Azithromycin for acute lower respiratory tract infections.
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia. Approximately five million people die from acute respiratory tract infections annually. Among these, pneumonia represents the most frequent cause of mortality, hospitalisation and medical consultation. Azithromycin is a macrolide antibiotic, structurally modified from erythromycin and noted for its activity against some gram-negative organisms associated with respiratory tract infections, particularly Haemophilus influenzae (H. influenzae). To compare the effectiveness of azithromycin to amoxycillin or amoxycillin/clavulanic acid (amoxyclav) in the treatment of LRTI, in terms of clinical failure, incidence of adverse events and microbial eradication. We searched CENTRAL (2014, Issue 10), MEDLINE (January 1966 to October week 4, 2014) and EMBASE (January 1974 to November 2014). Randomised controlled trials (RCTs) and quasi-RCTs, comparing azithromycin to amoxycillin or amoxycillin/clavulanic acid in participants with clinical evidence of an acute LRTI, such as acute bronchitis, pneumonia and acute exacerbation of chronic bronchitis. The review authors independently assessed all potential studies identified from the searches for methodological quality. We extracted and analysed relevant data separately. We resolved discrepancies through discussion. We initially pooled all types of acute LRTI in the meta-analyses. We investigated the heterogeneity of results using the forest plot and Chi(2) test. We also used the index of the I(2) statistic to measure inconsistent results among trials. We conducted subgroup and sensitivity analyses. We included 16 trials involving 2648 participants. We were able to analyse 15 of the trials with 2496 participants. The pooled analysis of all the trials showed that there was no significant difference in the incidence of clinical failure on about days 10 to 14 between the two groups (risk ratio (RR), random-effects 1.09; 95% confidence interval (CI) 0.64 to 1.85). A subgroup analysis in trials with acute bronchitis participants showed significantly lower clinical failure in the azithromycin group compared to amoxycillin or amoxyclav (RR random-effects 0.63; 95% CI 0.45 to 0.88). A sensitivity analysis showed a non-significant reduction in clinical failure in azithromycin-treated participants (RR 0.55; 95% CI 0.25 to 1.21) in three adequately concealed studies, compared to RR 1.32; 95% CI 0.70 to 2.49 in 12 studies with inadequate concealment. Twelve trials reported the incidence of microbial eradication and there was no significant difference between the two groups (RR 0.95; 95% CI 0.87 to 1.03). The reduction of adverse events in the azithromycin group was RR 0.76 (95% CI 0.57 to 1.00). There is unclear evidence that azithromycin is superior to amoxycillin or amoxyclav in treating acute LRTI. In patients with acute bronchitis of a suspected bacterial cause, azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxycillin or amoxyclav. However, most studies were of unclear methodological quality and had small sample sizes; future trials of high methodological quality and adequate sizes are needed.


Spinal fracture in a dog with diffuse idiopathic skeletal hyperostosis.
A six-year-old, spayed female Weimaraner dog was first presented with the complaint of hindlimb paresis and then hindlimb paralysis two years later after colliding with a tree. Radiographs and computed tomography revealed spinal fractures at lumbar vertebrae (L)2-3 and at L4-5. In addition, the spinal column was affected by new bone formation along the vertebral bodies, bridging the disc spaces, as seen in diffuse idiopathic skeletal hyperostosis (DISH). Open reduction and internal fixation was achieved with standard vertebral body plating. This is the first report of DISH-associated spinal fractures after minor trauma in a dog. Surgery resulted in return of the full function after the first, and in improvement of neurologic function after the second incident.


Supporting South Asian carers and those they care for: the role of the primary health care team.
Demographic and socioeconomic changes have increased policy interest in informal carers. However, despite the multicultural nature of British society, most research in this field has been in majority communities. To explore the role of the primary health care team (PHCT) in supporting carers from British South Asian communities. Qualitative study. Four South Asian communities in Leicestershire and West Yorkshire. Focus groups and in-depth interviews were used to assess male and female carers, supported by a literature review. Failure to recognise carers' needs, gaps in service provision, and communication and language issues compromised carers' ability to care. While some carers were positive about the PHCT role, the main weaknesses concerned poor consultation, PHCT attitudes towards carers, and access to appropriate services. South Asian carers' experiences largely parallel those of others, but there are some issues that are distinct, namely, language and communication barriers, culturally inappropriate services, and implicit or explicit racism. The multi-ethnic nature of Great Britain requires that professional practice enhances the ability of minority ethnic communities to provide informal care. The findings underline the important role of the PHCT in ensuring that carers' needs are taken seriously and that appropriate services reach them.


Muscle power output limits fast-start performance in fish.
Fast-starts associated with escape responses were filmed at the median habitat temperatures of six teleost fish: Notothenia coriiceps and Notothenia rossii (Antarctica), Myoxocephalus scorpius (North Sea), Scorpaena notata and Serranus cabrilla (Mediterranean) and Paracirrhites forsteri (Indo-West-Pacific Ocean). Methods are presented for estimating the spine positions for silhouettes of swimming fish. These methods were used to validate techniques for calculating kinematics and muscle dynamics during fast-starts. The starts from all species show common patterns, with waves of body curvature travelling from head to tail and increasing in amplitude. Cross-validation with sonomicrometry studies allowed gearing ratios between the red and white muscle to be calculated. Gearing ratios must decrease towards the tail with a corresponding change in muscle geometry, resulting in similar white muscle fibre strains in all the myotomes during the start. A work-loop technique was used to measure mean muscle power output at similar strain and shortening durations to those found in vivo. The fast Sc. notata myotomal fibres produced a mean muscle-mass-specific power of 142.7 W kg-1 at 20 degrees C. Velocity, acceleration and hydrodynamic power output increased both with the travelling rate of the wave of body curvature and with the habitat temperature. At all temperatures, the predicted mean muscle-mass-specific power outputs, as calculated from swimming sequences, were similar to the muscle power outputs measured from work-loop experiments.


New disease records for hatchery-reared sturgeon. II. Phaeohyphomycosis due to Veronaea botryosa.
A series of fungal cases in hatchery-reared juvenile and young adult Siberian sturgeon Acipenser baerii and white sturgeon A. transmontanus occurred at production facilities in Florida and California, USA, respectively. Affected fish exhibited abnormal orientation and/or buoyancy, emaciation, coelomic distension, exophthalmos, cutaneous erythema, and ulcerative skin and eye lesions. Necropsies revealed haemorrhage throughout the coelom, serosanguinous coelomic effusion and organomegaly with nodular or cystic lesions in multiple organs. Fungal hyphae were observed in 27 fish (24 A. baerii and 3 A. transmontanus) via microscopic examination of tissue wet mounts and on slides prepared from colonies grown on culture media. Histopathological examination of these infected tissues revealed extensive infiltration by melanised fungal hyphae that were recovered in culture. Phenotypic characteristics and sequencing of the fungal isolates with the use of the internal transcribed spacer region and 28S rRNA gene confirmed the aetiological agent as Veronaea botryosa. To our knowledge, this is the first documentation of V. botryosa infection in fish, although melanised fungi of the closely related genus Exophiala are well-known pathogens of freshwater and marine fishes.


Single virus and nanoparticle size spectrometry by whispering-gallery-mode microcavities.
Detecting and characterizing single nanoparticles and airborne viruses are of paramount importance for disease control and diagnosis, for environmental monitoring, and for understanding size dependent properties of nanoparticles for developing innovative products. Although single particle and virus detection have been demonstrated in various platforms, single-shot size measurement of each detected particle has remained a significant challenge. Here, we present a nanoparticle size spectrometry scheme for label-free, real-time and continuous detection and sizing of single Influenza A virions, polystyrene and gold nanoparticles using split whispering-gallery-modes (WGMs) in an ultra-high-Q resonator. We show that the size of each particle and virion can be measured as they continuously bind to the resonator one-by-one, eliminating the need for ensemble measurements, stochastic analysis or imaging techniques employed in previous works. Moreover, we show that our scheme has the ability to identify the components of particle mixtures.


Survey of physician practice behaviors related to diabetes mellitus in the U.S. I. Design and methods.
To conduct a survey among a representative sample of primary care physicians in the U.S. to assess practice behaviors, treatment goals, and beliefs related to management of diabetes mellitus and prevention of its complications. A mail survey with telephone follow-up was conducted among 3481 primary care physicians in active practice in the continental U.S. A stratified probability sample was selected using the files of the American Medical Association and American Osteopathic Association. Four specialties were selected to be included in the study: family physician, general practitioner, internist, and pediatrician. Two versions of a questionnaire were constructed: one for pediatricians containing questions about IDDM only and one for the other three specialties containing questions about both IDDM and NIDDM. Physicians who were not actively engaged in practice or did not see patients with diabetes were excluded. Completed questionnaires were received from 1502 of 3481 sampled physicians. Based on various assumptions of eligibility among nonresponders, an overall response rate to the survey was estimated to be between 65.7 and 86.5%. Discrepancies between specialty identifications as noted on the American Medical Association/American Osteopathic Association files and as self-designated were noted. This report describes the methodology used in the design and conduct of the survey, and data are provided to document the technical success of survey execution. This report provides the methodological basis for a series of separate reports on demographic characteristics of the physicians, their practices and their patients, and on specific attitudes, beliefs, and practice behaviors of primary care physicians in the U.S. with regard to diabetes mellitus.


Nicotine, cotinine, and anabasine inhibit aromatase in human trophoblast in vitro.
Epidemiologic studies suggest that women who smoke have lower endogenous estrogen than nonsmokers. To explore the possible link between cigarette smoking and decreased endogenous estrogens, we have examined the effects of constituents of tobacco on estrogen production in human choriocarcinoma cells and term placental microsomes. In choriocarcinoma cell cultures, nicotine, cotinine (a major metabolite of nicotine), and anabasine (a minor component of cigarette tobacco) all inhibited androstenedione conversion to estrogen in a dose-dependent fashion. Removal of nicotine, cotinine, and anabasine from the culture medium resulted in the complete reversal of the inhibition of aromatase. In the choriocarcinoma cell cultures, a supraphysiologic concentration of androstenedione (73 microM) in the culture medium blocked the inhibition of aromatase caused by nicotine, cotinine, and anabasine. In preparations of term placental microsomes, nicotine, cotinine, and anabasine inhibited the conversion of testosterone to estrogen. Kinetic analysis demonstrated the inhibition to be competitive with respect to the substrate. These findings suggest that some nicotinic alkaloids directly inhibit aromatase. This mechanism may explain, in part, the decreased estrogen observed in women who smoke.


Red Blood Cell Fatty Acids and Incident Diabetes Mellitus in the Women's Health Initiative Memory Study.
The relations between dietary and/or circulating levels of fatty acids and the development of type 2 diabetes is unclear. Protective associations with the marine omega-3 fatty acids and linoleic acid, and with a marker of fatty acid desaturase activity delta-5 desaturase (D5D ratio) have been reported, as have adverse relations with saturated fatty acids and D6D ratio. To determine the associations between red blood cell (RBC) fatty acid distributions and incident type 2 diabetes. Prospective observational cohort study nested in the Women's Health Initiative Memory Study. General population. Postmenopausal women. Self-reported incident type 2 diabetes. There were 703 new cases of type 2 diabetes over 11 years of follow up among 6379 postmenopausal women. In the fully adjusted models, baseline RBC D5D ratio was inversely associated with incident type 2 diabetes [Hazard Ratio (HR) 0.88, 95% confidence interval (CI) 0.81-0.95) per 1 SD increase. Similarly, baseline RBC D6D ratio and palmitic acid were directly associated with incident type 2 diabetes (HR 1.14, 95% CI 1.04-1.25; and HR 1.24, 95% CI 1.14-1.35, respectively). None of these relations were materially altered by excluding incident cases in the first two years of follow-up. There were no significant relations with eicosapentaenoic, docosahexaenoic or linoleic acids. Whether altered fatty acid desaturase activities or palmitic acid levels are causally related to the development of type 2 diabetes cannot be determined from this study, but our findings suggest that proportions of certain fatty acids in RBC membranes are associated with risk for type 2 diabetes.


Orbital sequelae of rhinosinusitis after cochlear implantation in children.
The objectives of this retrospective case review were to describe orbital complications in children after cochlear implantation, to define rhinosinusitis as a possible preoperative risk factor, and to suggest a possible pathophysiological mechanism for this previously unreported occurrence. Records of children undergoing cochlear implantation over a 7-year period at a tertiary academic medical center were reviewed. Four children who experienced postoperative orbital sequelae were identified. We describe the demographics, clinical course, and radiologic findings in these children. The records of 91 children who underwent cochlear implantation were reviewed. The mean age was 6.0 years (range, 0.9-16.9 years). Forty-nine children (54%) were female and 51 (56%) were white. Four children developed postoperative orbital complications on the ipsilateral side to implantation. Orbital complications were characterized by periorbital edema and preseptal cellulitis necessitating prolonged hospitalization in all four children (mean length of stay, 3.3 days). Each child's orbital complication resolved with medical therapy that included intravenous antibiotics and nasal saline. Temporal bone images before implantation showed evidence of rhinosinusitis in all four cases. Of 76 available preoperative scans from the unaffected children, only 11 (14%) studies showed evidence of rhinosinusitis. Children with preoperative radiologic evidence of rhinosinusitis may be at risk of orbital sequelae after cochlear implantation. Positioning of the patient during surgery, length of surgery, and minor trauma to the lamina papyracea during drilling of the mastoid may be important etiologic factors. A careful review of medical history and computed tomography imaging before implantation may identify at-risk children.


Experiments on PMMA models to predict the impact of corneal refractive surgery on corneal shape.
Flat and spherical PMMA surfaces were ablated with a standard refractive surgery laser system. The ratio of profiles on flat to spherical PMMA surfaces was used to estimate experimentally the radial change in ablation efficiency for PMMA and cornea. Changes in ablation efficiency accounted for most of the asphericity increase found clinically, using the same laser system. This protocol is useful to obtain a correction factor for any ablation algorithm and laser system, and to estimate the contribution of biomechanics to the increase of corneal asphericity in myopic refractive surgery.


Workplace rehabilitation and supportive conditions at work: a prospective study.
To investigate the impact of rehabilitation measures on work ability and return to work (RTW), specifically the association between workplace rehabilitation/supportive conditions at work and work ability and RTW over time, among women on long-term sick leave. Questionnaire data were collected (baseline, 6 and 12 months) from a cohort of women (n = 324). Linear mixed models were used for longitudinal analysis of the repeated measurements of work ability index (WAI), work ability score and working degree. These analyses were performed with different models; the explanatory variables for each model were workplace rehabilitation, supportive conditions at work and time. The individuals provided with workplace rehabilitation and supportive conditions (e.g. influence at work, possibilities for development, degree of freedom at work, meaning of work, quality of leadership, social support, sense of community and work satisfaction) had significantly increased WAI and work ability score over time. These individuals scored higher work ability compared to those individuals having workplace rehabilitation without supportive conditions, or neither. Additionally, among the individuals provided with workplace rehabilitation and supportive conditions, working degree increased significantly more over time compared to those individuals with no workplace rehabilitation and no supportive conditions. The results highlight the importance of integrating workplace rehabilitation with supportive conditions at work in order to increase work ability and improve the RTW process for women on long-term sick leave.


Thermobifida fusca cellulases exhibit limited surface diffusion on bacterial micro-crystalline cellulose.
Elucidation of cellulase-cellulose interactions is key to modeling biomass deconstruction and in understanding the processes that lead to cellulase inactivation. Here, fluorescence recovery after photobleaching and single molecule tracking (SMT) experiments are used to assess the surface diffusion of Thermobifida fusca cellulases on bacterial micro-crystalline cellulose. Our results show that cellulases exhibit limited surface diffusion when bound to crystalline cellulose and that a large fraction of the cellulases remain immobile even at temperatures optimal for catalysis. A comparison of our experimental results to Monte Carlo (MC) simulations, which use published diffusion coefficients to model cellulase displacements, shows that even those enzymes that are mobile on the cellulose surface exhibit significantly slower diffusive motions than previously reported. In addition, it is observed that the enzymes that show significant displacements exhibit complex, non-steady surface motions, which suggest that cellulose-bound cellulases exist in molecular states with different diffusive characteristics. These results challenge the notion that cellulases can freely diffuse over cellulose surfaces without catalyzing bond cleavage.


[A Cochrane review on the umbilical cord care and prevention of infections. Antiseptic solutions are not necessary in developed countries but life-saving in developing countries].
One million newborn infants die every year by bacterial infections, which often have entered the body via the umbilicus. A Cochrane systematic review on "Topical umbilical cord care at birth" by J Zupan and P Garner is reviewed. Zupan and Garner conclude that simply to keep the umbilical cord dry and clean is sufficient for healthy, term neonates in rich countries; disinfectants do not offer any advantage. However, cleaning the umbilical cord with disinfectants may reduce the risk of serious bacterial infections in babies in poor countries or in neonatal wards. Observational studies in poor countries indicate that the life of numerous infants can be saved if pregnant women are vaccinated against tetanus and disinfectants are substituted for harmful cord care traditions. This Cochrane review is credible, but it should be updated and considered tentative since no data on sepsis are included. The search strategy should be better described and observational studies (case control and cohort studies) from poor countries should be included since there are no randomized control trials from these countries.


TGR5-dependent hepatoprotection through the regulation of biliary epithelium barrier function.
We explored the hypothesis that TGR5, the bile acid (BA) G-protein-coupled receptor highly expressed in biliary epithelial cells, protects the liver against BA overload through the regulation of biliary epithelium permeability. Experiments were performed under basal and TGR5 agonist treatment. In vitro transepithelial electric resistance (TER) and FITC-dextran diffusion were measured in different cell lines. In vivo FITC-dextran was injected in the gallbladder (GB) lumen and traced in plasma. Tight junction proteins and TGR5-induced signalling were investigated in vitro and in vivo (wild-type [WT] and TGR5-KO livers and GB). WT and TGR5-KO mice were submitted to bile duct ligation or alpha-naphtylisothiocyanate intoxication under vehicle or TGR5 agonist treatment, and liver injury was studied. In vitro TGR5 stimulation increased TER and reduced paracellular permeability for dextran. In vivo dextran diffusion after GB injection was increased in TGR5-knock-out (KO) as compared with WT mice and decreased on TGR5 stimulation. In TGR5-KO bile ducts and GB, junctional adhesion molecule A (JAM-A) was hypophosphorylated and selectively downregulated among TJP analysed. TGR5 stimulation induced JAM-A phosphorylation and stabilisation both in vitro and in vivo, associated with protein kinase C-ζ activation. TGR5 agonist-induced TER increase as well as JAM-A protein stabilisation was dependent on JAM-A Ser285 phosphorylation. TGR5 agonist-treated mice were protected from cholestasis-induced liver injury, and this protection was significantly impaired in JAM-A-KO mice. The BA receptor TGR5 regulates biliary epithelial barrier function in vitro and in vivo through an impact on JAM-A expression and phosphorylation, thereby protecting liver parenchyma against bile leakage.


Effect of development on coronary vasodilator reserve in the isolated guinea pig heart.
Morphological studies have demonstrated an age-related decrease in capillary density and capillary surface area in the developing heart. However, the consequences of these changes on myocardial perfusion are not known. We tested the hypothesis that the decreased capillary density is associated with a reduction in coronary blood flow reserve. To test this hypothesis, we studied coronary responses to adenosine and sodium nitroprusside administration, reactive hyperemia, and autoregulatory capacity. We used a Langendorff-perfused heart preparation from guinea pigs of five different age groups (1 week and 1, 2, 12, and 18 months). Data are expressed as mean +/- SEM. Maximal coronary flows (ml/min per g) in response to adenosine (10(-6) to 10(-5) M) infusion are: 27 +/- 1.3, 18.5 +/- 1.4, 12.2 +/- 0.4, 10.3 +/- 0.3, and 10.6 +/- 0.8 at 1 week, 1, 2, 12, and 18 months, respectively, with the flows at 1 week and 1 month significantly higher than those at 2, 12, and 18 months. There is a similar trend for a decreased maximum coronary perfusion in response to sodium nitroprusside (10(-6) to 10(-5) M) and following a 45-second occlusion of the coronary inlet flow. Despite the decreased maximal pharmacological and reactive hyperemic flow reserve, autoregulation of flow is not altered with growth. The pressure-flow relationship exhibits autoregulation between 25 and 55 mm Hg perfusion pressure for all but the 1-week age group, which autoregulates within a narrower range of pressures (20-45 mm Hg). Total maximal coronary flow (ml/min) increases during development; this indicates that the growth of vessels continues with development.(ABSTRACT TRUNCATED AT 250 WORDS)


2-Amino-pyridin-1-ium triiodide.
The asymmetric unit of the title compound, C5H7N2 (+.)I3 (-), consists of one 2-amino-pyridin-1-ium cation (apyH(+)) and one triiodide anion, both located in general postions. The apyH(+) cation is planar within the experimental uncertainties. The short N-C distance [1.328 (5) Å] of the exocyclic NH2 group is typical for the imino-form of protonated 2-amino-pyridines. Consequently, the bond lengths within the six-membered ring vary significantly. The geometric parameters of the triiodide anion are in the typical range, with bond lengths of 2.8966 (3) and 2.9389 (3) Å and a bond angle of 176.02 (1)°. In the crystal, N-H ⋯ I hydrogen bonds connect adjacent ions into screwed chains along the b-axis direction. These chains are twisted pairwise into rectangular rods. The pyridinium moieties of neighbouring rods are arranged parallel to each other with a plane-to-plane distance of 3.423 (5) Å.


Cohort Profile: Multimorbidity in Children and Youth Across the Life-course (MY LIFE) Study.
This manuscript serves to provide an overview of the methods of the Multimorbidity in Children and Youth across the Life-course (MY LIFE) study, profile sample characteristics of the cohort, and provide baseline estimates of multimorbidity to foster collaboration with clinical and research colleagues across Canada. MY LIFE is comprised of 263 children (2-16 years) with a physical illness recruited from McMaster Children's Hospital, their primary caregiving parent, and their closest-aged sibling. Participants are followed with data collection at recruitment, 6, 12, and 24 months which includes structured interviews, self-reported measures, and biological samples and occur in a private research office or at participants' homes. Post-COVID-19, data collection transitioned to mail and telephone surveys. At recruitment, children were 9.4 (4.2) years of age and 52.7% were male. The mean duration of their physical illness was 4.5 (4.1) years; 25% represent incident cases (duration <1 year). Most (69.7%) had healthy body weight and intelligence in the average range (73.5%). Overall, 38.2% of children screened positive for ≥1 mental illness according to parent report (24.8% screened positive based on child self-report). Compared to 2016 Census data, the MY LIFE cohort overrepresents families of higher socioeconomic status. Multimorbidity is common among children and these baseline data will serve to measure relative changes in the mental health of children with physical illness over time. MY LIFE will provide new information for understanding multimorbidity among children, though underrepresentation of lower socioeconomic families may have implications for the generalizability of findings.


The interaction of selected semiconducting biomaterials with platelet-rich plasma and whole blood.
Copper and silicon are used as biomaterials in various forms. Silicon is a well-known semiconductor and has two distinct types (n-type and p-type), depending on the dopants used. The oxides (e.g., CuO and Cu2O) on the copper surface also behave as semiconductors. The electrochemical properties of these two selected semiconducting biomaterials were investigated by cyclic voltammetry, electrochemical impedance spectroscopy (EIS), and open-circuit potential (OCP) in an aerated Ringer's solution at 37 degrees C. Platelet-rich plasma (PRP) and whole blood from a healthy human donor were used to determine the degree of interaction with the selected semiconducting materials in vitro. Morphologies of adherent platelets and blood on these two biomaterials were examined by scanning electron microscopy (SEM). Experimental results indicated that the degree of interaction is a function of the electrochemical properties of these two biomaterials. Platelets and blood were found to react strongly with p-type biomaterials while little or no sign of interaction with n-type biomaterials was demonstrated. The difference in PRP and whole blood reactions between p-type and n-type semiconductors was quantified to be significant as p<0.05.


Seeing Is Believing: Photon Counting Computed Tomography Clearly Images Directional Deep Brain Stimulation Lead Segments and Markers After Implantation.
Directional deep brain stimulation (DBS) electrodes are increasingly used, but conventional computed tomography (CT) is unable to directly image segmented contacts owing to physics-based resolution constraints. Postoperative electrode segment orientation assessment is necessary because of the possibility of significant deviation during or immediately after insertion. Photon-counting detector (PCD) CT is a relatively novel technology that enables high resolution imaging while addressing several limitations intrinsic to CT. We show how PCD CT can enable clear in vivo imaging of DBS electrodes, including segmented contacts and markers for all major lead manufacturers. We describe postoperative imaging and reconstruction protocols we have developed to enable optimal lead visualization. PCD CT images were obtained of directional leads from the three major manufacturers and fused with preoperative 3T magnetic resonance imaging (MRI). Radiation dosimetry also was evaluated and compared with conventional imaging controls. Orientation estimates from directly imaged leads were compared with validated software-based reconstructions (derived from standard CT imaging artifact analysis) to quantify congruence in alignment and directional orientation. High-fidelity images were obtained for 15 patients, clearly indicating the segmented contacts and directional markers both on CT alone and when fused to MRI. Our routine imaging protocol is described. Ionizing radiation doses were significantly lower than with conventional CT. For most leads, the directly imaged lead orientations and depths corresponded closely to those predicted by CT artifact-based reconstructions. However, unlike direct imaging, the software reconstructions were susceptible to 180° error in orientation assessment. High-resolution photon-counting CT can very clearly image segmented DBS electrode contacts and directional markers and unambiguously determine lead orientation, with lower radiation than in conventional imaging. This obviates the need for further imaging and may facilitate anatomically tailored directional programming.


The effect of acute oral erythromycin on gallbladder motility and on upper gastrointestinal symptoms in gastrectomized patients with and without gallstones: a randomized, placebo-controlled ultrasonographic study.
Gastrectomy might be a risk factor for cholelithiasis and gallbladder stasis might play a major role. We studied fasting and postprandial gallbladder motility with 600 mg oral erythromycin or placebo in gastrectomized patients (with and without gallstones) and controls. Seventeen patients operated on for gastric cancer (subtotal gastrectomy: n = 10, total gastrectomy: n = 7) were compared with 20 sex- and body-size matched healthy controls. Subjects randomly received erythromycin or placebo 30 min before the ingestion of a standard 200 ml liquid test meal. Gallbladder volume was estimated by ultrasonography until 120 min after test meal. A visual analog scale monitored GI perception of appetite, satiety, nausea, abdominal fullness and epigastric pain. Gastrectomized patients had increased fasting gallbladder volume (35.9 +/- 3.4 ml versus 21.0 +/- 1.4 ml, p = 0.0005) with faster postmeal emptying (T/2 14.8 +/- 1.1 min versus 23.5 +/- 1.5 min, p = 0.00019) than controls. Six patients developed small and asymptomatic gallstones, which did not influence gallbladder motility. In these patients, fasting gallbladder volume increased with time after surgery (r = +0.82, p = 0.047). Perception of satiety, abdominal fullness, and epigastric pain after ingestion of the test meal were all significantly greater in patients than in controls. Erythromycin significantly enhanced gallbladder emptying during fasting (p = 0.001) and postprandially in both patients and controls (0.002 < p < 0.017) and significantly reduced postmeal satiety and epigastric discomfort in gastrectomized patients. Increased fasting volume might be a form of stasis, predisposing patients to gallstone formation. Erythromycin improves fasting and postprandial gallbladder emptying and decreases upper GI symptoms in gastrectomized patients.


New Evaluation Procedure for Multi-Dimensional Mechanical Strains and Tangent Moduli of Breast Implants: IDEAL IMPLANT® Structured Breast Implant Compared to Silicone Gel Implants.
The IDEAL IMPLANT® Structured Breast Implant is a dual lumen saline-filled implant with capsular contracture and deflation/rupture rates much lower than single-lumen silicone gel-filled implants. To better understand the implant's mechanical properties and to provide a potential explanation for these eight-year clinical results, a novel approach to compressive load testing was employed. Multi-dimensional strains and tangent moduli, metrics describing the shape stability of the total implant, were derived from the experimental load and platen spacing data. The IDEAL IMPLANT was found to have projection, diametric, and areal strains that were generally less than silicone gel implants, and tangent moduli that were generally greater than silicone gel implants. Despite having a relatively inviscid saline fill, the IDEAL IMPLANT was found to be more shape stable compared to gel implants, which implies potentially less interaction with the capsule wall when the implant is subjected to compressive loads. Under compressive loads, the shape stability of a higher cross-link density, cohesive gel implant was unexpectedly found to be similar to or the same as a gel implant. In localized diametric compression testing, the IDEAL IMPLANT was found to have a palpability similar to a gel implant, but softer than a cohesive gel implant.


Thermodynamic evidence for a dual transport mechanism in a POT peptide transporter.
Peptide transport plays an important role in cellular homeostasis as a key route for nitrogen acquisition in mammalian cells. PepT1 and PepT2, the mammalian proton coupled peptide transporters (POTs), function to assimilate and retain diet-derived peptides and play important roles in drug pharmacokinetics. A key characteristic of the POT family is the mechanism of peptide selectivity, with members able to recognise and transport >8000 different peptides. In this study, we present thermodynamic evidence that in the bacterial POT family transporter PepTSt, from Streptococcus thermophilus, at least two alternative transport mechanisms operate to move peptides into the cell. Whilst tri-peptides are transported with a proton:peptide stoichiometry of 3:1, di-peptides are co-transported with either 4 or 5 protons. This is the first thermodynamic study of proton:peptide stoichiometry in the POT family and reveals that secondary active transporters can evolve different coupling mechanisms to accommodate and transport chemically and physically diverse ligands across the membrane.


Staff judgements of responsibility for the challenging behaviour of adults with intellectual disabilities.
This study examines the importance of staff judgements of responsibility for challenging behaviour in predicting their emotional and intended helping responses. Sixty-two carers completed questionnaires rating attributions of internality, stability and controllability, emotions of sympathy and anger, judgements of responsibility for the development of challenging behaviour and for its resolution and intended effort in helping in response to a scenario describing an aggressive behaviour. Results showed significant correlations between judgements of responsibility and attributions, emotions and intended effort in helping. Regression analysis showed that the best predictor of intended helping is the emotion of sympathy and that sympathy is best predicted by the attribution of internality, the judgement that people are not responsible for the development of challenging behaviour and the judgement that they are responsible for the resolution of the behaviour. Judgements of responsibility predict emotional and intended behavioural responses of carers of people with intellectual disabilities and challenging behaviour. The results are discussed in relation to previous work on carer attributions in response to challenging behaviour. Implications for clinical work with carers are considered.


Cancer risk among tetrafluoroethylene synthesis and polymerization workers.
Tetrafluoroethylene (TFE), a compound used for the production of fluorinated polymers including polytetrafluoroethylene, increases the incidence of liver and kidney cancers and leukemia in rats and mice. This is the first time the cancer risk in humans has been explored comprehensively in a cohort mortality study (1950-2008) that included all polytetrafluoroethylene production sites in Europe and North America at the time it was initiated. A job-exposure matrix (1950-2002) was developed for TFE and ammonium perfluoro-octanoate, a chemical used in the polymerization process. National reference rates were used to calculate standardized mortality ratios (SMRs) and 95% confidence intervals. Among 4,773 workers ever exposed to TFE, we found a lower rate of death from most causes, as well as increased risks for cancer of the liver (SMR = 1.27; 95% confidence interval: 0.55, 2.51; 8 deaths) and kidney (SMR = 1.44; 95% confidence interval: 0.69, 2.65; 10 deaths) and for leukemia (SMR = 1.48; 95% confidence interval: 0.77, 2.59; 12 deaths). A nonsignificant upward trend (P = 0.24) by cumulative exposure to TFE was observed for liver cancer. TFE and ammonium perfluoro-octanoate exposures were highly correlated, and therefore their separate effects could not be disentangled. This pattern of findings narrows the range of uncertainty on potential TFE carcinogenicity but cannot conclusively confirm or refute the hypothesis that TFE is carcinogenic to humans.


Effect of computer-assisted interviewing on self-reported sexual behavior data in a microbicide clinical trial.
In a microbicide safety and effectiveness trial (HPTN 035) in Malawi, 585 women completed the same questionnaire through a face-to-face interview (FTFI) and an audio computer-assisted self-interview (ACASI). Concordance between FTFI and ACASI responses ranged from 72.0 % for frequency of sex in the past week to 95.2 % for anal intercourse (AI) in the past 3 months. Reported gel and condom use at last sex act were marginally lower with ACASI than FTFI (73.5 % vs. 77.2 %, p = 0.11 and 60.9 % vs. 65.5 %, p = 0.05, respectively). More women reported AI with ACASI than FTFI (5.0 % vs. 0.2 %, p < 0.001). Analyses of consistency of responses within ACASI revealed that 15.0 % of participants in the condom-only arm and 28.7 % in the gel arm provided at least one discrepant answer regarding total sex acts and sex acts where condom and gel were used (19.2 % reported one inconsistent answer, 8.1 % reported two inconsistent answers, and 1.4 % reported three inconsistent answers). While ACASI may provide more accurate assessments of sensitive behaviors in HIV prevention trials, it also results in a high level of internally inconsistent responses.


Spatial synchrony in sub-arctic geometrid moth outbreaks reflects dispersal in larval and adult life cycle stages.
Spatial synchrony in population dynamics can be caused by dispersal or spatially correlated variation in environmental factors like weather (Moran effect). Distinguishing between these mechanisms is challenging for natural populations, and the study of dispersal-induced synchrony in particular has been dominated by theoretical modelling and laboratory experiments. The goal of the present study was to evaluate the evidence for dispersal as a cause of meso-scale (distances of tens of kilometres) spatial synchrony in natural populations of the two cyclic geometrid moths Epirrita autumnata and Operophtera brumata in sub-arctic mountain birch forest in northern Norway. To infer the role of dispersal in geometrid synchrony, we applied three complementary approaches, namely estimating the effect of design-based dispersal barriers (open sea) on synchrony, comparing the strength of synchrony between E. autumnata (winged adults) and the less dispersive O. brumata (wingless adult females), and relating the directionality (anisotropy) of synchrony to the predominant wind directions during spring, when geometrid larvae engage in windborne dispersal (ballooning). The estimated effect of dispersal barriers on synchrony was almost three times stronger for the less dispersive O. brumata than E. autumnata. Inter-site synchrony was also weakest for O. brumata at all spatial lags. Both observations argue for adult dispersal as an important synchronizing mechanism at the spatial scales considered. Further, synchrony in both moth species showed distinct anisotropy and was most spatially extensive parallel to the east-west axis, coinciding closely to the overall dominant wind direction. This argues for a synchronizing effect of windborne larval dispersal. Congruent with most extensive dispersal along the east-west axis, E. autumnata also showed evidence for a travelling wave moving southwards at a speed of 50-80 km/year. Our results suggest that dispersal processes can leave clear signatures in both the strength and directionality of synchrony in field populations, and highlight wind-driven dispersal as promising avenue for further research on spatial synchrony in natural insect populations.


Aminopeptidase N activity predicts 5-year survival in colorectal cancer patients.
Aminopeptidase N (APN; EC 126.96.36.199) is a membrane dimeric metallopeptidase involved in differentiation, development, and proliferative processes of several tissues. Recent studies have demonstrated the increased expression and activity of this enzyme in several cancers. However, there are no available data about the impact of this peptidase in the biological aggressiveness and the survival of colorectal cancer (CRC) patients. The activity and mRNA expression of APN in tumor tissue (n = 81) and plasma (n = 40) of patients with CRC of low and high grades and stages were prospectively analyzed by fluorimetric and quantitative reverse transcriptase-polymerase chain reaction methods. Data obtained in adenoma and CRC were compared with those from the surrounding normal mucosa. Classic clinical and pathological parameters were stratified following APN data and analyzed for 5-year survival. mRNA levels of APN (ANPEP) were lower in colorectal adenomas and adenocarcinomas than in the surrounding uninvolved mucosa (Kruskal-Wallis, P < 0.001). Aminopeptidase N activity in CRC tissue was higher in patients with better overall survival (log-rank P < 0.05, Cox analysis P < 0.05). By contrast, higher plasmatic APN activity correlated with worse overall survival (log-rank P < 0.01, Cox analysis P < 0.05). Aminopeptidase N activity in tissue and plasma from CRC patients is an independent prognostic factor of 5-year survival. The determination of APN activity levels in the plasma may be a safe, minimally invasive, and inexpensive way to define the aggressiveness of CRC in daily practice.


Local area cartilage segmentation: a semiautomated novel method of measuring cartilage loss in knee osteoarthritis.
To assess the responsiveness and reader time of a novel semiautomated tool to detect knee cartilage loss over 2 years in subjects with knee osteoarthritis. A total of 122 subjects from the Osteoarthritis Initiative progression cohort were selected. A reader used the software method to segment cartilage on double-echo steady-state sequence scans in the medial compartment of the femur from the baseline and 24-month visits. Change in cartilage volume (ΔV) was measured at a fixed weight-bearing (WB) location with respect to the 3-dimensional coordinate system based on cylindrical coordinates. Change was measured for 5 regions of varying WB surface area centered on the fixed point. The average change (ΔV), the SD of ΔV, and the standardized response mean (SRM) are reported. The SRM was −0.52 for the largest region and decreased in magnitude as smaller regions of cartilage were probed. The average evaluation time was <20 minutes per knee compartment, split approximately evenly between a technician and a trained reader. The results establish that measurement of cartilage loss in a local region can be done efficiently and that the resultant measures are responsive to loss of cartilage over time. The coordinate system can potentially be used to objectively examine and establish a consistent location for all knees that is most responsive to change in cartilage volume. This technique can provide rapidly an objective quantitative measure of cartilage loss and could substantially reduce study costs for large trials and data sets.


The propagation of perturbations in rewired bacterial gene networks.
What happens to gene expression when you add new links to a gene regulatory network? To answer this question, we profile 85 network rewirings in E. coli. Here we report that concerted patterns of differential expression propagate from reconnected hub genes. The rewirings link promoter regions to different transcription factor and σ-factor genes, resulting in perturbations that span four orders of magnitude, changing up to ∼ 70% of the transcriptome. Importantly, factor connectivity and promoter activity both associate with perturbation size. Perturbations from related rewirings have more similar transcription profiles and a statistical analysis reveals ∼ 20 underlying states of the system, associating particular gene groups with rewiring constructs. We examine two large clusters (ribosomal and flagellar genes) in detail. These represent alternative global outcomes from different rewirings because of antagonism between these major cell states. This data set of systematically related perturbations enables reverse engineering and discovery of underlying network interactions.


Outcomes after stereotactic radiosurgery for schwannomas of the oculomotor, trochlear, and abducens nerves.
Cranial nerve (CN) schwannomas are intracranial tumors that are commonly managed by stereotactic radiosurgery (SRS). There is a large body of literature supporting the use of SRS for vestibular schwannomas. Schwannomas of the oculomotor nerves (CNs III, IV, and VI) are rare skull base tumors, occurring close to the brainstem and often involving the cavernous sinus. Resection can cause significant morbidity, including loss of nerve function. As for other schwannomas, SRS can be used to manage these tumors, but only a handful of cases have been published so far, often among reports of other uncommon schwannoma locations. The goal of this study was to collect retrospective multicenter data on tumor control, clinical evolution, and morbidity after SRS. This study was performed through the International Radiosurgery Research Foundation. Patients managed with single-session SRS for an oculomotor cranial nerve schwannoma (CN III, IV, or VI) were included. The diagnosis was based on diplopia or ptosis as the main presenting symptom and anatomical location on the trajectory of the presumed cranial nerve of origin, or prior resection confirming diagnosis. Demographic, SRS dose planning, clinical, and imaging data were collected from chart review of the treated patients. Chi-square and Kaplan-Meier analyses were performed. Seven institutions submitted data for a total of 25 patients. The median follow-up time was 41 months. The median age at the time of treatment was 52 years. There were 11 CN III schwannomas, 11 CN IV schwannomas, and 3 CN VI schwannomas. The median target volume was 0.74 cm3, and the median marginal dose delivered was 12.5 Gy. After SRS, only 2 patients (including the only patient with neurofibromatosis type 2) had continued tumor growth. Crude local control was 92% (23/25), and the 10-year actuarial control was 86%. Diplopia improved in the majority of patients (11/21), and only 3 had worsening following SRS, 2 of whom also had worsened ptosis, both in the context of tumor progression. SRS for schwannomas of the oculomotor, trochlear, and abducens nerves is effective and provides tumor control rates similar to those for other cranial nerve schwannomas. SRS allows improvement of diplopia in the majority of patients. SRS should therefore be considered as a first-line treatment option for oculomotor nerve schwannomas.


Atypical and anaplastic meningiomas: prognostic implications of clinicopathological features.
To evaluate patient outcome and investigate the prognostic factors of high-grade meningiomas by adopting the 2000 World Health Organization (WHO) classification system. Between 1986 and 2004, 74 patients were diagnosed with high-grade meningioma: 33 with atypical and 41 with anaplastic meningioma. The mean follow-up was 58.5 months. We reclassified all surgical specimens, according to the 2000 WHO classification system, using two expert neuropathologists. Forty of 74 meningiomas were reclassified as atypical meningioma and 24 as anaplastic meningioma. Overall and recurrence-free survivals were significantly longer in patients with atypical than in those with anaplastic meningioma: 142.5 versus 39.8 months and 138.5 versus 32.2 months, respectively (p<0.001). In patients with atypical meningiomas, brain invasion and adjuvant radiotherapy were not associated with survival; however, in the brain invasion subgroup, adjuvant radiotherapy improved patients' survival. In patients with anaplastic meningioma, the prognostic factors were brain invasion, adjuvant radiotherapy, malignant progression, p53 overexpression and extent of resection. The p53 overexpression was the only factor associated with malignant progression (p = 0.009). The 2000 WHO classification has identified the truly aggressive meningiomas better than did the previous criteria. A precise meningioma grading system may help to avoid over-treatment of patients with an atypical meningioma as, once the tumour has "declared itself" by recurrence and histological features, it becomes a tumour that is poorly amenable to current therapies.


Quantitative analysis of simultaneous EEG features during PET studies for childhood partial epilepsy.
To demonstrate the significance of simultaneous electroencephalography (EEG) recording during 2-deoxy-2-[(18)F] fluoro-D-glucose (FDG)-positron emission tomography (PET) in childhood partial epilepsy. We included 46 children with partial epilepsy who underwent simultaneous EEG during PET. We compared the epileptogenic area of several EEG features including epileptiform discharges, focal polymorphic slow waves, and electrographic seizures, with the abnormal metabolic region on PET. We also compared the epileptogenic area of simultaneous EEG and PET with findings on magnetic resonance imaging (MRI) and video/EEG, as well as the histopathological diagnosis of the resected cortical area, in eight patients who underwent surgical resection of the epileptogenic area. Hypometabolic regions on interictal PET were concordant with epileptogenic areas of epileptiform discharges and focal polymorphic slow waves, according to their frequency and/or severity, with odds ratios of 1.35 and 1.81, respectively (p<0.05). Hypermetabolic PET was also concordant with epileptogenic areas of ictal events longer than 20 seconds during the period of FDG uptake. Among the eight patients who underwent surgical resection, six patients, including two with non-lesional MRI, had concordant EEG and PET findings, were confirmed pathologically, and became seizure-free after surgery. Simultaneous EEG is useful in identifying epileptogenic areas due to a high concordance with abnormal PET metabolic areas. Moreover, simultaneous EEG may also prevent false lateralization of PET from postictal and mixed metabolism during ictal events, as well as abnormal hypermetabolism, during frequent interictal epileptiform discharges.


Joint blind restoration and surface recovery in photometric stereo.
We address the problem of simultaneous estimation of scene structure and restoration of images from blurred photometric measurements. In photometric stereo, the structure of an object is determined by using a particular reflectance model (the image irradiance equation) without considering the blurring effect. What we show is that, given arbitrarily blurred observations of a static scene captured with a stationary camera under different illuminant directions, we still can obtain the structure represented by the surface gradients and the albedo and also perform a blind image restoration. The surface gradients and the albedo are modeled as separate Markov random fields, and a suitable regularization scheme is used to estimate the different fields as well as the blur parameter. The results of the experimentations are illustrated with real as well as synthetic images.


A Novel Luciferase Assay For Sensitively Monitoring Myocilin Variants in Cell Culture.
Primary open angle glaucoma-associated mutations in myocilin (MYOC) cause protein "nonsecretion," rendering secreted MYOC difficult to detect using conventional techniques. This study focused on developing and using an assay that can quickly and easily detect mutant MYOC secretion. We fused Gaussia luciferase (eGLuc2) to MYOC variants and expressed the constructs in HEK-293T and NTM-5 cells. Secreted and intracellular levels of MYOC eGLuc2 variants were evaluated by Western blotting and compared to untagged and FLAG-tagged MYOC constructs. Secreted and soluble intracellular MYOC eGLuc2 were measured by a GLuc assay. The secretion of nine additional MYOC mutants was assayed in conditioned media from transfected cells to test the applicability of the assay for monitoring other MYOC variants. Myocilin eGLuc2 behaved similarly to untagged and FLAG-tagged MYOC with respect to secretion, soluble intracellular levels, and in response to drug treatment. The GLuc assay could sensitively detect Y437H MYOC secretion 30 minutes after media change. Gaussia luciferase fused variants followed anticipated trends; nonpathogenic variants (D208E, G244V) were secreted at wild-type (WT) levels, whereas predicted disease-causing variants (C245Y, G246R, E300K, Y437H, I477N) demonstrated substantial secretion defects. Secretion defects caused by the C245Y, G246R, and Y437H mutations were partially rescued by permissive growth temperature. Interestingly, however, this increase in secretion was independent of newly synthesized protein. Fusion of eGLuc2 to MYOC does not significantly change the behavior of MYOC. This newly developed MYOC reporter system can be used to study engineered MYOC variants and potentially to identify modulators of MYOC secretion and function.


Race/ethnicity, income, major risk factors, and cardiovascular disease mortality.
We explored differences between Black and White men for cardiovascular disease (CVD) mortality across major risk factor levels. Major CVD risk factors were measured among 300,647 White and 20,223 Black men aged 35 to 57 years who were screened for the Multiple Risk Factor Intervention Trial (MRFIT). Hazard ratios for CVD deaths for Black and White men over 25 years of follow-up were calculated for subgroups stratified according to risk factor levels. CVD was responsible for 2518 deaths among Black men and 30,772 deaths among White men. The age-adjusted Black-to-White CVD hazard ratio was 1.35 (95% confidence interval [CI]=1.29, 1.40); the risk- and income-adjusted ratio was 1.05 (95% CI=1.01, 1.10). CVD mortality rates were dramatically lower in cases of favorable risk profiles. However, fully adjusted Black-to-White CVD hazard ratios within groups at low, intermediate, high, and very high levels of overall risk were 1.76, 1.20, 1.10, and 0.94, respectively. Similar gradients were evident for individual risk factors. Higher CVD mortality rates among Black men were largely mediated by risk factors and income. These data underscore the need for sustained primordial risk factor prevention among Black men.


Foot orthoses for the treatment of plantar fasciitis.
The literature suggests mechanical interventions such as foot orthoses and night splints are effective in reducing pain from plantar fasciitis. There is, however, a lack of controlled trials. We studied the effects of foot orthoses and night splints, alone or combined, in a prospective, randomized trial with 1-year followup. Forty-three patients (34 women and nine men with a mean age of 46 years) with plantar fasciitis were randomized to receive foot orthoses (n = 13), foot orthoses and night splints (n = 15), or night splints alone (n = 15). Data were available for 34 (79%) patients after treatment (12 weeks), and for 38 (88%) at 1-year followup. Pain, functional limitations, and quality of life were evaluated with the Foot and Ankle Outcome Score. All groups improved significantly in all outcomes evaluated across all times (p < 0.04). At 12 weeks, pain reduction of 30% to 50% compared to baseline were seen (p < 0.03). At 52 weeks, pain reduction of 62% was seen in the two groups using foot orthoses compared to 48% in the night splint only group (p < 0.01). Better compliance and fewer side effects were reported for orthosis use. At 12 months, 19 of 23 patients reported still using foot orthoses compared to 1 of 28 still using the night splint. Foot orthoses and anterior night splints were effective both short-term and long-term in treating pain from plantar fasciitis. Parallel improvements in function, foot-related quality of life, and a better compliance suggest that a foot orthosis is the best choice for initial treatment plantar fasciitis.


Association between endogenous feline leukemia virus loads and exogenous feline leukemia virus infection in domestic cats.
Recently, we demonstrated that endogenous feline leukemia virus (enFeLV) loads may vary among cats of different populations and that FeLV-infected cats have higher enFeLV loads than uninfected cats. Thus, we hypothesized that enFeLV might influence the pathogenesis and outcome of FeLV infection. No significant difference in the infection outcome (regressive versus progressive infection) was observed between groups of cats with high or low enFeLV loads following FeLV-A challenge. However, cats with high enFeLV loads showed higher viral replication (plasma viral RNA and p27 antigen levels) than cats with low enFeLV loads in the early phase of the infection. The enFeLV transcription level varied at different time points, but no clear-cut pattern was observed. In conclusion, our results demonstrated an association between enFeLV loads and FeLV replication but not outcome of infection. enFeLV should be considered as an important confounder in experimental FeLV infection or vaccination studies.


Transplantation of CTLA4Ig gene-transduced adipose tissue-derived mesenchymal stem cells reduces inflammatory immune response and improves Th1/Th2 balance in experimental autoimmune thyroiditis.
Autoimmune thyroiditis is one of common organ-specific autoimmune disease. The aim of this study was to observe the effect of adipose tissue derived mesenchymal stem cells (ATMSC) and CTLA4Ig gene-transduced ATMSC on autoimmune thyroiditis. Experimental autoimmune thyroiditis was induced by immunization with thyroglobulin. Animals were divided into three groups: (i) a half million of human ATMSC, (ii) a half million of murine CLTA4Ig gene-transduced human ATMSC (CTLA4Ig-MSC), or (iii) normal saline (as control), which were administered intravenously four times within a 3-week period. Blood and tissue samples were collected 1 week after the last cell transplantation. The absorbance of serum thyroglobulin autoantibody (TgAA) in the CTLA4Ig-MSC group was considerably lower than those in other groups. In culture supernatant of LPS-stimulated spleen cells, both of the MSC-treated groups showed significantly lower absorbances of TgAA than the control. Flow cytometric analysis of spleen cells revealed a significant decrease in the proportion of CD3+ and CD11b in the CTLA4Ig-MSC group compared to the other groups. Lymphocyte infiltration in the thyroid glands was also dramatically decreased in both of MSC-treated groups. Cytokine analysis showed that ATMSC decreased the production of proinflammatory cytokines and improved the Th1/Th2 balance by down-regulating Th1 cytokines. Although CTLA4Ig-MSC transplantation had better result in reduction of serum TgAA, both of ATMSC and CTLA4Ig-MSC transplantations are promising treatments for autoimmune thyroiditis judging from the results of histopathology and cytokine analysis. They may be attractive candidates for treating organ-specific autoimmune disease.


Assessing Physician Adherence to Guidelines for Cervical Cancer Screening and Management of Abnormal Screening Results.
The aim of the study was to survey obstetrician-gynecologists' cervical cancer screening practices and management of cervical abnormalities to ascertain adherence to guidelines. From January to July 2019, obstetrician-gynecologists at 5 St. Louis area hospitals were surveyed online about cervical cancer screening and management practices through 13 clinical vignettes. Survey scores and the American Society of Colposcopy and Cervical Pathology (ASCCP) app use were compared using Mann-Whitney tests. When screening 30- to 65-year-old participants, 114 (98%) of the 116 total participants used co-testing, but only 71 (61%) screened at 5-year intervals. None used primary human papillomavirus (HPV) testing. For 21- to 29-year-old participants, 17 (15%) screened with annual cytology, whereas 14 (12%) used annual or every 3-year co-testing. Forty eight (41%) screened younger than 21 years, regardless of risk factors or only if immunocompromised. Eleven (9%) continued screening after total hysterectomy for benign indications. Only 2 (2%) responded to all clinical vignettes in adherence to guidelines. More than 30% of participants would pursue unnecessary HPV testing and/or loop electrosurgical excision procedure for persistent low-grade cytology. Fifty eight (48%) incorrectly reported hysterectomy as management for adenocarcinoma in situ on biopsy. Participants would undertreat young women with high-grade abnormalities including high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia 3 (48, 41%) and high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia 1 (65, 56%). Forty one (35%) reported exiting women from screening prematurely. The median score for participants using the ASCCP app was significantly greater than those who did not (79% vs 71%, p = .002). Midwestern obstetrician-gynecologists' adherence to the guidelines for cervical cancer screening and management of abnormal results is suboptimal. Although co-testing for women aged 30-65 years has been broadly adopted, primary HPV testing has not. Physicians overscreen, overtreat low-grade lesions, and undertreat high-grade lesions in young women.


Blending municipal solid waste with corn stover for sugar production using ionic liquid process.
Municipal solid waste (MSW) represents an attractive cellulosic resource for sustainable fuel production. However, its heterogeneity is the major barrier to efficient conversion to biofuels. MSW paper mix was generated and blended with corn stover (CS). It has been shown that both of them can be efficiently pretreated in certain ionic liquids (ILs) with high yields of fermentable sugars. After pretreatment in 1-ethyl-3-methylimidazolium acetate ([C2C1Im][OAc]), over 80% glucose has been released with enzymatic saccharification. We have also applied an enzyme-free process by adding mineral acid and water directly into the IL/biomass slurry to induce hydrolysis. With the acidolysis process in 1-ethyl-3-methylimidazolium chloride ([C2C1Im]Cl), up to 80% glucose and 90% xylose are released. There is a correlation between the viscosity profile and hydrolysis efficiency; low viscosity of the hydrolysate generally corresponds to high sugar yields. Overall, the results indicate the feasibility of incorporating MSW as a robust blending agent for biorefineries.


Effect of primary prophylactic granulocyte-colony stimulating factor use on incidence of neutropenia hospitalizations for elderly early-stage breast cancer patients receiving chemotherapy.
Chemotherapy is vital for breast cancer management, but early-onset toxicities like neutropenia hinder its administration, especially in the elderly. Primary prophylactic (PP) use of granulocyte-colony stimulating factors (G-CSF) helps prevent neutropenia and its complications while receiving chemotherapy. Nevertheless, evidence supporting the effectiveness of PPG-CSF in the elderly is limited. Thus, the American Society of Clinical Oncology (ASCO) guidelines for PPG-CSF use in the elderly are not explicit. This study analyzed the effects of administration of PPG-CSF and duration of administration on the occurrence of chemotherapy-induced neutropenia hospitalizations in elderly breast cancer patients. This retrospective observational study of newly diagnosed breast cancer patients receiving chemotherapy used Surveillance, Epidemiology, and End Results-Medicare data from 1994 to 2003. To account for the nonrandom nature of the observational data, a nonparametric matching technique was used to preprocess the data before parametrically estimating the treatment effects. Administration of PPG-CSF during the first course chemotherapy reduced neutropenia hospitalizations by 16% within the first 3 months and 17% within the first 6 months of chemotherapy initiation (P < 0.05). Hospitalization rates within the first 3 months of chemotherapy initiation were 3 times higher in women receiving less than 5 consecutive days of PPG-CSF compared with women receiving PPG-CSF for 5 or more days (P < 0.05). Hospitalization rates within the first 1 and 6 months were also lower with longer PPG-CSF duration (≥5 d) (P < 0.10). PPG-CSF use is associated with reductions in in-patient healthcare utilization. These findings have implications for ASCO guidelines and Medicare coverage policies for PPG-CSF administration in elderly breast cancer patients.


SU-E-J-167: Optimal Number of Respiratory Phases in 4D PET for Radiotherapy Planning: Motion-Simulated Phantom Study.
Four-dimensional PET/CT is increasingly used in radiotherapy treatment planning. One issue that is still under investigation is the optimal number of bins or phases into which the respiratory cycle needs to be divided. We performed 4D PET moving phantom study and compared results between 6 and 10 bins. A Jaszczak Phantom™ containing six hollow spheres (0.95 - 3.18 cm inner diameters) was used. Three sinusoidal motion patterns were accomplished with peak-to-peak amplitudes of 1, 1.5 and 2.0 cm with a respiratory period of 5 s. The background and the six spheres were filled with 18F-FDG solution to achieve three SBR: 1:3.65, 1:7.95, and 1:10.22. Data were collected in 3-D mode for 10 min. Images were reconstructed using OSEM reconstruction: 32 subsets with 2 iterations, variable FWHM Gaussian post-filter 5-8 mm, and using image matrix sizes of 128×128, 192×192 and 256×256. The spheres were auto-segmented using pre-calculated optimal thresholds for a 1:1 volumetric correlation between actual- and PET-delineated spheres from static phantom studies. According to the static data the following set of parameters are optimal for static PET target (sphere) delineation: OSEM reconstruction with 32 subsets and 2 iterations, FWHM of 5 mm, and image size 256×256. The 4D data studies (with pre-calculated optimal thresholds) have shown that a 6-bin set shows less volume distortions then the 10-bin set. The authors found that 6-bin reconstruction is more reliable for delineation of a target in motion than 10-bin reconstruction. Further investigation with optimal thresholds obtained from 4D data, not static, is required no conflict of interest for all authors.


Emergent polarization singularities.
Polarization singularities are shown to emerge spontaneously from the incoherent addition of uncorrelated optical fields that individually need not contain singularities. Examples of this phenomenon are given for both vector and ellipse fields. The incoherent addition of vector fields whose singularities have integer winding numbers is shown to yield fields whose singularities have half-integer winding numbers. These findings are used to make predictions about the singularities of the polarized component of the cosmic microwave background.


The hrpK operon of Pseudomonas syringae pv. tomato DC3000 encodes two proteins secreted by the type III (Hrp) protein secretion system: HopB1 and HrpK, a putative type III translocator.
Pseudomonas syringae is a gram-negative bacterial plant pathogen that is dependent on a type III protein secretion system (TTSS) and the effector proteins it translocates into plant cells for pathogenicity. The P. syringae TTSS is encoded by hrp-hrc genes that reside in a central region of a pathogenicity island (Pai). Flanking one side of this Pai is the exchangeable effector locus (EEL). We characterized the transcriptional expression of the open reading frames (ORFs) within the EEL of P. syringae pv. tomato DC3000. One of these ORFs, PSPTO1406 (hopB1) is expressed in the same transcriptional unit as hrpK. Both HopB1 and HrpK were secreted in culture and translocated into plant cells via the TTSS. However, the translocation of HrpK required its C-terminal half. HrpK shares low similarity with a putative translocator, HrpF, from Xanthomonas campestris pv. vesicatoria. DC3000 mutants lacking HrpK were significantly reduced in disease symptoms and multiplication in planta, whereas DC3000 hopB1 mutants produced phenotypes similar to the wild type. Additionally, hrpK mutants were reduced in their ability to elicit the hypersensitive response (HR), a programmed cell death associated with plant defense. The reduced HR phenotype exhibited by hrpK mutants was complemented by hrpK expressed in bacteria but not by HrpK transgenically expressed in tobacco, suggesting that HrpK does not function inside plant cells. Further experiments identified a C-terminal transmembrane domain within HrpK that is required for HrpK translocation. Taken together, HopB1 is a type III effector and HrpK plays an important role in the TTSS and is a putative type III translocator.


Arthroscopic capsulotomy, capsular repair, and capsular plication of the hip: relation to atraumatic instability.
The purpose of this systematic review was to critically evaluate the available literature exploring the role of the hip joint capsule in the normal state (stable) and pathologic states (instability or stiffness). Furthermore, we examined the various ways that arthroscopic hip surgeons address the capsule intraoperatively: (1) capsulotomy or capsulectomy without closure, (2) capsulotomy with closure, and (3) capsular plication. Two independent reviewers (B.D.G. and B.G.D.) performed a systematic review of the literature using PubMed and the reference lists of related articles by means of defined search terms. Relevant studies were included if these criteria were met: (1) written in English, (2) Levels of Evidence I to V, (3) focus on capsule and its role in hip stability, and (4) human studies and reviews. Articles were excluded if they evaluated (1) total hip arthroplasty constructs using bony procedures or prosthetic revision, (2) developmental dysplasia of the hip where reorientation osteotomies were used, (3) syndromic instability, and (4) traumatic instability with associated bony injury. By use of the search method described, 5,085 publications were reviewed, of which 47 met appropriate criteria for inclusion in this review. Within this selection group, there were multiple publications that specifically addressed more than 1 of the inclusion criteria. Relevant literature was organized into the following areas: (1) capsular anatomy, biomechanics, and physiology; (2) the role of the capsule in total hip arthroplasty stability; (3) the role of the capsule in native hip stability; and (4) atraumatic instability and capsulorrhaphy. As the capsuloligamentous stabilizers of the hip continue to be studied, and their role defined, arthroscopic hip surgeons should become facile with arthroscopic repair or plication techniques to restore proper capsular integrity and tension when indicated. Level IV, systematic review.


Size-controlled CdSe quantum dots to boost light harvesting capability and stability of perovskite photovoltaic cells.
Here, we report that incorporation of size-controlled CdSe quantum dots (QDs) into perovskite photovoltaic cells (PSCs) boosts their light harvesting capability. X-ray photoemission and optical absorption spectroscopy analyses also show that the electronic structure of CdSe QDs makes them efficient charge transfer mediators between perovskite and Spiro-MeOTAD layers. In addition, electrochemical impedance spectroscopy experiments demonstrate that QDs help to decrease charge transfer resistance at the interfaces. Additionally, time-correlated single photon counting measurements show that small (2 nm) QDs enhance visible light collection of PSCs in the short wavelength region via Förster resonance energy transfer while large (4 nm) QDs improve light collection of PSCs in the long wavelength region via enhanced light backscattering at the perovskite/QD interface. Moreover, the photocurrent density in the PSCs with QDs retained over 95% of the initial value in a 100 h stability test, thus supporting that the perovskite layer that has been encapsulated with QDs acts to prevent penetration of water molecules through the perovskite layer. Consequently, these results support that utilization of size-controlled hybrid QDs could open up a new route to realize high-performance PSCs even under humid conditions.


Current role of open surgery in adrenal tumors.
The aim of this retrospective evaluation is to assess the current role of open adrenalectomy, in particular in cases of adrenocortical carcinoma (ACC). From January 2009 to May 2019, 26 open out of 233 adrenalectomies were performed in our Academic Department. Open adrenalectomy was performed by the anterior approach. A midline abdominal incision or a subcostal surgical incision was used to reach the peritoneal cavity. The resection was defined R0 if the margins of the sample were negative for malignancy. Open adrenalectomy was performed in 26 patients: 10 men and 16 women with a mean age of 61±25.3 years and a mean BMI of 28.4±2.9. The right adrenal gland was removed in 15 cases Romaand the left in 11 cases.We reported 18 diagnosis of malignant pathology. The other diagnosis concerned 5 cases of pheochromocytoma, 1 case of Cushing's disease and 2 cases of hyperaldosteronism. Mean tumor size was 7.7±5.5. Mean operative time was 160 min (range=110-205 minutes). Mean postoperative stay was 7±2 days. Only 3 (10%) patient showed postoperative grade II complications, according to Clavien-Dindo classification. Midline abdominal incision was used in 18 patients, subcostalsurgical incision in 5 patients and bilateral subcostal surgical incision in 3 patients. 3 right nephrectomy was necessary to remove the entire tumor mass. An en bloc R0 tumor resection was accomplished in all cases.There was no intra and perioperative mortality. All patients recovered well from surgery. The mean follow-up period was 15 (range=6-48) months. In conclusion, our retrospective study points out the role of open adrenalectomy as the treatment of choice in selected cases with known or suspected malignant adrenal tumors and with size greater than 12 cm.


Oxidized CaMKII promotes asthma through the activation of mast cells.
Oxidation of calmodulin-dependent protein kinase II (ox-CaMKII) by ROS has been associated with asthma. However, the contribution of ox-CaMKII to the development of asthma remains to be fully characterized. Here, we tested the effect of ox-CaMKII on IgE-mediated mast cell activation in an allergen-induced mouse model of asthma using oxidant-resistant CaMKII MMVVδ knockin (MMVVδ) mice. Compared with WT mice, the allergen-challenged MMVVδ mice displayed less airway hyperresponsiveness (AHR) and inflammation. These MMVVδ mice exhibited reduced levels of ROS and diminished recruitment of mast cells to the lungs. OVA-activated bone marrow-derived mast cells (BMMCs) from MMVVδ mice showed a significant inhibition of ROS and ox-CaMKII expression. ROS generation was dependent on intracellular Ca2+ concentration in BMMCs. Importantly, OVA-activated MMVVδ BMMCs had suppressed degranulation, histamine release, leukotriene C4, and IL-13 expression. Adoptive transfer of WT, but not MMVVδ, BMMCs, reversed the alleviated AHR and inflammation in allergen-challenged MMVVδ mice. The CaMKII inhibitor KN-93 significantly suppressed IgE-mediated mast cell activation and asthma. These studies support a critical but previously unrecognized role of ox-CaMKII in mast cells that promotes asthma and suggest that therapies to reduce ox-CaMKII may be a novel approach for asthma.


Use of nonradioactive labeling to detect large gene rearrangements in 21-hydroxylase deficiency.
To establish the Southern blotting technique using hybridization with a nonradioactive probe to detect large rearrangements of CYP21A2 in a Brazilian cohort with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH-21OH). We studied 42 patients, 2 of them related, comprising 80 non-related alleles. DNA samples were obtained from peripheral blood, digested by restriction enzyme Taq I, submitted to Southern blotting and hybridized with biotin-labeled probes. This method was shown to be reliable with results similar to the radioactive-labeling method. We found CYP21A2 deletion (2.5%), large gene conversion (8.8%), CYP21AP deletion (3.8%), and CYP21A1P duplication (6.3%). These frequencies were similar to those found in our previous study in which a large number of cases were studied. Good hybridization patterns were achieved with a smaller amount of DNA (5 mug), and fragment signs were observed after 5 minutes to 1 hour of exposure. We established a non-radioactive (biotin) Southern blot/hybridization methodology for CYP21A2 large rearrangements with good results. Despite being more arduous, this technique is faster, requires a smaller amount of DNA, and most importantly, avoids problems with the use of radioactivity.


Clinical Occurrence of Canine Babesiosis in the Coastal Area of the Black Sea (Dobrogea) in Southeastern Romania and Associated Epidemiological Implications.
Canine babesiosis (CB) is a significant tick-borne disease caused by intra-erytrocytic protozoa of the genus Babesia (Apicomplexa: Piroplasmida) and is currently emerging or re-emerging in many European countries. Despite the increasing incidence of clinical CB, little is known of the epidemiology of this disease in Romania. Therefore, the present study was conducted to provide epidemiological data on CB in the coastal area of the Black Sea (Dobrogea), southeastern Romania. For this, 306 owned dogs presented during 2016-2018 at a veterinary clinic in the area and clinically suspected for CB were tested for the presence of intra-erytrocytic piroplasms using Giemsa-stained thin blood smears. Overall, 27.8% (95% CI: 22.83-33.16) of dogs were positive for large piroplasms. The Babesia spp.-positive dogs were 51 males and 34 females aged from 3 mo to 13 yr (mean 4.2 yr; SD = 3.6). A higher rate of infection was registered in Bichon Maltese (n = 13) and mixed-breed (n = 28) dogs. Most cases (76/85; 89.4%) were diagnosed from March to June, with only a few cases registered in November and December (1 case each). Infected dogs displayed different clinical presentations, varying from mild (38.8%) to moderate (29.4%) and severe disease (29.4%). Based on clinical- pathological changes, 38 (44.7%), 34 (40.0%), and 13 (15.3%) dogs were diagnosed with uncomplicated babesiosis, complicated babesiosis with a single organ dysfunction, and complicated babesiosis with multiple-organ-dysfunction syndrome (MODS), respectively. The recovery rate (81.6%, 70.1%, and 38.4%, respectively) was significantly different in these groups. The age of dogs appeared to be a risk factor for both severe disease (mean age of 5.8 yr) and MODS (mean age 6.8 yr). These findings document the common occurrence of CB in Dobrogea, southeastern Romania, and suggest that appropriate control measures need to be taken.


First Report of White Pine Blister Rust on Rocky Mountain Bristlecone Pine.
White pine blister rust caused by Cronartium ribicola was introduced into North America in the early 20th century and is spreading throughout the range of five-needle pines. In northern Colorado, this pathogen was first observed in 1998 on limber pine (Pinus flexilis) (1). It has not been reported on Rocky Mountain or Great Basin bristlecone pine (Pinus aristata and P. longaeva, respectively) in nature. However, Rocky Mountain bristlecone pine is susceptible to the disease when artificially inoculated (2). In October 2003, a Rocky Mountain bristlecone pine was found infected with C. ribicola in the Great Sand Dunes National Monument, Alamosa County, Colorado. Seven branch cankers were observed on the tree. Cankers ranged in length from 15 to 41 cm and were estimated to be approximately 5 to 7 years old. Distinct C. ribicola branch symptoms were observed, including flagging, spindle-shaped swellings, and 6 mm long aecial scars. A branch was deposited at the Colorado State Herbarium. Microscopic examination of spores within remnant aecial blisters revealed aeciospores characteristic of C. ribicola (yellow-orange, ellipsoid, verrucose, and 19 × 25 μm). Cankers were only observed on one bristlecone pine. However, most limber pines in the area were infected with C. ribicola, including a limber pine less than 1 m from the infected bristlecone pine. To our knowledge, this is the first report that shows Rocky Mountain bristlecone pine can become infected naturally, and the pathogen is further south in Colorado on limber pine than previously reported. These observations suggest the need for a more complete investigation of this disease on bristlecone pines. References: (1) D. W. Johnson and W. R. Jacobi. Plant Dis. 84:595, 2000. (2) B. R. Stephan, Allg. Forst Z. 28:695, 1985.


Transfer of small resting B cells into immunodeficient hosts results in the selection of a self-renewing activated B cell population.
We studied the role of bone marrow B cell production in the renewal of peripheral B cells and the feedback mechanisms that control the entry of newly formed B cells into the peripheral B cell pools. When resting lymph node B cells are injected into B cell-deficient hosts, a fraction of the transferred cells expands and constitutes a highly selected population that survives for prolonged periods of time by continuous cell renewal at the periphery. Although the number of donor B cells recovered is low, a significant fraction shows an activated phenotype, and the serum immunoglobulin (Ig)M levels are as in normal mice. This population of activated B cells is resistant to replacement by a new cohort of B cells and is able to feedback regulate both the entry of newly formed B cells into the peripheral pool and terminal differentiation. These findings suggest that peripheral B cell selection follows the first come, first served rule and that IgM-secreting cells are generated from a pool of stable activated B cells with an independent homeostasis.


Speech and language therapy to improve the communication skills of children with cerebral palsy.
The production of speech, language and gesture for communication is often affected by cerebral palsy. Communication difficulties associated with cerebral palsy can be multifactorial, arising from motor, intellectual and / or sensory impairments, and children with this diagnosis can experience mild to severe difficulties in expressing themselves. They are often referred to speech and language therapy (SLT) services, to maximise their communication skills and help them to take an independent a role as possible in interaction. This can include introducing augmentative and alternative communication (AAC) systems, such as symbol charts or speech synthesizers, as well treating children's natural forms of communication. Various strategies have been used to treat the communication disorders associated with cerebral palsy but evidence of their effectiveness is limited. To determine the effectiveness of SLT that focuses on the child or their familiar communication partners, as measured by change in interaction patterns. To determine if individual types of SLT intervention are more effective than others in changing interaction patterns. Searches were conducted of MEDLINE, CINAHL, EMBASE, PSYCH INFO, LLBA, ERIC, WEB of SCIENCE, NRR, BEI, SIGLE up to December 2002. References from identified studies were examined and relevant journals and conference reports were hand-searched. Any experimental study containing an element of control was included in this review. This includes non-randomised group studies and single case experimental designs in which two interventions were compared or two communication processes were examined. L Pennington searched for and selected studies for inclusion. J Goldbart and J Marshall independently assessed separate random samples each comprising 25% of all identified studies. Two reviewers independently abstracted data from each selected study. Disagreements were settled by discussion between the three reviewers. Eleven studies were included in the review. Seven studies evaluated treatment given directly to children, four investigated the effects of training for communication partners. Subjects in the studies varied widely in age, type and severity of cerebral palsy, cognitive and linguistic skills. Studies focusing directly on children suggest that this model of therapy delivery has been associated with increases in treated communication skills by individual children. However, methodological flaws prevent firm conclusions being made about the effectiveness of therapy. In addition, maintenance of these skills was not investigated thoroughly. The studies targeting communication partners describe small exploratory group projects which contain insufficient detail to allow replication, have very low power and cannot provide evidence of effectiveness of this type of treatment. Firm evidence of the positive effects of SLT for children with cerebral palsy has not been demonstrated by this review. However, positive trends in communication change were shown. No change in practice is recommended from this review. Further research is needed to describe this client group, and its possible clinical subgroups, and the methods of treatment currently used in SLT. Research is also needed to investigate the effectiveness of new and established interventions and their acceptability to families. Rigour in research practice needs to be extended to enable firm associations between therapy and communication change to be made.


Loss of Cyp11c1 causes delayed spermatogenesis due to the absence of 11-ketotestosterone.
The impacts of androgens and glucocorticoids on spermatogenesis have intrigued scientists for decades. 11β-hydroxylase, encoded by cyp11c1, is the key enzyme involved in the synthesis of 11-ketotestosterone and cortisol, the major androgen and glucocorticoid in fish, respectively. In the present study, a Cyp11c1 antibody was produced. Western blot and immunohistochemistry showed that Cyp11c1 was predominantly expressed in the testicular Leydig cells and head kidney interrenal cells. A mutant line of cyp11c1 was established by CRISPR/Cas9. Homozygous mutation of cyp11c1 caused a sharp decrease of serum cortisol and 11-ketotestosterone, and a delay in spermatogenesis which could be rescued by exogenous 11-ketotestosterone or testosterone, but not cortisol treatment. Intriguingly, this spermatogenesis restored spontaneously, indicating compensatory effects of other androgenic steroids. In addition, loss of Cyp11c1 led to undersized testes with a smaller efferent duct and disordered spermatogenic cysts in adult males. However, a small amount of viable sperm was produced. Taken together, our results demonstrate that cyp11c1 is important for testicular development, especially for the initiation and proper progression of spermatogenesis. 11-ketotestosterone is the most efficient androgen in tilapia.


Degree and direction of polarization of multiple scattered light. 1: homogeneous cloud layers.
The degree of polarization as well as the direction of the polarization are calculated by a Monte Carlo method for homogeneous layers. Two solar zenith angles and a range of optical thicknesses up to 10 are considered. The results are compared with calculations for single scattered photons. For a given pair of incident and scattered directions, there are only two possible values for the direction of the polarization for single scattering: it must be within or perpendicular to the scattering plane. The choice between these two values depends only on the sign of the element M(-) in the first row and second column of the scattering matrix in the I, Q, U, V representation. In most cases there is little change in the direction of the polarization when multiple scattering is taken into account, so that this quantity with respect to a meridian plane can usually be predicted from a very simple trigonometric relationship to good accuracy. The partial scattering angles at which M- changes sign are unique for a particular aerosol model. Thus different size distributions and indices of refraction can be distinguished by measurements of the direction of polarization.


Improved fourth-year medical student clinical decision-making performance as a resuscitation team leader after a simulation-based curriculum.
To determine the impact of simulation-based instruction on student performance in the role of emergency department resuscitation team leader. A randomized, single-blinded, controlled study using an intention to treat analysis. Eighty-three fourth-year medical students enrolled in an emergency medicine clerkship were randomly allocated to two groups differing only by instructional format. Each student individually completed an initial simulation case, followed by a standardized curriculum of eight cases in either group simulation or case-based group discussion format before a second individual simulation case. A remote coinvestigator measured eight objective performance end points using digital recordings of all individual simulation cases. McNemar chi2, Pearson correlation, repeated measures multivariate analysis of variance, and follow-up analysis of variance were used for statistical evaluation. Sixty-eight students (82%) completed both initial and follow-up individual simulations. Eight students were lost from the simulation group and seven from the discussion group. The mean postintervention case performance was significantly better for the students allocated to simulation instruction compared with the group discussion students for four outcomes including a decrease in mean time to (1) order an intravenous line; (2) initiate cardiac monitoring; (3) order initial laboratory tests; and (4) initiate blood pressure monitoring. Paired comparisons of each student's initial and follow-up simulations demonstrated significant improvement in the same four areas, in mean time to order an abdominal radiograph and in obtaining an allergy history. A single simulation-based teaching session significantly improved student performance as a team leader. Additional simulation sessions provided further improvement compared with instruction provided in case-based group discussion format.


A simple method to generate equal-sized homogenous strata or clusters for population-based sampling.
Statistical efficiency and cost efficiency can be achieved in population-based samples through stratification and/or clustering. Strata typically combine subgroups of the population that are similar with respect to an outcome. Clusters are often taken from preexisting units, but may be formed to minimize between-cluster variance, or to equalize exposure to a treatment or risk factor. Area probability sample design procedures for the National Children's Study required contiguous strata and clusters that maximized within-stratum and within-cluster homogeneity while maintaining approximately equal size of the strata or clusters. However, there were few methods that allowed such strata or clusters to be constructed under these contiguity and equal size constraints. A search algorithm generates equal-size cluster sets that approximately span the space of all possible clusters of equal size. An optimal cluster set is chosen based on analysis of variance and convexity criteria. The proposed algorithm is used to construct 10 strata based on demographics and air pollution measures in Kent County, MI, following census tract boundaries. A brief simulation study is also conducted. The proposed algorithm is effective at uncovering underlying clusters from noisy data. It can be used in multi-stage sampling where equal-size strata or clusters are desired.


NIH conference. Antiretroviral therapy in AIDS.
To review recent developments of antiretroviral therapy for the acquired immunodeficiency syndrome (AIDS) and related disorders. An edited and updated summary of a Clinical Staff Conference held 26 October 1988 at the National Institutes of Health. The speakers discussed their own work as well as related work from other groups. The discovery that human immunodeficiency virus (HIV) causes AIDS has permitted the development of rational antiviral therapy for this disease. Various steps in the replicative cycle of HIV can be targeted for intervention. More basic research into the life cycle of HIV is therefore likely to yield new therapeutic approaches. In 1985, nucleoside analogues called dideoxynucleosides were discovered to be potent inhibitors of HIV replication in vitro. Dideoxynucleosides selectively inhibit HIV reverse transcriptase after they are phosphorylated intracellularly to 5'-triphosphates. One dideoxynucleoside, 3'-azido-2',3'-dideoxythymidine (AZT or zidovudine) has been found to prolong the life of patients with AIDS. This drug can partially reverse HIV dementia and decrease short-term progression to AIDS; it has been approved for treating HIV-infected patients with fewer than 500 CD4+ cells/mm3. AZT is only a first step in developing new therapy for AIDS. Its use is associated with toxicities, particularly bone marrow suppression. Several groups have reported the development of AZT-resistant strains of HIV. Other dideoxynucleosides whose toxicity profiles differ from that of AZT have also shown activity against HIV in early clinical studies. Large-scale, randomized trials of these drugs are now under way. Studies have shown that the binding of HIV to CD4 may be blocked by genetically engineered forms of CD4 and that HIV protease may be inhibited by substrate analogues. Protease inhibitors are an excellent area for further study in patients. Antisense oligonucleotide therapy may target the regulatory genes of HIV and is also being considered. With these advances, AIDS is gradually changing from an imminently fatal disease to one that can be managed with the judicious use of drugs and biologics. Progress against AIDS will continue, provided that researchers adhere to the principles of controlled trials.


Generation and characterization of spiking and nonspiking oligodendroglial progenitor cells from embryonic stem cells.
Pluripotent stem cells (PSCs) have been differentiated into oligodendroglial progenitor cells (OPCs), providing promising cell replacement therapies for many central nervous system disorders. Studies from rodents have shown that brain OPCs express a variety of ion channels, and that a subset of brain OPCs express voltage-gated sodium channel (NaV ), mediating the spiking properties of OPCs. However, it is unclear whether PSC-derived OPCs exhibit electrophysiological properties similar to brain OPCs and the role of NaV in the functional maturation of OPCs is unknown. Here, using a mouse embryonic stem cell (mESC) green fluorescent protein (GFP)-Olig2 knockin reporter line, we demonstrated that unlike brain OPCs, all the GFP(+) /Olig2(+) mESC-derived OPCs (mESC-OPCs) did not express functional NaV and failed to generate spikes (hence termed "nonspiking mESC-OPCs"), while expressing the delayed rectifier and inactivating potassium currents. By ectopically expressing NaV 1.2 α subunit via viral transduction, we successfully generated mESC-OPCs with spiking properties (termed "spiking mESC-OPCs"). After transplantation into the spinal cord and brain of myelin-deficient shiverer mice, the spiking mESC-OPCs demonstrated better capability in differentiating into myelin basic protein expressing oligodendrocytes and in myelinating axons in vivo than the nonspiking mESC-OPCs. Thus, by generating spiking and nonspiking mESC-OPCs, this study reveals a novel function of NaV in OPCs in their functional maturation and myelination, and sheds new light on ways to effectively develop PSC-derived OPCs for future clinical applications.