Myocardial caspase-3 and NF-κB activation promotes calpain-induced septic apoptosis: The role of Akt/eNOS/NO pathway.
To explore the potential mechanism that the role of the Akt/eNOS/NO pathway in calpain-induced caspase-3 and NF-κB activation during septic apoptosis. Septic rats were stimulated by LPS (8 mg/kg, i.p.). Myocardial calpain, caspase-3, NO, TNF-α and IL-1β levels were detected by ELISA. The levels of Akt/p-Akt, eNOS/p-eNOS, iNOS proteins and number of apoptotic cells were evaluated by immunohistochemistry, western blot and TUNEL method. Compared with sham, LPS treatment resulted in 4.1-fold and 1.8-fold increases in myocardial calpain activity and caspase-3 activation, respectively, and a significant increase (6.8-fold) in apoptotic cardiomyocytes was observed. The administration of calpain inhibitors (calpain inhibitor-IV, PD150606 and PD151746) showed that p-Akt and p-eNOS protein levels were correlated with the levels of LPS-induced myocardial calpain and caspase-3 activity. In addition, the quantity of p-Akt protein and NO content were markedly attenuated by wortmannin, a phosphoinositide 3-kinase (PI3K) inhibitor. Pretreatment with L-NAME, an NOS inhibitor, induced a decrease in p-eNOS proteins and apoptosis in myocardial tissues, while iNOS proteins were strongly increased in septic rats. This study suggests that the Akt/eNOS/NO pathway might lead to a novel pharmacological therapy for cardiomyocytes apoptosis in sepsis.


Follicular factors, serum estradiol, and outcome of pregnancy following in vitro fertilization and embryo transfer.
Success rate of in vitro fertilization and embryo transfer (IVF-ET) depends upon clinical and laboratory variables. This study compared follicular measurements and serum estradiol (E2) between 23 delivered and 23 nonpregnant controls following IVF-ET. E2, number of large follicles (no.), E2/no. ratio, total diameter of large follicle (TD), and the E2/TD ratio were compared between the two groups and between 23 women who delivered and 10 who aborted. E2 (P = 0.03), E2/no. (P = 0.006), and E2/TD (P = 0.005) were found to differ significantly between delivered and controls and between delivered and those who aborted.


Extended resection and end-to-end anastomosis for aortic coarctation in infants: results of a tailored surgical approach.
The surgical repair of aortic coarctation in infants has evolved over time. This study evaluates our current approach utilizing extended end-to-end anastomosis without prosthetic material to enlarge all areas of aortic arch hypoplasia. The Michigan Congenital Heart Center database was reviewed for infants who underwent repair of isolated aortic coarctation from January 1, 1990, to January 1, 2000. Eighty-three infants underwent surgical repair of isolated coarctation during this decade. Median age at repair was 21 days (range, 2 to 365). Repair was performed through thoracotomy in 72 patients. Because of severe transverse arch hypoplasia, the remaining 11 infants underwent median sternotomy with circulatory arrest. There were 2 deaths: 1 due to pulmonary hypertension in a patient with alveolar capillary dysplasia and 1 late death due to pneumonia in a patient with noncardiac anomalies. Neither patient had residual coarctation. Technique-related complications of bronchial compression, chylothorax, and vocal cord paralysis were noted in 4 patients. Follow-up data were available for 66 patients (80%) with mean follow-up duration of 4.5 years (SD +/- 3.1). Reintervention was required in 4 patients (6%). One underwent reoperation after 1 month, and 3 underwent balloon angioplasty within 7 months of initial repair. The remaining 61 patients are asymptomatic, on no antihypertensive medications, and have aortic arch gradients less than 15 mm Hg. One developed subaortic stenosis necessitating resection. Tailored surgical repair for aortic coarctation has a low rate (6%) of residual and recurrent coarctation even when performed in infants. Mortality and morbidity are low.


Careful adjustment of Epo non-viral gene therapy for beta-thalassemic anaemia treatment.
In situ production of a secreted therapeutic protein is one of the major gene therapy applications. Nevertheless, the plasmatic secretion peak of transgenic protein may be deleterious in many gene therapy applications including Epo gene therapy. Epo gene transfer appears to be a promising alternative to recombinant Epo therapy for severe anaemia treatment despite polycythemia was reached in many previous studies. Therefore, an accurate level of transgene expression is required for Epo application safety. The aim of this study was to adapt posology and administration schedule of a chosen therapeutic gene to avoid this potentially toxic plasmatic peak and maintain treatment efficiency. The therapeutic potential of repeated muscular electrotransfer of light Epo-plasmid doses was evaluated for anaemia treatment in beta-thalassemic mice. Muscular electrotransfer of 1 microg, 1.5 microg, 2 microg, 4 microg or 6 microg of Epo-plasmid was performed in beta-thalassemic mice. Electrotransfer was repeated first after 3.5 or 5 weeks first as a initiating dose and then according to hematocrit evolution. Muscular electrotransfer of the 1.5 microg Epo-plasmid dose repeated first after 5 weeks and then every 3 months was sufficient to restore a subnormal hematrocrit in beta-thalassemic mice for more than 9 months. This strategy led to efficient, long-lasting and non-toxic treatment of beta-thalassemic mouse anaemia avoiding the deleterious initial hematocrit peak and maintaining a normal hematocrit with small fluctuation amplitude. This repeat delivery protocol of light doses of therapeutic gene could be applied to a wide variety of candidate genes as it leads to therapeutic effect reiterations and increases safety by allowing careful therapeutic adjustments.


Endoscopic treatment of intraventricular cystic tumors.
Intraventricular cystic tumors constitute a surgical challenge, because of their deep location and the histologically benign nature of most of them. We aim to present concisely, yet comprehensively, the role of neuroendoscopy in the treatment of intraventricular cystic tumors. A literature review searching for applications of endoscopy in the treatment of intraventricular cystic tumors is presented. Our experience is added to the presented data. In controversial issues, a comparison is made with traditional treatment methods. Intraventricular endoscopy has been successfully used in the treatment of the whole range of intraventricular cystic tumors. The most common indication is the treatment of colloid cysts. In the treatment of colloid cysts, a comparison with microsurgical techniques showed that endoscopy is advantageous in regard to operative morbidity and postoperative shunt dependency but is associated with a slightly higher recurrence rate. Intraventricular endoscopy has emerged as a viable option in the treatment of intraventricular cystic tumors.


Cognitive therapy for schizophrenia: a preliminary randomized controlled trial.
The aim of the current study was to assess whether patients with a DSM-IV diagnosis of schizophrenia and experiencing persistent positive and negative symptoms improve with the addition of cognitive-behavioural therapy to enriched standard treatment. A controlled study was completed with 42 patients randomized to either cognitive-behavioural therapy plus enriched treatment-as-usual (CBT-ETAU) (n = 24) or enriched treatment-as-usual only (ETAU) (n = 18). Enriched treatment-as-usual comprised comprehensive treatment within specialised schizophrenia treatment services. Cognitive-behavioural therapy was conducted on an individual basis for 6 months (20 sessions). Clinical assessments were done at pretreatment, posttreatment and at 6-month follow-up by raters blind to group allocation. Significant clinical effects were observed for positive, negative and overall symptom severity for patients treated in CBT-ETAU, although there were no statistically significant differences between the treatment groups at posttreatment. The most pronounced effect of CBT-ETAU in comparison to ETAU in this study was in the reduction of negative symptoms at follow-up. These results show promise for the impact of CBT on negative symptoms when explicitly targeted in treatment.


Costs of fall injuries in the STRIDE study: an economic evaluation of healthcare system heterogeneity and heterogeneity of treatment effect.
The Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) Study cluster-randomized 86 primary care practices in 10 healthcare systems to a patient-centered multifactorial fall injury prevention intervention or enhanced usual care, enrolling 5451 participants. We estimated total healthcare costs from participant-reported fall injuries receiving medical attention (FIMA) that were averted by the STRIDE intervention and tested for healthcare-system-level heterogeneity and heterogeneity of treatment effect (HTE). Participants were community-dwelling adults age ≥ 70 at increased fall injury risk. We estimated practice-level total costs per person-year of follow-up (PYF), assigning unit costs to FIMA with and without an overnight hospital stay. Using independent variables for treatment arm, healthcare system, and their interaction, we fit a generalized linear model with log link, log follow-up time offset, and Tweedie error distribution. Unadjusted total costs per PYF were $2,034 (intervention) and $2,289 (control). The adjusted (intervention minus control) cost difference per PYF was -$167 (95% confidence interval (CI), -$491, $216). Cost heterogeneity by healthcare system was present (p = 0.035), as well as HTE (p = 0.090). Adjusted total costs per PYF in control practices varied from $1,529 to $3,684 for individual healthcare systems; one system with mean intervention minus control costs of -$2092 (95% CI, -$3,686 to -$944) per PYF accounted for HTE, but not healthcare system cost heterogeneity. We observed substantial heterogeneity of healthcare system costs in the STRIDE study, with small reductions in healthcare costs for FIMA in the STRIDE intervention accounted for by a single healthcare system. Clinicaltrials.gov (NCT02475850).


Draft Genome Sequence of Lactobacillus collinoides CUPV237, an Exopolysaccharide and Riboflavin Producer Isolated from Cider.
Lactobacillus collinoides CUPV237 is a strain isolated from a Basque cider. Lactobacillus collinoides is one of the most frequent species found in cider from Spain, France, or England. A notable feature of the L. collinoides CUPV237 strain is its ability to produce exopolysaccharides.


A comparison of AmnioStat-FLM with three established methods of assessing fetal lung maturity.
A new rapid test of fetal lung maturity (the AmnioStat-FLM) was compared with two currently available rapid tests and with 2-dimensional thin-layer chromatography (2-d TLC). Forty-nine specimens of liquor obtained within 72 h of delivery were assessed, 27 of which were contaminated with blood or meconium. The AmnioStat-FLM compared well with spectrophotometry, the shake test and with 2-d TLC. Only the Amniostat-FLM and the 2-d TLC were reliable in the presence of contamination. The results suggest that the AmnioStat-FLM is a reliable, rapid test and unaffected by the presence of contamination.


Biomarker clusters differentiate phenotypes of lumbar spine degeneration and low back pain: The Johnston County Osteoarthritis Project.
Describe the association between biomarkers and lumbar spine degeneration (vertebral osteophytes [OST], facet joint osteoarthritis [FOA], and disc space narrowing [DSN]), for persons with and without low back pain (LBP) and determine whether clusters based on biomarkers differentiate lumbar spine structure with and without LBP. Using data from the Johnston County Osteoarthritis Project (2006-2010), we measured serum N-cadherin, Keratin-19, Lumican, CXCL6, RANTES, HA, IL-6, BDNF, OPG, and NPY, and urinary CTX-II. Biomarkers were used to group participants using k-means cluster analysis. Logistic regression models were used to compare biomarker clusters. The sample consisted of 731 participants with biospecimens and lumbar spine radiographic data. Three biomarker subgroups were identified: one characterized by structural degenerative changes; another characterized by structural degenerative changes and inflammation, with pain; and a referent cluster with lower levels of biomarkers, pain, and structural degenerative changes. Compared to the referent subgroup, the structural change subgroup was associated with DSN (OR = 1.94, 95% CI 1.30-2.90) and FOA (OR = 1.72, 95% CI 1.12-2.62), and the subgroup with structural degenerative change, inflammation, and pain was associated with OST with LBP (OR = 1.60, 95% CI 1.04-2.46), FOA with LBP (OR = 1.59, 95% CI 1.04-2.45), and LBP (OR = 1.63, 95% CI 1.11-2.41). The subgroup with structural degenerative changes was more likely to have OST (OR = 1.82, 95% CI 1.06-3.13) and less likely to have FOA with LBP (OR = 0.62, 95% CI 0.40-0.96) compared to the group with inflammation and pain. Clustering by biomarkers may assist in differentiating patients for specific clinical interventions aimed at decreasing LBP.


Bilateral arthroscopy of the temporomandibular joint: clinical outcomes and the role of a second intervention-a prospective study.
Evaluate the efficacy of bilateral temporomandibular joint (TMJ) arthroscopy in patients with different categories of severity based on Dimitroulis classification (categories 2-4) and the role of a second TMJ intervention in primary failure. A 3-year prospective study was designed, including patients submitted to bilateral TMJ arthroscopy. The primary outcome was TMJ pain (VAS, 0-10) and the secondary outcomes were the maximum mouth opening (MMO) and masticatory myalgia degree (0-3). In cases of symptomatic relapse, a second TMJ intervention was performed (TMJ arthrocentesis or TMJ open surgery). Eighty patients (93.4% women) were enrolled, with a mean age of 32.40 ± 11.41 years. With an average follow-up of 523.7 days (34-1606), a statistically significant improvement in TMJ pain, MMO, and myalgia degree was observed (P < 0.0001). The overall successful outcome of one-single bilateral arthroscopy was ~ 69%. Twenty-two patients relapsed: (1) arthralgia (n = 15, 68.18%); (2) arthralgia + myalgia (n = 4, 18.18%); (3) dislocated disc without reduction (DDwoR) (n = 2, 9.09%); (4) DDwoR + osteoarthrosis (OA) (n = 1, 4.55%). Arthralgia was re-managed with TMJ arthrocentesis with local anesthesia (n = 19, 86.36%). New DDwoR with or without OA was re-treated with TMJ open surgery (n = 3, 13.64%). After the second intervention, the success rate increased to 85%. Bilateral TMJ arthroscopy presented overall benefit in all parameters evaluated. This study highlights the importance of TMJ arthroscopy as the first line of treatment for moderate-severe temporomandibular disorders cases contributing to the reduction of TMJ open surgeries. In cases of arthroscopy unsuccess, TMJ arthrocentesis under local anesthesia was an effective and safe intervention for patients with recurrent TMJ arthralgia.


National trends in emergency department use of urinalysis, complete blood count, and blood culture for fever without a source among children aged 2 to 24 months in the pneumococcal conjugate vaccine 7 era.
The epidemiology of serious bacterial infections in children has changed since the introduction of the pneumococcal conjugate vaccine (PCV-7) in 2000. Whether emergency department (ED) physicians have changed diagnostic approaches to fever without a source (FWS) in response is unknown. We examine trends in rates of complete blood count (CBC), urinalysis (UA), and blood cultures among 2- to 24-month-old children with FWS since the introduction of PCV-7. The National Hospital Ambulatory Medical Care Survey-Emergency Department, 2001-2009, was used to identify visits to the ED by 2- to 24-month-old children with FWS. Rates of CBC, UA, neither CBC nor UA, and blood culture were tracked across time. Trends were identified using Joinpoint regression and bivariate and multivariate logistic regressions with year as the independent variables and ordering of each test as the dependent variables. In bivariate and multivariate analyses, CBC orders declined between 2004 and 2009 for visits by all children 2 to 24 months, children 2 to 11 months, and boys 2 to 24 months (adjusted odds ratio [aOR], 0.88 per year [P < 0.01]; aOR, 0.88 [P < 0.05]; and aOR, 0.83 [P < 0.01], respectively). Between 2004 and 2009, ordering neither CBC nor UA increased among all children 2 to 24 months (aOR, 1.10; P < 0.05) and among boys (aOR, 1.16; P < 0.05). Orders for blood cultures declined across the time period in bivariate analysis, but not in multivariate analysis. The rate of ordering a CBC for children in the 2- to 24-month age group presenting to the ED with FWS declined, a change coincident with the changing epidemiology of serious bacterial infection since the PCV-7 vaccine was introduced.


64-slice computed tomography assessment of coronary artery stents: a phantom study.
To compare the use of a new 64-slice computed tomography (CT) scanner with 16-slice CT in the visualization of coronary artery stent lumen. Eight different coronary artery stents, each with a diameter of 3 mm, were placed in a static chest phantom. The phantom was positioned in the CT gantry at an angle of 0 degrees and 45 degrees towards the z-axis and examined with both a 64-slice and a 16-slice CT scanner. Effective slice thickness was 0.6 mm with 64-slice CT and 1 mm with 16-slice CT. A reconstruction increment of 0.3 mm was applied in both scanners. Image quality was assessed visually using a 5-point grading scale. Stent diameters were measured and compared using paired Wilcoxon tests. Artificial lumen reduction was significantly less with 64-slice than with 16-slice CT. Average visible stent lumen was 53.4% using 64-slice CT and 47.5% with 16-slice MSCT. Most severe artifacts were seen in stents with radiopaque markers. Using 64-slice CT, image noise increased by approximately 30% due to thinner slice thickness. Improved spatial resolution of 64-slice CT resulted in superior assessment of coronary artery stent lumen compared to 16-slice CT. However, a relevant part of the stent lumen is still not assessable with multi-slice CT.


Ventilatory response to CO2 in birds. I. Measurements in the unanesthetized duck.
Ventilation and blood gases were measured in unanesthetized ducks at various levels of inspired CO2 partial pressure (PICO2). Ventilation was markedly augmented with increasing PICO2, whereas arterial and mixed venous PCO2 stayed essentially constant up to a PICO2 of about 20 torr and changed only slightly between that and the highest level tested (34 torr). After carbonic anhydrase had been blocked, blood PCO2 was elevated at all levels of PICO2 but the ventilatory response to increases in PICO2 were attenuated. The response to CO2 in the normal bird (before administration of acetazolamide) shows similarities to that in mammals. Qualitative differences between both classes of vertebrates after blockade of carbonic anhydrase may, however, suggest differences in their systems that control ventilation.


Whole Human Mitochondrial DNA Sequencing.
Mitochondrial DNA (mtDNA) can help in the identification of biological evidence recovered from crime scenes and human remains. Typically the hypervariable regions are targeted for sequencing; however, more discriminating profiles are obtained if the whole genome is sequenced. Different approaches exist as to how best amplify and sequence whole mtDNA from forensic specimens. Here, we describe a method based on two-round PCR, combining multiplex and simplex PCRs. This method has been used in the analysis of mitochondrial genomes from archival saliva samples applied to FTA® cards after 10 years of transportation and preservation, without special protection. It is expected that this technique can be also used for the analysis of other old biological specimens directly or with modifications related to the level of DNA degradation.


Integrating a simulated electronic medical record system and barcode medication administration into a pre-licensure nursing program.
Many healthcare facilities implement technology to reduce medication errors. Nursing schools are exploring implementing similar technology to promote best practice. Our institution developed a quality improvement project to evaluate the integration of similar technology into pre-licensure curriculum. Our quality improvement project examined using a simulated electronic medical record (EMR) and a barcode medication administration (BCMA) system in pre-licensure nursing curriculum. In our initial project, 96 second-semester BSN students participated in a skill check off using the system. Student perception was positive, 96% of respondents stated the system increased realism, and 94% indicated improved clinical preparedness. Implementing this system was a positive experience which enriched our pre-licensure curriculum.


The diagnostic utility of the GNAS mutation in patients with fibrous dysplasia: meta-analysis of 168 sporadic cases.
GNAS mutations have been implicated in the development of fibrous dysplasia and multiple endocrinopathies of the Albright-McCune syndrome. To investigate the diagnostic utility of GNAS mutations in patients with fibrous dysplasia, we performed mutational analyses of histologically confirmed fibrous dysplasia and conducted a meta-analysis of the literature. We collected 48 cases of fibrous dysplasia from 3 institutions from 2002 to 2011 and performed polymerase chain reaction and direct bidirectional sequencing of exons 8 and 9 of GNAS using paraffin-embedded tissues. We searched MEDLINE, PubMed, and the KoreaMed databases from 1997 to 2011 and included an additional 155 cases of fibrous dysplasia from 8 representative studies to conduct a meta-analysis. In our sample, 28 (58.3%) of 48 cases showed point mutations of codon 201 at exon 8. Twenty-five cases had a substitution of arginine at codon 201 for histidine (p.R201H), and 3 cases had a substitution for cysteine (p.R201C). One case had a new mutation at codon 224 (p.V224A). The incidence of GNAS mutations was significantly greater in cases that involved long bones than in cases that involved flat bones (P = .017) and was higher in polyostotic cases than in monostotic cases (P = .067). In meta-analysis, 9 studies and 203 patients were included. The overall positive rate of GNAS mutation in fibrous dysplasia was 71.9% (146/203). The major types of mutations were missense mutations such as R201H (66.4%) and R201C (30.8%). As a result, the detection of GNAS mutation could be a valuable adjunct to conventional histopathologic diagnosis of fibrous dysplasia.


Restrictive versus routine episiotomy among Southeast Asian term pregnancies: a multicentre randomised controlled trial.
To determine whether restrictive or routine episiotomy in term pregnant Southeast Asian women results in fewer complications. A multicentre randomised controlled trial. Two tertiary and two general hospitals in Thailand. 3006 singleton pregnant women 18 years or older, ≥37 weeks of gestation, cephalic presentation and planned vaginal delivery. This randomised controlled trial compared routine versus restrictive episiotomies in Thai women giving birth vaginally. Participants were singleton, term pregnant women with cephalic presentation. Block randomisation was stratified by study site and parity. Risk ratios (RR) and 95% confidence intervals (CI) were calculated to indicate between-group differences. Primary outcome was severe perineal laceration. Secondary outcomes included vaginal laceration, cervical laceration, and pregnancy outcomes. 3006 women were randomly assigned to restrictive (1502) and routine (1504) episiotomy. There was no difference in severe perineal laceration between the groups (RR 0.72, 95% CI 0.46-1.12). Restrictive episiotomy resulted in more intact perineums in multiparous women (RR 3.09, 95% CI 2.10-4.56). Restrictive episiotomy increased the risk of vaginal laceration in primiparous (RR 1.96, 95% CI 1.62-2.37) and multiparous women (RR 2.21, 95% CI 1.77-2.75) but did not lead to more suturing. There were comparable risks of cervical laceration, postpartum haemorrhage, wound complication, birth asphyxia, and admission to neonatal intensive care unit. Restrictive episiotomy results in more intact perineum in multiparous women. Risks of maternal and neonatal outcomes were comparable between the two practices. These results strengthen the certainty of the existing Cochrane review findings in supporting restrictive episiotomy. Restrictive episiotomy results in more intact perineums after vaginal birth in multiparous Southeast Asian women.


Bilateral hip imaging at 7 Tesla using a multi-channel transmit technology: initial results presenting anatomical detail in healthy volunteers and pathological changes in patients with avascular necrosis of the femoral head.
To evaluate 7-T MRI of both hips using a multi-channel transmit technology to compensate for inherent B1 inhomogeneities in volunteers and patients with avascular necrosis of the femoral head. A self-built, eight-channel transmit-receive coil was utilized for B1 modification at 7 T. Two shim modes (individual shim vs. CP2+ mode) were initially compared and the best shim result was used for all further imaging. Robustness of sequences against B1 inhomogeneities, appearance of anatomic and pathologic changes of the femoral heads of MEDIC, DESS, PD/T2w TSE, T1w TSE, and STIR sequences at 7 T were evaluated in 12 subjects on a four-point scale (1-4): four male volunteers and eight patients (seven males, one female) suffering from avascular necrosis treated by advanced core decompression. Successful MRI of both femoral heads was achieved in all 12 subjects. CP2+ mode proved superior in ten of 12 cases. DESS proved most robust against B1 inhomogeneity. Anatomical details (labrum, articular cartilage) were best depicted in PDw, MEDIC, and DESS, while for depiction of pathological changes PDw, DESS (0.76 mm(3)) and T1w were superior. Our initial results of ultra-high-field hip joint imaging demonstrate high-resolution, high-contrast images with a good depiction of anatomic and pathologic changes. However, shifting areas of signal dropout from the femoral heads to the center of the pelvis makes these areas not assessable. For clinical workflow CP2+ mode is most practical. Seven-Tesla MRI of the hip joints may become a valuable complement to clinical field strengths.


Cost analysis of fentanyl and remifentanil in coronary artery bypass graft surgery without cardiopulmonary bypass.
Opiates such as remifentanil have the potential to reduce time to extubation (TTE), shorten length of stay (LOS) and lower hospital costs, because of a short duration of action. However, the cost of remifentanil is approximately ten times higher than longer-acting opiates like fentanyl. The objective of this analysis was to compare TTE, LOS and total hospital costs between patients who received remifentanil and fentanyl during off-pump bypass surgery. The study was prospective and observational in design. Consecutive patients who underwent off-pump cardiac bypass surgery and received either remifentanil or fentanyl from September 1998 to August 1999 were screened for study entry. Patient bills and charges were converted to costs using hospital cost-to-charge ratios. The percent of patients' extubated in the operating room (OR), LOS and hospital costs were compared between the groups. The baseline demographics (age: 66 +/- 12 years mean +/- SD; female 36%) and intraoperative variables were similar between the remifentanil (n=39) and fentanyl (n=20) groups. Patients given remifentanil during surgery were significantly more likely to be extubated in the OR than patients given fentanyl (15 vs. 64%; P < 0.001). Mean LOS was similar in both groups (7.3 +/- 3.1 vs. 8.3 +/- 2.7 days; P=0.27). Patients who received remifentanil incurred lower pulmonary function testing ($0 +/- 0 vs. $34 +/- 103; P=0.045), recovery room ($31 +/- 40 vs. $65 +/- 33; P=0.002) and lower ward costs ($3973 +/- 1719 vs. $4808 +/- 1794; P=0.09) than patients who received fentanyl. Anesthesia costs were higher among patients who received remifentanil ($476 +/- 102 vs. $416 +/- 130; P=0.06). Medical and surgical supplies, OR, intensive care unit, laboratory, respiratory therapy, pharmacy, radiology and transfusion costs were similar between the two groups. The total cost was $15 272 +/- 5556 and $15 616 +/- 4169 in the remifentanil and fentanyl groups, respectively (P=0.81). Remifentanil, when used in off-pump bypass surgery, is associated with an increased likelihood of extubation in the OR. However, LOS and total hospital costs remain unchanged.


A web-based information system for management and analysis of patient data after refractive eye surgery.
The aim was to develop a software tool for refractive surgeons using a standard user-friendly web-based interface, providing the user with a secure environment to protect large volumes of patient data. The software application was named "Internet-based refractive analysis" (IBRA), and was programmed with the computer languages PHP, HTML and JavaScript, attached to the opensource MySQL database. IBRA facilitated internationally accepted presentation methods including the stability chart, the predictability chart and the safety chart; it was able to perform vector analysis for the course of a single patient or for group data. With the integrated nomogram calculation, treatment could be customised to reduce the postoperative refractive error. Multicenter functions permitted quality-control comparisons between different surgeons and laser units.


The effect of dexamethasone on neutrophil adherence in umbilical cord blood.
Neutrophil adherence immediately after delivery and after incubation with saline and with two different concentrations of dexamethasone was studied in umbilical cord blood of 27 full-term neonates. Dexamethasone was not found to have any significant effect on neutrophil adherence in vitro.


Engineering blood vessels from stem cells: recent advances and applications.
Endothelial cells organized into blood vessels are critical for the formation and maintenance of most tissues in the body and are involved in regulating physiological processes such as angiogenesis, inflammation and thrombosis. Endothelial cells are of great research interest, because of their potential to treat vascular diseases and to stimulate the growth of ischaemic tissue. They can be used to engineer artificial vessels, repair damaged vessels, and to induce the formation of vessel networks in engineered tissues. For such clinical applications, proliferating human endothelial progenitor cells can be isolated from adult tissues or embryonic stem cells. Recently, these cells were successfully used to engineer single vessels and to stimulate capillary networks, both in vitro and in vivo.


Extraction of epinephrine and norepinephrine by the dog pancreas in vivo.
This study determined the fractional extraction of epinephrine and norepinephrine by the in situ dog pancreas. Plasma samples for epinephrine measurements were taken simultaneously from the femoral artery and the superior pancreaticoduodenal vein. Pancreatic extraction of epinephrine was 73 +/- 5% when basal arterial epinephrine levels were 380 +/- 93 pg/mL, 76 +/- 4% when arterial levels were 896 +/- 123 pg/mL (epinephrine infused intravenously at 20 ng/kg/min), and 84 +/- 1% when arterial levels were 2,956 +/- 414 pg/mL (epinephrine infused intravenously at 80 ng/kg/min) suggesting that the process of epinephrine extraction by the pancreas is not saturable over this range. During a similar sampling protocol, norepinephrine was infused intravenously at 4 micrograms/kg/min; pancreatic extraction of norepinephrine was then 65 +/- 7% when arterial norepinephrine levels were 107,000 +/- 28,000 pg/mL. In separate experiments, lower rates of norepinephrine (12 to 1,200 ng/min) were infused directly into the pancreatic artery and pancreatic norepinephrine extraction was calculated; it ranged between 66% and 75%. Because the pancreas produces as well as extracts norepinephrine, a third technique was required to determine pancreatic norepinephrine extraction at the lower endogenous levels of norepinephrine; 3H-norepinephrine was infused intravenously and the arteriovenous difference of 3H-norepinephrine was measured. Fractional extraction of 3H-norepinephrine was 74 +/- 4% both in the basal state (arterial norepinephrine level = 202 +/- 44 pg/mL) and during systemic, glucopenic, stress induced by 2-deoxy-glucose (arterial norepinephrine level = 636 +/- 70 pg/mL). These data suggest that also the norepinephrine extraction process by the pancreas is not saturable.(ABSTRACT TRUNCATED AT 250 WORDS)


The rate of increase in rating of perceived exertion predicts the duration of exercise to fatigue at a fixed power output in different environmental conditions.
This study tested the hypothesis that the increase in rating of perceived exertion (RPE) predicts the duration of exercise to exhaustion during exercise in hot conditions. Seven subjects performed five cycling trials in an environmental chamber at temperatures of 15 degrees C (C) and 35 degrees C (H). The cool trials were performed at intensities of 65 and 70% and the hot trials at 55, 60 and 65%. RPE, rectal and skin temperature were measured during trials. Duration to fatigue was significantly shorter in H65 and C70 than H60, C65 and H55 (P < 0.05). RPE rose linearly throughout each trial and the rate of increase in RPE was significantly faster in H65 and C70 than H55 (P < 0.05). There was an inverse linear relationship between trial duration and rate of increase in RPE (r = 0.83). Rectal temperature increased linearly throughout the trial and correlated significantly with RPE (r = 0.92). This study shows that the rate of increase in RPE predicts the duration of exercise to exhaustion at a constant power output in different environmental conditions.


Twelve-hour reanimation of a human heart following donation after circulatory death.
Despite increasing use of donation after cardiac death (DCD) and encouraging results for non-cardiac transplants, DCD cardiac transplantation has not been widely adopted because, (1) the DCD heart sustains warm ischaemic injury during the death process and (2) conventional static cold storage significantly adds to the ischaemic injury. We have developed a simple system for perfusion of the DCD heart with cold crystalloid solution using gravity-feed that can reduce ischaemic injury and potentially render the heart suitable for transplantation. This report describes the first application of this technique to a human DCD heart with good functional metabolic recovery over 12h on an ex vivo rig.


Increased expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in rat cardiac allografts.
This study was designed to investigate the role of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) during chronic cardiac allograft rejection. Wistar rats were used as donors, and SD rats as recipients heterotopic cardiac transplants. Recipients pretreated with inoculation of donor splenocytes (SPC) followed by cyclophosphamide (CP) were divided into 4 groups: (A) untreated group (n = 18) without immunosuppression; (B) SPC plus CP-treated group (n = 18) that were euthanized at 15-120 days posttransplantation; (C) CsA-treated group (n = 18) euthanized at 2-3 months posttransplantation; and (D) tolerance group (n = 18) treated with SPC plus CP and monitored for at least 1 year posttransplantation. Cardiac allografts were harvested at various times for immunohistochemical studies performed to evaluate the expression of ICAM-1 and VCAM-1. Pretreatment of animals with SPC and CP induced long-term cardiac allograft survival. Immunohistochemical staining demonstrated a low level of ICAM-1 and VCAM-1 expression in cardiac allograft muscle and coronary arteries among Groups B and D. In contrast, the expressions of ICAM-1 and VCAM-1 in cardiac allografts of Groups A and C were significantly higher than those in Groups B and D. Our results suggested that the expression of ICAM-1 and VCAM-1 plays an important role during the development of chronic cardiac allograft rejection.


A major influence of sex-specific loci on alcohol preference in C57Bl/6 and DBA/2 inbred mice.
C57Bl/6 mice reproducibly prefer to ingest more 10% ethanol in a two-bottle choice paradigm than do DBA/2J mice. In this paper we report the identification of two new sex-specific alcohol preference (Alcp) loci. Melo and associates (1996) identified two loci: Alcp1, a male-specific locus on Chromosome (Chr) 2, and Alcp2, a female- and cross-specific locus on Chr 11. We have additionally identified Alcp3, a male-specific locus on Chr 3, and Alcp4, a female-specific locus on Chr 1. We have also performed a statistical analysis to exclude the possibility of undiscovered major alcohol preference loci that are not sex-specific in our backcross paradigm. Our results indicate that alcohol preference in C57BL/6 mice, as measured in our backcross, is largely controlled in a sex-specific manner.


Data on association between QRS duration on prehospital ECG and mortality in patients with confirmed STEMI.
Data presented in this article relates to the research article entitled "Association between QRS duration on prehospital ECG and mortality in patients with suspected STEMI" (Hansen et al., in press) [1]. Data on the prognostic effect of automatically recoded QRS duration on prehospital ECG and presence of classic left and right bundle branch block in 1777 consecutive patients with confirmed ST segment elevation AMI is presented. Multivariable analysis, suggested that QRS duration >111 ms, left bundle branch block and right bundle branch block were independent predictors of 30 days all-cause mortality. For interpretation and discussion of these data, refer to the research article referenced above.


Evidence for criterion shifts in visual perceptual learning: data and implications.
Work on visual perceptual learning for contrast detection has shown that reliable decreases in detection thresholds are accompanied by reliable increases in false alarm rates (Wenger & Rasche, 2006). The present study assesses the robustness and replicability of these changes, demonstrating that they are independent of a variety of task demands (i.e., the specific method used for perceptual practice and threshold estimation) and the presence or absence of trial-by-trial feedback and that the source of the increases can be found in shifts in changes in sensitivity and in bias for detection, identification, or both. Although the increase in false alarm rates suggests a strategic shift in response criteria for detection, we demonstrate that there are multiple potential explanations, including explanations that do not require strategic shifts on the part of the observer. The empirical evidence and analysis of alternative explanations reinforce the inference that visual perceptual learning may involve more than changes in perceptual sensitivity and that cortical circuits beyond the primary visual areas may be involved.


LSD1 represses a neonatal/reparative gene program in adult intestinal epithelium.
Intestinal epithelial homeostasis is maintained by adult intestinal stem cells, which, alongside Paneth cells, appear after birth in the neonatal period. We aimed to identify regulators of neonatal intestinal epithelial development by testing a small library of epigenetic modifier inhibitors in Paneth cell-skewed organoid cultures. We found that lysine-specific demethylase 1A (Kdm1a/Lsd1) is absolutely required for Paneth cell differentiation. Lsd1-deficient crypts, devoid of Paneth cells, are still able to form organoids without a requirement of exogenous or endogenous Wnt. Mechanistically, we find that LSD1 enzymatically represses genes that are normally expressed only in fetal and neonatal epithelium. This gene profile is similar to what is seen in repairing epithelium, and we find that Lsd1-deficient epithelium has superior regenerative capacities after irradiation injury. In summary, we found an important regulator of neonatal intestinal development and identified a druggable target to reprogram intestinal epithelium toward a reparative state.


High tea and vegetable consumption is associated with low ADMA generation in older healthy subjects.
Asymmetric dimethylarginine (ADMA) has been recognized as a marker of cardiovascular risk. We sought to investigate whether consumption of tea, coffee, fruit or vegetables is associated with ADMA. In 148 consecutive apparently healthy subjects (104 men and 44 women aged 40 to 70), daily tea, coffee, fruit and vegetable consumption was ascertained by questionnaire. Plasma ADMA, symmetric dimethylarginine (SDMA), and l-arginine levels were measured by high-performance liquid chromatography. Median tea and coffee consumption was 2 cups/d, while vegetable and fruit intake was 152 (120-179)g/d and 120 (108-134)g/d, respectively. Median plasma ADMA, SDMA and arginine were 0.47 (0.43-0.53)μmol/L, 0.59 (0.54-0.66)μmol/L and 86 (68-101)μmol/L, respectively. ADMA correlated inversely with tea (r = -0.70, P < .0001) and vegetable consumption (r = -0.50, P < .0001) even after adjustment for age, sex, body mass index, smoking status, and potential dietary and biochemical parameters. No association between ADMA and fruit consumption was found. ADMA correlated positively with coffee intake (r = 0.37, P < .0001), although these associations were less potent after adjustment for dietary factors. Higher tea and vegetable intake is associated with lower plasma ADMA levels in healthy middle-aged subjects.


Interplay between menin and Dnmt1 reversibly regulates pancreatic cancer cell growth downstream of the Hedgehog signaling pathway.
Menin, the product of the Men1 gene, which is frequently mutated in pancreatic neuroendocrine tumors, acts as a chromatin-remodeling factor to modulate the transcription of cell cycle regulators by interacting with histone modification factors. However, the function of menin and its underlying mechanisms in pancreatic ductal adenocarcinoma remain unknown. Here, we found that menin inhibited pancreatic cancer cell growth in vitro and in vivo and that its expression was gradually lost during pancreatic carcinogenesis. Menin overexpression significantly activated the expression of the cyclin-dependent kinase (CDK) inhibitors p18 and p27, accompanied with a decrease in DNA methylation levels of p18 and p27 promoters. Mechanistically, we found that interaction of menin with DNA methyltransferase 1 (Dnmt1) competitively pulled down Dnmt1 from p18 and p27 promoters, leading to the downregulation of DNA methylation levels. Moreover, menin expression was suppressed by Dnmt1 downstream of the Hedgehog signaling pathway, and menin overexpression strongly antagonized the promotion effect of hedgehog signaling on pancreatic cancer cell proliferation. Taken together, the interaction between menin and Dnmt1 reversibly regulates pancreatic cancer cell growth downstream of Hedgehog pathways with complex mutual modulation networks, suggesting that the Hedgehog/Dnmt1/menin axis is a potential molecular target for pancreatic cancer therapy.


Comments on 'Call for a follow-up study of experiments on long-term deprivation of human infants' by Micha Razel.
Razel's examination of the early work of McGraw and the Dennises puts a heavy requirement on studies of single subjects and on some possible interpretations for which, unfortunately, documentation is insufficient. Further, the Dennises placed more emphasis on the autotelic quality of motor mastery than Razel notes. Rather than looking for these persons whose behavior was studied long ago, direct study of motor mastery by systematic provision of enrichment conditions during early development is more likely to be instructive and a better use of scientific resources.


Flow cytometric analysis of fluorescence in situ hybridization with dye dilution and DNA staining (flow-FISH-DDD) to determine telomere length dynamics in proliferating cells.
Telomeres shorten during DNA replication; extensive erosion of telomeres likely promotes replicative senescence and chromosomal instability. Telomere length in individual cells has been quantified by flow cytometric analysis of fluorescence in situ hybridization (flow-FISH). To determine the rate of telomere attrition (telomere erosion per cell division), we combined flow-FISH with dye dilution and DNA staining (flow-FISH-DDD) and measured telomere-specific fluorescence in proliferating cells identified by cell generation and cell cycle phase. Peripheral blood mononuclear cells (PBMC) were stained with the cell division tracking dye carboxyfluorescein diacetate succinimidyl ester (CFSE), stimulated with phytohemagglutinin (PHA), grown for 5-6 days, hybridized with a telomere sequence-specific peptide nucleic acid fluorescent probe (PNA-Cy5), counterstained with DAPI, and analyzed by flow cytometry. The cell cycle distribution and cell division generations were respectively identified by analysis of DAPI emission and deconvolution of CFSE emission, and Cy5 emission was used to determine telomere-specific fluorescence, an indicator of telomere length, in each cell. In stimulated PBMC, in each cell cycle phase, the telomere-specific fluorescence diminished with increasing cell generation. The rate of decline of the telomere-specific fluorescence per cell generation did not significantly differ between cell cycle phases. Application of flow-FISH-DDD to measure mean telomere length and the rate of telomere attrition in proliferating cells may find use in studies of ageing and disease, the effects of telomere-modifying agents, and variability between individuals.


Clinical outcome and molecular characterization of brain metastases from esophageal and gastric cancer: a systematic review.
The aim of the study was to collect the available data on central nervous system (CNS) metastases from esophageal and gastric cancer. A PubMed, EMBASE, SCOPUS, Web of Science, LILACS, Ovid and Cochrane Library search was performed. Thirty-seven studies including 779 patients were considered. Among the data extracted, treatment of tumor and brain metastases (BMs), time to BMs development, number and subsite, extracerebral metastases rate, median overall survival (OS) and prognostic factors were included. For esophageal cancer, the median OS from diagnosis of BMs was 4.2 months. Prognostic factors for OS included: performance status, multimodal therapy, adjuvant chemotherapy, single BM, brain only disease and surgery. For gastric cancer, median OS was 2.4 months. Prognostic factors for OS included: recursive partitioning analysis class 2, stereotactic radiosurgery (SRT) and use of intrathecal therapy. HER2-positive gastric cancer was shown to be associated with a higher risk and shorter time to CNS relapse. Patients harboring BMs from gastric and esophageal tumors, except cases with single lesions that are treated aggressively, have a poor prognosis. SRT (plus or minus surgery and whole brain radiotherapy) seems to give better results in terms of longer OS after brain relapse.


Recent advances in the diagnosis, classification and molecular pathogenesis of cutaneous mesenchymal neoplasms.
The diagnosis of cutaneous mesenchymal neoplasms remains challenging, due to a combination of overlapping histological features, the rarity of some diagnoses and often inadequate sampling in superficial biopsies. Here, we describe recent advances in cutaneous mesenchymal neoplasms. We discuss improvements in our understanding of the molecular pathogenesis of non-neural granular cell tumour, epithelioid fibrous histiocytoma, composite and retiform haemangioendothelioma and dermatofibrosarcoma protuberans. We also discuss recently described tumour types, including some discovered via molecular testing: EWSR1::SMAD3-rearranged fibroblastic tumour, clear cell neoplasm with MITF::CREM rearrangement and melanocytoma with CRCT1::TRIM11 rearrangement, and some discovered via traditional histopathology: superficial CD34-positive fibroblastic tumour, plexiform myofibroblastoma and clear cell neoplasm with melanocytic differentiation and ACTIN::MITF translocation.


Adequacy of lymph node examination in colorectal surgery: contribution of the hospital versus the surgeon.
Examination of at least 12 lymph nodes (LNs) in the staging of colon cancer (CC) was recommended by the National Comprehensive Cancer Network in 2000; however, rates of an adequate examination remain low. This study compares the impact of the hospital contextual variance against that of the operating surgeon on delivery of an adequate LN examination. Retrospective analysis of California Cancer Registry data for all CC operations (2001-2006). Hierarchical models predicted the adequacy of LN examination as a function of patient, surgeon, and hospital characteristics. Models were created using penalized quasi-likelihood approximation with second order Taylor linearization as implemented in MLwiN 2.15. A total of 25,606 resections involving 3376 surgeons operating in 346 hospitals were analyzed. Half of cases had an adequate examination. Hierarchical models showed the median odds of an adequate examination associated with the hospital context [(MORhosp 2.05; 95% confidence interval, 1.9-2.2) was much higher than that associated with the surgeon (MORsurg 1.34; 95% confidence interval, 1.2-1.4)]. Hospital characteristics teaching and high volume predicted higher odds of an adequate examination. There was no association with hospital revenue. Approximately half of patients undergoing surgery for CC received an adequate LN examination. Hospital contextual factors had a stronger association with receipt of an adequate examination than surgeon factors. Our results suggest that quality improvement initiatives and incentives should be targeted at the hospital level to achieve the highest impact. Furthermore, we have identified nonteaching and low volume settings as rational targets for these efforts.


Design, Synthesis, Pharmacological Evaluation, In silico Modeling, Prediction of Toxicity and Metabolism Studies of Novel 1-(substituted)-2-methyl- 3-(4-oxo-2-phenyl quinazolin-3(4H)-yl)isothioureas.
Although exhaustive efforts to prevent and treat tuberculosis (TB) have been made, the problem still continues due to multi-drug-resistant (MDR) and extensively drugresistant TB (XDR-TB). It clearly highlights the urgent need to develop novel "druggable" molecules for the co-infection treatment and strains of MDR-TB and XDR-TB. In this approach, a hybrid molecule was created by merging two or more pharmacophores. The active site of targets may be addressed by each of the pharmacophores and proffers the opportunity for selectivity. In addition, it also reduces undesirable side effects and drug-resistance. In this study, a novel quinazolinone analog was designed and synthesized by substituting thiourea nucleus and phenyl ring at N-3 and C-2 position of quinazoline ring, respectively. All title compounds were tested for antitubercular activity by in vitro M. tuberculosis and anti-human immunodeficiency virus (HIV) activity by MT-4 cell assay method. The agar dilution method was used to test the antibacterial potency of entire prepared derivatives against various strains of grampositive and gram-negative microorganisms. The title compounds, 1-(substituted)-2-methyl-3-(4-oxo-2-phenyl quinazolin-3(4H)-yl) isothioureas (QTS1 - QTS15) were synthesized by the reaction between key intermediate 3-amino- 2-phenylquinazolin-4(3H)-one with various alkyl/aryl isothiocyanates followed by methylation with dimethyl sulphate. Among the series, compound 1-(3-chlorophenyl)-2-methyl-3-(4-oxo-2-phenyl quinazolin- 3(4H)-yl) isothioureas (QTS14) showed the highest potency against B. subtilis, K. pneumonia and S. aureus at 1.6 μg/mL. The compound QTS14 exhibited the most potent antitubercular activity at the MIC of 0.78 μg/mL and anti-HIV activity at 0.97 μg/mL against HIV1 and HIV2. The results obtained from this study confirm that the synthesized and biologically evaluated quinazolines showed promising antimicrobial, antitubercular and anti-HIV activities. The new scaffolds proffer a plausible lead for further development and optimization of novel antitubercular and anti-HIV drugs.


Efficient unfolding of virtual endoscopy using linear ray interpolation.
Unfold rendering enables us to understand the internal structure of organs more precisely. The most commonly used unfolding method is to cast rays radially along a pre-computed camera path. However, this may produce images of false pathological structures. Details on the organ surface may be lost when the organ's curvature is relatively large due to adjacent ray planes crossing. Several methods are presented to avoid the penetration of ray planes. These methods result in severe computational overhead. We propose an efficient method of penetration-free ray casting for unfolding. It computes ray planes that do not intersect neighboring planes, using the noble intersection avoidance method. It determines the direction of all the rays fired from intermediate sampling points, by linearly interpolating the direction of the rays on two of the original ray planes. Experimental results show that it does not produce erroneous images since it exploits simple linear interpolation.


Atrioventricular valvular anomalies and their role in the etiopathogenesis of cardiorespiratory syndrome in farmed common foxes (Vulpes vulpes).
Cardiorespiratory syndrome of common foxes is associated with a mortality rate ranging from 2.1% to 20%. The aim of this study was to analyze the prevalence of cardiac abnormalities in common foxes (Vulpes vulpes) from Polish farms with a history of cardiorespiratory syndrome. The prevalence of cardiac abnormalities in common foxes from a Polish farm with a history of cardiorespiratory syndrome was assessed as well as morphological examination of 60 heart specimens from clinically healthy animals. In addition, 38 foxes were examined echocardiographically and subjected to postmortem examination. Atrioventricular valvular abnormalities were found in 57 out of the 98 (58%) analyzed hearts. The abnormalities of the mitral valve documented in more than 20% of the foxes in involved tendinous chords (completely lacking or shortened), papillary muscles and mitral cusps associated with both insufficiency and stenosis of the left atrioventricular orifice. Abnormalities of the tricuspid valve included significant shortening of the tendinous chords and thickening of the valve cusps with the impairment of their mobility. The results of the echocardiographic and postmortem examination were consistent in 79% of the cases. The specimens collected from animals with and without atrioventricular valvular anomalies did not differ significantly in terms of cardiomyocyte width, number of inflammatory cells, adipose tissue content and presence of polychromatic cardiomyocytes. Congenital atrioventricular valvular defects may be involved in the etiology of cardiorespiratory syndrome in common foxes, and echocardiography can be used as a measure of stock's health and a criterion for selection for mating.


Genetic and clinical characterization of 73 Pigmentary Mosaicism patients: revealing the genetic basis of clinical manifestations.
Pigmentary mosaicism constitutes a heterogeneous group of skin pigmentation alterations associated with multisystem involvement. The aim of this study was to establish a complete cytogenetic and molecular characterization of PM patients, emphasizing on searching for possible low chromosomal mosaicism and on establishing an accurate genotype-phenotype correlation. A total of 73 patients were included (3 months to 18 years of age), 52% male and 48% female. Observed in 69 (95%) patients, the most frequent pattern of pigmentation was fine and whorled BL, which was associated with disseminated skin extent in 41 (59%) patients. Central nervous system (84%) alterations were the most frequent observed in the group of patients, followed by the musculoskeletal (53%) and ophthalmologic (27%) alterations. Considering the pattern of pigmentation, no significant differences in association with skin extent or extracutaneous manifestations were detected. Following a strict cytogenetic analysis strategy, screening metaphases from three different tissues (peripheral blood, hyperpigmented and hypopigmented skin) we found that 23/73 patients had chromosomal abnormalities classified as follows: 1) Mosaic with 2 or more different cell lines with structural alterations n = 19; 2) Polyploidy (mosaic) n = 1 and 3) Alterations in all cells in three different tissues n = 3. SNP array, array CGH and FISH were useful for the complete characterization of the chromosomal aberrations, for the detection of microdeletions in patients with normal karyotype but with strong clinical suspicious of chromosomal alteration, and for a better establishment of genotype-phenotype correlation. In 2 patients we found genes associated with some of the extracutaneous manifestations (SHH, MNX1, PPP2R2C). This group of 73 patients finely described is the largest series of patients with pigmentary mosaicism reported worldwide. As we showed in this study, the followed analysis strategy allowed the detection of cytogenetic and molecular abnormalities, and made possible the establishment of genotype-phenotype associations in some patients. An important limitation of our study was the analysis of fibroblasts cultures instead of melanocytes and keratinocytes. In some cases the direct molecular DNA analysis of skin biopsy could be another choice.


The crystal structure of an acid protease from Rhizopus chinensis at 2.5 A resolution.
This paper contains a preliminary report of the crystal structure of the acid protease from Rhizopus chinensis at 2.5 A resolution. The molecule is bilobal with a large cleft between the lobes. Pepstatin binds in the cleft near the catalytically active Asp-35. The overall folding of the molecule consists primarily of antiparallel beta-strands, there being only four small helices.


Creation and initial validation of a genetic counseling supervisory self-efficacy scale.
Fieldwork supervision is the "signature pedagogy" for training genetic counseling students, ensuring that students have the experience necessary to become minimally competent genetic counselors. According to the National Society of Genetic Counselors 2022 Professional Status Survey, roughly 40% of genetic counselors serve as supervisors for genetic counseling graduate students. Despite fieldwork supervision being essential for training, there are currently no validated supervision skill assessment tools for genetic counseling fieldwork supervisors to use for professional development. While a self-efficacy scale for genetic counselors currently exists, a comprehensive self-efficacy scale for genetic counseling supervision skills does not. The purpose of the study was to develop and validate a genetic counseling supervisory self-efficacy scale (GCSSES). This study was comparative, quantitative, and cross-sectional, with data collected via an online questionnaire which assessed supervision self-efficacy (95 items), derived from 154 published GC supervision competencies, demographics (5), experience (9), and supervisory development (18), using the Psychotherapy Supervisory Development Scale (PSDS). A total of 119 board-certified genetic counselors completed the survey. Factor analysis eliminated 40 items due to insufficient factor loading, and item-item correlation eliminated one item with elevated inter-item correlation, leaving 54 items on the finalized GCSSES. Exploratory factor analysis derived four GCSSES factors, which accounted for 65% of the variance in the scale: (a) Goal Setting, Feedback, and Evaluation; (b) Complex Aspects of Supervision; (c) Conflict Resolution; and (d) Working Alliance. Preliminary analyses show the GCSSES has high reliability and internal consistency (Cronbach's alpha = 0.99). Positive correlations between experience variables and supervisory self-efficacy were identified. A 54 item GCSSES was developed by this study. The GCSSES may serve as a tool for genetic counseling supervisors and graduate programs to assess skills, monitor professional development, and target training. A genetic counseling supervisory self-efficacy scale can also be used in future studies regarding training of genetic counseling supervisors.


Use of ELISA to G4 antigen to quantitate neurite outgrowth in the chick both in vivo and in vitro.
The G4 glycoprotein is found on the earliest developing neurite tracts of the chick embryo. An ELISA is introduced here to quantify the amount of G4-expressing neurites in the picogram range. In this double-sandwich assay, an anti-G4 monoclonal antibody fixes the G4 antigen to the plastic surface, which then is detected by a polyclonal antiserum; nonspecific background is decreased by competitive displacement. The sensitivity of the assay allows us to follow quantitatively the very first neurite growth in embryonic heads, trunks, retinae, and brains. G4-based neurite growth is shown to occur earlier in heads than in trunks; in brain it is nearly 10-fold higher than in the retina by embryonic day 8. By determination of acetylcholinesterase (AChE) activities from the same homogenates, our earlier histochemical findings are verified now on a quantitative basis, again showing that AChE consistently precedes G4 antigen. Moreover, as an in vitro example, the G4 ELISA is applied to the nerve growth factor (NGF) standard bioassay on dorsal root ganglia; the half-maximal response is reached at approximately 10 ng/ml of NGF for G4-based neurite growth and at approximately 1 ng/ml of NGF for AChE expression, respectively.


Comparative Study on Macro-Tribological Properties of PLL-g-PEG and PSPMA Polymer Brushes.
An ultra-low friction and high load capacity could be obtained on the surfaces grafted by a polymer brush even at relatively slow friction speeds in aqueous lubrication environments, which has attracted widespread attention to study the lubrication mechanism of polymer brushes; however, it has yet to be fully understood. The macroscopic tribological performance of two different polymer brushes, which were prepared by the method of "grafting to" and "grafting from" and named as PLL-g-PEG and PSPMA, respectively, were investigated. The friction results demonstrated that PLL-g-PEG obtained a lower friction coefficient than polymer brush PSPMA, which was ascribed to its unique "self-healing" behavior. The lubrication film was in situ observed and the film thickness induced by the polymer brush was measured using a laboratory set for film thickness measurement apparatus based on interference technology. It was found that PSPMA exhibited excellent lubrication performance not found in PLL-g-PEG, and two film-forming mechanisms highly dependent on velocity were revealed, which may be important to interpret the lubrication mechanism of polymer brushes in aqueous lubricants.


Validity of Fitbit activity monitoring for adults with progressive muscle diseases.
Measuring physical activity informs activity recommendations in clinical practice and provides outcomes in clinical trials that are meaningful to patients. Activity assessment in muscle disease is challenging and there is insufficient evidence to support any single activity measure; however, multi-modal activity measurement might have potential. This two-part study included 20 and 95 adults with progressive muscle diseases with mobility ranging from independent to assisted, including wheelchair users. Their activity was measured using a multi-sensor Fitbit activity monitor, for which criterion validity and acceptability were tested in study 1 and validity, reliability, and responsiveness were tested in the longitudinal, home-based study 2. Study 1: Fitbit was acceptable and had strong criterion validity (rho/kappa ≥0.90), although up to 15% measurement error. Study 2: Fitbit had satisfactory concurrent and construct validity, reliability, and responsiveness. However, Fitbit active minutes registered 75 min more activity per week than gold standard moderate and vigorous physical activity (MVPA) time. Fitbit had satisfactory measurement properties for monitoring physical activity in adults with progressive muscle diseases. However, Fitbit should not be considered an exact step counter, heart rate monitor or calorimeter and Fitbit active minutes are not synonymous with MVPA time.Implications for rehabilitationPeople with progressive muscle diseases mobilise independently, with walking aids and with wheelchairs; physical activity measurement can be challenging in this population.Multisensor smart activity monitoring by Fitbit had satisfactory validity, reliability, responsiveness, and acceptability for the estimation of physical activity in adults with progressive muscle diseases.Fitbit active minutes are not synonymous with moderate and vigorous physical activity (MVPA) time measured using a research grade accelerometer.


Conflicting Cultural and Religious Views on Cosmesis: The Modern Women's Dilemma.
Women from countries with conflicting views on cosmesis may avoid these procedures for the fear of being rejected by the community. Understanding the motives that drive patients from these countries to seek cosmetic procedures helps discern possible causes of postoperative dissatisfaction, which can be prevented by careful selection of patients and individualizing their management protocols. This study helps identify the factors that affect Egyptian Muslim women's attitude toward cosmetic procedures. The main factors tested were female gender role stress (FGRS), body dysmorphic disorder (BDD), and religious attitude. The secondary factors investigated were health evaluation, life satisfaction, self-satisfaction, social media use, TV exposure, spouse/friends/family influence, and internalization of beauty standards. Women willing to undergo cosmetic procedures were compared with those who were not. A survey exploring demographics and the different motives were posted for the public online. Among 502 participants, 288 were willing to undergo cosmetic procedures and 214 were not. Our findings showed a statistically significant difference for the degree of BDD, FGRS, and religiousness between willing and unwilling groups. Moreover, greater pressure from partner to change appearance, influence of friends and family on opinion regarding beauty of oneself, internalization of beauty standards, and lower ratings of life and self-satisfaction showed statistically significant association with willingness to undergo cosmetic treatment. BDD, FGRS, and religious attitude are among the highest predictors of the willingness of women to undergo cosmetic procedures together with many other factors. This study is the first of its kind to evaluate several unexplored motives and opens the door for future research. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Evaluation of the role of rat liver Golgi endo-alpha-D-mannosidase in processing N-linked oligosaccharides.
Golgi membranes from rat liver have been shown to contain an endo-alpha-D-mannosidase which can convert Glc1Man9GlcNAc to Man8GlcNAc with the release of Glc alpha 1----3Man (Lubas, W. A., and Spiro, R. G. (1987) J. Biol. Chem. 262, 3775-3781). We now report that this enzyme has the capacity to cleave the alpha 1----2 linkage between the glucose-substituted mannose residue and the remainder of the polymannose branch in a wide range of oligosaccharides (Glc3Man9GlcNAc to Glc1Man4GlcNAc) as well as glycopeptides and oligosaccharide-lipids. Whereas the tri- and diglucosylated species (Glc3Man9GlcNAc and Glc2Man9GlcNAc), which yielded Glc3Man and Glc2Man, respectively, were processed more slowly than Glc1Man9GlcNAc, the monoglucosylated components with truncated mannose chains (Glc1Man8GlcNAc to Glc1Man4GlcNAc) were trimmed at an increased rate which was inversely related to the number of mannose residues present. The endomannosidase was not inhibited by a number of agents which are known to interfere with N-linked oligosaccharide processing by exoglycosidases, including 1-deoxynojirimycin, castanospermine, bromoconduritol, 1-deoxymannojirimycin, swainsonine, and EDTA. However, Tris and other buffers containing primary hydroxyl groups substantially decreased its activity. After Triton solubilization, the endomannosidase was observed to be bound to immobilized wheat germ agglutinin, indicating the presence of a type of carbohydrate unit consistent with Golgi localization of the enzyme. The Man8GlcNAc isomer produced by endomannosidase action was found to be processed by Golgi enzymes through a different sequence of intermediates than the rough endoplasmic reticulum-generated Man8GlcNAc variant, in which the terminal mannose of the middle branch is absent. Whereas the latter oligosaccharide is converted to Man5GlcNAc via Man7GlcNAc and Man6GlcNAc at an even rate, the processing of the endomannosidase-derived Man8GlcNAc stalls at the Man6GlcNAc stage due to the apparent resistance to Golgi mannosidase I of the alpha 1,2-linked mannose of the middle branch. The results of our study suggest that the Golgi endomannosidase takes part in a processing route for N-linked oligosaccharides which have retained glucose beyond the rough endoplasmic reticulum; the distinctive nature of this pathway may influence the ultimate structure of the resulting carbohydrate units.


The good, the bad, and the opportunities of the complement system in neurodegenerative disease.
The complement cascade is a critical effector mechanism of the innate immune system that contributes to the rapid clearance of pathogens and dead or dying cells, as well as contributing to the extent and limit of the inflammatory immune response. In addition, some of the early components of this cascade have been clearly shown to play a beneficial role in synapse elimination during the development of the nervous system, although excessive complement-mediated synaptic pruning in the adult or injured brain may be detrimental in multiple neurogenerative disorders. While many of these later studies have been in mouse models, observations consistent with this notion have been reported in human postmortem examination of brain tissue. Increasing awareness of distinct roles of C1q, the initial recognition component of the classical complement pathway, that are independent of the rest of the complement cascade, as well as the relationship with other signaling pathways of inflammation (in the periphery as well as the central nervous system), highlights the need for a thorough understanding of these molecular entities and pathways to facilitate successful therapeutic design, including target identification, disease stage for treatment, and delivery in specific neurologic disorders. Here, we review the evidence for both beneficial and detrimental effects of complement components and activation products in multiple neurodegenerative disorders. Evidence for requisite co-factors for the diverse consequences are reviewed, as well as the recent studies that support the possibility of successful pharmacological approaches to suppress excessive and detrimental complement-mediated chronic inflammation, while preserving beneficial effects of complement components, to slow the progression of neurodegenerative disease.


Effect of oestriol gel on dyspareunia in postmenopausal women in 2 weeks of treatment: a pilot study.
This brief report evaluates the early effect of ultra-low dose 0.005% oestriol vaginal gel on dyspareunia in postmenopausal women within the first 2 weeks of treatment. This was a prospective and multicentre single-arm pilot study and the effect of the treatment on dyspareunia was evaluated by using a diary. In total 23 women and 150 coitus were studied. 8 coitus were painless in the first week and 42 during the second week (p < .0001). A reduction in pain from the baseline was seen in 116 (77.3%) out of the 150 coitus. 0.005% oestriol vaginal gel produced a rapid and progressive improvement in dyspareunia from the very first days of treatment in postmenopausal women.IMPACT STATEMENTWhat is already known on this subject? Local oestrogen therapy has shown efficacy in the treatment of genitourinary syndrome of menopause (GSM) and dyspareunia when used for a duration of greater than 3 weeks.What do the results of this study add? This study shows that the use of oestriol gel produces clinical effects from the beginning of its use, decreasing dyspareunia in postmenopausal women within just 14 days of daily use.What are the implications of these findings for clinical practice and/or further research? In cases of dyspareunia in relation to menopause, therapy with local oestrogens, in our case oestriol gel, produces an improvement from the beginning of its use. This information is clinically relevant when evaluating therapeutic options.


When asleep, one is cooler on beta-blockade than on placebo. A study of pulmonary arterial blood temperature and skeletal muscle heat production in anaesthetized man.
The effect of beta 1-adrenergic blockade on body temperature was studied during general anaesthesia by means of a thermistor in an indwelling pulmonary arterial catheter. Metoprolol (200 mg daily) or placebo was given double-blind preoperatively for at least 2 weeks to 27 hypertensive patients undergoing abdominal surgery. A significantly greater temperature fall was observed in the metoprolol group compared with the placebo group. Heat production in the rectus abdominis muscle, measured by direct microcalorimetry, was significantly lower after metoprolol. The hypothermic effect of beta-adrenergic blockade during anaesthesia deserves special attention.


Systematic review of pre-clinical chronic myeloid leukaemia.
Studies of a provisional entity pre-clinical chronic myeloid leukaemia (CML), which precedes chronic phase (CP) without leucocytosis or blood/marrow feature of CML CP, has been increasing. To perform a systematic review of pre-clinical CML and analysis the data relevant to disease progression to CML CP. We performed a literature search on 16 July 2017 using EBSCOhost Research Databases interface and Western Pacific Region Index Medicus. Two authors selected the studies, extracted the data and evaluated the quality of studies using an 8-item tool, independently. The outcomes were percentage of Philadelphia chromosome in the number of metaphases examined (Ph%), correlation between Ph% and blood count and time progress to CML. Our initial search returned 4770 studies. A total of 10 studies with a total 17 subjects were included. The lowest Ph%, which eventually progresses to CML, was 10%. Absolute basophil count seemed to correlate better with Ph% compared to total white cell and absolute eosinophil count. The time from the first documented pre-clinical CML to CML ranged from 12 to 48 months. The overall quality of the included studies was average. This is the first systematic review on pre-clinical CML. This entity requires additional large-scale studies.


Drug-induced mononucleosis-like hepatic injury in a patient with systemic lupus erythematosus.
A case of systemic lupus erythematosus (SLE) with mononucleosis-like hepatic injury was described. An emergent cesarean section was performed in a 25 yr-old house wife at 34 weeks gestation, followed by administration of several antibiotics. After the surgery she complained of high fever, hepatomegaly and dull right hypochondralgia, and mild liver dysfunction was also found. The liver biopsy showed prominent mononuclear cell infiltration in the sinusoids with minimum hepatocellular necrosis and mild triaditis, resembling hepatic lesion in infectious mononucleosis (mononucleosis-like injury). There were no clinical and serological features suggestive of infectious mononucleosis. This hepatic lesion was thought to be a manifestation of allergic reaction to drugs to which the lymphocyte stimulation test was found to be positive. Immunological abnormalities inherent in SLE might be related to occurrence of such allergic drug reaction.


Priming with anti-cholinesterases--the effect of different priming doses of edrophonium.
The effect of different priming doses of edrophonium were studied in 77 patients divided into seven groups (n = 11 in each). Edrophonium 1.0 mg.kg-1 was administered either in a single bolus dose (Group I; controls) or in an initial dose of 0.05, 0.1, 0.15, 0.2, 0.25 or 0.3 mg.kg-1 followed one minute later by the remainder of the 1.0 mg.kg-1 dose in Groups II to VII respectively. Reversal was attempted at ten per cent spontaneous recovery of twitch height (T1) from atracurium-induced neuromuscular blockade. Increasing the size of the priming dose from 0.05 to 0.2 mg.kg-1 resulted in a stepwise increase (p less than 0.05) in recovery of T1 and train-of-four (TOF) ratio. Higher priming doses (0.25 and 0.3 mg.kg-1) were not associated with further improvement in T1 and TOF recovery. Reversal time, that is the time taken from the first injection of edrophonium until the TOF ratio value had reached 0.75 was significantly faster (p less than 0.01) following priming with edrophonium 0.2 mg.kg-1 (Group V) when compared to Groups I, II, III, IV and VI. Reversal times were also significantly faster in Groups IV and VI when compared to the control group. It is concluded that 0.2 mg.kg-1 appears to be the optimal priming dose for administration of edrophonium in divided doses.


Extraosseous Ewing sarcoma in children and adolescents: A retrospective series from a referral pediatric oncology center.
Extraosseous Ewing sarcoma is a rare entity and less is known about its clinical behavior and optimal treatment than for its counterpart in bone. This study is a retrospective analysis on a cohort of patients <21 years treated according to a "soft tissue sarcoma approach." The "extraosseous" origin of the tumor was established on radiological findings, based on the lack of any bone involvement. Patients were treated using a multimodality approach including surgery, radiotherapy, and chemotherapy. All patients received chemotherapy with alkylating agents and anthracyclines for 25 weeks (nine courses). Radiotherapy (45-54.8 Gy) was required for all cases except those who had an initial R0 resection of tumors smaller than 5 cm. Fifty-seven patients (age 2-20 years, median 14) were treated from 1990 to 2020. Ten-year event-free survival (EFS) and overall survival (OS) were 77.5% and 85.5% in patients with localized disease, and 11.1% and 29.6% in those with metastatic disease (p < .001) (follow-up 5-349 months, median 107 months). In patients with localized disease, the most recent IVADo-IVE regimen achieved excellent survivals, that is, 10-year EFS 95.5%. Our study showed that satisfactory results were achieved in patients with localized extraosseous Ewing sarcoma treated with a tailored approach derived from soft tissue sarcoma protocols, which was less intensive and shorter as compared to the standards utilized for the management of bone Ewing sarcoma. Our study suggests that the extraskeletal site might be considered as a variable to stratify patients and modulate treatment intensity accordingly in Ewing sarcoma protocol.


Comparison of effects of a thrombin-based femoral artery closure device with those of a mechanical compression device on serum C-reactive protein and amyloid A after percutaneous coronary intervention.
The present study evaluates whether the closing procedure of the femoral artery after percutaneous coronary intervention influences the degree of inflammation related to the procedure as measured by C-reactive protein (CRP) and serum amyloid A (SAA). A thrombin-based device (Duett sealing device) was compared with a mechanical compression device (FemoStop).


Author Correction: Proteome evolution under non-substitutable resource limitation.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Absence of cross-resistance between two alkylating agents: BCNU vs bifunctional galactitol.
Dianhydrogalactitol (DAG) increased the life span of both BCNU-sensitive and -resistant L1210 tumor-bearing mice. However, the BCNU-resistant strain showed slightly lower sensitivity against DAG, which could be overcome by an increase in drug dose of ca. 20%. The somewhat lower sensitivity was proportional to a slightly reduced DNA cross-linking formation induced by DAG in BCNU-resistant cells. The amount of DNA cross-links was determined by measurement of the 1,6-di(guaninyl)-galactitol content of DNA. The slight reduction in cross-links is not attributable to DNA repair but rather to other factors that seem to prevent the formation of DNA-drug adducts. The absence of cross-resistance is explained by different kinds of DNA damage caused by the two alkylating agents and the presumably different defense mechanisms developed by cells against these lesions.


Interaction of biogenic amines with ethanol.
Ethanol through its primary catabolite, acetaldehyde, competitively inhibits oxidation of aldehyde dehydrogenase substrates. As a consequence biogenic amines form increased quantities of alcohols rather than the corresponding acids. During this biotransformation, condensation reactions between deaminated and intact amines may occur which can yield tetrahydropapaverolines. These compounds are closely related to precursors of opioids which is cause to link ethanol abuse to morphine addiction. There is, however, no pharmacological or clinical evidence suggesting similarities between ethanol dependence or opiod addiction. Acetaldehyde plays an additional role in alkaloidal formation in vitro. Biogenic amines may react with acetaldehyde to form isoquinoline or carboline compounds. Some of these substances have significant pharmacological activity. Furthermore, they may enter neural stores and displace the natural neurotransmitter. Thus, they can act as false neurotransmitters. Some investigators believe that chronic ethanol ingestion leads to significant formation of such aberrant compounds which may then upset autonomic nervous system balance. This disturbance may explain the abnormal sympathetic activity seen in withdrawal. While these ideas about the etiology of alcohol abuse have a definite appeal, they are naturally based on in vitro preliminary work. Much study of the quantitative pharmacology of these compounds in animals is required before judgement can be made as to the merits of the proposed hypotheses. In the meantime, pharmacological studies on the ability of ethanol to depress respiration in the mouse has revealed that unlike opioids or barbituates, respiratory depression induced by ethanol requires the presence in brain of serotonin. This neurotransmitter also mediates the respiratory effects of several other alcohols but curiously, not chloral hydrate, yet this compound is purported to alter biogenic amine metabolism much like ethanol. Thus, the response to ethanol can be pharmacologically separated from other major narcotic classes such as opioids and barbiturates by respiratory depression effects. The specific requirement for serotonin mediation exhibited by ethanol and several other alcohols opens the door for a rational therapeutic approach to the treatment of alcohol abuse. At the same time, this finding tends to lessen the probability that alcoholism is in some way connected with the formation of addictive alkaloids.


[Comparison of laparoscopic vs. laparotomy treatment in ovarian teratomas].
Benign cystic teratoma is one of the most common benign tumors of the ovary, according to international series represents between 44 and 62% of all ovarian tumors diagnosed in women younger than 40 years. To evaluate and compare the efficacy and safety between laparoscopy and laparotomy in the management of ovarian teratomas, as well as the recurrence between both techniques. Retrospective, clinical series study involving 169 cases of ovarian teratomas operated at the Instituto Nacional de Perinatología Isidro Espinosa de los Reyes in the period comprehended between 2000-2008. The cases were divided into the ones solved by laparoscopy, corresponding to group 1 (102 cases) and 67 cases solved by laparotomy, corresponding to group 2. Group 1 (laparoscopic approach) consisted of 102 patients (60.3%), and group 2 (laparotomy approach) had 67 patients (39.7%). Surgical bleeding: 55.7 +/- 21.4 mL vs. 91.6 +/- 29.2 mL (p < 0.0001), hospital stay: 1.6 +/- 0.57 vs. 2.7 +/- 0.42 days (p < 0.0001), surgical time: 110.3 +/- 27.2 vs. 83.6 +/- 26.9 minutes (p < 0.0001), teratoma size: 7.2 +/- 2.3 vs. 11.5 +/- 4.2 cm (p < 0.0001) in groups 1 and 2, respectively. Teratoma rupture had 57.8% incidence (59 cases) in group 1, and 16.4% in group 2 (11 cases). Laparoscopy was a risk factor for broken open for ovarian cyst (OR: 6.9; CI 95%: 3.3-14.8). Not a single case was complicated by chemical peritonitis in any study group. Laparoscopic approach to teratomas is a safe and efficient procedure, it does not increase complications in comparison to the laparotomy approach; it presents less bleeding and short hospital stay, offering a quick recovery.


EMG changes in rat hind limb muscles following bilateral deafferentation.
Bilateral section of dorsal roots was performed in 9 adult rats in order to ascertain whether the tendency to extension, the appearance of spontaneous electromyographic (EMG) activity in extensor muscles and other symptoms of postdenervation hypersensitivity after unilateral deafferentation are not due to the sensory inflow from the contralateral limb. EMG activity from the soleus (SOL) and tibialis anterior (TA) muscles was bilaterally recorded before and at various periods after deafferentation by a previously implanted electrode array. The postural activity in both SOL muscles disappeared after the operation. One to two days later, however, spontaneous tonic EMG activity, similar to that found in the SOL after unilateral deafferentation, appeared in these bilaterally deafferented muscles. The tonic spontaneous EMG activity in hind limb extensor muscles after deafferentation is apparently due to hypersensitivity of spinal neurones to supraspinal influences, since this activity completely disappears after myelotomy. The paradoxical inhibitory EMG response to stretch of the deafferented SOL frequently appeared 1-2 weeks after bilateral dorsal rhizotomy. The performance of movement was highly atactic after bilateral deafferentation. However, the basic locomotor EMG pattern persisted, although simultaneous activation of homonymous muscles was also occasionally recorded.


Alternative routes for recovery of hand functions after corticospinal tract injury in primates and rodents.
Recent studies on various corticospinal tract (CST) lesions have shown the plastic changes at a variety of motor systems after the lesion. This review provides the alternative routes associated with the motor functional recovery after the CST lesions at various levels in nonhuman primates and rodents. In the case of the motor cortical lesions, the perilesional area compensates for the lesion. In contrast, sprouting of the corticoreticular tracts was observed after the lesions involving sensorimotor cortical areas. After the internal capsule lesion, sprouting in the cortico-rubral pathway contributes to the recovery. In case of the pyramidal lesion, rubrospinal and reticulospinal tracts play a role of the functional recovery. After the dorsolateral funiculus (DLF) lesion at C4/C5, the indirect pathway via propriospinal tract contributes to the recovery. In case of the hemisection at lower cervical cord, the CST fibers sprouted from the bilateral motor cortex and descended to the contralesional DLF and crossed below the lesion area. The central pathways can change their structure and activity dynamically depending on the lesion sites and size. Revealing the difference of the alternative pathways should be crucial to understand the whole recovery mechanism and develop the further neurorehabilitative treatment.


Making sense of postoperative CT imaging following laparoscopic partial nephrectomy.
The increasing popularity of laparoscopic partial nephrectomy (LPN) necessitates radiologists to become familiar with the operative techniques as well as normal and abnormal postoperative findings. Due to the varying presentation of abnormal changes following LPN and their similarities with other disease entities, radiologists should be cognizant of common pitfalls to avoid inadvertent misdiagnosis. A few common pitfalls discussed in this paper are the identification of laparoscopic port placement issues, recognizing a myriad of post-surgical materials, differentiating haemostatic materials from postoperative abscess and infection, non-absorbable suture material mimicking rim calcifications, as well as hints for differentiating exuberant granulation tissue from tumour recurrence.


Perceptual and attentional processes following callosal section in humans.
Studies are reviewed that examine how perceptual and attentional systems operate in the cortically disconnected human. The data indicate that even though both simple and complex perceptual information associated with the cognitive activities of each disconnected half brain show virtually no interactions, the attentional system remains largely integrated in the split-brain patient. It also appears that the human brain is subject to a set of finite resources it can allocate to cognitive activities. These resources are not changed following cortical disconnection. Taken together, studies to date support the view that the attentional system is an independently functioning and integrated entity, following brain bisection, that participates in both perceptual and cognitive activities of each hemisphere.


[Comparison of conventional PAP smear with liquid based cytology method (LBC)].
Our aim was to summarize our and foreign experience in screening of cervical cancer, using conventional PAP smear and liquid-based cytology-LBC. In the Department of Obstetrics and Gynecology of Medical university of Varna, Bulgaria we made clinical trial on 100 patients, that has the goal of comparing the results of liquid -based cytology with conventional PAP smear in different criteria. There are significant advantages of LBC mainly due to the lower number of unsatisfactory results and higher specificity for LSIL. Compared to foreign results our results are showing the same tendencies and values. Our and foreign authors results for the benefits of LBC are undisputable, although this method is still rarely used in our country.


Diffusion of transferrin receptor clusters.
Two dimensional motion of membrane receptors provides a mechanism for interaction among receptors in the plane of the membrane. In some cases the lateral diffusion leads to formation of clusters which may also be mobile. We have used image cross-correlation (ICCS) spectroscopy technique to measure the translational motion of transferrin receptors in the membrane of 3T3 fibroblasts and HEp2 carcinoma cells. The technique is based on the measurement and analysis of fluctuations in the intensity observed in fluorescence confocal microscope images measured as a function of time. The fluorescence fluctuations arise from stochastic concentration fluctuations about the equilibrium concentration caused by movement of receptors. The amplitude of the fluctuations depend on the number of fluorescent molecules in the observation volume and the dynamics provide the rate of movement. The diffusion observed by this analysis is orders of magnitude slower than that measured by conventional photobleaching techniques. The slower motion corresponds to the diffusion of receptor clusters which provide the more dominant fluctuations.


Parallel effects of joint receptors on motor neurones and intersegmental interneurones in the locust.
At the distal end of a mesothoracic tibia of the locust, Schistocerca gregaria, is a chordotonal organ which monitors the position and movement of the tarsus relative to the tibia. It contains approximately 35 receptors that variously encode different spatial and temporal parameters (position, velocity and direction of movement). Some excite intersegmental interneurones that respond phasically or tonically, with directional sensitivity to active or imposed movements of the tarsus. Some of these interneurones are also excited by intrinsic movements of the tarsal segments. Others, besides being excited by tarsal proprioceptive inputs, are also excited by exteroreceptors on the tarsus. When stimulated mechanically or electrically, chordotonal afferents evoke excitatory postsynaptic potentials with a central latency of between 0.9 and 1.4 ms simultaneously in the intersegmental interneurones and in tarsal motor neurones. The central arborizations of the afferents, the intersegmental interneurones and the tarsal motor neurones overlap in certain neuropilar regions of the mesothoracic ganglion. Other afferents cause an inhibition of the motor neurones, with a longer and non-consistent latency suggesting the involvement of other intercalated interneurones. These results indicate that proprioceptive inputs from the tarsal joint receptors are transmitted in parallel and monosynaptically to tarsal motor neurones and to the intersegmental interneurones.


Repair of rabbit duodenal mucosa after acid injury in vivo and in vitro.
Epithelial repair after luminal acid exposure was studied in the rabbit duodenum in vivo and in vitro. Hydrochloric acid (200 mM, 30 min in vivo; 10 mM, 10 min in vitro) caused a uniform damage of the mucosa confined to the villi. After demarcation and detachment of the necrotic tissue the defect was bridged by the remaining viable epithelial cells, resulting in a reduction of villus height. This process of mucosal repair proceeded continuously, so that 9 h after acid damage only 33% of villi in the proximal duodenum and 41% in the distal duodenum remained not fully restored, at both luminal pH 7 and luminal pH 3. The difference is due to the higher acid susceptibility of the distal duodenum. In vitro, most of the mucosal surface was reconstituted 5 h after acid injury, at both luminal pH 7.4 and luminal pH 3. The potential difference declined and reversed after mucosal damage; restitution to original values was only observed at luminal pH 7 in vivo and luminal pH 7.4 in vitro.


Matrix stiffness mediates stemness characteristics via activating the Yes-associated protein in colorectal cancer cells.
Matrix stiffness is an essential physical microenvironment in solid cancer. However, its influence on cancer stemness still remains elusive. Colorectal cancer (CRC) cell line HCT-116 was cultured in the matrix with various stiffness. The siYAP was applied to detect the changes of stemness markers. The cancer stemness markers, Yes-associated protein (YAP), Lamin A/C and downstream protein molecules, and their activation were measured after the treatment with anti-β1-integrin and FAK inhibitors. In CRC tissue samples, collagen deposition and the expression of α-SMA and CD133 were detected. The study found that the expression level of stemness markers and Lamin A/C increased as the matrix stiffness raised and was regulated by YAP activation in CRC stem cells. Inhibition of β1-integrin and FAK activation in a high stiffness cell culture medium significantly decreased the activation of YAP, PI3K, and AKT. Collagen was highly deposited in the CRC invasive tumor front (ITF), and the expression of CD133 was higher in ITF compared with normal tissue and the tumor cells. Moreover, the expression level of α-SMA was positively correlated with CD133 expression level. Together, our results suggest that activation of YAP in CRC plays an important role in the promotion of cancer stem cell properties by extracellular matrix stiffness in CRC.


High frequency of promoter hypermethylation of RASSF1A in tumorous and non-tumourous tissue of breast cancer.
To determine the presence of RASSF1A promoter methylation in tumorous and non-tumorous tissues of breast cancer. Methylation-specific PCR was used to detect RASSF1A methylation in DNA extracted from tumorous and paired non-tumorous tissues of 40 breast cancer patients. The associations of RASSF1A hypermethylation with clinicopathological characteristics in tumorous and non-tumorous breast tissues were analysed. RASSF1A promoter hypermethylation was detected in 38 of the 40 breast cancer tissues (95%) and 37 of the paired non-tumorous tissues (92.5%). When compared with the non-tumorous tissues, aberrant methylation was detected to be higher in 24 of the tumorous tissues (60%). The latter was found to be associated with lower histological grade tumours (p=0.048). RASSF1A promoter hypermethylation occurred at a high frequency in breast cancer tumorous and non-tumorous tissues; the majority of tumours have a higher level of methylation status when compared with non-tumorous tissues. This supports the notion that RASSF1A methylation is an early and premalignant alteration.


In vitro Reconstitution of the S. aureus 30S Ribosomal Subunit and RbfA Factor Complex for Structural Studies.
Ribosome-binding factor A (RbfA) from Staphylococcus aureus is a cold adaptation protein that is required for the growth of pathogenic cells at low temperatures (10-15°C). RbfA is involved in the processing of 16S rRNA, as well as in the assembly and stabilization of the small 30S ribosomal subunit. Structural studies of the 30S-RbfA complex will help to better understand their interaction, the mechanism of such complexes, and the fundamental process such as 30S subunit assembly that determines and controls the overall level of protein biosynthesis. This article describes protocols for preparation of RbfA and the small 30S ribosomal subunits and reconstitution and optimization of the 30S-RbfA complex to obtain samples suitable for cryo-electron microscopy studies.


cyclo-Tetra-kis-(μ-2,4,6-tri-methyl-phenyl-κC 1:κC 1)bis-(tri-methyl-phosphane)-1κP,3κP-tetra-copper(I).
The title compound, [Cu4(C9H11)4(C3H9P)2] or [Cu4(Mes)4(PMe3)2] (Mes = 2,4,6-tri-methyl-phenyl), was synthesized from copper(I) mesityl and tri-methyl-phosphane in THF as solvent. The mol-ecular structure of the complex has C 2 symmetry and consists of four copper(I) atoms bridged by four μ-mesityl groups, giving an eight-membered puckered {Cu4C4} ring. Additionally, two copper(I) atoms at opposite corners of the Cu4 rhomb are each linked to a terminal PMe3 ligand. The PMe3-bearing copper(I) atoms exhibit a distorted trigonal-planar coordination mode whereas the remaining Cu atoms linked to two mesityl groups are nearly linearly coordinated.