Effects of porcine calcitonin on human platelet fuction.
The effects of different doses of porcine calcitonin (pCT) were tested in vitro and in vivo. In vitro, pCT at a concentration ranging from 0.1 to 5 M. R. C. Units/ml induced a dose-dependent inhibition of ADP (1.2 microM) and collagen- (2 micrograms/ml) induced platelet aggregation, showing a prevalent action on the second wave of ADP-induced aggregation and causing prolongation of the lag time and reduction of both maximum aggregation and slope in collagen-induced aggregation. 45Ca uptake by platelets in the presence of the ionophore A23187 and 14C-serotonin release were also inhibited in a dose-related fashion, using concentrations ranging from 1 to 10 M. R. C. Units of pCT. The in vivo tests, performed before and after a 7-day treatment with 2 different doses of pCT (1 and 160 M. R. C. Units/daily, i. m.) confirmed the inhibitory effect of pCT on ADP- and collagen-induced platelet aggregation. It should be stressed that the effect of 1 unit was stronger than that of 160 units. It is therefore postulated that in vitro and in vivo effects of pCT on platelet functions probably depend on different mechanisms of action.


A case of midbrain infarction with acute bilateral cerebellar ataxia visualized by diffusion tensor imaging.
An 85-year-old woman with hypertension was admitted with a sudden onset of gait disturbance and dysarthria. On admission, the patient showed severe bilateral cerebellar ataxia with moderate right medial longitudinal fasciculus (MLF) syndrome. Magnetic resonance (MR) imaging showed an acute infarction in the lower and medial part of midbrain. Diffusion tensor imaging (DTI) started from both cerebellar peduncles revealed that the lesion of the acute infarction matched the decussation of superior cerebellar peduncle where crossing of tract was seen and a part of its tract was interrupted at the site. Interruption of the cerebellum red nuclear path at the medial part of midbrain was considered to be the reason for bilateral cerebellar ataxia and visualization of cerebellum red nuclear path by DTI can give better understanding of the neurological symptom.


[Nursing of tracheostomy].
In this abstract we have analyzed the different techniques of tracheostomy, considering new semplified methods of this procedure and therefore the common use of it in weaning from mechanical ventilation the critical care patients. We've tried to summarize guide lines of the preoperative, operative and postoperative procedures of tracheostomy, comparing our nursing clinical experience in ICU and the latest literature. We've primarily analyzed the nursing aspects of this issue, trying to focus on the priority of the treatment of the tracheostomezed patient.


In Vitro and In Vivo Assessment of Aqueously Extractable Estrogens in Poultry Manure after Pilot-scale Composting.
Poultry manure contains free and conjugated forms of the natural estrogens 17β-estradiol and estrone, which can be transported to receiving waters via runoff when land-applied. Previous studies have demonstrated estrogens in runoff from poultry manure-amended fields but have not tracked changes in estrogenicity within this water over time. Microbial conversion of conjugated estrogens (a major portion of water-extractable estrogens) to parent forms may result in temporary increases in estrogenicity in natural water bodies. The present study created 80-L batches of simulated poultry manure runoff, which were investigated over 10 d for estrogenicity by bioluminescent yeast estrogen screen assay and fathead minnow () vitellogenin induction model. The efficacy of different compost conditions (in-vessel aeration ± turning, and piling) on reduction/elimination of aqueously extractable estrogens in poultry manure was also investigated. Results indicate 3- to 10-fold increases in estrogenicity in various poultry manure mixtures during 10-d observations. Estrogenicity returned to low levels in postcompost treatments but remained elevated in the precompost treatment. Aerated compost resulted in >75% reductions in initial, peak, and 10-d mean estrogenicity in aqueous mixtures (0.3, 0.8, and 0.5 ng 17β-estradiol equivalents [EEQ] L, respectively) compared with the precompost mixture (1.4, 4.8, and 2.1 ng EEQ L, respectively). Estrogenicity was significantly higher in the aqueous extract from the piled treatment than the aerated treatment, and 10-d exposure of male fish to the piled treatment resulted in statistically significant vitellogenin induction. Collectively, our results suggest a need to investigate estrogenicity in surface waters for several days after receiving manure-influenced runoff.


The treatment of Wilms' tumor: results of the Second National Wilms' Tumor Study.
One-hundred-eighty-eight children up to 16 years of age were randomized in the second National Wilms' Tumor Study (NWTS) with tumors that were confined to the kidney and that had been totally excised (Group I). Most fared well whether treated for six or for 15 months with both actinomycin D (AMD) and vincristine (VCR). No postoperative radiation therapy (RT) was given. The two-year relapse-free survival (RFS) and two-year survival rates were 88 and 95%, respectively. Two-hundred-sixty-eight randomized patients with more advanced local lesions (Groups II and III) and 57 with distant metastases (Group IV) had postoperative RT and were scheduled for 15 months treatment with either AMD and VCR (Reg. C) or AMD plus VCR plus Adriamycin (Reg. D). The 77% two-year RFS rate for Reg. D was significantly different from the 63% with Reg. C. As in the first NWTS, patients with tumors of unfavorable histology (UH) had a significantly worse prognosis than those with favorable histology (FH), as did those with positive nodes. Survival rates at two years were 54% for UH vs. 90% for FH, and 54% vs. 82% for those with and without lymph node involvement.


Personal and household factors involved in recent Rickettsia exposure in a rural population from Yucatán, Mexico.
The aim of the study was to describe the epidemiological factors associated with the risks of recent Rickettsia exposure in inhabitants of a rural population from Yucatán, Mexico. The study included 130 inhabitants from Maxcanú, Yucatán. Blood samples were collected to detect IgM and IgG antibodies against Rickettsia typhi and Rickettsia rickettsii by an indirect immunofluorescence antibody test. Additionally, nested polymerase chain reaction was performed to amplify fragments of the 17kDa and sca5 genes. Previously, an epidemiological questionnaire was applied focused on collecting information on personal and housing exposure variables related to the recent infection with Rickettsia to determine epidemiological associations. Results that exhibited a p-value < .25 were included in a generalized multinomial logistic linear model to determine the variables involved with the risk of contact or Rickettsia infection. In all, 76% (99/130) of the participants presented with immunoglobulin titres against the Rickettsia species evaluated, while rickettsial DNA was detected in 35.4% (46/130) of the participants. The association analysis with the personal exposure variables showed that the productive age group (OR = 0.32; 95% CI = 0.10-1.03) and the elders group (OR = 0.12; 95% CI = 0.01-0.83) were protective factors for recent infection with R. typhi, taking as reference the school group. The presence of a family orchard in the home (OR = 7.56; 95% CI = 1.62-35.29) was a risk factor for recent infection with R. rickettsii. Presumably, the presence of ectoparasites (OR = 2.71; 95% CI = 0.90-8.09) at home was a risk factor for recent infection with both Rickettsia species. Recent infection was demonstrated in inhabitants from Maxcanú, Yucatán. A high seropositive frequency was obtained. The results highlight the importance of the family garden and the presence of ectoparasites in the home as risk factors associated with recent infection with Rickettsia in inhabitants from Maxcanú.


Diamond quantum sensors in microfluidics technology.
Diamond quantum sensing is an emerging technology for probing multiple physico-chemical parameters in the nano- to micro-scale dimensions within diverse chemical and biological contexts. Integrating these sensors into microfluidic devices enables the precise quantification and analysis of small sample volumes in microscale channels. In this Perspective, we present recent advancements in the integration of diamond quantum sensors with microfluidic devices and explore their prospects with a focus on forthcoming technological developments.


KeyLoop: Mechanical Retraction of the Abdominal Wall for Gasless Laparoscopy.
Background. Despite favorable outcomes of laparoscopic surgery in high-income countries, its implementation in low- and middle-income countries (LMICs) is challenging given a shortage of consumable supplies, high cost, and risk of power outages. To overcome these barriers, we designed a mechanical retractor that provides vertical tension on the anterior abdominal wall. Methods. The retractor design is anatomically and mathematically optimized to provide exposure similar to traditional gas-based insufflation methods. Anatomical data from computed tomography scans were used to define retractor size. The retractor is constructed of biocompatible stainless steel rods and paired with a table-mounted lifting system to provide 5 degrees of freedom. Structural integrity was assessed through finite element analysis (FEA) and load testing. Functional testing was performed in a laparotomy model. Results. A user guide based on patient height and weight was created to customize retractor size, and 4 retractor sizes were constructed. FEA data using a 13.6 kg mass (15 mm Hg pneumoperitoneum) show a maximum of 30 mm displacement with no permanent deformation. Physical load testing with applied weight from 0 to 13.6 kg shows a maximum of 60 mm displacement, again without permanent deformation. Retraction achieved a 57% larger field of view compared to an unretracted state in a laparotomy model. Conclusions. The KeyLoop retractor maintains structural integrity, is easily sterilized, and can be readily manufactured, making it a viable alternative to traditional insufflation methods. For surgeons and patients in LMICs, the KeyLoop provides a means to increase access to laparoscopic surgery.


Alterations in cardiac rate and rhythm in miniature swine during simulated aerial combat maneuver +Gz stress.
Electrocardiograms (McFee-axial reference system) were recorded from 18 chronically instrumented, conscious, female miniature swine before, during, and after exposures to +Gz stress. The animals were exposed to five simulated aerial combat maneuver (SACM) type acceleration profiles which spanned approximately 106 s and included two 5-s +9Gz peaks. A 5-min rest period separated each SACM exposure. Maximum heart rates during +Gz decreased over the course of the 5 SACM's-241 +/- 4 b/m and 224 +/- 5 b/m for the first and last exposures, respectively. Resting heart rates obtained 5 min after each SACM exposure were steadily increased from a control of 86 +/- 5 b/m to a final of 129 +/- 8b/m. Of the 18 animals studied, 10 developed arrhythmias during +Gz, or within the first minute after +Gz exposure. Arrhythmias exhibited included premature atrial and ventricular contractions, intraventricular conduction defects, sinus arrhythmias, premature junctional contractions, atrial bigeminy, ectopic atrial and ventricular rhythms, complete A-V dissociation, left anterior arborization-block, and junctional rhythms with aberrant conduction. While arrhythmias were not uncommonly observed during +Gz, most occurred at the end of the SACM profile or immediately following the SACM.


Learning Microvascular Anastomosis in Low Socioeconomic Vascular Models During Residency.
Microvascular anastomosis procedure has become an essential practice for the management of most neurovascular diseases. Increasing use of neurosurgical techniques necessitates intensive laboratory training in microsurgery. Umbilical artery is used for quantifiable representation to set up microvascular anastomosis model for the beginners. These arteries are found to be between 4 and 5 mm in diameter. Chicken wings are set up as second anastomosis model. Five to six centimeter long brachial artery extracted from a chicken is measured approximately 1-2 mm in diameter. These arteries are practiced for end-to-end, end-to-side, or side-to-side anastomosis under the microscope. Umbilical cord and chicken wing model hold several advantages. These essentials are inexpensive, convenient to manage, and easy to obtain for educational purposes. They neither need detailed facilities for maintenance like in animal model nor any anesthetic prerequisite. Moreover, the diameter and structure of the material are identical to those of human cortical vessels. Low-cost laboratory training during residency is more relevant in source restraint areas. It has several added benefits in refining the procedural dexterity on anastomosing smaller size vessel identical to a cortical vessel of middle cerebral artery and distal branches of the superficial temporal artery.


Sphingosine-1-Phosphate Metabolism and Its Role in the Development of Inflammatory Bowel Disease.
Beyond their role as structural molecules, sphingolipids are involved in many important cellular processes including cell proliferation, apoptosis, inflammation, and migration. Altered sphingolipid metabolism is observed in many pathological conditions including gastrointestinal diseases. Inflammatory bowel disease (IBD) represents a state of complex, unpredictable, and destructive inflammation of unknown origin within the gastrointestinal tract. The mechanisms explaining the pathophysiology of IBD involve signal transduction pathways regulating gastro-intestinal system's immunity. Progressive intestinal tissue destruction observed in chronic inflammation may be associated with an increased risk of colon cancer. Sphingosine-1-phosphate (S1P), a sphingolipid metabolite, functions as a cofactor in inflammatory signaling and becomes a target in the treatment of IBD, which might prevent its conversion to cancer. This paper summarizes new findings indicating the impact of (S1P) on IBD development and IBD-associated carcinogenesis.


Extra-cutaneous melanin.
Extra-cutaneous melanocytes derive from either the neural crest, the outer wall of the optic cup, or the cranial neural tube. Those of neural crest origin reach most bodily regions, and may give rise to primary melanoma in various tissues. The Kupffer cell produces a form of melanin, but is hardly a melanocyte. Melanocytes of the internal ear may be concerned with secretion of endolymph, trans-epithelial ion transport, and with protection against ototoxic drugs and high-intensity noise damage. There is evidence from albino animals that retinal pigment epithelium determines co-ordinates of the neural retina, and its decussation pattern during development. Neuromelanin derives from Dopamine, and is found in dopaminergic neurons widely distributed throughout the brain-stem and hypothalamus, and which project to the striatum and limbic system. Parkinsonism is due to degeneration of melanin-containing dopaminergic neurons of locus coeruleus and substantia nigra, and MPTP provides an investigative probe for studying the causes of Parkinsonism. Neuromelanin should not be regarded as a waste-product, but as something which can affect the firing properties of neurons with specific functional effect.


Effect of dialysis modality on plasma fibrinogen concentration: a meta-analysis.
Concentrations of plasma fibrinogen, a vascular risk factor, tend to be greater in patients on peritoneal dialysis (PD) than hemodialysis (HD) therapy, like concentrations of serum cholesterol, lipoprotein(a), and transthyretin, despite the substantial loss of protein during PD. Worse vascular outcome has been noted in PD patients compared with HD patients in several studies. In this study, the mean difference in plasma fibrinogen levels (PD-HD) was quantified by means of meta-analysis of mean differences found in 12 cohorts with both PD and HD patients (set 1; N = 630) by using a fixed-effects model and meta-analysis of mean fibrinogen values reported in 30 cohorts of patients on a single dialysis modality (set 2; 8 PD cohorts, 22 HD cohorts; N = 2,096) by using a mixed model. On meta-analysis, the weighted mean difference (PD-HD) was 105 mg/dL (95% confidence interval [CI], 86 to 124 [3.1 micromol/L; 95% CI, 2.5 to 3.6]) in set 1 and 103 mg/dL (95% CI, 53 to 153 [3.0 micromol/L; 95% CI, 1.6 to 4.5) in set 2. Like other vascular risk factors, such as cholesterol and lipoprotein(a), plasma fibrinogen level is markedly greater in PD than HD patients, with an approximate difference of 100 mg/dL [2.9 mumol/L]. Different plasma reference ranges for fibrinogen need to be defined for PD and HD patients. The mechanism for the difference and the possible role of hyperfibrinogenemia in worsening vascular disease in PD patients deserve study.


Impact of dynamic 18F-FDG PET on the early prediction of therapy outcome in patients with high-risk soft-tissue sarcomas after neoadjuvant chemotherapy: a feasibility study.
Dynamic PET (dPET) studies with (18)F-FDG were performed in patients with soft-tissue sarcomas who received neoadjuvant chemotherapy early in the course of therapy. The goal of the study was to evaluate the impact of early dPET studies and assess their value with regard to the therapy outcome using histopathologic data. The evaluation included 31 patients with nonmetastatic soft-tissue sarcomas, who were treated with neoadjuvant chemotherapy consisting of etoposide, ifosfamide, and doxorubicin. Patients were examined before the onset of therapy and after the completion of the second cycle. Histopathologic response served for reference and was available for 25 of 31 patients. Response was defined as less than 10% viable tumor tissue in the resected tumor tissue. The following parameters were retrieved from dPET studies: standardized uptake value (SUV); fractal dimension; 2-compartment model with computation of K(1), k(2), k(3), and k(4) (unit, 1/min); fractional blood volume; and influx according to Patlak. The mean SUV was 4.6 before therapy and 2.8 after 2 cycles. The mean influx was 0.059 before therapy and 0.043 after 2 cycles. The mean SUV was 3.9 in the responders and 5.5 in the nonresponders before therapy. After therapy, responders revealed a mean SUV of 2.5, whereas nonresponders had a mean SUV of 3.5. We used linear discriminant analysis to categorize the patients into 2 groups: response (n = 12) and nonresponse (n = 13). The correct classification rate of the responders (positive predictive value) was generally higher (>67%) than that for the nonresponders. Finally, the combined use of the 2 predictor variables, namely SUV and influx, of each study led to the highest accuracy of 83%. This combination was particularly useful for the prediction of responders (positive predictive value, 92%). The use of the percentage change in maximum SUV led to an accuracy of 58%. On the basis of these results, only a multiparameter analysis based on kinetic (18)F-FDG data of a baseline study and after 2 cycles is helpful for the early prediction of chemosensitivity in patients with soft-tissue sarcomas receiving neoadjuvant chemotherapy.


The effect of TGFβ1 on thermogenic markers is dependent on the degree of adipocyte differentiation.
Transforming growth factor β (TGFβ) a multifunctional cytokine is known to regulate cell proliferation, differentiation, migration and survival. Although there is variable expression of modulators of TGFβ action during differentiation, a differential effect on fat cell metabolism at the different stages of adipocyte differentiation was unclear. In the present study, 3T3L1 cells were used as an in vitro model to study the effect of TGFβ on adipogenic and thermogenic markers at various stages of preadipocyte to mature adipocyte differentiation. As in our earlier studies on the effect of TGFβ on CEBP's, we used a standard differentiation mix, and one with the addition of rosiglitazone. RhTGFβ1 was added to undifferentiated adipocytes (preadipocytes) and to adipocytes at day 0 (commitment stage) as well as day 10 (terminal differentiation). Cellular responses in terms of Pref1, PPARγ, TLE3, PGC1α, PRDM16, UCP1 and UCP2 mRNA levels and selected protein products, were determined. Increases in PPARγ, PRDM16, UCP1 and UCP2 mRNA and decreases in Pref1 are good indicators of successful differentiation. The early addition of rhTGFβ1 during commitment stage decreased PPARγ, PRDM16, TLE3, UCP1 and UCP2 mRNA and decreased PRDM16 protein consistent with our earlier report on the inhibition of CEBP's by TGFβ and CCN2. The addition of rhTGFβ1 to mature adipocyte at day 10 increased UCP1 mRNA and increased PRDM16 and UCP1 proteins. In the present study, our results suggest that TGFβ1 added late enhances the thermogenic potential of mature cells and causes 3T3L1 cells to differentiate to resemble brown or beige rather than white adipose tissue.


On the forces in single-ended and push-pull electret transducers.
The equations for the electromechanical force conversion in single-ended and push-pull electret transducers are derived. Traditionally, the charge distribution has been modeled as a concentrated layer at an arbitrary distance from the surface of the dielectric. For the purpose of this analysis, a negative charge is assumed to be evenly distributed throughout the dielectric. The membrane has a conductive coating in which a positive charge is induced, giving an overall dipole charge. The resulting formulas are used to derive the voltage sensitivity of a microphone and the equivalent electrical circuit for the electromechanical transduction part of a microphone or loudspeaker. An equivalent external polarizing voltage is then derived that would produce the same driving force in a conventional electrostatic loudspeaker without a stored charge. The condition for the static stability of a circular electret membrane is also determined.


Morphology of the bacteriophages of lactic streptococci.
Electron microscope studies have been made of a number of phages of lactic streptococci, seven of which were phages of Streptococcus lactis C10. Two of the phages are thought to be identical; five have been classified by the method of Tikhonenko as belonging to group IV (phages with noncontractile tails) with type III tail plates; one belongs to group V (phages with tails possessing a contractile sheath). Both prolate polyhedral heads and isometric polyhedral heads are represented among the group IV phages. The phage drc3 of S. diacetilactis DRC3 has been shown to have similar structure to the group IV phages of S. lactis C10 with prolate polyhedral heads. The phages ml1, hp, c11, and z8 of the S. cremoris strains ML1, HP, C11, and Z8, respectively, were shown to belong to the group IV phages with type III tail plates by the method of Tikhonenko. All had octahedral heads and tended to be larger than most of the other phages studied.


Hyperfine Sublevel Correlation Spectroscopy Studies of Iron-Sulfur Cluster in Rieske Protein from Green Sulfur Bacterium Chlorobaculum tepidum.
The magnetic properties of the Rieske protein purified from Chlorobaculum tepidum were investigated using electron paramagnetic resonance and hyperfine sublevel correlation spectroscopy (HYSCORE). The g-values of the Fe2S2 center were gx = 1.81, gy = 1.90, and gz = 2.03. Four classes of nitrogen signals were obtained by HYSCORE. Nitrogens 1 and 2 had relatively strong magnetic hyperfine couplings and were assigned as the nitrogen directly ligated to Fe. Nitrogens 3 and 4 had relatively weak magnetic hyperfine couplings and were assigned as the other nitrogen of the His ligands and peptide nitrogen connected to the sulfur atom via hydrogen bonding, respectively. The anisotropy of nitrogen 3 reflects the different spin density distributions on the His ligands, which influences the electron transfer to quinone.


The evolution of drug-resistant malaria: the role of drug elimination half-life.
This paper seeks to define and quantify the influence of drug elimination half-life on the evolution of antimalarial drug resistance. There are assumed to be three general classes of susceptibility of the malaria parasite Plasmodium falciparum to a drug: Res0, the original, susceptible wildtype; Res1, a group of intermediate levels of susceptibility that are more tolerant of the drug but still cleared by treatment; and Res2, which is completely resistant to the drug. Res1 and Res2 resistance both evolve much faster if the antimalarial drug has a long half-life. We show that previous models have significantly underestimated the rate of evolution of Res2 resistance by omitting the effects of drug half-life. The methodology has been extended to investigate (i) the effects of using drugs in combination, particularly when the components have differing half-lives, and (ii) the specific example of the development of resistance to the antimalarial pyrimethamine-sulphadoxine. An important detail of the model is the development of drug resistance in two separate phases. In phase A, Res1 is spreading and replacing the original sensitive forms while Res2 remains at a low level. Phase B starts once parasites are selected that can escape drug action (Res1 genotypes with borderline chemosensitivity, and Res2): these parasites are rapidly selected, a process that leads to widespread clinical failure. Drug treatment is clinically successful during phase A, and health workers may be unaware of the substantial changes in parasite population genetic structure that predicate the onset of phase B. Surveillance programs are essential, following the introduction of a new drug, to monitor effectively changes in treatment efficacy and thus provide advance warning of drug failure. The model is also applicable to the evolution of antibiotic resistance in bacteria: in particular, the need for these models to incorporate drug pharmacokinetics to avoid potentially large errors in their predictions.


Origin of disinfection by-products in cheese.
The disinfection of water, equipment and surfaces in a cheese factory is one of the factors that can originate disinfection by-products (DBPs) in cheese. This research has focused on studying cheese factories in order to evaluate the individual contribution of each step of the cheese-making process that can contribute to the presence of DBPs in cheese. Ten factories were selected according to their salting processes (brine or dry salting). Each factory was monitored by the collection of six representative samples (factory water supply, brine solution, milk, whey, curd and cheese) in which the concentrations of up to eight chemicals were detected. The study shows that contact with brine solutions containing significant levels of DBPs is the main source of these chemicals in cheese. A minor factor is the pasteurised milk used in their manufacture.


Antipsychotic polypharmacy in patients with schizophrenia: a multicentre comparative study in East Asia.
Previous studies of the prescription patterns of psychotropic medications in patients with schizophrenia have highlighted a high rate of antipsychotic polypharmacy, but data in Asia are sparse. This study seeks to examine the prevalence of antipsychotic polypharmacy in patients with schizophrenia and compare the differences between patients receiving one vs. those receiving more than one antipsychotic. Antipsychotic prescription for a sample of 2399 patients with schizophrenia from six countries and territories was evaluated. Daily doses of antipsychotic medications were converted to standard chlorpromazine equivalents (CPZ). Antipsychotic polypharmacy was found in 45.7% (n = 1097) of the patients with wide intercountry variations. Polypharmacy was associated with male gender [odds ratio (OR) 1.24, 95% confidence interval (CI) 1.06, 1.46, P < 0.01], advanced age (t = -7.81, d.f. = 2396, P < 0.001), psychiatric hospital setting (OR 1.34, 95% CI 1.11, 1.62) as well as higher daily CPZeq doses (411.47 vs. 983.10 CPZeq day(-1), z = -25.94, P < 0.001), anticholinergic use (OR 3.17, 95% CI 2.65, 3.79, P < 0.001) and less use of an atypical antipsychotic drug (OR 0.83, 95% CI 0.71, 0.98, P < 0.05). On multivariate analysis, country, age and duration of illness were significantly associated with antipsychotic polypharmacy. This study highlighted the wide intercountry variations of antipsychotic polypharmacy which are likely to be influenced by a complex combination of clinical, setting, cultural and personal practice factors, requiring more research.


Effect of pre-diabetes on future risk of stroke: meta-analysis.
To assess the association between pre-diabetes and risk of stroke, and to evaluate whether this relation varies by diagnostic criteria for pre-diabetes. Systematic review and meta-analysis of prospective studies. A search of Medline, Embase, and the Cochrane Library (1947 to 16 July 2011) was supplemented by manual searches of bibliographies of key retrieved articles and relevant reviews. Prospective cohort studies that reported multivariate adjusted relative risks and corresponding 95% confidence intervals for stroke with respect to baseline pre-diabetes were included. Two independent reviewers extracted data on pre-diabetes status at baseline, risk estimates of stroke, study quality, and methods used to assess pre-diabetes and stroke. Relative risks were pooled using random effects models when appropriate. Associations were tested in subgroups representing different characteristics of participants and studies. Publication bias was evaluated with funnel plots. The search yielded 15 prospective cohort studies including 760,925 participants. In 8 studies analysing pre-diabetes defined as fasting glucose 100-125 mg/dL (5.6-6.9 mmol/L), the random effects summary estimate did not show an increased risk of stroke after adjustment for established cardiovascular risk factors (1.08, 95% confidence interval 0.94 to 1.23; P = 0.26). In 5 studies analysing pre-diabetes defined as fasting glucose 110-125 mg/dL (6.1-6.9 mmol/L), the random effects summary estimate showed an increased risk of stroke after adjustment for established cardiovascular risk factors (1.21, 1.02 to 1.44; P = 0.03). In 8 studies with information about impaired glucose tolerance or combined impaired glucose tolerance and impaired fasting glucose, the random effects summary estimate showed an increased risk of stroke after adjustment for established cardiovascular risk factors (1.26, 1.10 to 1.43; P < 0.001). When studies that might have enrolled patients with undiagnosed diabetes were excluded, only impaired glucose tolerance or a combination of impaired fasting glucose and impaired glucose tolerance independently raised the future risk of stroke (1.20, 1.07 to 1.35; P = 0.002). Pre-diabetes, defined as impaired glucose tolerance or a combination of impaired fasting glucose and impaired glucose tolerance, may be associated with a higher future risk of stroke, but the relative risks are modest and may reflect underlying confounding.


Late-life depression in primary care: a nationwide Italian epidemiological survey.
To assess 1-week prevalence of International Classification of Disease, Tenth Edition (ICD-10) current depression, physical comorbidity, associated disability, and healthcare utilization in older primary care patients. Comparisons with younger patients are also reported. Cross-sectional, two-phase epidemiological study. One hundred ninety-one primary care clinics. Six hundred six patients aged 60 and older and 1,290 patients aged 14 to 59. Screening was conducted using the General Health Questionnaire-12. Probable cases were assessed by primary care physicians (PCPs) with the World Health Organization ICD-10 Checklist for depression to diagnose ICD-10 current depression and subsyndromal depression. Other instruments included the Brief Disability Questionnaire and the PCPs' rating of the severity of physical illness. The prevalence of current depression was 8.6%; 3.6% for subsyndromal depression (8.3% and 5.5%, respectively, in younger subjects). Current depression was associated with physical illness, physical disability, days lost from work or days unable to perform activities of daily living, and frequency of PCP consultation. Both physical illness and current depression independently resulted in increased disability, and, when the two conditions coexisted, there was a further increase in disability. Comorbidity with physical illness was the hallmark of late-life depression, distinguishing this condition from depression in younger patients. Moreover, depressed older patients were more disabled and had a higher frequency of PCP consultation than younger depressed patients. The prevalence of current depression does not decrease with age in primary care, in contrast to that seen in community studies. Late-life depression is characterized by physical comorbidity and associated with significant disability. The specific features of late-life depression call for intervention programs taking into account the relationship between the mental, physical, and functional aspects of this condition.


Concurrent illness and complications associated with canine hyperadrenocorticism.
Complications associated with canine HAC include thromboembolism, infection, diabetic mellitus, pancreatitis, or growing pituitary tumor. The serious consequences of the multisystemic effects of cortisol excess show the need for careful examination and monitoring of animal patients with HAC so that the many associated complications may be recognized, treated, and in some cases prevented.


ADHD through the life span: the role of bupropion in treatment.
Attention-deficit/hyperactivity disorder (ADHD) is a common problem that begins early in life and in many cases persists through the life span. Psychostimulants have been the psychopharmacologic treatment of choice. Not all patients respond to psychostimulants, and some patients have significant side effects. This paper reviews the use of a nonstimulant psychopharmacologic agent, bupropion, to treat ADHD in both children and adults.


Sex and stress hormone dysregulation as clinical manifestations of hypothalamic function in migraine disorder: A meta-analysis.
Migraine is a leading cause of disability in young adults. It occurs more frequently in females, often comorbidly with stress disorders, suggesting an association with hypothalamic sex and stress hormonal function and a likely interaction with autonomic nervous system activation. Thus, this study aimed to meta-analyse current literature pertaining to female and male sex hormones (estrogen, progesterone and testosterone concentration), hypothalamic-pituitary-adrenal axis (HPA axis) cortisol responses and heart rate variability (HRV) in migraineurs and controls aged 13-65 years. A systematic search of MEDLINE, Embase, PsycINFO, PubMed, CINAHL and Web of Science databases on 29/08/2022 identified 29 studies for meta-analysis (encompassing 719 migraineur and 592 control participants) that met inclusion and NHLBI risk of bias criteria. Results demonstrated that estrogen concentrations of female migraineurs were reduced (g = -.60, 95% CI [-.91, -.29], p < .001) in the luteal phase of the menstrual cycle, compared to controls. No differences were found in progesterone levels overall in female migraineurs, nor in testosterone levels in male migraineurs compared to controls. Further, early diurnal cortisol concentrations were elevated (g = .32, 95% CI [.00, .63], p = .036) in female and male migraineurs compared to controls, though no differences were found in HRV of female or male migraineurs compared to controls. These findings of dysregulation of estrogen in females and cortisol dysregulation in female and male migraineurs indicate perturbed hypothalamic function and highlight the association of migraine with stress and the need for further rigorous investigation of hypothalamic neuroendocrine functions in migraineurs of both sexes.


Uropathogenic Escherichia coli.
The urinary tract is among the most common sites of bacterial infection, and Escherichia coli is by far the most common species infecting this site. Individuals at high risk for symptomatic urinary tract infection (UTI) include neonates, preschool girls, sexually active women, and elderly women and men. E. coli that cause the majority of UTIs are thought to represent only a subset of the strains that colonize the colon. E. coli strains that cause UTIs are termed uropathogenic E. coli (UPEC). In general, UPEC strains differ from commensal E. coli strains in that the former possess extragenetic material, often on pathogenicity-associated islands (PAIs), which code for gene products that may contribute to bacterial pathogenesis. Some of these genes allow UPEC to express determinants that are proposed to play roles in disease. These factors include hemolysins, secreted proteins, specific lipopolysaccharide and capsule types, iron acquisition systems, and fimbrial adhesions. The current dogma of bacterial pathogenesis identifies adherence, colonization, avoidance of host defenses, and damage to host tissues as events vital for achieving bacterial virulence. These considerations, along with analysis of the E. coli CFT073, UTI89, and 536 genomes and efforts to identify novel virulence genes should advance the field significantly and allow for the development of a comprehensive model of pathogenesis for uropathogenic E. coli.Further study of the adaptive immune response to UTI will be especially critical to refine our understanding and treatment of recurrent infections and to develop vaccines.


[Substance P and human skin].
Substance P (SP) is a neuropeptide that is a neurotransmitter and a neuromodulator in the central and peripheral nervous system. SP is known to have regulatory effects on nervous or non nervous cells, including immune cells. SP is involved in the physiopathology of local inflammation, including inflammatory dermatoses. The purpose of this review is to relate the localization of SP and its receptors to illustrate the immunomodulatory functions of SP through its effects on various immune cells and to focus on the localization of SP in human skin and on its effects on cutaneous cells. The probable implication of SP in inflammatory dermatoses will be discussed.


LIGSITEcsc: predicting ligand binding sites using the Connolly surface and degree of conservation.
Identifying pockets on protein surfaces is of great importance for many structure-based drug design applications and protein-ligand docking algorithms. Over the last ten years, many geometric methods for the prediction of ligand-binding sites have been developed. We present LIGSITEcsc, an extension and implementation of the LIGSITE algorithm. LIGSITEcsc is based on the notion of surface-solvent-surface events and the degree of conservation of the involved surface residues. We compare our algorithm to four other approaches, LIGSITE, CAST, PASS, and SURFNET, and evaluate all on a dataset of 48 unbound/bound structures and 210 bound-structures. LIGSITEcsc performs slightly better than the other tools and achieves a success rate of 71% and 75%, respectively. The use of the Connolly surface leads to slight improvements, the prediction re-ranking by conservation to significant improvements of the binding site predictions. A web server for LIGSITEcsc and its source code is available at scoppi.biotec.tu-dresden.de/pocket


Coccidoidouria: clinical significance.
Twelve patients had urine cultures positive for Coccidioides immitis. Ten patients showed the usual criteria for dissemination, but 2 were believed, before urine culture, to have only chronic pulmonary involvement. In 8 patients, there was impairment of host defense mechanisms due either to associated disease or immunosuppressive drug therapy. Only 2 of 11 patients tested reacted to coccidioidin skin-test antigen. Colony counts of C. immitis in the first voided morning urine spacimens ranged from 0.03/ml to 17/ml. With prostatic involvement, colony counts in the expressed secretions ranged from 15/ml to 120/ml. The site of urinary tract coccidioidomycosis, which could be adduced in 9 patients, was the upper tract in 1, lower tract in 6, and in both upper and lower tracts in 2. In patients with lower tract infection, the prostate was involved in 4 and the epididymis in 2.


Localized Defects on Copper Sulfide Surface for Enhanced Plasmon Resonance and Water Splitting.
Surficial defects in semiconductor can induce high density of carriers and cause localized surface plasmon resonance which is prone to light harvesting and energy conversion, while internal defects may cause serious recombination of electrons and holes. Thus, it is significant to precisely control the distribution of defects, although there are few successful examples. Herein, an effective strategy to confine abundant defects within the surface layer of Cu1.94 S nanoflake arrays (NFAs) is reported, leaving a perfect internal structure. The Cu1.94 S NFAs are then applied in photoelectrochemical (PEC) water splitting. As expected, the surficial defects give rise to strong LSPR effect and quick charge separation near the surface; meanwhile, they provide active sites for catalyzing hydrogen evolution. As a result, the NFAs achieve the top PEC properties ever reported for Cux S-based photocathodes.


Acute paraquat exposure determines dose-dependent oxidative injury of multiple organs and metabolic dysfunction in rats: impact on exercise tolerance.
This study investigated the pathological morphofunctional adaptations related to the imbalance of exercise tolerance triggered by paraquat (PQ) exposure in rats. The rats were randomized into four groups with eight animals each: (a) SAL (control): 0.5 ml of 0.9% NaCl solution; (b) PQ10: PQ 10 mg/kg; (c) PQ20: PQ 20 mg/kg; and (d) PQ30: PQ 30 mg/kg. Each group received a single injection of PQ. After 72 hours, the animals were subjected to an incremental aerobic running test until fatigue in order to determine exercise tolerance, blood glucose and lactate levels. After the next 24 h, lung, liver and skeletal muscle were collected for biometric, biochemical and morphological analyses. The animals exposed to PQ exhibited a significant anticipation of anaerobic metabolism during the incremental aerobic running test, a reduction in exercise tolerance and blood glucose levels as well as increased blood lactate levels during exercise compared to control animals. PQ exposure increased serum transaminase levels and reduced the glycogen contents in liver tissue and skeletal muscles. In the lung, the liver and the skeletal muscle, PQ exposure also increased the contents of malondialdehyde, protein carbonyl, 8-hydroxy-2'-deoxyguanosine, superoxide dismutase and catalase, as well as a structural remodelling compared to the control group. All these changes were dose-dependent. Reduced exercise tolerance after PQ exposure was potentially influenced by pathological remodelling of multiple organs, in which glycogen depletion in the liver and skeletal muscle and the imbalance of glucose metabolism coexist with the induction of lipid, protein and DNA oxidation, a destructive process not counteracted by the upregulation of endogenous antioxidant enzymes.


Atypical central neurocytoma.
The proliferative potential of central neurocytomas was determined in a biopsy series of 36 cases and compared with clinical outcome. The mean size of the growth fraction, as determined by MIB-1 labeling index (MIB-1 LI) at first biopsy, was 2.8 +/- 2.5 with a range of 0.1 to 8.6%. Neurocytomas with an MIB-1 LI > 2% comprised 39% of cases and showed a close correlation with the presence of vascular proliferation (p = 0.0006). The Kaplan-Meier analysis showed a highly significant difference in disease-free survival between the 2 groups (p = 0.0068). Over an observation time of 150 months, there was a 22% relapse among patients with an MIB-1 LI less than 2% and a 63% chance of relapse among those with an MIB-1 LI greater than 2%. We propose the term "atypical central neurocytoma" for the latter subset, corresponding to WHO grade II.


Vascular Endothelial Growth Factor Receptor-3 Expression Predicts Sentinel Node Status in Primary Cutaneous Melanoma.
This study analysed the expression of vascular endothelial growth factor-A (VEGF), VEGFR-2, and VEGFR-3 in primary cutaneous melanomas with positive and negative sentinel node status (SLN) (a total of 58 specimens divided into 2 groups of 29 for each status). The specimens were collected from the pathological archive of the department of Dermatology, Venereology and Allergology of the University Medical Center Heidelberg. A quantification score was developed for protein expression, by considering the percentage of positive melanoma cells (0: 0%, 1: up to 1%, 2: 2-10%, 3: 11-50%, and 4: > 50%) in relation to the intensity of staining (0: negative, 1: low, 2: medium, 3: strong). Tumoural VEGFR-3 expression (mean ± standard deviation) in SLN+ tumours (9.62 ± 3.09) was significantly stronger than in SLN- tumours (6.13 ± 3.87; p < 0.001). A binary logistic regression model proved VEGFR-3 expression and tumour thickness to be significant independent predictors of SLN. These data provide evidence that VEGFR-3 expression may play a critical role in the pathogenesis of malignant melanoma and that its investigation may help to improve the selection of patients with primary cutaneous melanoma for sentinel node biopsy.


Overexpression of CRIP in transgenic mice alters cytokine patterns and the immune response.
Cysteine-rich intestinal protein (CRIP), which contains a double zinc finger motif, is a member of the Group 2 LIM protein family. Our results showed that the developmental regulation of CRIP in neonates was not influenced by conventional vs. specific pathogen-free housing conditions. Thymic and splenic CRIP expression was not developmentally regulated. A line of transgenic (Tg) mice that overexpress the rat CRIP gene was created. When challenged with lipopolysaccharide, the Tg mice lost more weight, exhibited increased mortality, experienced greater diarrhea incidence, and had less serum interferon-gamma (IFN-gamma) and more interleukin (IL)-6 and IL-10. Similarly, splenocytes from the Tg mice produced less IFN-gamma and IL-2 and more IL-10 and IL-6 upon mitogen stimulation. Delayed-type hypersensitivity response was less in the Tg mice. Influenza virus infection produced greater weight loss in the Tg mice, which also showed delayed viral clearance. The observed responses to overexpression of the CRIP gene are consistent with a role for this LIM protein in a cellular pathway that produces an imbalance in cytokine pattern favoring Th2 cytokines.


Cerebellum lesions and finger use.
We tested monkeys, patients, and normal control human subjects in a task that requires skilled use of the fingers. Animals and patients with lesions of the cerebellum, particularly of the cerebellar hemispheres, were severely impaired in retrieving raisins from small holes (monkeys) or shifting beads from place to place through a series of such holes, using the index finger alone or in apposition (humans). As they descend through the pontine nuclei, pyramidal tract fibres give off a collateral to pontine cells. The axons of pontine cells, in turn, project to the cerebellar cortex, where they terminate as mossy fibres. We suggest that the corollary discharge from pyramidal tract fibres to the cerebellum via the pontine nuclei is required for skilled, co-coordinated, simultaneous or sequential movements.


Genetic influences in antisocial personality and drug use disorders.
While an association between antisocial personality disorder (APD) and substance use disorder (SUD) has been frequently observed, the causes of the comorbidity remain unclear. Adoption and twin studies have found evidence of both genetic and environmental influences in APD and SUD. Therefore, comorbidity between APD and SUD may be the result of shared genetic influences, shared environmental influences, or a combination of the two. However, only a limited number of adoption and twin studies have addressed this issue and the results have not been conclusive. In future studies, a distinction should be made between alcohol and drug abuse and between juvenile and adult APD symptoms. Twin samples of adequate size would allow use of structural equation analytical methods for estimation of the relative magnitude of genetic and environmental influences shared between the two conditions, as well as influences contributing to each specifically. Results would be highly relevant for the clinical setting as well as for efforts to identify the genes involved in either trait.


Dominant negative connexin26 mutation R75W causing severe hearing loss influences normal programmed cell death in postnatal organ of Corti.
The greater epithelial ridge (GER) is a developmental structure in the maturation of the organ of Corti. Situated near the inner hair cells of neonatal mice, the GER undergoes a wave of apoptosis after postnatal day 8 (P8). We evaluated the GER from P8 to P12 in transgenic mice that carry the R75W + mutation, a dominant-negative mutation of human gap junction protein, beta 2, 26 kDa (GJB2) (also known as connexin 26 or CX26). Cx26 facilitate intercellular communication within the mammalian auditory organ. In both non-transgenic (non-Tg) and R75W + mice, some GER cells exhibited apoptotic characteristics at P8. In the GER of non-Tg mice, both the total number of cells and the number of apoptotic cells decreased from P8 to P12. In contrast, apoptotic cells were still clearly evident in the GER of R75W + mice at P12. In R75W + mice, therefore, apoptosis in the GER persisted until a later stage of cochlear development. In addition, the GER of R75W + mice exhibited morphological signs of retention, which may have resulted from diminished levels of apoptosis and/or promotion of cell proliferation during embryogenesis and early postnatal stages of development. Here we demonstrate that Cx26 dysfunction is associated with delayed apoptosis of GER cells and GER retention. This is the first demonstration that Cx26 may regulate cell proliferation and apoptosis during development of the cochlea.


Post-transplant indolent T cell lymphoproliferative disorder in living donor liver transplantation: a case report.
Post-transplant lymphoproliferative disorder (PTLD) of T cell type has been rarely reported. Accurate diagnosis of this life-threatening rare form of PTLD is important for the treatment strategy. A 7-year-old boy had severe diarrhea and weight loss progressively at 7 years post-living donor liver transplantation (LDLT) for biliary atresia. Endoscopy in the gastrointestinal (GI) tract revealed multiple erosions and ulcer lesions with prominent intraepithelial lymphocytosis in the duodenum and terminal ileum. Immunohistochemical examination demonstrated that these accumulated lymphocytes mainly comprised small- to medium-sized T cells expressing CD3, CD4, CD5, CD7, and CD103, but lacking CD8, CD56, and Epstein-Barr virus-encoded small RNAs. In addition, T cell receptor β gene rearrangement was detected by polymerase chain reaction analysis. Comprehensively, the lesions were best interpreted as post-transplant indolent T cell lymphoproliferative disorder (LPD) of the intestine. Clinical remission was achieved by reducing the immunosuppressant. A rarely reported indolent type of T cell LPD in post-LDLT was diagnosed by direct inspection and histological investigation. Although the histological classification and therapeutic strategy for post-transplant indolent T cell LPD have not been established, reducing immunosuppression allowed complete remission in our case. To prevent the incidence of PTLD and de novo malignancy, developing a methodology to set a proper dose of immunosuppressant is required.


Primary localized orbital amyloidosis: a case report.
Amyloidosis refers to a heterogeneous group of disorders associated with deposition of chemically distinct fibril proteins. Isolated orbital amyloidosis is a rare condition and requires systemic examination. The authors report a case of amyloid deposit in the orbit whose systemic investigation has been negative. A 64-year-old woman presented to the eye clinic with left-sided orbital mass, mild exophthalmos with downward ocular displacement, and ptosis. The patient presented also visual acuity loss and ocular hypertension. No systemic involvement was noted by systemic workup and it confirmed the primary orbital amyloidosis. The patient was subject to full clinical examination, laboratory examinations, orbital echography, magnetic resonance imaging and total body computed tomography scans, rectal mucosa, and temporal artery biopsies. It was necessary to exclude systemic amyloidosis. The presence of amyloid deposits was confirmed by biopsy of orbital mass. The chemical nature of deposit was characterized using light microscopy, immunohistochemistry, and electron microscopy. Orbital amyloidosis is a very rare disease. It should be considered in the diagnosis of patients with ptosis and exophthalmos. The treatment usually consists of surgical removal of the amyloid mass and follow-up for a likely local recurrence. In our case, mass excision determined the decrease of exophthalmos and intraocular pressure.


Enhanced osteopontin expression in a murine model of allergen-induced airway remodelling.
Airway remodelling is a central pathophysiological feature of chronic asthma. A wide variety of cytokines and growth factors are likely to be involved in the development of airway remodelling. Osteopontin (OPN) is a cytokine with pro-fibrotic properties; however, its role in airway remodelling in asthma has not been explored. To determine the expression and cellular sources of OPN in a murine model of chronic allergen-induced airway remodelling. BALB/c mice were sensitized and exposed to ovalbumin (OVA) or saline inhalations for 5 weeks and killed 24 h after the last inhalation. The following parameters of inflammation and remodelling were assessed: differential cell counts in bronchoalveolar lavage (BAL) fluid lung collagen content (colorimetric biochemical assay) and peribronchial smooth muscle content (immunohistochemistry, followed by image analysis). OPN expression in BAL and lung tissue was determined by PCR and ELISA. The cellular source and distribution of OPN were evaluated by immunohistochemistry and immunofluorescence. OPN expression is up-regulated in lung tissue and in BAL fluid of OVA-treated mice and correlates with collagen content and peribronchial smooth muscle area. In addition, OPN significantly increases collagen deposition in vitro in a murine lung cell line. Cells producing OPN include the airway epithelium and cells of the submucosal inflammatory infiltrate (T cells, eosinophils, and macrophages). Positive staining for OPN was also observed in bronchial tissue from human asthmatic subjects. OPN expression in the lungs is increased in a murine model of allergen-induced chronic airway remodelling, suggesting a role for this cytokine in airway remodelling in asthma.


[Detection of myocardial ischemia by 99mTc-Teboroxime myocardial SPECT: a comparison with 201Tl myocardial SPECT].
Exercise myocardial SPECT using 99mTc-Teboroxime was performed and the regions of ischemic area were compared with 201Tl myocardial SPECT in 8 patients with coronary artery disease. All patients had no evidence of previous myocardial infarction, and underwent bicycle ergometer exercise according to a standardized multistage exercise protocol. At peak exercise, 555 MBq 99mTc-Teboroxime or 75 MBq 201Tl was injected intravenously. After termination of exercise, images were obtained with a gamma camera rotating through a 180 degrees arc from 45 degrees right anterior oblique to 45 degrees left posterior oblique. The concordance of 99mTc-Teboroxime SPECT and 201Tl SPECT was 63% in ischemic region and 83% in normal region. Furthermore, one patient underwent dipyridamole infusion and 99mTc-Teboroxime SPECT was carried out. The images obtained by dipyridamole 99mTc-Teboroxime SPECT were equivalent to the images of exercise 201Tl SPECT. 99mTc-Teboroxime SPECT seems useful for the detection of the coronary artery disease. It was suggested that evaluation of the myocardial viability in acute phase of myocardial infarction can be possible by using 99mTc-Teboroxime SPECT.


Exploring the microbial community (microflora) associated with ovine Haemonchus contortus (macroflora) field strains.
High-throughput sequencing technology has shown tremendous promise for microbial community composition and diversity. Illumina MiSeq platform was exploited to study the microbial community associated with the different stages of the life-cycle of ovine Haemonchus contortus field strains using two distinct amplification primer sets (targeting V3-V4, and V5-V7). Scanning electron microscope and polymerase chain reaction coupled with Illumina MiSeq platform were employed to confirm the absence of any parasite surface contamination by intact bacteria or their DNA products. Results showed 48 (V3-V4 tags) and 28 (V5-V7 tags) bacterial genera comprised the microbial flora of H. contortus microbiome. The dominant bacterial genera belonged to Escherichia-Shigella, Pseudomonas and Ochrobactrum, which were shared in all the stages of the parasite life-cycle using V3-V4 and V5-V7 amplicons. Moreover, the parasite microbiome could reflect the external micro-organisms (i.e. micro- and macro-habitats). There is abundant room for further progress in comparing microbiome of different helminths, which has, and will continue to offer considerable potential for better understanding a wide-variety of devastating animal and human diseases.


Correlation between receptor-interacting protein 140 expression and directed differentiation of human embryonic stem cells into neural stem cells.
Overexpression of receptor-interacting protein 140 (RIP140) promotes neuronal differentiation of N2a cells via extracellular regulated kinase 1/2 (ERK1/2) signaling. However, involvement of RIP140 in human neural differentiation remains unclear. We found both RIP140 and ERK1/2 expression increased during neural differentiation of H1 human embryonic stem cells. Moreover, RIP140 negatively correlated with stem cell markers Oct4 and Sox2 during early stages of neural differentiation, and positively correlated with the neural stem cell marker Nestin during later stages. Thus, ERK1/2 signaling may provide the molecular mechanism by which RIP140 takes part in neural differentiation to eventually affect the number of neurons produced.


Diazadithia[7]helicenes: Synthetic Exploration, Solid-State Structure, and Properties.
Diazadithia[7]helicenes were synthesized from the readily available building block ethyl 7-chloro-8-formylthieno[3,2-f]quinoline-2-carboxylate by a Wittig reaction-photocyclization strategy. The helicene core was functionalized by nucleophilic aromatic substitution with a variety of nucleophiles (e.g., O-, N-, and C-centered) and palladium-catalyzed reactions such as Suzuki coupling and Buchwald-Hartwig amination. Racemization studies confirmed that the enantiopure forms of these [7]helicenes are conformationally stable compared to their lower analogues. The solid-state structures of the novel diazadithia[7]helicenes were determined by single-crystal X-ray diffraction. The crystal structures of these azathia[7]helicenes show columnar stacking in antiparallel fashion. The HOMO-LUMO gaps of the new compounds were determined on the basis of electrochemical and optical measurements.


[Staffing levels and patient needs in the intensive care unit].
The current study sought to utilize a patient classification system to investigate staffing and patient needs along with nursing care distribution in our intensive care units. The study employed a factor type analysis to design a patient need checklist (for our six ICUs) in order to determine staff load and nursing requirements. Snapshot observations were also taken to survey the distribution of nursing care time. The results of the two methods provide an estimate of current staffing needs, they also show that there is no significant difference between our surgical and internal medicine wards. On average, direct care accounts for 40.1% of the time schedule; indirect care, 37.3%; related care, 6.0%; and individual time, 16.6%. The average patient grade lies between I and III; and workload index, between 4.4 and 11.5. The average nursing time per patient per shift is 2.88 hours, and the average workload per person is estimated at 5.7-5.8 hours. By comparing the number of personnel currently employed and the estimated number needed, we discovered that two units are understaffed, and three are overstaffed. The understaffed units are all surgical units; the overstaffed ones, internal medicine units. To conclude the study, we examined the nature and complexity of nursing duties in the hopes of returning non-nursing responsibilities to the proper medical organizations. Our ultimate goal is to realize the full potential and improve the quality of our nursing personnel.


A tertiary center's experience with second review of 3885 thyroid cytopathology specimens.
Although the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) has standardized the diagnostic terminology for thyroid fine-needle aspiration (FNA), morphological interpretation remains subjective, and interobserver discrepancies are expected. This study quantifies the frequency and magnitude of these discrepancies in a single tertiary center's experience and elucidates key factors that are associated with changes in diagnosis. Institutional consultation for 3885 thyroid cytological samples over 45 months were reviewed. BSRTC classification made by the sending institution was compared with that of our institution. An ANOVA was performed to determine factors that may be associated with interinstitutional diagnostic differences. Histopathology diagnoses were available for 1049 (27%) nodules; the malignancy rates for inside and outside BSRTC classifications were calculated. There were 937 1-step changes and 301 ≥2-step diagnostic discrepancies comprising 24% and 8% of all cases, respectively. Second review decreased the indeterminate rate 38% to 28% (P < .000001). Indeterminate diagnostic category before second review, low specimen cellularity, Hashimoto's thyroiditis, and low volume of consults from the sending institution were associated with discordance. Of the 1049 thyroid nodules operated for which unequivocal histopathology was available, the malignancy rates for the BSRTC categories before and after second review were compared. Categorical upgrades were associated with a malignancy rate of 84%, whereas downgrades were associated with a malignancy rate of 38% (P < .000001). This is the largest series to date of thyroid cytology second review. The BSRTC classification changed 32% of the time, potentially resulting in significant changes in clinical and surgical management. Because certain specimen characteristics (indeterminate diagnostic category before second review, low specimen cellularity, Hashimoto's thyroiditis, and low volume of consults from the sending institution) were particularly associated with a diagnosis change, morphological second review may be of potential benefit in these settings.


Fission and Internal Fusion of Protocell with Membraneless "Organelles" Formed by Liquid-Liquid Phase Separation.
Construction of protocells with hierarchical structures and living functions is still a great challenge. Growing evidence demonstrates that the membraneless organelles, which facilitate many essential cellular processes, are formed by RNA, protein, and other biopolymers via liquid-liquid phase separation (LLPS). The formation of the protocell in the early days of Earth could follow the same principle. In this work, we develop a novel coacervate-based protocell containing membraneless subcompartments via spontaneous liquid-liquid phase separation by simply mixing single-stranded oligonucleotides (ss-oligo), quaternized dextran (Q-dextran), and poly(l-lysine) (PLL) together. The resulting biphasic droplet, with PLL/ss-oligo phase being the internal subcompartments and Q-dextran/ss-oligo phase as the surrounding medium, is capable of sequestering and partitioning biomolecules into distinct regions. When the droplet is exposed to salt or Dextranase, the surrounding Q-dextran/ss-oligo phase will be gradually dissociated, resulting in the chaotic movement and fusion of internal subcompartments. Besides, the external electric field at a lower strength can drive the biphasic droplet to undergo a deviated circulation concomitant with the fusion of localized subcompartments, while a high-strength electric field can polarize the whole droplet, resulting in the release of daughter droplets in a controllable manner. Our study highlights that liquid-liquid phase separation of biopolymers is a powerful strategy to construct hierarchically structured protocells resembling the morphology and functions of living cells and provides a step toward a better understanding of the transition mechanism from nonliving to living matter under prebiotic conditions.


Early intervention improves clinical responses to seasonal allergic rhinitis by stimulation in sphenopalatine ganglion (Xinwu acupoint).
To examine the efficacy of early intervention (4 weeks before pollen dispersal) with sphenopalatine ganglion (Xinwu acupoint) stimulation in patients with allergies after the onset of seasonal allergic rhinitis (SAR). This is a prospective, randomized and unblinded half-open study. Forty-one SAR volunteers were randomly assigned to either the sphenopalatine ganglion (SPG) acupuncture plus supplementary acupuncture (SPG group) or the sham-SPG acupuncture plus supplementary acupuncture (SA group) stimulation 4 weeks before the onset of allergy season. The changes of the total nasal symptom score (TNSS) and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores were measured on the first week in the onset of allergy season. Four patients dropped out due to local hematoma and pain in the SPG and SA groups. The remaining 37 patients continued through to the end of the trial. After early intervention 4 weeks before the onset of allergy season, the sneezing, nasal congestion and itchiness scores in the first week of onset time were significantly lower in the SPG group than in the SA group patients ( 0.001). The RQLQ score obtained at the onset of symptoms indicated that symptoms were more significantly ameliorated in the SPG group than in the SA group (0.001). The results of this study confirmed that early intervention by sphenopalatine ganglion (Xinwu acupoint) stimulation can effectively improve the symptoms and the quality of SAR patients' daily lives.


Chlamydia trachomatis' struggle to keep its host alive.
Bacteria of the phylum Chlamydiae infect a diverse range of eukaryotic host species, including vertebrate animals, invertebrates, and even protozoa. Characteristics shared by all Chlamydiae include their obligate intracellular lifestyle and a biphasic developmental cycle. The infectious form, the elementary body (EB), invades a host cell and differentiates into the replicative form, the reticulate body (RB), which proliferates within a membrane-bound compartment, the inclusion. After several rounds of division, RBs retro-differentiate into EBs that are then released to infect neighboring cells. The consequence of this obligatory transition between replicative and infectious forms inside cells is that Chlamydiae absolutely depend on the viability and functionality of their host cell throughout the entire infection cycle. We recently conducted a forward genetic screen in Chlamydia trachomatis, a common sexually transmitted human pathogen, and identified a mutant that caused premature death in the majority of infected host cells. We employed emerging genetic tools in Chlamydia to link this cytotoxicity to the loss of the protein CpoS (Chlamydia promoter of survival) that normally localizes to the membrane of the pathogen-containing vacuole. CpoS-deficient bacteria also induced an exaggerated type-1 interferon response in infected cells, produced reduced numbers of infectious EBs in cell culture, and were cleared faster from the mouse genital tract in a transcervical infection model in vivo. The analysis of this CpoS-deficient mutant yielded unique insights into the nature of cell-autonomous defense responses against Chlamydia and highlighted the importance of Chlamydia-mediated control of host cell fate for the success of the pathogen.


A novel method to expand large numbers of CD56(+) natural killer cells from a minute fraction of selectively accessed cryopreserved cord blood for immunotherapy after transplantation.
Umbilical cord blood transplantation (UCBT) is increasingly used to treat acute leukemias. UCB units are thawed and infused in their entirety at transplant, precluding later use as immunotherapy to prevent or treat leukemia relapse. We developed a device that selectively thaws only 1 mL of the UCB unit, leaving the remaining UCB unit cryopreserved for subsequent transplantation. We also show that large numbers of CD56(+) natural killer (NK) cells can be expanded from these 1-mL fractions of selectively accessed UCB. Immunomagnetic depletion of CD3(+) cells of the 1-mL fraction was performed, and the cells were subsequently stimulated with irradiated Epstein-Barr virus-transformed lymphoblastoid cell lines (EBV-LCLs) and set to culture in media containing interleukin (IL)-2. When a 1:20 ratio of total nucleated cells to EBV-LCL feeder cells was used, day-21 and day-35 NK cell cultures initiated from 1 mL of UCB contained a median of 430 × 10(6) (range: 44-4321 × 10(6)) and 6092 × 10(6) (range: 165-20947 × 10(6)) CD3(-)CD56(+) NK cells. These cells expressed high levels of CD161, LFA-1, CD69, NKG2D, NKp30, NKp44, NKp80 and NKp46. UCB-derived NK cells were highly cytotoxic against K562 leukemia cells, although cytotoxicity was slightly lower than in expanded PBMC-derived NK cells. We have developed and optimized a strategy to selectively access a small fraction from cryopreserved UCB and show that large numbers of CD56(+) cells can be expanded from this selectively accessed fraction. This strategy presents a method to explore whether early adoptive transfer of NK cells expanded from the same UCB unit used for transplantation can prevent leukemic relapse and decrease graft-versus-host disease after UCBT.


Accuracy of clinically estimated fetal weight in pregnancies complicated by diabetes mellitus and obesity.
To determine the accuracy of clinically estimated fetal weight (CEFW) in patients with gestational diabetes (GDM), pregestational diabetes (DM), and obesity. This is a retrospective analysis of Consortium of Safe Labor data. Subjects were classified into six groups: DM, DM and obese, GDM, GDM and obese, nondiabetic obese, and controls. The mean difference between birth weight (BW) and CEFW, the percent of accurate CEFW (defined as < 10% difference), and the sensitivity for identifying BW > 4,000 g and > 4,500 g were calculated for each group. The accuracy of CEFW in our population was 54.3 to 64.4% and was significantly lower in patients with DM and obesity and patients with obesity but not diabetes. When CEFW was analyzed in the >4,000-g and > 4,500-g groups, its accuracy was 20 to 51% and 14 to 40%, respectively. CEFW overestimated BW more commonly in GDM, obese GDM, and obese groups. The sensitivity of CEFW for diagnosing BW > 4,000 g or > 4,500 g was 19.6% and 9.6%, respectively, and it improved in pregnancies complicated by diabetes. CEFW is a poor predictor of macrosomia in pregnancies complicated by obesity and diabetes.


Laser-assisted fluoroscopic puncture: a new technique for accessing the kidney.
We developed a laser pointer device that is mounted on the image intensifier of a C-arm fluoroscope. The laser-assisted fluoroscopic puncture technique (LAFPT) is an alternative method of accessing the kidney. The LAFPT was assessed both in an in vitro model and in a series of cases. The in vitro model was composed of Foley balloons filled with contrast medium of different volumes (2-6 mL) embedded in silicone pads. The total fluoroscopy times and attempts required for a successful puncture with LAFPT were compared with those of conventional fluoroscopic access. The number of attempts required to puncture the 2-mL balloons was significantly greater with the conventional fluoroscopic technique than with LAFPT. The fluoroscopy time in vitro was reduced 50% with LAFPT. However, there was no statistically significant difference in the time required for the two techniques in the clinical series. The laser-assisted fluoroscopic puncture technique allows accurate positioning of a needle with reduced radiation exposure.


Personalized feedback to improve CPAP adherence in obstructive sleep apnea.
Obstructive sleep apnea (OSA) is effectively treated with continuous positive airway pressure (CPAP). Low rates of CPAP adherence led to the development of a personalized feedback intervention requiring minimal provider burden. In a comparison of the intervention to standard information, group differences failed to reach significance. Explanations for the findings include low power, that machines were not provided, and an atypical sample. Effect sizes were medium to large at 2 weeks, suggesting that sufficiently powered studies may be warranted.


Randomized clinical trials of raloxifene: reducing the risk of osteoporosis and breast cancer in postmenopausal women.
The P-1 trial of tamoxifen versus placebo for breast cancer prevention in high-risk women provided proof of the concept that chemoprevention was effective. The approval of tamoxifen for this indication in 1998 provided a pharmaceutical agent as an alternative to bilateral mastectomy and/or oophorectomy for women at high risk. Although for some women and their physicians this was a welcome alternative, fear of toxicities from tamoxifen has been a major barrier to its use. Four trials evaluating the role of raloxifene in breast cancer prevention have resulted in the recent approval by the US Food and Drug Administration for postmenopausal women with osteoporosis or at high risk of breast cancer. It has a more favorable toxicity profile than tamoxifen and provides an alternative for postmenopausal women.


Eosinophil 15-lipoxygenase is a leukotriene A4 synthase.
5-Lipoxygenase is the first committed enzyme in the leukotriene biosynthetic pathway and is known to catalyze not only the first oxygenation of arachidonate to form 5(S)-hydroperoxyeicosatetraenoic acid (5(S)-HPETE), but also dehydration of this intermediate into leukotriene A4 (LTA4) by an activity termed leukotriene A4 synthase. Inhibition of cytosolic 5-lipoxygenase prepared from human blood granulocytes with zileuton (100 microM) was virtually complete, but LTA4 synthase activity was only inhibited by 47%. Structural characterization of eicosanoids synthesized in these preparations revealed an abundance of 15-lipoxygenase metabolites including 15-HETE when arachidonate was used as substrate and 5(S),15(S)-dihydroxy-6,8,11,13(E,E,Z,Z)-eicosatetraenoic acid when 5(S)-HPETE was used as substrate. When neutrophils were prepared that contained less than 1% eosinophil contamination, zileuton was found to almost completely inhibit all 5-lipoxygenase, as well as LTA4 synthase products. Immunochemical analysis of the supernatants from purified neutrophils and eosinophils confirmed the previous observation that neutrophils do not express 15-lipoxygenase. Incubation of 5(S)-HPETE with recombinant mammalian 15-lipoxygenase resulted in the formation of 6-trans-LTB4 and 6-trans-12-epi-LTB4 as LTA4 products, as well as the 12-lipoxygenase product 5(S),12(S)-diHPETE. The mechanism of action of 15-lipoxygenase acting as an LTA4 synthase is proposed to involve removing the pro-R hydrogen atom at carbon-10 of 5(S)-HPETE, which is antarafacial to the hydroperoxy group to yield LTA4.


Embedding Raman Tags between Au Nanostar@Nanoshell for Multiplex Immunosensing.
Novel Raman tags with various reporter molecules embedded in between gold nanostar (AuNS) and gold nanoshell are developed, showing significantly enhanced surface-enhanced Raman scattering intensity compared to gold nanoparticle-based composites. Immunoassay using these AuNS@tag@shell structures is highly specific with sensitivity down to 0.1 pg mL-1 , and is capable of multiplex detection, making them highly promising for biosensing applications.


Antebrachial fractures in four captive polar bears (Ursus maritimus).
To identify common risk factors for antebrachial fractures of captive polar bears and to evaluate outcome after fracture repair. Retrospective study. Four captive polar bears. United States zoological collections were surveyed to determine the prevalence of fractures in captive polar bears. Medical records of captive polar bears that had antebrachial fractures were reviewed for signalment, history, physical and radiographic findings, fracture management, postoperative care, and outcome. Serum samples from healthy bears and bears with antebrachial fractures were assayed for 25-hydroxyvitamin D (25-OHD) concentrations. Nineteen fractures (12 polar bears) occurred from 1974 to 2002; 12 fractures involved the antebrachium. Management of 4 antebrachial fractures was reviewed; 3 were repaired by internal fixation and 1 by external coaptation. Fractures healed and bears were returned to exhibit on average 3 months postfracture. Of 11 serum samples assayed for 25-OHD concentrations, 6 were below normal, 1 was low normal and 4 were within normal reference intervals. The 7 bears with subnormal or low normal values were housed in 2 zoos. Subnormal vitamin D concentrations were identified in 2 of 3 bears with fractures. Fracture disease is not uncommon in captive polar bears. Additional research is necessary to explore the role of nutrition in polar bear fracture disease. Internal fixation of antebrachial fractures is feasible and reasonably well tolerated in captive polar bears.


Acute liver failure secondary to acute antibody mediated rejection after compatible liver transplant: A case report.
The liver has traditionally been regarded as resistant to antibody-mediated rejection (AMR). AMR in liver transplants is a field in its infancy compared to kidney and lung transplants. In our case we present a patient with alpha-1-antitrypsin disease who underwent ABO compatible liver transplant complicated by acute liver failure (ALF) with evidence of antibody mediated rejection on allograft biopsy and elevated serum donor-specific antibodies (DSA). This case highlights the need for further investigations and heightened awareness for timely diagnosis. A 56 year-old woman with alpha-1-antitrypsin disease underwent ABO compatible liver transplant from a deceased donor. The recipient MELD at the time of transplant was 28. The flow cytometric crossmatches were noted to be positive for T and B lymphocytes. The patient had an uneventful recovery postoperatively. Starting on postoperative day 5 the patient developed fevers, elevated liver function tests, distributive shock, renal failure, and hepatic encephalopathy. She went into ALF with evidence of antibody mediated rejection with portal inflammation, bile duct injury, endothelitis, and extensive centrizonal necrosis, and C4d staining on allograft biopsy and elevated DSA. Despite various interventions including plasmapheresis and immunomodulating therapy, she continued to deteriorate. She was relisted and successfully underwent liver retransplantation. This very rare case highlights AMR as the cause of ALF following liver transplant requiring retransplantation.


Legal needs of adults with life-limiting illness: what are they and how are they managed? A qualitative multiagency stakeholder exercise.
Little is known about legal needs in the context of life-limiting illness, particularly the need for advice concerning legal arrangements, rights and entitlements. This UK-based multiagency stakeholder engagement exercise scoped legal needs associated with life-limiting illness and identified support structures, gaps and opportunities for practice improvement. Snowball sampling generated a stakeholder group from a wide range of regional and national organisations involved in care of people with life-limiting illness, spanning health, social care, legal support, advice, charities, prison services as well as patient and carer representatives. A coproduced survey of three open questions generated qualitative data, interpreted by thematic analysis. Stakeholders reported a broad spectrum of problems and needs raising legal issues, with no consistency of definition. A classification is proposed, identifying matters concerning rights and entitlements of patients/carers in day-to-day life and decisions around care, both immediate and in the future, as well as professional responsibilities in delivering personalised care. The support structures identified were predominantly online literature, although there was some availability of remote and face-to-face services. Limited awareness of the issues, variable service configuration, fragmentation of care and inequitable access were identified as barriers to support. Stakeholders recognised the need for education and closer multiagency working. 'Legal needs' incorporate wide-ranging issues, but there is inconsistency in perceptions among stakeholders. Practice is variable, risking unmet need. Opportunities for improvement include more formal integration of social welfare legal services in the health context, generating clearer pathways for assessment and management.


[Surgical interventions for ameliorating of equilibrium disorders refractory to conservative therapy].
In cases of vertigo resistant to conservative treatment, surgery can be valuable for labyrinthine fistula, perilymphatic fistula, cupulolithiasis and Menière's disease. For instance, covering a labyrinthine fistula by a fascial graft relieves the vertigo in an amazingly short time. Perilymphatic fistula is verified and treated by tympanotomy and is used for patients with special auditory and/or vestibular features. Cupulolithiasis usually requires no surgical treatment: special postural training will speed recovery, but a few cases need neurectomy of the inferior vestibular nerve. There are several methods of surgical treatment for Menière's disease. In our experience neurectomy of the superior and inferior vestibular nerves on the diseased side together with decompression of the eighth cranial nerve via an extended transtemporal approach to the middle fossa is an excellent method of treating patients with vertigo attacks.


Modeling longitudinal performances on the United States Medical Licensing Examination and the impact of sociodemographic covariates: an application of survival data analysis.
This study models time to passing United States Medical Licensing Examination (USMLE) for the computer-based testing (CBT) start-up cohort using the Cox Proportional Hazards Model. The number of days it took to pass Step 3 was treated as the dependent variable in the model. Covariates were: (1) gender; (2) native language (English or other); (3) medical school location (United States or other); and (4) citizenship (United States or other). Examinees were .59 times as likely to pass USMLE if they were trained abroad. Additionally, examinees who reported having English as their primary language and U.S. citizenship were more likely to ultimately pass USMLE. Finally, though gender was also associated with passing USMLE, its practical significance was very small. Cox regression provides a useful tool for modeling performances in a continuous delivery model. Findings suggest that passing the USMLE sequence tends to be associated with native English-speaking USMGs who also hold U.S. citizenship.


Visual Guidance of Smooth Pursuit Eye Movements.
Smooth pursuit eye movements provide a model system for studying how visual inputs are transformed into commands for accurate movement. The neural circuit for pursuit eye movements is largely known and has strong parallels to the circuits for many other movements. Here, we outline progress in defining the conceptual operations that are performed by the pursuit circuit and in aligning those functions with neural circuit mechanisms. We discuss how the visual motion that drives pursuit is represented in the visual cortex, and how the visuomotor circuits decode that representation to estimate target direction and speed and to create motor commands. We outline a modulatory influence called gain control that evaluates the reliability and value of visual inputs and programs appropriate motor activity. Future research on pursuit in nonhuman primates holds the potential to reveal, at an unprecedented level of detail, how visuomotor circuits create coordinated actions.


Transmission and virological studies of a malignant catarrhal fever syndrome in the Indonesian swamp buffalo (Bubalus bubalis).
A malignant catarrhal fever-like syndrome in indonesian swamp buffalo was experimentally transmitted to one of 2 Bos indicus and 3 of 3 Bos javanicus cattle by intravenous inoculation of 250 ml of citrated, whole blood from affected buffaloes. The 4 cattle developed clinical signs of disease on average 32.5 days after receiving the inoculation of blood. The 4 cattle died after a variable period of illness. None of a further 3 B. javanicus cattle inoculated intravenously with a spleen homogenate prepared from another affected buffalo developed the disease. The experimental disease was clinically and pathologically similar to the natural disease in buffaloes although differences were noted. Attempts to adapt the agent to mice, guinea pigs and rabbits failed. A cytopathic agent (Japanese encephalitis virus) was isolated from the spleen of one buffalo with clinical signs but was not considered significant. Sixty-three B. indicus, 7 B. javanicus (and 6 of their crosses), 3 B. taurus and 4 Bubalus bubalis (Murrah buffalo) were kept in the same quarters where 50 of 177 swamp buffaloes died between September 1979 and May 1982. Four of the 7 B. javanicus cattle developed the clinical signs of disease and died. All the other cattle in contact remained healthy.


The monoclonal antibody 41H16 detects the Leu 4 responder form of human Fc gamma RII.
Human FcR for IgG can be divided into three classes (Fc gamma RI, II, and III) based on their structure and reactivity with mAb. Fc gamma RII can be further subdivided into two categories based on functional and biochemical assays. These two Fc gamma RII subtypes were initially recognized by the failure of T cells from 40% of individuals to proliferate in response to mAb Leu 4 (mouse IgG1, anti-CD3), a response that requires the binding of the Fc region of the Leu 4 mAb to Fc gamma RII on monocyte accessory cells. Inas-much as mouse IgG1, does not bind efficiently to the nonresponder form of Fc gamma RII, mAb Leu 4 is unable to induce proliferation in these individuals. IEF data on Fc gamma RII from Leu 4 responder and nonresponder individuals suggested that the structural gene for Fc gamma RII consisted of two allelic forms R (responder) and N (nonresponder) producing the phenotypes RR, RN, and NN. Thus, exclusive expression of the nonresponder allele in monocytes of "nonresponder" individuals, appeared to be responsible for the lack of proliferation observed. In cooperation with the IVth International Conference on Human Leukocyte Differentiation Antigens, we analyzed CDw32 mAb to determine if they could distinguish the responder and nonresponder forms of Fc gamma RII. We report that mAb 41H16 binds preferentially to the responder allotypic form of Fc gamma RII expressed on human monocytes. When quantitative flow cytometry is used to measure the binding of both mAb 41H16 (responder Fc gamma RII) and mAb IV.3 (all myeloid cell Fc gamma RII), we are able to subdivide the responder population into homozygous and heterozygous responders. In addition, mAb 41H16 blocks the binding of mAb IV.3 to monocytes and inhibits proliferation when added to cells before addition of mAb Leu 4. We also show that polymorphonuclear leukocytes and platelets have the same allotypic differences in the binding of 41H16 as do monocytes. However, a subset of lymphocytes (previously shown to be B cells) expresses the 41H16 epitope with no evidence for donor to donor variability.


Use of the chop hook to stabilize the capsular bag in patients with crystalline lens dislocations and cataracts.
Objective To observe the treatment effects of chop hook-assisted phacoemulsification surgery in patients with crystalline lens dislocation. Methods Thirty-seven eyes with cataracts and crystalline lens dislocations underwent cataract surgery. An L-shaped chop hook was introduced into the anterior chamber, and the tip was pushed or pulled to the centre of the anterior capsular edge of the zonular dialysis during the cataract operation. Postoperative follow-up was conducted for ≥ 1 month. Results All patients' postoperative visual abilities improved except one patient with glaucoma. One patient who underwent -5D intraocular lens implantation exhibited vision of 1/50. Visual acuity was less than 6/20 in 6 eyes, 6/20 to 10/20 in 7 eyes, and greater than 10/20 in 22 eyes. Conclusions L-shaped chop hooks can be used to push or pull the anterior capsular edge of the zonular dialysis for protection and avoidance of further zonular damage. This strategy provides satisfactory effects and reduces use of additional instruments.


Fat digestion and exocrine pancreatic function in primary biliary cirrhosis.
Intestinal bile salt deficiency marginally impairs fat absorption in cholestatic patients. The finding of massive steatorrhea in some patients with primary biliary cirrhosis led us to systematically study and compare fat digestion in control subjects (n = 4) and patients with biliary cirrhosis with (n = 11) and without (n = 3) steatorrhea. The jejunum was anatomically and functionally intact in all subjects, as demonstrated by normal gastrointestinal radiology and xylose absorption, respectively. The intestinal contents were recovered during digestion of a fat meal. Lipolysis, pH, and trypsin activity were measured in whole intestinal contents, whereas bile salts, total lipid, and fatty acid were determined in both total and aqueous phases. The results obtained in controls and patients without steatorrhea were similar. Percentage of lipolysis and intraluminal pH were normal in controls and in both patient groups. The intestinal contents of the patients with steatorrhea had a significantly lesser capacity to solubilize both total lipid and fatty acid in relation to abnormally low aqueous bile salt concentrations. No bile salt deconjugation and only minimal bile salt precipitation were found, thus low aqueous bile salts were strictly related to bile secretory failure. Steatorrhea was always present when aqueous bile salt levels were below 3.0 mM. Intestinal trypsin activity was subnormal in patients with steatorrhea; decreased trypsin activity was related (r = 0.82, p less than 0.001) to reduced intestinal bile salt levels. One patient was found to have severe exocrine pancreatic failure. Administration of medium chain triglycerides was uniformly effective in improving nutrition in patients with steatorrhea, but the course of the disease was unaffected. These results indicate that overt pancreatic failure is uncommon in primary biliary cirrhosis, and that fat maldigestion and steatorrhea, regardless of what degree, are due mainly to low intestinal bile salt levels secondary to bile secretory failure. Finally, subnormal pancreatic function in this disease appears to be related to the bile secretory failure, suggesting either that the lack of bile or bile salts in the intestine depresses pancreatic exocrine function or that both biliary and pancreatic secretions decrease in parallel as part of a widespread secretory failure syndrome.


Characterization and subgrouping of Campylobacter concisus strains using protein profiles, conventional biochemical testing and antibiotic susceptibility.
To characterize and subgroup clinical strains of Campylobacter concisus isolated from patients with gastrointestinal disease. A total of 109 C. concisus isolates from 98 patients obtained between June 1997 and December 1998 were analysed using protein profiles, conventional biochemical tube tests, ApiCampy, and susceptibility patterns by Neosensitabs and E-test. Two groups were identified by using protein profiles. One resembled the ATCC 33237 type strain of oral origin, and a second group differing from it, particularly in the high molecular weight zone. Considerable diversity exists in the lower molecular range of the gels, also within assigned subgroups. Biochemical testing showed differences between the groups in the ability to reduce nitrate, ApiCampy testing also yielded differences between the two assigned groups, although reactions were highly heterogeneous. Resistance to erythromycin, ciprofloxacin, ampicillin, ceftriaxone and tetracycline occurred in 3%, 13%, 7%, 11% and 0% of the isolates when using Neosensitabs. The E-test yielded comparable results 7%, 5%, 0%, 2% and 3%, respectively. Results indicate that C. concisus can be assigned to two broad groups based on differences in protein profiles. No distinct phenotypic marker was identified. Susceptibility patterns are not suitable for discrimination between the two assigned groups. Further studies using a polyphasic approach including the application of genetic methods are needed to assess the complex taxonomy of this potential pathogen.


Analysis of carboxylesterase 2 transcript variants in cynomolgus macaque liver.
Carboxylesterase (CES) is important for the detoxification of a wide range of drugs and xenobiotics. In this study, the hepatic level of CES2 mRNA was examined in cynomolgus macaques used widely in preclinical studies for drug metabolism. Three CES2 mRNAs were present in cynomolgus macaque liver. The mRNA level was highest for cynomolgus CES2A (formerly CES2v3), much lower for cynomolgus CES2B (formerly CES2v1) and extremely low for cynomolgus CES2C (formerly CES2v2). Most various transcript variants produced from cynomolgus CES2B gene did not contain a complete coding region. Thus, CES2A is the major CES2 enzyme in cynomolgus liver. A new transcript variant of CES2A, CES2Av2, was identified. CES2Av2 contained exon 3 region different from wild-type (CES2Av1). In cynomolgus macaques expressing only CES2Av2 transcript, CES2A contained the sequence of CES2B in exon 3 and vicinity, probably due to gene conversion. On genotyping, this CES2Av2 allele was prevalent in Indochinese cynomolgus macaques, but not in Indonesian cynomolgus or rhesus macaques. CES2Av2 recombinant protein showed similar activity to CES2Av1 protein for several substrates. It is concluded that CES2A is the major cynomolgus hepatic CES2, and new transcript variant, CES2Av2, has similar functions to CES2Av1.


Magnetic resonance-only simulation and dose calculation in external beam radiation therapy: a feasibility study for pelvic cancers.
The clinical feasibility of using pseudo-computed tomography (pCT) images derived from magnetic resonance (MR) images for external bean radiation therapy (EBRT) planning for prostate cancer patients has been well demonstrated. This paper investigates the feasibility of applying an MR-derived, pCT planning approach to additional types of cancer in the pelvis. Fifteen patients (five prostate cancer patients, five rectal cancer patients, and five gynecological cancer patients) receiving EBRT at Turku University Hospital (Turku, Finland) were included in the study. Images from an MRCAT (Magnetic Resonance for Calculating ATtenuation, Philips, Vantaa, Finland) pCT method were generated as a part of a clinical MR-simulation procedure. Dose calculation accuracy was assessed by comparing the pCT-based calculation with a CT-based calculation. In addition, the degree of geometric accuracy was studied. The median relative difference of PTV mean dose between CT and pCT images was within 0.8% for all tumor types. When assessing the tumor site-specific accuracy, the median [range] relative dose differences to the PTV mean were 0.7 [-0.11;1.05]% for the prostate cases, 0.3 [-0.25;0.57]% for the rectal cases, and 0.09 [-0.69;0.25]% for the gynecological cancer cases. System-induced geometric distortion was measured to be less than 1 mm for all PTV volumes and the effect on the PTV median dose was less than 0.1%. According to the comparison, using pCT for clinical EBRT planning and dose calculation in the three investigated types of pelvic cancers is feasible. Further studies are required to demonstrate the applicability to a larger cohort of patients.


Statistical Analysis of Zebrafish Locomotor Response.
Zebrafish larvae display rich locomotor behaviour upon external stimulation. The movement can be simultaneously tracked from many larvae arranged in multi-well plates. The resulting time-series locomotor data have been used to reveal new insights into neurobiology and pharmacology. However, the data are of large scale, and the corresponding locomotor behavior is affected by multiple factors. These issues pose a statistical challenge for comparing larval activities. To address this gap, this study has analyzed a visually-driven locomotor behaviour named the visual motor response (VMR) by the Hotelling's T-squared test. This test is congruent with comparing locomotor profiles from a time period. Different wild-type (WT) strains were compared using the test, which shows that they responded differently to light change at different developmental stages. The performance of this test was evaluated by a power analysis, which shows that the test was sensitive for detecting differences between experimental groups with sample numbers that were commonly used in various studies. In addition, this study investigated the effects of various factors that might affect the VMR by multivariate analysis of variance (MANOVA). The results indicate that the larval activity was generally affected by stage, light stimulus, their interaction, and location in the plate. Nonetheless, different factors affected larval activity differently over time, as indicated by a dynamical analysis of the activity at each second. Intriguingly, this analysis also shows that biological and technical repeats had negligible effect on larval activity. This finding is consistent with that from the Hotelling's T-squared test, and suggests that experimental repeats can be combined to enhance statistical power. Together, these investigations have established a statistical framework for analyzing VMR data, a framework that should be generally applicable to other locomotor data with similar structure.