rat platelet membranes by incubation with sterol-rich liposomes in vitro. Cholesterol-enriched platelets showed increased aggregability to collagen compared with controls. Platelets containing the cholesterol analogues pregn-5-en-3 beta-ol and chol-5-en-3 beta-ol were even more sensitive to aggregation and could aggregate spontaneously on stirring. The size of the platelets containing pregn-5-en-3 beta-ol was markedly reduced when compared with controls in the scanning electron microscope. The results suggest that the sterol content and structure of the platelet membrane can have a critical role in maintaining the normal function of the cell.


[Management of urological complications after renal transplantation].
Urological complications after kidney transplantation can cause a major reduction in renal function. Surgical complications like urinary leakage and ureteral obstruction need to be solved by a specialist in the field of endourological procedures and open surgical interventions. The article summarizes this and other common urological problems after kidney transplantation.


Pneumonectomy for severe inflammatory lung disease. Results in 64 consecutive cases.
Severe inflammatory lung disease resulting in severe unilateral pulmonary pathology necessitating pneumonectomy is still encountered in third world populations. A retrospective study of the last 64 patients undergoing pneumonectomy was performed. The underlying lung pathology was: destroyed lung due to tuberculosis in 33 patients; severe bronchiectasis in 25; necrotizing pneumonia in 4; lung abscess in 1 and hypoplastic lung in 1 patient. The perioperative management of these patients is outlined. Perioperative complications included respiratory failure in 4, secondary haemorrhage in 2 and post-pneumonectomy empyema in 5 patients. There were 2 mortalities (3.1%), both due to contralateral spillage with fulminant respiratory failure. Excellent results were achieved in 89% of the patients.


Bronchiolar adenoma-like tumour with monolayered component: Represent malignant transformation of bronchiolar adenoma? A series of five cases.
Pulmonary bronchiolar adenoma (BA) is a rare lung tumour, it is unclear whether BA can develop into a malignancy. We presented five cases of BA-like tumour with monolayered components. This type of tumour may represent the malignant transformation of BA. Histologically, these tumours showed acinar and lepidic growth patterns. The acinar components were well-differentiated. The glandular tumour cells in these tumours contained cuboidal to columnar cells resembling type II pneumocytes or club (Clara) cells. A small number of mucinous cells were found in two cases. A few scattered ciliated cells were detected in three cases. The ciliated cells only existed in the bilayered components. The basal cells were highlighted by CK5/6 and p40 in a partial region of the tumour rather than in the entire tumour. The glandular tumour cells, including those in the bilayered component, were diffusely positive for TTF-1 and napsin-A. EGFR Exon19 deletions were found in four cases, and BRAF V600E mutation was found in one case. These BA-like tumours have biphasic morphological and molecular characteristics of BA and lung adenocarcinoma, suggesting distal-type BA may develop into a malignancy. More cases should be studied and especially cases with metastasis should be searched to further prove the malignant transformation.


Smad4 is required to regulate the fate of cranial neural crest cells.
Smad4 is the central mediator for TGF-beta/BMP signals, which are involved in regulating cranial neural crest (CNC) cell formation, migration, proliferation and fate determination. It is unclear whether TGF-beta/BMP signals utilize Smad-dependent or -independent pathways to control the development of CNC cells. To investigate the functional significance of Smad4 in regulating CNC cells, we generated mice with neural crest specific inactivation of the Smad4 gene. Our study shows that Smad4 is not required for the migration of CNC cells, but is required in neural crest cells for the development of the cardiac outflow tract. Smad4 is essential in mediating BMP signaling in the CNC-derived ectomesenchyme during early stages of tooth development because conditional inactivation of Smad4 in neural crest derived cells results in incisor and molar development arrested at the dental lamina stage. Furthermore, Smad-mediated TGF-beta/BMP signaling controls the homeobox gene patterning of oral/aboral and proximal/distal domains within the first branchial arch. At the cellular level, a Smad4-mediated downstream target gene(s) is required for the survival of CNC cells in the proximal domain of the first branchial arch. Smad4 mutant mice show underdevelopment of the first branchial arch and midline fusion defects. Taken together, our data show that TGF-beta/BMP signals rely on Smad-dependent pathways in the ectomesenchyme to mediate epithelial-mesenchymal interactions that control craniofacial organogenesis.


Current perception of social accountability of medical schools in Japan: A qualitative content analysis.
The concept of social accountability in medical schools is globally accepted, but data regarding Japanese medical schools are lacking and unclear. This study aimed to elucidate the perception of social accountability of medical schools in Japan and compare this to global frameworks. A document on Japanese medical accreditation standards (Basic Medical Education: Japanese Specifications WFME Global Standards for Quality Improvement) was used for this study. We included 45 medical schools in a qualitative content analysis done via inductive category formation. The documents were also assessed using the social obligation scale. Three main categories and 15 categories were identified. The three main categories were as follows: Issues in society, Quality assurance of medical school, and Improvement of individual quality. Most categories were common to those in global frameworks, but some were characteristic of the Japanese context. The distribution of schools on the social obligation scale in six elements varied mainly 'from responsibility to responsiveness' or equal unless the elements were promoted by national policy. The social accountability of Japanese medical schools is mostly common with the global frameworks. Our findings will help the social accountability of medical schools to become better understood and developed beyond contextual borders.


Multiple idiopathic external resorption of teeth.
Three cases of multiple idiopathic external resorption are presented. The condition is characterised by the absence of any widespread inflammatory response both in the gingival tissues and within the dental pulp. The only curative treatment is exodontia.


Conditioning the neuroimmune response to ethanol using taste and environmental cues in adolescent and adult rats.
A combined odor and taste cue was paired with a binge-like ethanol exposure (4 g/kg intraperitoneal) using a single-trial learning paradigm. Re-exposure to the CS alone was sufficient to evoke a conditioned Interleukin (IL)-6 elevation in the amygdala in adolescents, an effect that was not observed in young adults. This demonstrates a particular sensitivity of adolescents to alcohol-associated cues and neuroimmune learning, whereas prior work indicated that adults require multiple pairings of ethanol to the CS in order to achieve a conditioned amygdala IL-6 response. While the role of immune conditioning has been studied in other drugs of abuse, these findings highlight a previously unknown aspect of alcohol-related learning. Given the emergent importance of the neuroimmune system in alcohol abuse, these findings may be important for understanding cue-induced reinstatement of alcohol intake among problem drinkers.


Associations between adherence to the Taiwan Daily Food Guide and psychiatric morbidity: A population-based study in Taiwan.
Mental health has become a public health concern worldwide, and the number of affected individuals is rising. Therefore, further research must be conducted to identify potential risk factors to develop optimal prevention strategies to mitigate mental health disorders. Using Taiwanese Nutrition and Health Survey data collected from 2013-2016, we conducted a cross-sectional study to examine whether adherence to the Taiwan Daily Food Guide affects mental health conditions. Study participants were adults aged ≥19 years. The dietary assessment was conducted using a validated food frequency questionnaire. The presence of psychiatric morbidity was defined as a five-item Brief Symptom Rating Scale (BSRS-5) score of ≥10. Logistic regression models were used to determine whether Taiwan Daily Food Guide adherence was related to the presence of psychiatric morbidity. After adjusting for potential confounders, we observed protective associations between adherence to the Taiwan Daily Food Guide and psychiatric morbidity risk. The Taiwan Daily Food Guide might reduce the risk associated with psychiatric morbidity and could be a reference for developing a national food guide for mental health.


Occupational Medicine and Prevention of Chronic and Infectious Diseases.
Occupational medicine is a clinical discipline that draws attention to the health of workers and their ability to work [...].


Limited clinical significance of tissue calprotectin levels in bowel mucosa for the prediction of complicated course of the disease in children with ulcerative colitis.
Fecal calprotectin (F-CPT) represents one of the most widely used biomarkers for intestinal inflammation. However, the levels may be false negative or false positive in some situations. To evaluate the usefulness of immunohistochemical (IHC) detection of tissue calprotectin (T-CPT) in bowel mucosa in children with ulcerative colitis (UC). We focused at correlation of T-CPT with levels of F-CPT and endoscopic and microscopic disease activity at the time of diagnosis and tested whether T-CPT could serve as predictor of complicated course of the disease. Forty-nine children with newly diagnosed UC between 6/2010-1/2018 entered the study. Endoscopic activity was objectified using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), clinical activity by Pediatric Ulcerative Colitis Activity Index (PUCAI) and microscopic activity by Geboes and Nancy score. The IHC staining for CPT antigen was performed on bioptic samples from 6 bowel segments and the number of CPT + cells were counted per 1HPF. During the minimal follow-up of 12 months we searched for presence of complications. As outcome for Cox regression model we used composite endpoints: A) Acute Severe Colitis, colectomy, anti-TNF treatment; B) systemic corticotherapy; C) systemic 5-aminosalicylic acid therapy. Neither levels of T-CPT nor values of UCEIS, Geboes or Nancy score predicted the given complications. We found F-CPT levels (HR 2.42 and 2.52) and PUCAI > 40 points (HR 2.98) as predictors of time to endpoints B and C. Good correlation was found between T-CPT levels and Geboes score (k = 0.65) and Nancy score (k = 0.62) and modest with F-CPT (k = 0.44), UCEIS (k = 0.38) and PUCAI (k = 0.42). T-CPT correlated well with microscopic scores. F-CPT and PUCAI appear to be better predictors of unfavorable outcome in patients with UC.


Propagation of human hepatitis A virus in a hepatoma cell line.
Hepatitis A virus (HAV) was isolated directly from human feces and propagated serially in an HBsAg producing human hepatoma cell line. No cytopathic effect was observed in the tissue culture and no detectable amounts of HAV were present in the tissue culture supernatant fluid. However, increasing amounts of hepatitis A antigen (HAAg) were detected by radioimmunoassay in the cell extracts obtained by freezing and thawing of cells. Specificity of the HAAg determination was shown by neutralization with convalescent sera of marmosets experimentally infected with the MS-1 strain of hepatitis A and by the absence of this neutralization with preinoculation sera. HAAg was first detected after four weeks in the cell extract of infected cultures after inoculation of 10(2)--10(4) tissue culture infectious doses of HAV from second passage.


PCR m typing: a new method for rapid typing of group a streptococci.
A new approach for the M-typing of Streptococcus pyogenes is reported. Oligonucleotide primers were used in a PCR to amplify the N-terminal region of the emm gene. The presence of the PCR amplification product is associated with the corresponding M serotype. This technique offers potential advantages over other molecular typing methods.


Genetic alteration of the metal/redox modulation of Cav3.2 T-type calcium channel reveals its role in neuronal excitability.
In this study, we describe a new knock-in (KI) mouse model that allows the study of the H191-dependent regulation of T-type Cav3.2 channels. Sensitivity to zinc, nickel and ascorbate of native Cav3.2 channels is significantly impeded in the dorsal root ganglion (DRG) neurons of this KI mouse. Importantly, we describe that this H191-dependent regulation has discrete but significant effects on the excitability properties of D-hair (down-hair) cells, a sub-population of DRG neurons in which Cav3.2 currents prominently regulate excitability. Overall, this study reveals that the native H191-dependent regulation of Cav3.2 channels plays a role in the excitability of Cav3.2-expressing neurons. This animal model will be valuable in addressing the potential in vivo roles of the trace metal and redox modulation of Cav3.2 T-type channels in a wide range of physiological and pathological conditions. Cav3.2 channels are T-type voltage-gated calcium channels that play important roles in controlling neuronal excitability, particularly in dorsal root ganglion (DRG) neurons where they are involved in touch and pain signalling. Cav3.2 channels are modulated by low concentrations of metal ions (nickel, zinc) and redox agents, which involves the histidine 191 (H191) in the channel's extracellular IS3-IS4 loop. It is hypothesized that this metal/redox modulation would contribute to the tuning of the excitability properties of DRG neurons. However, the precise role of this H191-dependent modulation of Cav3.2 channel remains unresolved. Towards this goal, we have generated a knock-in (KI) mouse carrying the mutation H191Q in the Cav3.2 protein. Electrophysiological studies were performed on a subpopulation of DRG neurons, the D-hair cells, which express large Cav3.2 currents. We describe an impaired sensitivity to zinc, nickel and ascorbate of the T-type current in D-hair neurons from KI mice. Analysis of the action potential and low-threshold calcium spike (LTCS) properties revealed that, contrary to that observed in WT D-hair neurons, a low concentration of zinc and nickel is unable to modulate (1) the rheobase threshold current, (2) the afterdepolarization amplitude, (3) the threshold potential necessary to trigger an LTCS or (4) the LTCS amplitude in D-hair neurons from KI mice. Together, our data demonstrate that this H191-dependent metal/redox regulation of Cav3.2 channels can tune neuronal excitability. This study validates the use of this Cav3.2-H191Q mouse model for further investigations of the physiological roles thought to rely on this Cav3.2 modulation.


Structure-activity studies of bufokinin, substance P and their C-terminal fragments at bufokinin receptors in the small intestine of the cane toad, Bufo marinus.
Bufokinin is a substance P-related tachykinin peptide with potent spasmogenic actions, isolated from the intestine of the cane toad, Bufo marinus. Bufokinin acts via a tachykinin receptor with similarities to the mammalian NK(1) receptor. In this structure-activity study of bufokinin, substance P (SP) and their C-terminal fragments, we have used isolated segments and homogenates of toad small intestine to compare the contractile potencies and abilities to compete for the binding of [125I]-Bolton-Hunter bufokinin. In general, potency was very similar in both studies (r=0.956) and was primarily related to peptide length, with the natural undecapeptide tachykinins bufokinin - ranakinin>SP- cod SP -trout SP being most potent. The weakest peptides were [Pro(9)]SP, BUF(7-11) and SP(7-11). Bufokinin fragments (BUF) were approximately equipotent to the corresponding SP fragments, with only BUF(5-11) showing unexpectedly low binding affinity. Data obtained with SP, bufokinin and fragments were subjected to quantitative structure--activity (QSAR) analysis which demonstrated that molecular connectivity and shape descriptors yielded significant regression equations (r approximately 0.90). The predictive capacity of the equations was confirmed using ranakinin, trout SP and cod SP, but not using the synthetic analogs [Pro(9)]SP and [Sar(9)]SP. The study suggests that the full undecapeptide sequence of bufokinin is required for optimal activity, with high potency conferred by Lys(1), Pro(2), Gly(9) and probably Tyr(8). The finding that receptor-ligand interactions were correlated with the shape descriptor 2kappa(alpha) and favored by basic and rigid residues at position 1-3 is consistent with an important role of conformation at the N-terminus of bufokinin.


A Real-World Analysis of Commonly Prescribed FVIII Products Based on U.S. Medical Charts: Consumption and Bleeding Outcomes in Hemophilia A Patients.
Patients with hemophilia A are commonly treated with replacement recombinant factor VIII (rFVIII) products, which can be standard-acting or long-acting. Long-acting products have modifications, offering the potential for reduced dosing frequency while maintaining therapeutic benefit. Extended dosing intervals reduce patient burden and can improve quality of life and adherence. To assess real-world data for the use of 6 commonly prescribed standard-acting and long-acting FVIII products in the United States: octocog alfa, BAY 14-2222, BAY 81-8973, rVIII-SingleChain, rFVIIIFc, and polyethylene glycol (PEG)-rFVIII. We summarized annualized bleeding rates (ABRs), dosing frequency, and factor consumption in patients treated with each product, with subgroup analyses for patients with severe disease. De-identified patient data were collected from 11 hemophilia treatment centers in the United States. Patients treated with octocog alfa, BAY 14-2222, BAY 81-8973, rVIII-SingleChain, rFVIIIFc, or PEG-rFVIII prophylaxis for ≥ 8 weeks at the time of data collection were included in the analysis. Among the 6 treatment groups, matching was attempted for patient age and disease severity where possible. Data were obtained for 240 patients, of whom 191 patients had severe disease. Patients receiving long-acting FVIII products were dosed less frequently than those receiving standard-acting FVIII products. The proportion of patients dosed 2 times weekly or less was 65.0%, 70.0%, 72.5%, 25.0%, 40.0%, and 47.5% with rVIII-SingleChain, rFVIIIFc, PEG-rFVIII, octocog alfa, BAY 14-2222, and BAY 81-8973, respectively. Median ABRs ranged from 2.0 to 3.0 (mean 2.6 to 4.4) across the 6 products for all patients and were similar for patients with severe disease (median 2.0 to 3.0 and mean 2.5 to 4.8). The proportion of patients experiencing 0 bleeding episodes ranged from 7.5% to 25.0% for all patients and 12.0% to 28.6% for patients with severe disease. For all patients, median (mean) weekly FVIII product consumption was lowest for rVIII-SingleChain among the 6 products (P = 0.045); 91.9 (91.1) IU per kg per week for rVIII-SingleChain, 108.5 (103.6) for rFVIIIFc, 97.6 (111.0) for PEG-rFVIII, 114.0 (117.5) for octocog alfa, 102.5 (102.6) for BAY 14-2222, and 95.1 (100.7) for BAY 81-8973. Similar differences in weekly consumption among the 6 products were observed for patients with severe disease (P = 0.014). Real-world data demonstrate that long-acting products may be beneficial compared with standard-acting products because of reduced dosing frequency while maintaining effectiveness. The 6 products evaluated showed statistically comparable ABRs and percentage of patients with 0 bleeds for all patients including those with severe disease. rVIII-SingleChain demonstrated lowest mean consumption for all patients, as well as for patients with severe hemophilia A, which may lead to potential savings in health care costs. This study was funded by CSL Behring. Simpson reports consulting honoraria for participation in advisory boards for Bayer, CSL Behring, HEMA Biologics, Novo Nordisk, Octapharma, and Takeda and speakers bureau for Bayer and Novo Nordisk. Yan and Desai are employees of CSL Behring. Maro is an employee of Adivo Associates, which conducted the analyses for this study. Data were presented in part at the Hemostasis and Thrombosis Research Society; May 9-11, 2019; New Orleans, LA; at the International Society on Thrombosis and Haemostasis; July 6-10, 2019; Melbourne, Australia; and have been published in part in "Comparing Factor Use and Bleed Rates in U.S. Hemophilia A Patients Receiving Prophylaxis with 3 Different Long-Acting Recombinant Factor VIII Products," by Mindy L. Simpson, Vidhi Desai, Géraldine S. Maro, Songkai Yan (J Manag Care Spec Pharm. 2020;26[4]:504-12).


Radial-arm maze deficits produced by colchicine administered into the area of the nucleus basalis are ameliorated by cholinergic agents.
Rats were given bilateral injections of colchicine into the area of the nucleus basalis. Colchicine produced dose-dependent alterations in the acquisition of a food-reinforced working-memory task. Colchicine-induced deficits in maze performance were attenuated by cholinergic agents, including physostigmine, RS-86 (2-ethyl-8-methyl-2,8-diazospiro-(4,5)-decan-1,3-dione-hydro bromide) and nicotine. Naloxone and vasopressin did not affect radial-arm maze performance of colchicine-treated rats. Subsequent neurochemical analysis showed that colchicine decreased choline acetyltransferase (ChAT) activity and levels of norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid in the neocortex. However, ChAT activity and other neurochemical measures were not altered in the hippocampus or corpus striatum. Histological assessment indicated damage limited to the injection in the area of the nucleus basalis and enlarged cerebrolateral ventricles. These data suggest the possible utility of the colchicine model in the study of cognitive deficits associated with neurodegenerative diseases.


Effect of histamine H2 antagonism by metiamide on the response of the canine gastric mucosa to acid and bile salt.
Prevention of acute gastric erosions with histamine H2-receptor blocking agents suggests that these drugs may improve the ability of the gastric mucosa to maintain electrical, ionic, and protein concentration gradients. In 5 awake mongrel dogs, transmural potential difference, ion fluxes, and protein loss were measured across Heidenhain pouches topically exposed to isotonic solutions containing either 80 mM HCl or 80 mM HCl plus 20 mM sodium taurocholate (BS). The dogs received an intravenous infusion of either saline (as a control) or the H2 antagonist metiamide, 10 mumoles per kg-hr. Metiamide increased the H+ clearance rate found after acid test solution exposure but had no significant effect on potential difference or ion fluxes. H2 antagonism decreased the protein loss but not the increase in cation permeability due to BS. Net H+ loss actually increased, which, along with a decrease in Cl- gain, suggests inhibition of acid secretion by metiamide in BS-exposed gastric mucosa. These effects of metiamide point to histamine as a likely mediator of the gastric mucosal damage due to BS.


Color Doppler ultrasound of spiral artery blood flow for prediction of hypertensive disorders and intra uterine growth restriction: a longitudinal study.
To construct reference ranges for spiral artery (SA) flow velocities and examine the possibility to predict intra uterine growth restricted (IUGR) fetuses, pregnancy-induced hypertension (PIH) and/or preeclampsia. Spiral artery flow velocity measurements were performed using Color Doppler between 11 to 13 + 6, between 14 to 17 + 6 and between 18 to 24 weeks of gestation, each measurement was performed twice. Spiral artery flow velocities were analyzed with multilevel modeling: individual regression curves were estimated and combined to obtain the reference intervals for SA flow velocities in normal pregnancies. Mann-Whitney U tests was used to compare the deviation from expected flow velocity between normal and complicated pregnancies. One hundred and eight pregnancies were included; 4 pregnancies were complicated with preeclampsia, 10 pregnancies with IUGR fetuses (<P10) and 7 with PIH. In the uncomplicated pregnancies, systolic/diastolic (SD) ratios, resistance index (RI) and pulsatility index (PI) decreased progressively with advancing gestational age. The best fits for SD, RI and PI versus gestational age were linear regression equations. According to these equations, the mean predicted SD ratio decreased from 1.75 at 11 weeks of gestation (P5-P95: 1.32-2.17) to 1.48 at 24 weeks of gestation (P5-P95: 1.01-2.20). The predicted RI en PI showed similar decrement: mean RI from 0.44 (P5-P95: 0.26-0.60) at 11 weeks of gestation to 0.34 (P5-P95: 0.15-0.50) at 24 weeks of gestation, mean PI from 0.59 (P5-P95: 0.31-0.75) at 11 weeks of gestation to 0.40 (P5-P95: 0.11-0.66) at 24 weeks of gestation. The Mann-Whitney tests found no difference in PI, SD-ratio or PI in pregnancies complicated by PE and IUGR fetuses. However, significantly lower RI, PI and SD-ratio were found preclinically in pregnancies complicated by PIH. Spiral artery flow velocities decrease progressively with advancing gestational age. Reference ranges for SA blood velocities are wide and early measurements of PI, RI or SD-ratios are not sensitive enough to predict preeclampsia, PIH or IUGR fetuses. The significantly lower spiral artery impedance values preceding pregnancies complicated by PIH are likely caused by a hyperdynamic circulation in women with preexistent hypertension.


Evaluation of Left Ventricular Function Long Term After Arterial Switch Operation for Transposition of the Great Arteries.
Long-term after arterial switch operation for transposition of the great arteries, abnormal coronary anatomy and altered loading conditions could compromise ventricular function. The current study investigates whether left ventricular function, measured with echocardiographic bi-plane ejection fraction and deformation imaging, in patients long term after arterial switch operation for transposition of the great arteries differs from healthy peers. A cross-sectional cohort study of patients at least 12 years after arterial switch operation was analyzed with bi-plane Simpson's left ventricular ejection fraction (LVEF) and deformation (speckle tracking) echocardiography. 81 patients, median age 20.6 (interquartile range 13.5-28.4) years, were included. LVEF was normal on average at 55.5 ± 6.1%. Global longitudinal strain (GLS) was lower in patients compared to healthy peers throughout all age groups and on pooled average (- 15.4 ± 1.1% vs. - 23.2 ± 0.9%). Although LVEF is normal on average in patients after arterial switch operation for transposition of the great arteries, GLS is impaired compared to healthy peers. The reduced GLS could indicate sub-clinical myocardial dysfunction.


Determination of mercury in phosphate fertilizers by cold vapor atomic absorption spectrometry.
In this paper, a method for the determination of mercury in phosphate fertilizers using slurry sampling and cold vapor atomic absorption spectrometry (CV QT AAS) is proposed. Because mercury (II) ions form strong complexes with phosphor compounds, the formation of metallic mercury vapor requires the presence of lanthanum chloride as a release agent. Thiourea increases the amount of mercury that is extracted from the solid sample to the liquid phase of the slurry. The method is established using two steps. First, the slurry is prepared using the sample, lanthanum chloride, hydrochloric acid solution and thiourea solution and is sonicated for 20 min. Afterward, mercury vapor is generated using an aliquot of the slurry in the presence of the hydrochloric acid solution and isoamylic alcohol with sodium tetrahydroborate solution as the reducing agent. The experimental conditions for slurry preparation were optimized using two-level full factorial design involving the factors: thiourea and lanthanum chloride concentrations and the duration of sonication. The method allows the determination of mercury by external calibration using aqueous standards with limits of detection and quantification of 2.4 and 8.2 μg kg(-1), respectively, and precision, expressed as relative standard deviation, of 6.36 and 5.81% for two phosphate fertilizer samples with mercury concentrations of 0.24 and 0.57 mg kg(-1), respectively. The accuracy was confirmed by the analysis of a certified reference material of phosphate fertilizer that was provided by the National Institute of Standards & Technology (NIST). The method was applied to determine mercury in six commercial samples of phosphate fertilizers. The mercury content varied from 33.97 to 209.28 μg kg(-1). These samples were also analyzed employing inductively coupled plasma mass spectrometry (ICP-MS). The ICP-MS results were consistent with the results from our proposed method.


Neuroblastoma.
Neuroblastoma originates in the adrenal medulla or anywhere in the body that sympathetic tissue normally is present. It may present with a variety of symptoms due to primary tumor, metastatic disease, or unusual signs and symptoms such as opsoclonus-myoclonus or severe diarrhea. Despite the fact that this neoplasm responds to a variety of therapeutic modalities, it remains one of the most frustrating and difficult childhood tumors to treat and cure.


Effects of colipase on hydrolysis of monomolecular films by lipase.
In a system free of bile salts we measured lipase hydrolysis of 1,3-didecanoylglycerol films in the presence or absence of colipase at different surface pressures. The strong, but not absolutely specific protective effect of colipase, most visible at low surface pressure, can account for the higher enzyme activity in the presence of colipase. This can be understood by taking into account simultaneous penetration and surface inactivation fluxes. Using radioactively labeled lipase, we have shown for the first time in a bile salt-free system that the critical surface pressure above which lipase can no longer penetrate a 1,2-didodecanoylphosphatidylglycerol monlayer is around 23 dynes/cm. Colipase increased this critical surface pressure to 30 dynes/cm indicating that it enables lipase penetration between 23 and 30 dynes/cm. The transfer experiment showed that colipase acts by first penetrating the lipid film and then serving as an anchor for lipase into the film.


Importin beta contains a COOH-terminal nucleoporin binding region important for nuclear transport.
Proteins containing a classical NLS are transported into the nucleus by the import receptor importin beta, which binds to cargoes via the adaptor importin alpha. The import complex is translocated through the nuclear pore complex by interactions of importin beta with a series of nucleoporins. Previous studies have defined a nucleoporin binding region in the NH2-terminal half of importin beta. Here we report the identification of a second nucleoporin binding region in its COOH-terminal half. Although the affinity of the COOH-terminal region for nucleoporins is dramatically weaker than that of the NH2-terminal region, sets of mutations that perturb the nucleoporin binding of either region reduce the nuclear import activity of importin beta to a similar extent ( approximately 50%). An importin beta mutant with a combination of mutations in the NH2- and COOH-terminal regions is completely inactive for nuclear import. Thus, importin beta possesses two nucleoporin binding sites, both of which are important for its nuclear import function.


Construction and hydrophilic modification of dual-network structured nonwoven/UHMWPE composite membranes for water processing.
Water pollution caused by the continuous development of industrialization has always been a common concern of mankind. Herein, a novel strategy to fabricate a high-performance composite membrane based on dual-network structured nonwoven net/UHMWPE nanopores via a thermal phase separation and composite technique is reported. By thermal phase separation of ultra-high-molecular weight polyethylene (UHMWPE)/liquid paraffin (LP), this approach enables 3D nanopores to tightly bond with a nonwoven net to form a dual-network structure. The dual-network composite membrane possesses the integrated features of pore structure and high porosity (89.9%). After modification with hyperbranched polymers (HBPs), the composite membrane with the desirable surface chemistry achieves high-efficiency filtration (water flux = 1054 L m-2 h-1, rejection rate = 50 nm PS nanospheres almost close to 100%, and antibacterial properties). The fabrication of such composites may provide new insights into the design and development of high-performance filtration and separation materials for various applications.