Subcellular effects of some anesthetic agents on rat myocardium.
The effects of ether, chloroform, and halothane on calcium accumulation and ATPase activity of rat heart microsomes and mitochondria as well as on myofibrillar ATPase activity were investigated. Chloroform and halothane depressed microsomal and mitochondrial calcium uptake and binding in a parallel fashion. Ether decreased microsomal calcium binding and mitochondrial calcium uptake to varying degrees, while mitochondrial calcium binding was slightly enhanced. Whereas ether had no effect, chloroform depressed microsomal and mitochondrial total APTase activities and halothane decreased microsomsl ATPase and slightly stimulated mitochondrial total ATPase activities. Halothane was found to depress myofibrillar Mg2+-ATPase and ether was capable of decreasing myofibrillar Ca2+-ATPase. Chloroform was seen to inhibit both myofibrillar enzymes. These results suggest that the cardiodepressant actions of volatile anesthetic agents may be due to alterations in the calcium accumulating abilities of microsomal and mitochondrial membranes while direct myofibrillar effects may contribute to the depression seen with relatively higher concentrations of anesthetics.


Contribution of skin temperature regularity to the risk of developing pressure ulcers in nursing facility residents.
The purpose of the study was to determine whether characterizing skin temperature regulation as a functional property of the skin as it relates to tissue tolerance improves the clinician's understanding of pressure ulcer risk prediction. A 2-group time-series design was used to observe skin temperature regularity (entropy) and self-similarity (spectral exponent). Twenty nursing facility residents wore skin temperature monitors continuously for 5 days. One bathing episode was observed because bathing is a commonly occurring care procedure. Difference in skin temperature multiscale entropy and spectral exponent by risk category and pressure ulcer outcome. Multiscale entropy (MSE) for skin temperature was lowest in those who developed pressure ulcers, F1,18 = 35.14, P < .001. Skin temperature mean MSE, F1,17 = 5.55, P = .031 and the skin temperature spectral exponent, F1,17 = 6.19, P = .023 differentiated the risk groups. The change in skin temperature entropy during bathing was significant, t(16) = 2.55, P = .021. Skin temperature MSE and the spectral exponent were significantly different between low-risk and higher risk residents and residents who did and did not develop pressure ulcers. The study supports measurement of skin temperature regulation as a component of tissue tolerance to pressure.


Structure-Kinetics Correlations in Isostructural Crystals of α-(ortho-Tolyl)-acetophenones: Pinning Down Electronic Effects Using Laser-Flash Photolysis in the Solid State.
Aqueous suspensions of nanocrystals in the 200-500 nm size range of isostructural α-(ortho-tolyl)-acetophenone (1a) and α-(ortho-tolyl)-para-methylacetophenone (1b) displayed good absorption characteristics for flash photolysis experiments in a flow system, with transient spectra and decay kinetics with a quality that is similar to that recorded in solution. In contrast to solution measurements, reactions in the solid state were characterized by a rate limiting hydrogen transfer reaction from the triplet excited state and a very short-lived biradical intermediate, which does not accumulate. Notably, the rate for δ-hydrogen atom transfer of 1a (2.7 × 10(7) s(-1)) in the crystalline phase is 18-fold larger than that of 1b (1.5 × 10(6) s(-1)). With nearly identical molecular and crystal structures, this decrease in the rate of δ-hydrogen abstraction can be assigned unambiguously to an electronic effect by the para-methyl group in 1b, which increases the contribution of the (3)π,π* configuration relative to the reactive (3)n,π* configuration in the lowest triplet excited state. These results highlight the potential of relating single crystal X-ray structural data with absolute kinetics from laser flash photolysis.


[Caries preventive effect of fluoride lacquer after several year's use in children].
The course and result of a study in caries prophylaxis with fluoride varnish (Duraphat) is reported which was carried out under the auspices of the youth health organisation of the Land Hessen on pupils of the districts of Hanau Stadt and Land. During the course of 3 years the preparation was applied 5 or 6 times by a quick touch method. It resulted in significant marked decrease in the spread of caries as compared with control pupils.


Impact of chronic kidney disease and stress myocardial perfusion imaging as a predictor of cardiovascular events.
Stress myocardial perfusion imaging (MPI) is an established means of predicting cardiovascular events and is suitable in chronic kidney disease (CKD) patients. We aimed to evaluate the prognostic value of CKD parameters and an abnormal stress MPI for cardiovascular events. A total of 495 patients with suspected coronary artery disease (CAD) or history of CAD including 130 CKD patients not undergoing hemodialysis, underwent stress MPI (313 males, mean age 70 years) and were followed up for 14 months (mean period). CKD was defined as an estimated GFR of <60 ml/min/1.73 m(2) and/or persistent proteinuria. Cardiovascular events were defined as sudden cardiac death, acute coronary syndrome and congestive heart failure requiring hospitalization. Cardiovascular events occurred in 41 (8.3%) patients. Multivariate Cox regression analysis indicated that CKD [hazard ratio (HR) = 3.76, p < 0.001] and a stress MPI summed difference score (SDS) of ≥2 (HR = 3.78, p < 0.001) were independent predictors of cardiovascular events; CKD plus abnormal stress MPI was also a strong predictor of cardiovascular events (non-CKD and SDS <2 vs. CKD and SDS ≥2, HR = 15.9, p < 0.001). Both CKD and myocardial ischemia detected by stress MPI are independent predictors for cardiovascular events. Coexistence of CKD and myocardial ischemia detected by stress MPI is more useful for short-term risk stratification of cardiovascular events.


Left atrial backward ejection in symptomatic hypertrophic cardiomyopathy--assessment by transthoracic and transesophageal Doppler echocardiography.
During atrial contraction, the left atrium produces both forward ejection to the left ventricle and backward ejection to pulmonary veins. To determine quantitatively left atrial ejection performance in symptomatic hypertrophic cardiomyopathy (HCM) patients by using left atrial systolic time intervals. Thirty-one patients with symptomatic HCM and sinus rhythm and 31 normal subjects were studied with transthoracic and transesophageal Doppler echocardiography. Left atrial pre-ejection period (APEP), corrected atrial pre-ejection period (APEPc), and the duration (AET) and the time velocity integral (IA) of the atrial contraction wave in transmitral flow were determined. The duration (PV-AET) and the time velocity integral (PV-IA) of reverse pulmonary venous flow during atrial contraction were also determined. For normal subjects, significant correlations were found between APEP and electrocardiographic P wave duration (r = 0.78, p < 0.001), and between APEPc and left atrial forward ejection indices (AET: r = -0.42, p = 0.01, IA: r = -0.54, p < 0.05, respectively), but not between APEP and either of the two latter indices. These findings indicate that, for normal subjects, APEPc is a better index of left atrial systolic function than APEP. In contrast, for HCM patients, significant correlations were found between APEPc and left atrial backward ejection indices (PV-AET: r = -0.49; p < 0.005, PV-IA: r = -0.66; p < 0.001, respectively), but not between APEPc and left atrial forward ejection indices. Augmentation of left atrial afterload may result in decreased left atrial forward ejection and increased left atrial backward ejection. Thus, both left atrial forward ejection and left atrial backward ejection must be considered in the assessment of left atrial ejection performance in patients with symptomatic HCM.


"Accomodated" pig endothelial cells promote nitric oxide-dependent Th-2 cytokine responses from human T cells.
Cardiac and renal allo- and xenografts can become naturally resistant to vascular rejection. Understanding this process of "accommodation" would enhance our understanding of vascular inflammatory responses and have implications for immune manipulation and tolerance induction. A feature of these grafts is infiltration by leukocytes secreting a Th-2 pattern of cytokines. HLA-DR-1-transfected, immortalized porcine endothelial cells (IPEC) were incubated with polyclonal human immunoglobulin G (IgG) for 6 days before incubation with purified human CD4+ T cells. IgG-incubated IPEC stimulated a normal proliferative response from alloreactive T cells. However, interferon (IFN)-gamma levels were significantly reduced, whereas interleukin (IL)-5 and IL-10 were maintained at levels equivalent to those stimulated by control IPEC. Cognate interaction between T cells and IPEC was not required for this effect, because IgG-incubated, MHC-class II-negative IPEC caused reduced IFN-gamma secretion during a response to human Epstein-Barr virus-transformed B cells. Experiments with the nitric oxide (NO) donor, (z)-1-2-[2-Aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO), and the NO synthase inhibitor, NG-monomethyl-L-arginine.monoacetate (L-NMMA), showed that NO released by the IgG-incubated IPEC was actively involved in the development of this phenotype. These data suggest a novel, IgG-mediated, NO-dependent mechanism by which endothelial cells (EC) influence T cell responsiveness and that the Th-2 cytokine skewing seen in "accommodated" grafts may be a secondary phenomenon, resulting from the T-EC interactions.


Genome-wide association study of drought tolerance and biomass allocation in wheat.
Genome wide association studies (GWAS) are important in discerning the genetic architecture of complex traits such as biomass allocation for improving drought tolerance and carbon sequestration potential of wheat. The objectives of this study were to deduce the population structure and marker-trait association for biomass traits in wheat under drought-stressed and non-stressed conditions. A 100-wheat (Triticum aestivum L.) genotype panel was phenotyped for days to heading (DTH), days to maturity (DTM), shoot biomass (SB), root biomass (RB), root to shoot ratio (RS) and grain yield (GY). The panel was sequenced using 15,600 single nucleotide polymorphism (SNPs) markers and subjected to genetic analysis using the compressed mixed linear model (CMLM) at false discovery rate (FDR < 0.05). Population structure analysis revealed six sub-clusters with high membership ancestry coefficient of ≤0.65 to their assigned sub-clusters. A total of 75 significant marker-trait associations (MTAs) were identified with a linkage disequilibrium threshold of 0.38 at 5cM. Thirty-seven of the MTAs were detected under drought-stressed condition and 48% were on the B genome, where most quantitative trait loci (QTLs) for RB, SB and GY were previously identified. There were seven pleiotropic markers for RB and SB that may facilitate simultaneous selection. Thirty-seven putative candidate genes were mined by gene annotation on the IWGSC RefSeq 1.1. The significant MTAs observed in this study will be useful in devising strategies for marker-assisted breeding for simultaneous improvement of drought tolerance and to enhance C sequestration capacity of wheat.


Sympathetic responses to vestibular activation in humans.
Activation of sympathetic neural traffic via the vestibular system is referred to as the vestibulosympathetic reflex. Investigations of the vestibulosympathetic reflex in humans have been limited to the past decade, and the importance of this reflex in arterial blood pressure regulation is still being determined. This review provides a summary of sympathetic neural responses to various techniques used to engage the vestibulosympathetic reflex. Studies suggest that activation of the semicircular canals using caloric stimulation and yaw rotation do not modulate muscle sympathetic nerve activity (MSNA) or skin sympathetic nerve activity (SSNA). In contrast, activation of the otolith organs appear to alter MSNA, but not SSNA. Specifically, head-down rotation and off-vertical axis rotation increase MSNA, while sinusoidal linear accelerations decrease MSNA. Galvanic stimulation, which results in a nonspecific activation of the vestibule, appears to increase MSNA if the mode of delivery is pulse trained. In conclusion, evidence strongly supports the existence of a vestibulosympathetic reflex in humans. Furthermore, attenuation of the vestibulosympathetic reflex is coupled with a drop in arterial blood pressure in the elderly, suggesting this reflex may be important in human blood pressure regulation.


Reevaluation of the phenomena of the first night effect.
Thirty subjects, who were between the ages of 24 and 60 years and were free of sleep disorders, were evaluated for impotency by use of polysomnograms recorded over 2 consecutive nights. No statistical differences between the first and second nights' recordings were found in latency to rapid eye movement and stage 4 sleep, sleep efficiency, and movement time with or without awakening. No differences were noted in times spent in different sleep stages, nor between the first 3 h and the second 3 h of sleep across both nights of polysomnography. This confirms previous findings that questioned the efficacy of the first night effect. This study also emphasizes the need to compare sleep disorder patients with matched normal controls.


Development, Reproduction, Survival, and Demographic Patterns of Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) on Different Commercial Tomato Cultivars.
The increase in the production of tomato, Solanum lycopersicon Mill. (Solanaceae), has favored the proliferation of pests, especially Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae). In this study, the development, reproduction, survival, and demographic parameters of T. absoluta reared on six commercial tomato cultivars (Cherry, Cordilheira, Giuliana, Nemoneta, Paron, and Santa Clara) were evaluated. Tuta absoluta completed its development in all tomato cultivars. Development from newly hatched caterpillar to newly emerged adult varied between 24.8 and 28.2 days. Female fecundity ranged from 126.3 to 166.9 eggs, with fertility from 54.2 to 84.1%. Mortality during egg-adult development varied between 21.4 and 46.4% for insects reared on cultivars Cherry and Giuliana, respectively. The cultivars Cordilheira, Giuliana, and Santa Clara are promising options to tomato producers in order to decrease the attack and proliferation of T. absoluta. However, the development and population growth of T. absoluta is faster on the tomato cultivar Cherry.


Inflammatory cytokines in the tears of patients with ocular rosacea.
The purpose of the study is to compare tear fluid concentrations of interleukin-1alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), and epidermal growth factor (EGF) in ocular rosacea with those in control subjects and to examine the relation between tear functions, such as production and clearance rate, and the concentrations of cytokines in tear fluid. Fourteen patients with severe meibomian gland disease, facial rosacea, and symptoms of ocular irritation were examined for ocular surface disease, tear production, and tear clearance rate (TCR). Twelve control subjects, frequency-matched for age, and 15 ideal normal subjects with no ocular symptoms and normal tear function were assessed using the same parameters. Minimally stimulated tear samples (20 microl) were drawn from each subject and analyzed using a sandwich enzyme-linked immunosorbent assay to detect IL-1alpha, TNF-alpha, and EGF. Tear IL-1alpha concentration was significantly higher in patients with rosacea than in age-matched (P = 0.003) and ideal control subjects (P < 0.001). Tumor necrosis factor-alpha was not detected in patients or control subjects, indicating levels of less than 10 pg/ml. Epidermal growth factor was not significantly higher in patients with rosacea than in age-matched control subjects. Tear turnover LN(TCR) was lower in patients with rosacea than in both age-matched (P = 0.048) and ideal control subjects (P = 0.002). Schirmer I scores were statistically lower in patients with rosacea than in ideal control subjects (P = 0.013), but not age-matched control subjects. Interleukin-1alpha was correlated inversely with LN(TCR) (r= -0.58, P < 0.0001) and Schirmer I (r = -0.39, P = 0.012). Concentrations of IL-1alpha are present in normal tears but are elevated in ocular rosacea, whereas TNF-alpha is not present in either case. The reduced tear turnover, LN(TCR), its inverse correlation with IL-1alpha, and the absence of TNF-alpha in the tears of these patients suggest that the increased concentration of IL-1alpha observed may be largely because of clearance failure of cytokine normally produced at the ocular surface.


Injectable treatments for adipose tissue: terminology, mechanism, and tissue interaction.
Just as injectable fillers have addressed the need for non-surgical methods to restore desired volume, a number of injectable therapies purpor to play a comparable role to reduce undesired volume. To review published literature on the history, mechanism of action, and tissue interaction of injectable methods that aim to reduce localized collections of fat. Mesotherapy is an injection technique that has medical and cosmetic applications and is often confused with injectable fat loss therapies; injection lipolysis describes non-ablative fat reduction with agents (such as beta-agonists) that activate adipocyte lipolytic pathways; and adipolytic therapy using biologic detergents (such as deoxycholate) leads to permanent adipocyte ablation. None of these therapies have been cleared for use in fat reduction by any regulatory authority worldwide. The mechanism of action and tissue effects of injectable fat reducing compounds are diverse but are becoming increasingly understood.


[Evaluation of highly active antiretroviral therapy (HAART) in a cohort of patients with HIV infection in Mexico].
The use of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency virus (HIV) infection induces suppression of viral replication, which has been associated with a significant decrease in disease progression. The use of HAART in open populations may have a different efficacy rate than that reported in controlled clinical trials. To describe the frequency of use of HAART and the rate of successful responses, and to identify the factors associated with therapeutic failure. A cohort study was conducted in an open Mexican community attending the AIDS clinic of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ). We included 155 HIV-infected patients admitted to the clinic between January 1997 and January 2000, who started HAART and had a minimum follow-up of 6 months and at least one viral load determination after starting treatment. Clinical characteristics, HIV viral load, and CD4+ T lymphocyte counts were analyzed. Sixty four percent of our study population achieved undetectable viral load after initiation of treatment, and 50% maintained this response during a mean follow-up period of 13.8 months. In the multivariate analysis, factors associated with therapeutic failure were: previous use of antiviral therapy, weight loss greater than 10% during treatment, and receiving HAART outside of a clinical trial. The use of HAART in this setting had a very low success rate, similar to that reported in other studies. The use of suboptimal therapeutic regimens should be discouraged. Identification of the factors underlying the high success rate seen in controlled clinical trials as compared to the use of HAART in the community may help improve the overall results of this therapy.


Peripheral and axial measurements of trabecular bone density in patients suspected of idiopathic vertebral osteoporosis.
In 18 patients with idiopathic crush fracture syndrome, iliac trabecular bone volume measured in 8 mm trephine biopsies correlated well with trabecular bone density as estimated in low thoracic or high lumbar vertebrae by computed tomography (CT). The CT of trabecular bone in the radius correlated poorly with the other two measurements, but it discriminated fairly well between patients and age-matched controls. These results suggest that abnormally low trabecular bone density values in the radius may be useful in predicting some patients at risk for crush fractures, but ranking patients in order of severity of axial bone loss after they have acquired a fracture requires measurements on the spine or iliac crest.


Perspective and Potential of A2A and A3 Adenosine Receptors as Therapeutic Targets for the Treatment of Rheumatoid Arthritis.
Adenosine is a purine nucleoside which is an effective controller of inflammation. The inflammatory effect of adenosine is expressed via its four receptor subtypes viz. A1, A2A, A2B and A3. The various inflammatory conditions including rheumatoid arthritis (RA) are initiated by adenosine receptors of which A2A and A3 play a vital role. RA primarily is an auto-immune disorder which is manifested as chronic inflammation in the synovial lining of joints. In order to develop an effective treatment, the role of cytokines, IL-1, TNF-α and IL-6 is crucial. Besides, the knowledge of PI3K-PKB/Akt and NF-kB signaling pathway is also important to understand the antiinflammatory targets. Methotrexate along with various other molecules like, NSAIDs and DMARDs are presently used as treatment lines for controlling RA. The enhanced knowledge of the preclinical stages and pathogenesis along with recent potent therapeutics raises the hopes that RA can be prevented in the near future.


Calculating the basic reproductive rate Ro when there are 2 or more pathogens.
Some reasons why observed prevalences of the 3 major trypanosomes in cattle and livestock animals might not be independent are discussed. Apart from genuine interactions between the infections, averaging over heterogeneous populations produces an apparent correlation between pathogens. More subtly, chemotherapy and mortality both induce a positive correlation between pathogens. The calculation of the basic reproductive rate Ro for one pathogen in the endemic presence of another is explained, and illustrated by a simple calculation. Although multi-pathogen calculations are difficult, the calculation of Ro is both useful and feasible.


Endobronchial brachytherapy-A novel approach for the management of airway amyloidosis.
Airway amyloidosis is an uncommon condition and may have variable clinical course. There is no proven systemic therapy, and the management mainly relies on local invasive treatments. Several reports have found external beam radiotherapy to produce durable responses. The optimal dose and fractionation has not been determined. Endobronchial brachytherapy (EBB) has never been reported to affect this disease. The study includes a retrospective chart review of all patients with airway amyloidosis treated with EBB at the Davidoff Cancer Center. Data include symptoms, radiotherapy method and dose, treatment outcomes, and toxicities. Three patients were included. Patients were either symptomatic with extensive airway involvement or have undergone multiple local procedures with rapid recurrence of the amyloid deposits. Two patients had upper and 1 patient had lower airway involvement. Two were treated with external beam radiotherapy and EBB and 1 was treated with EBB only. All patients achieved rapid improvement of symptoms with visible improvement in followup bronchoscopies. EBB doses ranged from 7.5 to 10 Gy. Of the seven lesions treated with EBB, only one lesion recurred 6 months from treatment. No major toxicities were reported. EBB is effective and safe for the management of airway amyloidosis and can offer long-term control. This is the first report of EBB for this indication. EBB should be further explored as means of minimizing the irradiated lung volume.


Ready for Children: Assessing Pediatric Care Coordination and Psychomotor Skills Evaluation in the Prehospital Setting.
Objective: Pediatric patients represent low frequency but potentially high-risk encounters for emergency medical services (EMS) providers. Scant information is available from EMS agencies on the frequency of pediatric skill evaluation and the presence of pediatric emergency care coordination, both which may help EMS systems optimize care for children. The objective of our study was to assess the frequency and type of methods used to assess psychomotor skills competency using pediatric-specific equipment and pediatric care coordination in EMS ground transport agencies. Methods: A web-based assessment was sent to EMS agency directors in 58 states/territories to determine the presence of pediatric care coordination defined as an individual who oversees pediatric issues (Pediatric Care Coordinator or PECC) and the process for evaluating psychomotor skills of EMS providers using of pediatric equipment. Basic demographic information of each agency was collected. Descriptive statistics, odds ratios, and 95% confidence intervals were used for analyses. Results: The response rate was 78% (8,166/10,463 agencies). Almost 80% of agencies respond to fewer than 100 pediatric calls a year; over half of the agencies are located in urban areas and provide Advanced Life Support care. Twenty-three percent (23%) of EMS agency administrators report having a PECC and 28% have plans or interest in adding one. Of those agencies with a PECC, 26% report sharing the position among several agencies. Almost half (47%) of EMS agencies evaluate pediatric psychomotor skills at least twice a year. Agencies with a PECC, those with a medium to medium high pediatric call volume and agencies located in urban areas are more likely to evaluate psychomotor skills at least twice a year. Conclusions: Although few EMS agencies currently have a PECC, there is interest among EMS agency administrators to integrate one into their system. Pediatric-specific psychomotor skills testing is more common in EMS agencies that respond to a higher pediatric call volume and have a PECC. For EMS agencies that infrequently treat children, the presence of a PECC may enhance the frequency of pediatric psychomotor skills evaluation. The presence of a PECC can potentially increase provider confidence and safety for all pediatric prehospital patients regardless of volume and location.


The Effect of Aging on Memory for Recent and Remote Egocentric and Allocentric Information.
The present study explores recent and well-consolidated spatial memory within the egocentric and allocentric frames of reference in young and elderly people. The research included young and old participants, within the range of normality. All the participants were tested on four spatial tasks requiring allocentric and egocentric judgments, based on recent as well as remote spatial information, using a Multivariate Regression Analysis. An age effect on both egocentric and allocentric tasks was present in recently learned spatial information. The age effect was not present in tasks regarding well-consolidated spatial information. Finally, sex influenced the performance in allocentric tasks regarding both recent and well-consolidated memory. These data were discussed according to the Multiple Trace Theory, supporting the idea that the magnitude of difference between egocentric and allocentric judgments in aging is somewhat attributable to the characteristic of spatial tasks. In general, a lower difference between the performance of young and elderly participants is shown in tasks based on well-consolidated information when compared with tasks based on episodic information. Well-consolidated information seemed to be better preserved in memory and less prone to the impairment.


The role of appendectomy as part of the treatment of a mucinous borderline ovarian tumor.
Guidelines in surgical treatment of mucinous ovarian neoplasms recommend the use of appendectomy as a measure to rule out a primary appendiceal origin of the ovarian tumor and proper staging. In extension this guideline is also applied for mucinous borderline ovarian tumors (mBOTs). As borderline ovarian tumors (BOTs) are often diagnosed postoperatively, most patients must undergo a second surgery to add appendectomy and staging to their surgical treatment. To assess the role of appendectomy as part of the surgical treatment of mucinous BOTs. A retrospective single institute based study was carried out. The authors evaluated the clinical charts of patients undergoing surgical treatment by a gynecologic oncologist in their institution for a mucinous BOT between January 1990 and January 2014. Twenty-seven patients were included. Appendectomy was performed in 30% of patients during primary or secondary surgical treatment. No appendiceal carcinoma was identified in any of the cases. Five patients already had a previous appendectomy. In eight patients the appendix was described as normal during surgery and left in place. For six patients the authors did not retrieve any information on previous appendectomy neither on the intraoperative state of the appendix. In the present overall study population, 78% showed no appendiceal involvement. For the remaining patients this information was missing. Secondary appendectomy to rule out a primary appendiceal origin of the mucinous BOT should not be performed when the appendix is described as grossly normal during primary laparoscopic surgery.


A Monte Carlo simulation for modelling outcomes of AIDS treatment regimens.
Healthcare providers are often faced with the need to make treatment decisions about antiretroviral therapy regimens for patients with HIV infection without definitive information as to the optimal sequencing of drug regimens. In this paper we describe our model developed to simulate the impact of differing drug sequencing strategies used in the treatment of patients with HIV/AIDS. In addition, we present the methods used to estimate the efficacy and duration of antiretroviral therapies to populate the model at baseline. We conducted a hypothetical application of the model using three alternative series of therapies: a series containing no drug therapy, a series starting with a protease inhibitor-containing regimen, and a series starting with a non-nucleoside reverse transcriptase inhibitor-containing regimen. The model described in this article can be used to compare and contrast the relative impact of different treatment guidelines in the absence of necessary clinical data and may serve as a means of evaluation until clinical trials or observational databases provide guidance as to the optimal treatment regimen(s). The model is flexible and permits adaptation to the changing treatment environment in HIV infection.


Release of cardiac troponin I after temporally graded acute coronary ischaemia with electrocardiographic ST depression.
Elevation of cardiac biochemical markers and ST segment depression in the electrocardiogram have important roles in the risk stratification of unstable coronary syndromes. We assessed graded duration of acute coronary ischaemia with ST depression versus release of cardiac troponin I (cTnI) and conventional cardiac markers in 15 ischaemic pigs and 11 controls. Coronary ischaemia was induced via percutaneous technique by semiinflating an angioplasty balloon in the left circumflex artery. Blood velocity monitored by Doppler was reduced until ST depression > or =0.1 mV was obtained. Among 26 pigs, six controls had jugular vein sheath introduced only, five controls jugular vein and bilateral femoral sheaths, and 15 pigs were divided into three equal groups (n=5) in which ischaemia was maintained for 10, 20 and 30 min, respectively. Mean blood flow velocity (cm/s) at baseline was 16.3+/-6.5 and was reduced to 4.1+/-3.2 (25% of normal, range 20-29%) during ischaemia. cTnI (microg/l) did not increase in controls but increased from 0.05 to 0.52 (P<0.05) and 0.76 (P<0.05) with 10 and 20 min of ischaemia, and to 30.77 (P<0.05) with 30 min of ischaemia. A rise of myoglobin and conventional cardiac enzymes did not distinguish controls with arterial cut-down from the ischaemia groups. Release of cTnI depends on the duration of ST depression ischaemia. The critical time for a major release seems to be between 20 and 30 min. Thus, very early intervention in patients with prolonged ST depression ischemia should be focused on in future clinical trials.


Pertussis in neonates.
Despite the increasing prevalence of pertussis in young adults and infants, reports of maternal-neonatal pertussis are rare. Our study involves three neonates who apparently acquired pertussis from their adolescent mothers. The diagnosis of pertussis was initially missed in all of the patients. The mothers had mild respiratory disease. All three newborns presented with life-threatening coughing and choking spells without a characteristic inspiratory whoop. Two neonates had apnea, bradycardia, cyanosis, and unresponsiveness, but were without the initial lymphocytosis that is distinctive of pertussis. These two neonates had a clinical course that was consistent with the historic "100-day-cough." They required prolonged ventilatory support and hospitalization at a high cost. The other neonate had a terminal pulmonary hemorrhage. Strategies for the early diagnosis, treatment, and prevention of this potentially lethal disease in neonates are discussed.


Dual-task performance in older adults during discrete gait perturbation.
The dual-task (motor and cognitive) performance of eight older adults (72.0 ± 6.4 years; 5 female; 3 male) was evaluated. Vocal choice reaction times (cognitive task) were measured at standstill as well as during unperturbed and perturbed gait (motor task). The perturbation was administered using customized shoes instrumented to lower a small (18.4 mm high) aluminum flap suddenly under the medial or lateral forefoot during a single swing phase of 12 of 30 gait trials. The ankle inverted or everted an average of 10 or 9 degrees, respectively, depending on the flap deployed. Medial and lateral perturbations were randomized between the left and right feet. The results show that vocal choice reaction time was significantly prolonged by gait, both perturbed (614.7 ± 80.2 ms) and unperturbed (529.9 ± 119.3 ms), compared to standstill (332.8 ± 76.5 ms; p = 0.0015). Further, the prolongation associated with gait perturbation was significant, compared to that with unperturbed gait (p = 0.016). The kinematics of the first post-perturbation (recovery) step, with or without concomitant vocal choice reaction task performance, was not significantly different from those of the average step during unperturbed gait. We conclude that in healthy older adults, the requirement to respond to a gait challenge resulted in deterioration in the performance of a concurrent cognitive task as indicated by significant prolongation of response time in the vocal choice reaction task. In contrast, performance of the motor task was not adversely affected.


SYNTHESIS AND IN VITRO ANTIMICROBIAL EVALUATION OF PIPERAZINE SUBSTITUTED QUINAZOLINE-BASED THIOUREA/THIAZOLIDINONE/CHALCONE HYBRIDS.
In frames of the search for new biological entities to fight against recent drug-resistant microbial strains, we report a library of quinazoline-based thiourea/4-thiazolidinone/chalcone hybrids. The newly synthesized compounds were studied for efficacy against several bacteria (Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Klebsiella pneumoniae) and fungi (Candida albicans and Aspergillus clavatus) using the broth dilution technique. From the biological evaluation, (E)-3-(3,4-dimethoxyphenyl)-1-(4-((4-(4-ethylpiperazin-1-yl)quinazolin-2-yl)amino)phenyl)prop-2-en-1-one was found to be the most active analogue (microbial inhibition concentration 3.12 μg/mL) to inhibit the bacterial growth. The rest of the compounds showed equipotent efficacy (3.12-12.5 μg/mL) as compared to the standard. Final compounds were characterized by FT-IR, 1H NMR, 13C NMR, mass spectroscopy, and elemental analysis.


The potential of neurotrophic tyrosine kinase (NTRK) inhibitors for treating lung cancer.
Molecular alterations in neurotrophic tyrosine kinase (NTRK) genes have been identified in several solid tumors including lung cancer. Pre-clinical and clinical evidence suggested their potential role as oncogenic drivers and predictive biomarkers for targeted inhibition, leading to the clinical development of a new class of compounds blocking the NTRK molecular pathway, which are currently undner early clinical investigation. This review describes the biology of the NTRK pathway and its molecular alterations in lung cancer. It focuses on the pre-clinical and clinical development of emerging NTRK inhibitors, which have shown very promising activity in early phase I studies. Among the several NTRK-inhibitors, entrectinib and LOXO-101 are those in more advanced stage of clinical development. Both agents have shown encouraging activity along with a tolerable safety profile in patients with different solid tumors harboring NTRK-fusions, emerging as new promising therapeutic options for molecularly selected patients with advanced Trk-driven lung cancers. Results from ongoing phase II basket trials are eagerly awaited.


[A medical image authentication method based on restorable watermarking].
In this paper, a restorable watermarking algorithm is proposed for medical image content authentication. Important DWT coefficients are chosen to be coded with the SPIHT algorithm for generating watermarking. The improved security watermark scrambled by Arnold transformation was then embedded into the lower bits of the image data. Finally, the chain structure was used to detect the watermarking and identify the altered positions. The altered data in an image was restored by SPIHT decoding. The experimental results demonstrated that the watermarked image not only possessed good perceptual transparence but also allowed location and restoration of the tampered content.


Healthy eating: what does it mean to adolescents?
The objective of this study was to investigate the meanings of "healthy" and "unhealthy" eating and the importance of healthy eating among adolescents. Twenty-five structured focus groups were conducted. These focus groups consisted of 203 adolescent girls and boys enrolled in three senior high schools and one junior high school. The variables measured were adolescents' self-report of perceptions of healthy and unhealthy eating and their descriptions of the importance of healthy eating to adolescents. Data analysis was done by general content coding and specific content coding. Adolescents have a significant amount of knowledge regarding healthy foods and believe that healthy eating involves moderation, balance, and variety. Despite this knowledge, they find it difficult to follow healthy eating recommendations and frequently consume foods that they perceive as unhealthy. Barriers to healthy eating include a lack of time, limited availability of healthy foods in schools, and a general lack of concern regarding following healthy eating recommendations. These findings suggest that healthy eating messages based on the Dietary Guidelines for Americans are reaching adolescents, but interventions are needed that assist adolescents with the translation of this knowledge into healthy behaviors. Interventions should help make healthy eating easy for youth to apply and explain the consequences of unhealthy eating in terms that they value, stressing meaningful short-term benefits.


Effect of counterregulatory hormones on kinetic response to ingested glucose in dogs.
The disposal of ingested glucose was quantitated in dogs during individual and combined infusion of glucagon, epinephrine, and cortisol. Initial splanchnic extraction of ingested glucose, endogenous glucose production, and glucose uptake were quantitated using a double-tracer technique. Glucagon or cortisol individually had no effect on the kinetic response to glucose ingestion, whereas epinephrine increased glucose levels by 50-100 mg/dl. Epinephrine caused a reduced suppression of glucose production and a marked inhibition of the initial rise in glucose uptake. Initial splanchnic glucose extraction, plasma insulin, and glucagon were not significantly altered. The addition of glucagon and cortisol to epinephrine did not accentuate hyperglycemia, except after 150 min when glucose production increased. We conclude that a) epinephrine produces glucose intolerance when infused individually, b) this effect is primarily dependent on inhibition of glucose uptake and, to a lesser extent, on a reduction in suppression of endogenous glucose output, and c) addition of glucagon and cortisol has only a minor effect on epinephrine-induced changes in glucose disposal. Our data suggest an important role of epinephrine in stress-induced glucose intolerance.


Quantitation of the effect of L-carnitine on the levels of acid-soluble short-chain acyl-CoA and CoASH in rat heart and liver mitochondria.
The steady state levels of mitochondrial acyl-CoAs produced during the oxidation of pyruvate, alpha-ketoisovalerate, alpha-ketoisocaproate, and octanoate during state 3 and state 4 respiration by rat heart and liver mitochondria were determined. Addition of carnitine lowered the amounts of individual short-chain acyl-CoAs and increased CoASH in a manner that was both tissue- and substrate-dependent. The largest effects were on acetyl-CoA derived from pyruvate in heart mitochondria using either state 3 or state 4 oxidative conditions. Carnitine greatly reduced the amounts of propionyl-CoA derived from alpha-ketoisovalerate, while smaller effects were obtained on the branched-chain acyl-CoA levels, consistent with the latter acyl moieties being poorer substrates for carnitine acetyltransferase and also poorer substrates for the carnitine/acylcarnitine translocase. The levels of acetyl-CoA in heart and liver mitochondria oxidizing octanoate during state 3 respiration were lower than those obtained with pyruvate. The rate of acetylcarnitine efflux from heart mitochondria during state 3 (with pyruvate or octanoate as substrate, in the presence or absence of malate with 0.2 mM carnitine) shows a linear response to the acetyl-CoA/CoASH ratio generated in the absence of carnitine. This relationship is different for liver mitochondria. These data demonstrate that carnitine can modulate the aliphatic short-chain acyl-CoA/CoA ratio in heart and liver mitochondria and indicate that the degree of modulation varies with the aliphatic acyl moiety.


[Subcutaneous fat tissue drainage in obese pregnant women after caesarean section].
The authors have analyzed the outcome of cesarean section celiotomy in obese pregnant women. The occurrence of postoperative wound infections, eventually dehiscence, in 2015 pregnant women who underwent caesarean section in a 3-year interval at the Craiova 1st Clinic of Obstetrics was studied. The analysis revealed the relation between postoperative wound infection and its topography, the type of fat tissue drainage (if done), and skin suture. The authors present a very effective method of subcutaneous drainage in obese pregnant women after cesarean section.


Safety of intravenous infusion of doripenem.
Carbapenems remain a mainstay for the empirical treatment of serious nosocomial infection. Although the tolerance and safety profile of the carbapenems as a class is favorable, the primary safety concern is the potential for treatment-emergent seizures. In preclinical testing, doripenem, a new carbapenem antibiotic, showed negligible neurotoxic effects. The safety and tolerability of intravenous doripenem was evaluated in 1 phase 2 and in 6 phase 3 clinical trials conducted with patients with nosocomial pneumonia, including ventilator-associated pneumonia; complicated intra-abdominal infection; and complicated urinary tract infection. Safety data were available from 1817 patients who received doripenem and 1325 patients who received 1 of 4 active comparator drugs as part of this development program. Overall, intravenous doripenem was found to be safe and well tolerated, demonstrating a safety profile comparable to that of comparator agents and a limited propensity to induce seizures, including when administered via 1-h or 4-h infusion. j.


[Early diagnosis of acute hematogenic osteomyelitis in children].
As evidenced by the author's findings, the use of the method of ultrasonic echolocation of long tubular bones facilitates the recognition of acute osteomyelitis in the stage of intramedullary abscess and also makes it possible to reduce the number of diagnostic errors and improve the results of treatment.


Cholesterol: free radical peroxidation and transfer into phospholipid membranes.
Cholesterol, when sequestered in saturated liposomes of dimyristoylphosphatidylcholine (DMPC) or dipalmitoylphosphatidylcholine (DPPC), undergoes peroxidation thermally initiated either by a lipid-soluble or a water-soluble azo initiator and in both cases the reaction is inhibited effectively by the water-soluble antioxidant, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylate (Trolox). Quantitative kinetic methods of autoxidation show that the oxidizability, kp/(2kt)1/2 (where kp and 2kt are the rate constants of radical chain propagation and termination, respectively) of cholesterol in DMPC or DPPC multilamellar liposomes, where kp/(2kt)1/2 is 3.0.10(-3) to 4.3.10(-3) M-1/2 s-1/2 at 37-45 degrees C, is similar to that measured in homogeneous solution in chlorobenzene, where kp/(2kt)1/2 is 3.32.10(-3). However, its oxidizability in smaller unilamellar vesicles of DMPC or DPPC increases by at least 3-times that measured in multilamellar systems. Autoxidation/antioxidant methods show that cholesterol partitions directly from the solid state into DMPC or DPPC liposomes by shaking and this is confirmed by 31P and 2H quadrupole NMR spectra of deuterated cholesterol when membrane bound. Analytical studies indicate that up to 21 mol% cholesterol will partition into the membranes by shaking.


The pathogenesis of skin damage in venous disease: a review.
Venous ulceration remains a major cause of morbidity. Treatment has not improved significantly in recent years, possibly because our understanding of the pathophysiological mechanisms at work is still incomplete. We review the principal abnormalities found in the macro- and microcirculation in this condition and discuss the various theories put forward to explain the mechanism by which skin damage occurs.


[Glucooxidative stress and spontaneous abortion in pregnant women with diabetes mellitus type 1].
The pregnancies in women with Diabetes mellitus are in condition of increased glucooxidative stress, which could be toxic for the developing embryo. END-POINTS: To evaluate the levels of selenium and glutation peroxidase in pregnant women with Diabetes mellitus type 1 in the first trimester of pregnancy and to establish whether there is a correlation between the diabetic glycemic control and occurrence of spontaneous abortions. Prospective study of 75 women for 1 year period. he pregnant women were divided in 3 groups as follows: 1st group--30 pregnant women with Diabetes mellitus type 1 with normal outcome; 2nd group--16 pregnant women with Diabetes mellitus type 1 with spontaneous abortion; 3rd group--29 healthy pregnant controls. The activity of GI-Px in red blood cells was measured in hemolysat of EDTA plasma in Germany. The levels of glucosylated haemoglobin were also evaluated. 1. In all pregnant women the levels of selenium were lower without significant difference between them 1st group--0.12 +/- 0.6 mmol/l, 2ndd group 0.13 +/- 0.1 mmol/l, 3rd group 0.13 +/- 0.7 mmol/l (P > 0.05). 2. There is an increase in the activity of GI-Px, which is statistically significant in the healthy pregnant women 47.8 +/- 13.3 U/g Hb and diabetic pregnant women with normal outcome 48. 6 +/- 8.4 U/g Hb. There is no statistically significant difference in the activity of GI-Px in diabetic pregnant women with spontaneous abortions and the healthy controls (P > 0. 05). 3. Negative correlation between the levels of selenium and the activity of GI-Px was proved in healthy pregnant women (r = - 0.4; P < 0.05). No correlation was found between the level of the selenium and the activity of GI-Px into the two groups of diabetic pregnant women. 4. There is a correlation in the levels of diabetic pregnant women with spontaneous abortions (r = -0.38; P < 0.001). The increased activity of GI-Px in diabetic pregnant women with spontaneous abortions is a result of increased antioxidative defense of the cell. Probably the ineffective antioxidant defense, leading to a spontaneous abortion is due to the low levels of selenium and high level of pre-prandial glycaemia.


[Pathogenetic role of tissue factor in endothelial-injury in graft-versus-host disease].
To study the pathogenetic role of tissue factor (TF) in endothelial-injury in GVHD. Gene and protein expressions of TF in the organs of allogenic hematopoietic stem cell transplantation (allo-HSCT) and autologous HSCT (auto-HSCT) mice were determined by real-time PCR and Western blot. The effect of allogeneic T lymphocytes on the expression of TF and other cytokines and activation of MAPKs in human umbilical vein endothelial cells (HUVECs) was detected by flow cytometry, real-time PCR or Western blot. The influence of TF antibodies (SB203580 and SP600125) on allogeneic T lymphocytes-induced cytokines expression was also tested. (1) TF gene and protein expression in the liver, skin, small intestine and stomach of allo-HSCT mice was significantly elevated about 15.1+/-2.1, 5.5+/-1.4, 9.7+/-2.3, 14.2+/-2.9 folds and 13.5+/-2.7, 6.2+/-0.9, 7.9+/-1.6, 15.3+/-3.2 folds respectively compared with that of auto-HSCT mice. (2) Allogeneic CD4+ CD8+ T lymphocytes significantly enhanced TF, VCAM-1, TNF-alpha, IFN-gamma and IL-6 expression in TNF-alpha prestimulated HUVECs. (3) Allogeneic T lymphocytes enhanced p38MAPK and JNK phosphorylation in HUVECs, but did not affect ERK phosphorylation. p38 MAPK JNK inhibitors SB203580 and SP600125 reduced allogeneic T lymphocytes-induced TF expression in HUVECs. (4) SB203580 and SP600125 down-regulated allogeneic T lymphocytes-induced VCAM-1, TNF-alpha, IFN-gamma, IL-6 expression in HUVECs. TF mediates vascular endothelial-injury and activation in GVHD via phosphorylation of p38MAPK and JNK.


Polyamines in lymphomas: their value in disease staging and monitoring of therapy efficiency.
The urinary polyamines putrescine and spermindine were evaluated in a population of 49 patients with malignant lymphomas (40 with non-Hodgkin's lymphoma and 9 with Hodgkin's disease). Analyses were performed on a regular basis during the course of treatment. Polyamine levels were found to increase significantly with the disease stage. Results show that: (a) polyamines closely reflect disease evolution (clinical deterioration/clinical improvement); (b) comparison of polyamine measurements effected 24 h prior to and 48 h after initiation of a chemotherapy course allows evaluation of the response to treatment.


Effect of dietary zinc on lipid peroxidation, glutathione, protein thiols levels and superoxide dismutase activity in rat tissues.
Dietary zinc deficiency can cause increased lipid peroxidation while zinc supplementation inhibited this process. The aim of this study was to investigate the effect of dietary zinc on malondialdehyde (MDA) product as an index of endogenous lipid peroxidation, glutathione (GSH) and protein thiols (PrSHs) as well as superoxide dismutase (SOD) activity in rat blood, liver and pancreas. Young male rats were fed a zinc deficient (ZD) basal diet containing congruent to 0.5 ppm zinc or were fed ad libitum (AL) a zinc adequate diet (30 ppm zinc) for 3 weeks. The ZD rats were then fed the basal diet supplemented with either 100 ppm zinc or 1000 ppm zinc for another 3 weeks. The zinc concentration of the investigated tissues reflected the dietary zinc content. Plasma, liver and pancreas MDA measurements from ZD rats revealed significant increases (P < 0.05, < 0.001) as compared to AL control values, the highest increase was in pancreas. ZD rats also displayed significant decreases in their blood and liver GSH content (P < 0.001, < 0.05) and SOD activity (P < 0.001) as well as serum PrSHs (P < 0.001) as compared to AL control values. However, these measurements in pancreas were insignificantly changed except GSH content was significantly increased (P < 0.05). Feeding ZD rats a diet containing 100 ppm or 1000 ppm zinc resulted in a significant reduction of the endogenous MDA formation (P < 0.05, < 0.001) in their tissues with the reversal of changes in the other parameters, so that their levels were nearly restored to AL control values especially in response to 1000 ppm zinc.(ABSTRACT TRUNCATED AT 250 WORDS)


R-CHOP versus dose-adjusted R-EPOCH in frontline management of primary mediastinal B-cell lymphoma: a multi-centre analysis.
Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is an uncommon subtype of non-Hodgkin lymphoma (NHL) that presents with a mediastinal mass and has unique clinicopathological features. Historically, patients with PMBCL were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy ± involved field radiation. Since a phase II trial, published in April 2013, demonstrated excellent results using dose-adjusted (DA) R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), this treatment has gained popularity. We performed a retrospective, multicentre analysis of patients aged ≥18 years with PMBCL since January 2011. Patients were stratified by frontline regimen, R-CHOP versus DA-R-EPOCH. 132 patients were identified from 11 contributing centres (56 R-CHOP and 76 DA-R-EPOCH). The primary outcome was overall survival. Secondary outcomes included progression-free survival, complete response (CR) rate, and rates of treatment-related complications. Demographic characteristics were similar in both groups. DA-R-EPOCH use increased after April 2013 (79% vs. 45%, P < 0·001), and there was less radiation use after DA-R-EPOCH (13% vs. 59%, P < 0·001). While CR rates were higher with DA-R-EPOCH (84% vs. 70%, P = 0·046), these patients were more likely to experience treatment-related toxicities. At 2 years, 89% of R-CHOP patients and 91% of DA-R-EPOCH patients were alive. To our knowledge, this represents the largest series comparing outcomes of R-CHOP to DA-R-EPOCH for PMBCL.


Guidelines and realities of asthma management. The Philadelphia story.
Guidelines from the National Heart, Lung, and Blood Institute, Bethesda, Md, have encouraged more frequent use of inhaled steroids in asthma management. To determine (1) whether prescription rates for inhaled steroids have increased compared with prescriptions for bronchodilators and (2) significant associations of demographic factors with bronchodilator-inhaled steroid prescription ratios and with rates of inhaled steroid prescriptions. Cross-sectional analysis of monthly bronchodilator and inhaled steroid prescription rates, numbers and types of asthma care providers, and demographic factors. Philadelphia, Pa. Using univariate and multivariate analyses, bronchodilator and inhaled steroid prescription rates were determined for 45 ZIP codes and studied for associations with race and ethnicity, poverty, educational attainment, marital status, gender, total numbers of asthma drug prescriptions, and numbers and types of asthma care providers. Monthly bronchodilator-inhaled steroid prescription ratios increased from July 1991 to June 1993 (P < .001). Prescription rates for inhaled steroids and inhaled bronchodilators declined, but rates for oral bronchodilators (beta-agonists and theophylline) increased. By stepwise multiple regression, higher bronchodilator-inhaled steroid prescription ratios and lower inhaled steroid prescription rates were each significantly associated with ZIP codes in which greater proportions of residents lacked a high school diploma (P < .001); associations that approached statistical significance were found for higher bronchodilator-inhaled steroid ratios and fewer asthma care providers (P = .05) and for lower inhaled steroid prescription rates and lower proportions of asthma specialists (P = .04). In Philadelphia, a gap exists between optimal asthma drug prescribing and actual prescribing patterns that has widened from July 1991 to June 1993. Underuse of inhaled steroids is most closely associated with lower educational attainment, suggesting that interventions that include addressing the special asthma care needs of a low-literacy population will be required to achieve the goals of the National Asthma Education Program.


A tool to assess the cognitively impaired elderly.
When elderly persons become cognitively impaired, decision-making and case management can be intensely frustrating for health care providers who must make provisions for both short-term and long-term care. Numerous barriers pose challenges to the case managers in addition to those that occur when health care terminology does not fit easily into the legal vocabulary of the judge who makes the ultimate decision naming a guardian or conservator. Ongoing research by the authors has been involved in identifying criteria to determine incompetency by both formal and informal caregivers of cognitively impaired elderly. A scale, currently consisting of 10 criteria, has been developed and continues to be refined by the authors.


Maternal periconceptional alcohol consumption and risk for conotruncal heart defects.
In this study we investigated whether the risk of delivering infants with conotruncal heart defects was increased among mothers who consumed alcohol during the periconceptional period (i.e., 1 month before conception to 3 months after conception). Data were obtained from a population-based case-control study of California births from 1987-1988. Information concerning alcohol consumption was obtained via telephone interviews with mothers of 207 (87% of eligibles) case infants and 481 (76%) nonmalformed control infants. Bivariate results indicated that relative to nonconsumers, women who consumed alcohol less than once a week had a 1.3-fold increased risk of delivering infants with a conotruncal heart defect (95% confidence interval (CI) 1.0, 1.9), and women who consumed alcohol once a week or more had a 1.9-fold increased risk (95% CI 1.0, 3.4). The risks associated with consuming five or more drinks per drinking occasion were 1.6 (95% CI 0.8, 3.2) for less than once a week, and 2.4 for once a week or more (95% CI 0.6, 9.7). The results for the phenotypic subgroups were similar to those for all cases. Adjustment for potential covariates resulted in somewhat weaker, but still elevated, risks. This study found that the risk of conotruncal heart defects in offspring was moderately elevated among women who consumed alcoholic beverages during the periconceptional period, and that risk was higher with increased frequency of drinking or increased number of drinks consumed per occasion. Most of the risk estimates were imprecise, and chance could not be ruled out as an explanation for the observed findings.


[Red blood cell's deformability in obstructive jaundice].
Several factors with well known haemorheological consequences are identified in obstructive jaundice e.g.: hyperlipidemia, endotoxemia, changes in oxidant-antioxidant status. Previous investigations have shown the decrease of red blood cell deformability. They have been assessed by filtration technique in obstructive jaundice without the exclusion of patients with systemic inflammatory response syndrome. The aim of this study is the examination of red blood cell deformability by laser diffractometry in patients with obstructive jaundice. Seven patients with obstructive jaundice (total serum bilirubin 163 +/- 69 mmol/l) without systemic inflammatory response syndrome and 24 healthy adults underwent red blood cell deformability measurement by laser diffractometer Rheodyn SSD. Significant increase of elongation indexes of erythrocytes in all coagulation tensions has been observed. In obstructive jaundice the increase of erythrocyte deformability has been detected.


Initial stability of uncemented hip stems: an in-vitro protocol to measure torsional interface motion.
The difficulty in quantitatively assessing the inherent variables of surgical stem insertion and interfemur differences continues to be a problem in experimental methodologies which assess hip stem stability. An in-vitro torsional stability protocol was developed which limited the mechanical testing variability and provided a reproducible micromotion measurement of an uncemented stem in synthetic composite femurs. Using a controlled mechanical stem insertion resulted in less interfemur variability within each group with the coefficient of variation being reduced from 35% overall to less than 20%. Femurs with shallow stem insertion depths had significantly larger micromotion than femurs having deep stem insertion depths. The sensitivity of the experimental protocol and the synthetic composite femurs to the varied functional behaviour of three different stem designs was demonstrated. The stem with a hollowed anterior-to-posterior proximal section experienced significantly more motion than the two stems with full proximal sections, reinforcing the need for proximal contact to ensure minimal micromotion in torsional loading.


[Validation of a diagnostic scoring system (Ohmann score) in acute appendicitis].
A diagnostic scoring system, recently published by Ohmann et al. in this journal, was validated by analyzing the clinicopathological data of a consecutive series of 2,359 patients, admitted for suspicion of acute appendicitis. The results of the scoring system were compared to the results of clinical evaluation by junior (provisional) and senior surgeons (final clinical diagnosis). To assess the diagnostic ability of the score, the accuracy and positive predictive value were defined as the major diagnostic performance parameters; the rate of theoretical negative laparotomies and that of diagnostic errors served as the major procedural performance parameters. Of 2,359 patients admitted for suspected acute appendicitis, 662 were proven to have acute appendicitis by histology, for a prevalence of 28%. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the provisional clinical diagnosis were 0.50, 0.94, 0.77, 0.83, and 0.82; 0.93, for the score 0.63, 0.93, 0.77, 0.86 and 0.84, and for the final clinical diagnosis 0.90, 0.94, 0.85, 0.96, and 0.93, respectively. Of the main diagnostic performance parameter, the accuracy of the score was significantly better than that of provisional clinical diagnosis (P < 0.05, chi 2 test). The score yielded a rate of negative appendecomies and laparotomies of 14.3 and 12.3%. With respect to the rate of overlooked cases of acute apendicitis, the score demonstrated a superior performance, with only 6 cases missed (0.9%). However, the number of patients with acute appendicitis, including those with perforated disease, who were not identified by the score, was almost four times that of the final clinical diagnosis (245 vs 63). With regard to the main procedural performance parameter, the score resulted in a significantly smaller number of diagnostic errors than the provisional clinical investigator (P < 0.05, chi 2 test). The results of this study indicate that the diagnostic scoring system might be helpful when experienced investigators or additional diagnostic modalities such as ultrasonography are not available. It may therefore be of value in the preclinical evaluation of patients with suspected acute appendicitis and may be instrumental as a quality control tool and in clinical guidelines.


[Design and application of medical knowledge model on SAGE].
As an methodology for promoting the quality and efficiency of health care, clinical decision support systems (CDSSs) have gained much improvement. The knowledge base (KB) plays an important role in DSS. For CDSSs, the construction of KB means modeling the medical knowledge based on a suitable model. This study analyzes the SAGE model, then implements it on knowledge of diagnosis and treatment of Metabolic Syndrome (MS), and improves the SAGE to enhance its expression ability. The model is constructed as the KB in CDSS, and be applied in hospital. The evaluation result of CDSS reveals that the SAGE model should be useful in clinical application. Finally, this study propounds some points yet to be improved in the SAGE.


[Telomerase and telomere: their structure and dynamics in health and disease].
Telomerase is the enzyme responsible for the maintenance of telomere length by adding guanine-rich repetitive sequences. Its activity can be seen in gametes, stem cells and tumor cells. In human somatic cells the proliferative potential is limited, reaching senescence after 50-70 cell divisions, because the DNA polymerase is not able to copy the DNA at the ends of chromosomes. By contrast, in most tumor cells the replicative potential is unlimited due to the maintenance of the telomeric length given by telomerase. Telomeres have additional proteins that regulate the binding of telomerase, likewise telomerase associates, with a protein complex that regulates its activity. This work focuses on the structure and function of the telomere/telomerase complex and how changes in its behavior lead to the development of different diseases, mainly cancer. Development of inhibitors of the telomere/telomerase complex could be a target with promising possibilities.


The potential risk of carotid injury in cochlear implant surgery.
The advent of cochlear implantation has revolutionized the options afforded to the deaf population. With the increase in the prevalence of this procedure have come larger experiences in the associated technical challenges and complications. We present the evaluation and management of a patient with an unusual complication of improper placement of the implant electrode into the carotid canal and its management. We discuss the anatomy of the carotid artery and its proximity to the cochlea to emphasize the potential risk to this large vessel. Damage to the carotid canal and the carotid artery is a potential risk of cochlear implant surgery. When available, we recommend intraoperative electrical testing of the cochlear implant be performed. If there is doubt as to the placement of the electrode, a radiograph should be obtained before the patient is taken out of the operating room to avoid this complication.


Complex interventional procedures for the management of early postoperative left main coronary artery embolism after bioprosthetic aortic valve insertion.
The incidence of calcified debris coronary embolism after aortic valve replacement (AVR) with a bioprosthesis is a rare but potentially life-threatening condition. We sought to describe a case of immediate postoperative left main coronary artery embolism, resulting to severe acute coronary syndrome and cardiogenic shock, after aortic valve surgery due to severe aortic valve stenosis, with the use of bioprosthesis. Complex interventional procedures and possible diagnostic challenges are being described.


Plasma levels of zinc, copper, copper/zinc ratio, and activity of carbonic anhydrase in equine piroplasmosis.
We have determined the plasma concentrations of copper, zinc, copper/zinc ratio, and carbonic anhydrase activity in horses infected with Babesia equi. The study was conducted in 14 horses with the disease and 10 healthy animals that served as controls. The infection was confirmed by the clinical manifestations of the disease and by Giemsa staining of thin blood smears showing the parasites inside red blood cells. The horses with piroplasmosis had lower plasma levels of zinc, elevated copper, and increased activity of carbonic anhydrase. Consequently, the copper/zinc ratio was also higher than in the healthy controls.


Effects of intraoperative irradiation on gastric and urinary bladder incisions in the dog.
Fourteen adult dogs of mixed breeding were given intraoperative irradiation (25 Gy) after surgical incisions were made into the greater curvature of the stomach and the ventral surface of the urinary bladder. Sequential biopsy samples were obtained 10 days to 180 days after surgical operation. All irradiated stomachs developed gastritis and persistent ulceration of the irradiated field. Microscopic changes induced by irradiation of both the bladder and stomach progressed from severe submucosal edema to severe submucosal fibrosis. A parallel progression of fibrinoid degeneration of the small blood vessels was seen in both organs. Severe gastric ulceration persisted up to 180 days after irradiation, although a degree of mucous neck cell and gastric gland regeneration did occur. Pathologic changes were less severe in the bladder than in the stomach. The bladder had greater resiliency and capability for healing and, in contrast to the stomach, showed a capability to reepithelialize the radiation-induced ulcers. Conclusions of this study are as follows: (a) the canine urinary bladder tolerated intraoperative radiation therapy after tissue resection better than did the canine stomach, (b) the combination of surgical operation and irradiation resulted in a more prolonged and complicated healing pattern than did either procedure alone, and (c) the introduction of a surgical procedure upon irradiated tissue within an undetermined time span relative to irradiation resulted in a similar pattern of disturbed healing.


The temporal characteristics of functional activation in Broca's area during overt picture naming.
The opercular and triangular sections of the inferior frontal gyrus, also known as Broca's area, have been shown to be involved in various language tasks. In the current study we investigated both the functional role, as well as the precise temporal involvement of Broca's area during picture naming. We applied online event-related transcranial magnetic stimulation (TMS) to Broca's area at five different time points after picture presentation, aiming to cover the complete language production process. Applying real TMS at 300 msec after picture presentation led to an increase in picture naming latency, whereas sham stimulation and real stimulation at earlier and later time windows did not result in any changes in reaction time (RT). Our methodological approach enabled us to get insight into the temporal characteristics of the involvement of this brain area during picture naming. Making use of this information and directly relating it to psycholinguistic models, we conclude that Broca's area may be involved in the process of syllabification during overt speech production.


Induction of renal and hepatic mixed function oxidases in the hamster and guinea pig.
A marked species difference exists in the induction of renal and hepatic mixed function oxidase (MFO) activity between rats and rabbits. However, little is known about MFO induction in these organs from other laboratory animals. Male Golden Syrian hamsters and male Hartley guinea pigs were administered phenobarbital (PB) or beta-napthoflavone (BNF) at 70 and 40 mg/kg, respectively, as daily i.p. injections for 4 days. Polybrominated biphenyl (PBB) (Firemaster BP-6) was given as a single i.p. injection (50 mg/kg). Hamster hepatic microsomal ethoxyresorufin-O-deethylase (EROD) and benzphetamine-N-demethylase (BPND) were selectively induced by BNF and PB, respectively. PBB administration induced both hamster hepatic EROD and BPND. In contrast, hepatic microsomal MFO activity from the guinea pig was inducible by PB, PBB and BNF. Renal microsomal MFO activity in both species was inducible by BNF and PBB as arylhydrocarbon hydroxylase and EROD were induced approximately 10-fold. On the other hand, hamster BPND was induced by PB whereas guinea pig MFO activity was unaffected. Total renal cytochrome P-450 content was not affected by any of these inducers in either species. These data demonstrate selective patterns of induction in both hamster and guinea pig liver and kidney suggesting the involvement of multiple forms of cytochrome P-450.


Evaluation of acotiamide for the treatment of functional dyspepsia.
The treatment for functional dyspepsia (FD) (indigestion) remains unsatisfactory. Acotiamide is a new prokinetic that has been recently approved and used in Japan for the treatment of FD. This review introduces the pharmacodynamics, pharmacokinetics and efficacy data from current clinical trials from literature sourced using the PubMed search tools. Future principles for developing drugs and designing clinical trials to test them for treating FD are also discussed. Acotiamide can contribute to the treatment of the specific subset of symptoms defined as postprandial FD by reducing the impaired fundic relaxation and accommodation after eating. The agent has the added benefit of a very good safety profile.


Reward value of attractiveness and gaze.
Faces are visual objects in our environment that provide strong social cues, with the eyes assuming particular importance. Here we show that the perceived attractiveness of an unfamiliar face increases brain activity in the ventral striatum of the viewer when meeting the person's eye, and decreases activity when eye gaze is directed away. Depending on the direction of gaze, attractiveness can thus activate dopaminergic regions that are strongly linked to reward prediction, indicating that central reward systems may be engaged during the initiation of social interactions.


Knowledge level and coping strategies according to coagulation levels in older persons with atrial fibrillation.
The present study examined the knowledge level and the coping strategies of older persons with atrial fibrillation, who were on oral anticoagulant therapy. The relationship among knowledge level, problem and affective-oriented coping strategies, and the level of anticoagulant effectiveness were examined. We also compared differences between subjects who were within a therapeutic range for International Normalized Ratio levels with those who were not. The research design was descriptive and correlational. One hundred older persons completed the Jaloweic Coping Scale (a knowledge questionnaire) and socio-demographic, contextual and clinical characteristic questions. The findings suggested that the knowledge levels were low (53%), and problem-oriented coping strategies were most often used (32.62%) compared to affective-oriented coping strategies (18.96%). Other than praying and putting one's trust in God (P = 0.05), it appeared that no other significant coping strategies differentiated the subjects regarding their level of anticoagulant effectiveness. It is recommended that further examination of the reasons for older persons' low knowledge level, in regard to their oral anticoagulant therapy, occurs and that use of problem-oriented coping strategies, to improve self-care measures, be encouraged.


To what extent do high-intensity statins reduce low-density lipoprotein cholesterol in each of the four statin benefit groups identified by the 2013 American College of Cardiology/American Heart Association guidelines? A VOYAGER meta-analysis.
The 2013 American College of Cardiology and American Heart Association (ACC/AHA) guidelines identify four patient groups who benefit from moderate- or high-intensity statin treatment; those with: 1) atherosclerotic cardiovascular disease (ASCVD); 2) low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dl; 3) diabetes; or 4) a 10-year ASCVD risk ≥7.5%. High-intensity statins, anticipated to reduce LDL-C by ≥50%, were identified as rosuvastatin 20-40 mg and atorvastatin 40-80 mg. Individual patient data (32,258) from the VOYAGER database of 37 studies were used to calculate least-squares mean (LSM) percentage change in LDL-C during 8496 patient exposures to rosuvastatin 20-40 mg, and atorvastatin 40-80 mg in the four patient benefit groups. LSM percentage reductions in LDL-C with rosuvastatin 20 and 40 mg were greater than with atorvastatin 40 mg, overall and in each statin benefit group, and with rosuvastatin 40 mg were greater than with atorvastatin 80 mg overall and in three of the four benefit groups (all p < 0.05). For example, in the ASCVD group, 40%, 59%, 57% and 71% of patients treated with atorvastatin 40 mg, atorvastatin 80 mg, rosuvastatin 20 mg and rosuvastatin 40 mg, respectively, had a ≥50% reduction in LDL-C. The choice and dose of statin have an impact both on the percentage LDL-C reduction and achievement of ≥50% reduction in LDL-C, overall and within each of the four statin benefit groups outlined by the 2013 ACC/AHA guidelines. This may be of importance for clinicians in their choice of treatment for individual patients.


Optimization and maintenance of soluble methane monooxygenase activity in Methylosinus trichosporium OB3b.
Soluble methane monooxygenase (sMMO) maximization studies were carried out as part of a larger effort directed towards the development and optimization of an aqueous phase, multistage, membrane bioreactor system for treatment of polluted groundwater. A modified version of the naphthalene oxidation assay was utilized to determine the effects of methane:oxygen ratio, nutrient supply, and supplementary carbon sources on maximizing and maintaining sMMO activity in Methylosinus trichosporium OB3b. Methylosinus trichosporium OB3b attained peak sMMO activity (275-300 nmol of naphthol formed h-1 mg of protein-1 at 25 degrees C) in early stationary growth phase when grown in nitrate mineral salts (NMS) medium. With the onset of methane limitation however, sMMO activity rapidly declined. It was possible to define a simplified nitrate mineral salts (NMS) medium, containing nitrate, phosphate and a source of iron and magnesium, which allowed reasonably high growth rates (mu max 0.08 h-1) and growth yields (0.4-0.5 g cells/g CH4) and near maximal activities of sMMO. In long term batch culture incubations sMMO activity reached a stable plateau at approximately 45-50% of the initial peak level and this was maintained over several weeks. The addition of d-biotin, pyridoxine, and vitamin B12 (cyanocobalamin) increased the activity level of sMMO in actively growing methanotrophs by 25-75%. The addition of these growth factors to the simplified NMS medium was found to increase the plateau sMMO level in long term batch cultures up to 70% of the original peak activity.


Digital stereology in neuropathology.
Two-dimensional quantitative methods have frequently been used to address questions in neuropathological research; however, they face important limitations which design-based stereology may overcome by offering a set of methods to quantify two-dimensional histological sections into three-dimensional structural knowledge. Accordingly, stereology is a science based on statistical sampling principles and geometric measures. The application of stereology to neuropathological studies allows the researcher to efficiently obtain a precise estimate of various structural quantities. This neuropathological review will therefore present the relevant stereological estimators for obtaining reliable quantitative structural data from brains and peripheral nerves when using digital light microscopy. It is discussed how to obtain brain and nerve fibre samples to fulfil the requirements for the estimators. A presentation of design-based stereological probes for obtaining global volume, total number, local volume, total length, total surface area, cross-sectional area and diameter will be followed by discussion of the error variances of the methods. No mathematical equations or calculations are shown in this review.


An electrochemical signal-on apta-cyto-sensor for quantitation of circulating human MDA-MB-231 breast cancer cells by transduction of electro-deposited non-spherical nanoparticles of gold.
A highly simple, sensitive, specific and low-cost electrochemical apta-cyto-sensor for determination of circulating human MDA-MB-231 breast cancer cells was fabricated. Non-spherical nanoparticles of gold were electro-deposited in the presence of ethosuximide as a shape directing and size controlling agent. The nanoparticles had dimensions ranging 50-150 nm, and covered the underlying surface with a roughness factor of 8.03. The Non-spherical nanoparticles were then employed as the apta-cyto-sensor transducer. A 83-mer DNA aptamer that is specific to capturing the cell surface proteins was immobilized on the transducer surface, and binding with the cells was followed using the ferro/ferricyanide redox marker. The aptamer was immobilized within ∼200 min on the transducer surface. The cells were quantified with an equation of regression of ΔIp(μA) = (1.028 ± 0.027) log (C (cell mL-1)) + (0.2199 ± 0.0944), a sensitivity of 1.028 μA (log (concentration / cell mL-1))-1 and a quantitation limit of 2 cell mL-1, in a concentration range of 5 to 2 × 106 cell mL-1. The apta-cyto-sensor selectivity was also evaluated toward AsPC-1, Calu-6, HeLa, MCF-7 and melanoma B16/F10 cell lines. The apta-cyto-sensor had a fabrication reproducibility of 4.2%, regeneration capability of 5.1%, a stability of 35 days, and a potential application for the detection of MDA-MB-231 cells in the spiked blood serum samples with a sensitivity of 0.8975 μA (log (concentration / cell mL-1))-1 and a quantitation limit of 5 cell mL-1, in a concentration range of 10 to 1 × 103 cell mL-1. The apta-cyto-sensor would be applicable for breast cancer diagnosis at early stage.


Prognostic role of chemotherapy-induced nausea and vomiting in recurrent ovarian cancer patients: results of an individual participant data meta-analysis in 1213.
The aim of this study was to analyze the potential impact of chemotherapy-induced nausea and vomiting (CINV) on dose reductions, discontinuation of chemotherapy, and survival. This study was designed as individual participant data meta-analysis with the original study data of three phase II/III trials that were conducted by the North-Eastern German Society of Gynecological Oncology (NOGGO) including 1213 patients with recurrent ovarian cancer. Logistic and Cox regression analyses were used to estimate odds and hazard ratios after adjusting for age, ECOG, amount of delivered cycles, amount of recurrences, and amount of comedications and study. The majority of patients developed nausea (58.1%) and almost one third experienced vomiting (31.0%). CINV was not associated with FIGO stage, grading, histology, and number of recurrences. The necessity of dose reduction and discontinuation of chemotherapy did not correlate to nausea and vomiting (p = 0.88, p = 0.39 and p = 0.25, p = 0.54 respectively). Progression-free survival was shorter in patients with grade III/IV nausea and vomiting (p = 0.02; hazard ratio (HR) for grade III/IV nausea 1.58, 95% CI 1.14-2.20, and p = 0.02; HR for grade III/IV vomiting 1.67, 95% CI 1.15-2.42 respectively). CINV grade III/IV was also associated with poorer overall survival (p < 0.001; HR for grade III/IV nausea 2.35, 95% CI 1.64-3.37, and p < 0.001; HR for grade III/IV vomiting 1.67, 95% CI 1.15-2.42 respectively). CINV is significantly associated with poorer prognosis in recurrent ovarian cancer patients while there was no correlation found with the necessity of dose reduction and prior discontinuation of treatment. This study underlines the importance of prevention and treatment of CINV as part of early best supportive care.


Association of polymorphism in FcGR3A gene and progression of low-grade precursor lesions of cervical carcinoma.
Polymorphisms in receptors of the constant part of antibodies (FcR) have been associated with susceptibility to disease and viral infections but have not been studied in cervical carcinogenesis. The distribution of the polymorphism V158F (rs396991) in FcGR3A in cervical smears was detected in a group of 84 women with stable or regressed low-grade squamous intraepithelial lesions (group I) and a group of 54 women with high-grade squamous intraepithelial lesions (HSIL) (group II). Human papillomavirus (HPV) genotyping was also performed. In 27.4% of women from group I, FF genotype was found, whereas this genotype was observed in 51.9% of patients in group II (p = 0.003; odds ratio = 2.856 (95% confidence interval = 1.4-5.8)). When only women infected with high-risk HPV were analyzed these differences were found to be even higher (p = 0.0013; odds ratio = 3.8 (95% confidence interval = 1.7-8.8)). FF genotype in FcGR3A gene seems to be associated with increased risk of low-grade squamous intraepithelial lesions to HSIL progression suggesting that its presence may play a role in HPV tolerance, persistent infection, and HSIL development.


[Treatment of squamous cell carcinoma of the pancreas with gemcitabine].
Primary squamous cell carcinoma of the pancreas is a rare tumor. We report a case of a 49 years old patient with a metastatic squamous cell carcinoma of the pancreas. Histological diagnosis was established by echoguided biopsy of the liver. Due to that, we cannot be sure that this tumor was not adenosquamous with a metastatic component from only the squamous part of the lesion. Two types of chemotherapy have been performed. The first one was radiochemotherapy with an association of 5FU and cisplatinum. Gemcitabin was the second one. An objective response was obtained with gemcitabin and the patient's health improved. To our knowledge, this has never had been reported beforehand. However the prognosis of this cancer remains poor. Overall survival was 8 months.


Preoperative pulmonary function as a predictor of respiratory complications and mortality in patients undergoing lung cancer resection.
We evaluated preoperative pulmonary function as a predictor of respiratory complications and mortality in patients undergoing lung cancer resection to confirm the guideline of the British Thoracic Society: lung cancer surgery in patients with predictive postoperative FEV(1.0) (%FEV(1.0)ppo) > 40% and predictive postoperative diffusion capacity for carbon monoxide (%DL(co)ppo) > 40% can be carried out with average risk. We retrospectively studied 356 consecutive patients who underwent pulmonary resection at our Department from January 1992 to December 2001. Preoperative pulmonary function tests included vital capacity (VC), %VC, forced expiratory volume in one second (FEV(1.0)), FEV(1.0)%, diffusion capacity for carbon monoxide (DL(co)), predictive postoperative FEV(1.0) (FEV(1.0)ppo), postoperative respiratory function expressed as a percentage of the predicted normal value (%FEV(1.0) ppo, %DL(co)ppo). Postoperative complications were divided into 2 groups: respiratory complications (pneumonia, atelectasis, etc) and other complications (bronchopleural fistula, prolonged air leak, arrhythmia, etc). Postoperative deaths occurred in 14 (3.9%) patients. Postoperative respiratory complications developed in 27 (7.6%) patients. Pneumonectomy (p < 0.001), preoperative chemotherapy (p < 0.01) and advanced stage (p < 0.05) were identified as risk factors of postoperative deaths. Patients undergoing lobectomy with FEV(1.0) > or = 1,500 ml did not die of respiratory complications. Patients undergoing pneumonectomy with FEV(1.0)ppo > or = 800ml/m2 did not die of respiratory complications. Patients undergoing pneumonectomy with %FEV(1.0)ppo < 40% and %DL(co)ppo < 40% did not survive. Five of the 7 patients who died of respiratory complications were treated with preoperative chemotherapy. The values of their %DL(co)ppo were all less than 40%. By multivariate analysis, %FEV(1.0)ppo was significant independent factor associated postoperative death. We conclude that the guideline is useful for the selection for surgery of lung cancer patients. If preoperative chemotherapy is performed, the measurement of %DL(co) is recommended before surgery.


Customer advisory groups: another way to listen to the marketplace.
Customer advisory groups (CAGs) are formal groups of customers (referring physicians, patients, health insurance brokers, etc.) who meet regularly to share their ideas and to provide feedback to proposed or existing marketing strategies, programs, and activities. While CAGs are very prevalent in other industries they appear to be relatively underutilized in health care. This article provides an overview of how CAGs work, their advantages and disadvantages, tips on how to make them work better, and insights from interviews with 39 healthcare chief marketing officers on their use of CAGs.


Fermi-edge singularity and the functional renormalization group.
We study the Fermi-edge singularity, describing the response of a degenerate electron system to optical excitation, in the framework of the functional renormalization group (fRG). Results for the (interband) particle-hole susceptibility from various implementations of fRG (one- and two-particle-irreducible, multi-channel Hubbard-Stratonovich, flowing susceptibility) are compared to the summation of all leading logarithmic (log) diagrams, achieved by a (first-order) solution of the parquet equations. For the (zero-dimensional) special case of the x-ray-edge singularity, we show that the leading log formula can be analytically reproduced in a consistent way from a truncated, one-loop fRG flow. However, reviewing the underlying diagrammatic structure, we show that this derivation relies on fortuitous partial cancellations special to the form of and accuracy applied to the x-ray-edge singularity and does not generalize.


MicroRNA pharmacogenomics: post-transcriptional regulation of drug response.
The field of pharmacogenomics aims to predict which drugs will be most effective and safe for a particular individual based on their genome sequence or expression profile, thereby allowing personalized treatment. The bulk of pharmacogenomic research has focused on the role of single nucleotide polymorphisms, copy number variations or differences in gene expression levels of drug metabolizing or transporting genes and drug targets. In this review paper, we focus instead on microRNAs (miRNAs): small noncoding RNAs, prevalent in metazoans, that negatively regulate gene expression in many cellular processes. We discuss how miRNAs, by regulating the expression of pharmacogenomic-related genes, can play a pivotal role in drug efficacy and toxicity and have potential clinical implications for personalized medicine.


Age-Related Differences in Gait Kinematics, Kinetics, and Muscle Function: A Principal Component Analysis.
Age-related increased hip extensor recruitment during gait is a proposed compensation strategy for reduced ankle power generation and may indicate a distal-to-proximal shift in muscle function with age. Extending beyond joint level analyses, identifying age-related changes at the muscle level could capture more closely the underlying mechanisms responsible for movement. The purpose of this study was to characterize and compare muscle forces and induced accelerations during gait in healthy older adults with those of young adults. Simulations of one gait cycle for ten older (73.9 ± 5.3 years) and six young (21.0 ± 2.1 years) adults walking at their self-selected speed were analyzed. Muscle force and induced acceleration waveforms, along with kinematic, kinetic, and muscle activation waveforms, were compared between age-groups using principal component analysis. Simulations of healthy older adults had greater gluteus maximus force and vertical support contribution, but smaller iliacus force, psoas force, and psoas vertical support contribution. There were no age-group differences in distal muscle force, contribution, or ankle torque magnitudes. Later peak dorsiflexion and peak ankle angular velocity in older adults may have contributed to their greater ankle power absorption during stance. These findings reveal the complex interplay between age-related changes in neuromuscular control, kinematics, and muscle function during gait.


High fructose corn syrup and diabetes prevalence: a global perspective.
The overall aim of this study was to evaluate, from a global and ecological perspective, the relationships between availability of high fructose corn syrup (HFCS) and prevalence of type 2 diabetes. Using published resources, country-level estimates (n =43 countries) were obtained for: total sugar, HFCS and total calorie availability, obesity, two separate prevalence estimates for diabetes, prevalence estimate for impaired glucose tolerance and fasting plasma glucose. Pearson's correlations and partial correlations were conducted in order to explore associations between dietary availability and obesity and diabetes prevalence. Diabetes prevalence was 20% higher in countries with higher availability of HFCS compared to countries with low availability, and these differences were retained or strengthened after adjusting for country-level estimates of body mass index (BMI), population and gross domestic product (adjusted diabetes prevalence=8.0 vs. 6.7%, p=0.03; fasting plasma glucose=5.34 vs. 5.22 mmol/L, p=0.03) despite similarities in obesity and total sugar and calorie availability. These results suggest that countries with higher availability of HFCS have a higher prevalence of type 2 diabetes independent of obesity.


Endoscopic coalition resection.
Excision of symptomatic tarsal coalitions, after failure of attempted conservative treatment, is a widely accepted surgical procedure, when the surrounding joints are not degenerated. Historically, the literature has supported open resection. Recently, arthroscopic/endoscopic resection has been described for both calcaneonavicular (CNC) and talocalcaneal (TCC) coalitions. This article describes indications, preoperative planning, surgical techniques, and results of arthroscopic/endoscopic CNC and TCC resection.


Immunological and microbiological investigations of patients with burn injuries.
Susceptibility of patients with burn injuries to infections is associated with disturbances of the humoral and cell-mediated immunity. The aim of the present study was to investigate the dynamics of phagocytic indices and serum immunoglobulin levels in patients with burn injuries as there is a high risk of colonization and infection of the burn wound. Between December 2004 and April 2005, we studied the dynamics of the following indices of the phagocytic system and humoral immunity of 30 burned patients: phagocytic index, phagocytic number, nitro blue tetrazolium chloride test, leukocyte number in the peripheral blood, the percentage of the neutrophilic leukocytes from the differential blood count, serum levels of immunoglobulins A, G and M and the percentage of lymphocytes. In addition, microbiological tests of the wound secretions were performed using conventional microbiological methods. The changes in the phagocytic indices suggested that it is the decreased phagocytic index and number that are important for the evaluation of wound infection risks. The increased total number of leukocytes and elevation of the neutrophil levels usually observed in burned patients indicate the presence of bacterial infection and the prompt involvement of the phagocytic mechanisms. The lower percentage of lymphocyte in comparison with the healthy controls was indicative also of a possible involvement of the cell-mediated immune response. The characteristic humoral mechanisms of the immune response (serum immunoglobulins) in patients with thermal injuries altered only slightly. The analyzed data may be of help in evaluating the risk of colonization and infection of the burn wound in patients with burn injuries. We would like to recommend a compulsory battery of microbiological tests and several immunological investigations phagocytic index, phagocytic number, leukocyte number, differential blood test and serum immunoglobulins with a view to applying an adequate antimicrobial and immune modulating treatment.


Design, synthesis, and biological activity of a family of novel ceramide analogues in chemoresistant breast cancer cells.
Resistance to chemotherapy and endocrine therapy is a major cause of breast cancer treatment failure. We have synthesized six novel analogues using C8-ceramide as the lead analogue and studied their effect on hormone therapy resistant (MDA-MB-231) and chemoresistant (MCF-7TN-R) breast cancer cells. Pharmacologic intervention using these ceramide analogues inhibited clonogenic survival and induced apoptosis, with one analogue being more effective than C8-ceramide. Our results show ceramide-based therapy has therapeutic potential in treating drug resistant breast cancer.


Factors influencing the presence of hemiparesis in chronic subdural hematoma.
OBJECTIVEChronic subdural hematoma (CSDH) has a variety of clinical presentations, including hemiparesis. Hemiparesis is of the utmost importance because it is one of the major indications for surgical intervention and influences outcome. In the current study, the authors intended to identify factors influencing the presence of hemiparesis in CSDH patients and to determine the threshold value of hematoma thickness and midline shift for development of hemiparesis.METHODSThe authors retrospectively reviewed 325 patients (266 with unilateral and 59 with bilateral hematomas) with CSDH who underwent surgical evacuation, regardless of presence or absence of hemiparesis.RESULTSIn univariate analysis, hematoma loculation, age, hematoma maximal thickness, and midline shift were significantly associated with hemiparesis. Moreover, patients with unilateral hematomas had a higher rate of hemiparesis than patients with bilateral hematomas. Sex, trauma history, anticoagulant and antiplatelet drug use, presence of comorbidities, Glasgow Coma Scale score, hematoma density characteristics on CT scan, and hematoma signal intensity on T1- and T2-weighted MRI were not associated with hemiparesis. In multivariate analysis, the presence of loculation and hematoma laterality (unilateral vs bilateral) influenced hemiparesis. For unilateral hematomas, maximal hematoma thickness of 19.8 mm and midline shift of 6.4 mm were associated with a 50% probability of hemiparesis. For bilateral hematomas, 29.0 mm of maximal hematoma thickness and 6.8 mm of shift were associated with a 50% probability of hemiparesis.CONCLUSIONSPresence of loculations, unilateral hematomas, older patient age, hematoma maximal thickness, and midline shift were associated with a higher rate of hemiparesis in CSDH patients. Moreover, 19.8 mm of hematoma thickness and 6.4 mm of midline shift were associated with a 50% probability of hemiparesis in patients with unilateral hematomas.