Quantification of ovine bone adaptation to altered load: morphometry, density, and surface strain.
Mechanical loading in the sheep proximal radius was increased by ulnar osteotomy (Group O), decreased by Steinmann pinning (Group P) and unaltered in sham operated controls (Group C). A series of intravenous fluochromes was given to label bone formation and the adaptive response was measured at intervals up to 24 weeks. Surface strains, measured in an in vitro rig, were reduced in Group P and increased significantly in Group O. Cross-sectional area (CSA) peaked in all groups at 6 weeks consistent with a regional acceleratory phenomenon (RAP) and the formation of fibrolamellar bone of low density. In Groups C and P the extent of the RAP was related to the degree of operative trauma and the newly-formed bone was subsequently resorbed. In Group P, CSA fell below control levels suggesting negative adaptation. The increase in area was sustained in Group O and bone density increased due to mineralisation and infilling. Periosteal labelling of the scaffold of parallel-fibred bone peaked at 10 weeks, followed by labelling of lamellar bone filling the gaps in the structure. This adaptive response reduced surface strains to near normal levels by 24 weeks in Group O. Positive adaptation was distinguished from the non-specific RAP due to surgical trauma. The adaptive response is both 'intelligent', in that it utilises and adds to the RAP, and accurate, as no further increase in cross-sectional area was required after 6 weeks.


Syphilis in injecting drug users: clues for high-risk sexual behaviour in female IDUs.
The objective was to measure the gender-specific differences for syphilis and for the sexual transmission of human immunodeficiency virus (HIV) in a cross-sectional analysis of injecting drug users (IDUs) admitted to detoxification between February 1987 and January 1990. HIV was determined by enzyme-linked immunosorbent assay (ELISA) and confirmed with Western blot. For syphilis reactive samples to a rapid plasma reagent (RPR) were confirmed with treponemal tests (FTA-ABS or MHA-TP). Of the 386 heterosexual IDUs, 68% were HIV-positive and 4.7% had serologic syphilis (RPR and FTA-ABS or MHA-TP positive). Syphilis was higher in women (12%) than in men (3%), and women reported a significantly (P < 0.001) higher number of sex partners. Men had an IDU as a sex partner more often than women did (P = 0.001). Serologic syphilis in women was associated with having had more than one sexual partner in the previous year (P = 0.028) but this association was not present in men. HIV infection was not associated with syphilis in male IDUs. However, HIV was present in all women with syphilis that reported more than one partner.


Does Whey Protein Supplementation Improve the Nutritional Status in Hypoalbuminemic Peritoneal Dialysis Patients?
Limited data are available regarding the effects of whey protein on the nutritional status of the peritoneal dialysis population. This study evaluated the effects of whey protein supplementation for 12 weeks on the nutritional status in hypoalbuminemic peritoneal dialysis patients. Thirty-six stable adult patients on maintenance peritoneal dialysis with serum albumin levels <3.5 g/dL were enrolled in the study and were divided into two groups similar in their serum albumin and normalized protein equivalent of total nitrogen appearance (nPNA). Nineteen patients were instructed to receive 1.2 g/kg per day of protein diet and additional whey protein supplement at a dose of 25% of the instructed daily protein diet (whey protein group), and 17 patients were instructed to receive 1.2 g/kg per day protein diet without additional whey protein supplementation (control group). Nutritional status was assessed using two measures: nPNA and lean tissue mass index (LTI) obtained by whole-body bioimpedance spectroscopy technique. In the whey protein group serum albumin and nPNA significantly increased from baseline to week 6 (P < 0.001, P = 0.034; respectively) and from week 6 to week 12 (P < 0.001, P = 0.001; respectively); LTI significantly increased from week 6 to week 12 (P = 0.022). Compared to the control group at week 12, serum albumin, nPNA and LTI values were significantly higher in the whey protein group (P < 0.001, P = 0.002, P = 0.001; respectively). This study demonstrated for the first time that oral supplementation with whey protein improves nutritional status and is well tolerated in hypoalbuminemic PD patients.


IncobotulinumtoxinA for Post-stroke Upper Limb Spasticity in Neutralizing Antibody-positive Patients after Botulinum Toxin Therapy: A Report of Two Cases.
Botulinum toxin type A is an effective treatment widely used to address post-stroke spasticity. Long-term repeated treatment with botulinum toxin type A may result in reduced efficacy due to the induction of neutralizing antibodies. Based on data from a phase 3 study of incobotulinumtoxinA for post-stroke upper limb spasticity, we describe the therapeutic response to botulinum toxin type A treatment in two neutralizing antibody-positive patients previously treated with other preparations of botulinum toxin type A. Two patients (a 65-year-old woman and a 36-year-old woman) with post-stroke upper limb spasticity were previously treated with onabotulinumtoxinA, and neutralizing antibodies were detected in their sera at baseline using the mouse hemidiaphragm assay. After onabotulinumtoxinA had been discontinued for at least 16 weeks, incobotulinumtoxinA (400 U) was administered in three or four injection cycles. Good therapeutic responses, manifested by a reduction of 1-2 points on the modified Ashworth scale, were noted after each injection. The patients' sera remained positive for neutralizing antibodies throughout the incobotulinumtoxinA treatment period. These patients, who were previously treated with onabotulinumtoxinA and were neutralizing antibody positive throughout the clinical study period, showed stable therapeutic responses following incobotulinumtoxinA treatment. IncobotulinumtoxinA could be initiated for patients with neutralizing antibodies induced by onabotulinumtoxinA.


Cajal-like cells in the human upper urinary tract.
Interstitial cells of Cajal (ICCs) have an important role in the regulation of gut motility as they are responsible for the slow wave activity of smooth muscle. It is still unknown if ICCs also occur in the human upper urinary tract. Since these cells express and are marked by the c-kit receptor CD117, we investigated its occurrence and distribution along the human upper urinary tract. Tissues from 56 human ureters, spanning proximal, middle and distal ureter segments, were analyzed by indirect immunohistochemistry using the alkaline phosphatase-anti-alkaline phosphatase method and double labeling immunofluorescence on consecutive tissue sections. Several monoclonal and polyclonal antibodies to c-kit receptor were used in combination with various cell markers for histiocytic, mast cell, endothelial, epithelial, neuronal, smooth muscle and stem cell differentiation. The c-kit receptor was found in 3 cell types of the ureter and in round or spindle-shaped cells. Due to their antigenic profile the first one was revealed as mast cells occurring in all layers of the ureteral wall except the urothelium. In contrast, the population of spindle-shaped cells was only marked by c-kit receptor, thus, resembling ICCs. These ICC-like cells were found among the inner and outer smooth muscle layers, and in the lamina propria. They showed a slight decrease from proximal to distal ureteral segments. However, unlike intestinal ICCs their cytomorphology differed and some cells, representing the third group of c-kit receptor positive cells, were found within the urothelium. Our data demonstrate the presence of ICC-like cells and their ubiquitous distribution in the human ureter. The physiological importance and pathological significance of these findings must be evaluated by functional studies and investigations of certain pathological with urinary outflow disturbance conditions.


Antibacterial and herbicidal activity of ring-substituted 3-hydroxynaphthalene-2-carboxanilides.
In this study, a series of twenty-two ring-substituted 3-hydroxy-N-phenylnaphthalene-2-carboxanilides were prepared and characterized. The compounds were tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Primary in vitro screening of the synthesized compounds was also performed against four Staphylococcus strains and against two mycobacterial species. 3-Hydroxy-N-(2-methoxyphenyl)naphthalene-2-carboxamide showed high biological activity (MIC = 55.0 µmol/L) against S. aureus as well as methicillin-resistant strains. N-(2-Fluorophenyl)-3-hydroxynaphthalene-2-carboxamide showed higher activity (MIC = 28.4 µmol/L) against M. marinum than the standard isoniazid and 3-hydroxy-N-(4-nitrophenyl)naphthalene-2-carboxamide expressed higher activity (MIC = 13.0 µmol/L) against M. kansasii than the standard isoniazid. Cytotoxicity assay of effective antimicrobial compounds was performed using the human monocytic leukemia THP-1 cell line. The PET-inhibiting activity expressed by IC50 value of the most active compound 3-hydroxy-N-(3-nitrophenyl)naphthalene-2-carboxamide was 16.9 μmol/L. The structure-activity relationships of all compounds are discussed.


Cell association and surface features in cultures of juvenile rat seminiferous tubules.
Short pieces of seminiferous tubules from juvenile rats were grown in tissue culture and studied by phase contrast light microscopy while living and by transmission and scanning electron microscopy after fixation and appropriate processing. The pieces of tubules remodeled in vitro, with the original explant becoming surrounded closely by a sheet of epithelioid cells and more peripherally by elongate cells. The epithelioid cells were identifiable as Sertoli cells because of the presence of characteristic Sertoli-Sertoli cell junctions near their upper surface. The elongate cells were derived from peritubular tissues, but could not be specifically identified as to cell type. Clusters of stellate cells and of round cells were present on the upper surface of the Sertoli cell sheets, but not on the elongate cells or the bare floor of the culture dish. The stellate cells were spermatogonia and the round cells were spermatocytes, as identified by fine structural features. Intercellular bridges were maintained between germ cells in culture without being surrounded by processes of Sertoli cells. Rudimentary junctions were present between germ cells and Sertoli cells in culture. The shape of germ cells in vitro was the same as the shape in situ, indicating that shape is an inherent feature of germ cells and is not determined by surrounding Sertoli cells.


Factors affecting pediatric isotonic fluid resuscitation efficiency: a randomized controlled trial evaluating the impact of syringe size.
Goal-directed therapy guidelines for pediatric septic shock resuscitation recommend fluid delivery at speeds in excess of that possible through use of regular fluid infusion pumps. In our experience, syringes are commonly used by health care providers (HCPs) to achieve rapid fluid resuscitation in a pediatric fluid resuscitation scenario. At present, it is unclear which syringe size health care providers should use when performing fluid resuscitation to achieve maximal fluid resuscitation efficiency. The objective of this study was therefore to determine if an optimal syringe size exists for conducting manual pediatric fluid resuscitation. This 48-participant parallel group randomized controlled trial included 4 study arms (10, 20, 30, 60 mL syringe size groups). Eligible participants were HCPs from McMaster Children's Hospital, Hamilton, Canada blinded to the purpose of the trial. Consenting participants were randomized using a third party technique. Following a standardization procedure, participants administered 900 mL (60 mL/kg) of isotonic saline to a simulated 15 kg child using prefilled provided syringes of the allocated size in rapid sequence. Primary outcome was total time to administer the 900 mL and this data was collected through video review by two blinded outcome assessors. Sample size was predetermined based upon a primary outcome analysis using one-way ANOVA. 12 participants were randomized to each group (n=48) and all completed trial protocol to analysis. Analysis was conducted according to intention to treat principles. A significant difference in fluid resuscitation time (in seconds) was found between syringe size group means: 10 mL, 563s [95% CI 521; 606]; 20 mL, 506s [95% CI 64; 548]; 30 mL, 454s [95% CI 412; 596]; 60 mL, 455s [95% CI 413; 497] (p<0.001). The syringe size used when performing manual pediatric fluid resuscitation has a significant impact on fluid resuscitation speed, in a setting where fluid filled syringes are continuously available. Greatest efficiency was achieved with 30 or 60 mL syringes. ClinicalTrials.gov, NCT01494116.


Disorders of childhood growth and development: childhood obesity.
The incidence of childhood obesity in the United States is estimated at 17%, or 12 million children ages 2 to 19 years. Obesity is a multifactorial condition with syndromic and nonsyndromic variants. Genetic, social, ethnic, endocrinologic, and behavioral issues are all potential etiologic factors. Preventive efforts should begin with monitoring from birth and include breastfeeding until age 6 months, avoiding juices, and promoting fruit and vegetable consumption and adequate exercise. Childhood obesity is diagnosed based on body mass index; a child is considered overweight at the 85th to 95th percentiles and obese at or above the 95th percentile. After obesity is diagnosed, testing should include blood pressure levels, fasting lipid profile, diabetes screening, and liver function tests. The physician should obtain a detailed history of the physical activity level and food intake and assess possible complications of obesity, including depression and hypertension, annually. Lifestyle interventions with family involvement are the mainstay of management, with pharmacotherapy or bariatric surgery considered for adolescents only if intensive lifestyle modifications have failed and in the presence of comorbidities. Intervention by multiple disciplines (ie, medicine, nutrition, psychology) is recommended, and family physicians are encouraged to become more involved in encouraging physical activity and improved nutrition for children.


Synthesis, structures, and physical properties of copper(II)-gadolinium(III) complexes combining ferromagnetic coupling and quadratic nonlinear optical properties.
Two copper(II)-gadolinium(III) metal complexes of formula CuIIGdIIILX3 are reported. H2L stands for the Schiff base ligand obtained by condensation of 3,4-dimethoxysalicylaldehyde with ethylenediamine (complex 1) or 1R,2R-(+)-1,2-diphenylethylenediamine (complex 2). While 1 reveals a centrosymmetric crystal structure, 2 crystallizes in the noncentrosymmetric P212121 space group and exhibits an efficiency 0.3 time that of urea in second harmonic generation. Due to a trend for dissociation in solution, the molecular hyperpolarizabilities (beta) cannot be determined experimentally for 1 and 2. Nevertheless, the electric field induced second harmonic (EFISH) technique, in connection with spectroscopic data and a ZINDO semiempirical approach, leads to a beta value of -6.5 x 10(-30) cm5 esu(-1), for the related CuIIL monomers, as an indicative range of magnitude in all these Schiff base complexes. In addition, 1 and 2 exhibit a ferromagnetic coupling in solid state with J = 3.3 and 1.3 cm-1, respectively (J being the parameter of the exchange Hamiltonian = -JSCu x SGd).


[Studies on the preparation and evaluation of Kijitsu, the immature citrus fruits. IV. Biological activities of immature fruits of different citrus species].
Biological activities of the 50% ethanolic extract of Kijitsu, dried immature Citrus fruits prepared from C. hassaku Hort. ex Tanaka (H), C. natsudaidai Hayata (N) or allied plants (T, A) were observed. Weak toxicities, weak intestine or uterine relaxant activities, beta-adrenergic activities were shown by in vitro experiments and antiasthmatic activity by intraperitoneal administration. These activities among each extract did not differ. The content of flavonoids (narirutin, naringin hesperidin, neohesperidin) or synephrine did not show much difference among the four dried immature Citrus fruits. These results suggest that H can be used for medicine as the substitute for N, T or A which has been commonly used as Kijitsu. This method is generally applicable to the proof of the biological equivalency of the crude drug and its substitutes.


Voxel-based morphometry in epileptic baboons: Parallels to human juvenile myoclonic epilepsy.
The epileptic baboon represents a natural model for genetic generalized epilepsy (GGE), closely resembling juvenile myoclonic epilepsy (JME). Due to functional neuroimaging and pathological differences between epileptic (SZ+) and asymptomatic control (CTL) baboons, we expected structural differences in gray matter concentration (GMC) using voxel-based morphometry (VBM). Standard anatomical (MP-RAGE) MRI scans using a 3T Siemens TIM Trio (Siemens, Erlangen, Germany) were available in 107 baboons (67 females; mean age 16±6years) with documented clinical histories and scalp-electroencephalography (EEG) results. For neuroimaging, baboons were anesthetized with isoflurane 1% (1-1.5 MAC) and paralyzed with vecuronium (0.1-0.3mg/kg). Data processing and analysis were performed using FSL's VBM toolbox. GMC was compared between CTL and SZ+ baboons, epileptic baboons with interictal epileptic discharges on scalp EEG (SZ+/IED+), asymptomatic baboons with abnormal EEGs (SZ-/IED+), and IED+ baboons with (IED+/PS+) and without (IED+/PS-) photosensitivity, and the subgroups amongst themselves. Age and gender related changes in gray matter volumes were also included as confound regressors in the VBM analyses of each animal group. Significant increases in GMC were noted in the SZ+/IED+ subgroup compared to the CTL group, including bilaterally in the frontopolar, orbitofrontal and anterolateral temporal cortices, while decreases in GMC were noted in the right more than left primary visual cortices and in the specific nuclei of the thalamus, including reticular, anterior and medial dorsal nuclei. No significant differences were noted otherwise, except that SZ+/IED+ baboons demonstrated increased GMC in the globus pallidae bilaterally compared to the SZ-/IED+ group. Similar to human studies of JME, the epileptic baboons demonstrated GMC decreases in the thalami and occipital cortices, suggesting secondary injury due to chronic epilepsy. Cortical GMC, on the other hand, was increased in the anterior frontal and temporal lobes, also consistent with human JME studies. This VBM study may indicate a combination of developmental and acquired structural changes in the epileptic baboon.


Canards in a minimal piecewise-linear square-wave burster.
We construct a piecewise-linear (PWL) approximation of the Hindmarsh-Rose (HR) neuron model that is minimal, in the sense that the vector field has the least number of linearity zones, in order to reproduce all the dynamics present in the original HR model with classical parameter values. This includes square-wave bursting and also special trajectories called canards, which possess long repelling segments and organise the transitions between stable bursting patterns with n and n + 1 spikes, also referred to as spike-adding canard explosions. We propose a first approximation of the smooth HR model, using a continuous PWL system, and show that its fast subsystem cannot possess a homoclinic bifurcation, which is necessary to obtain proper square-wave bursting. We then relax the assumption of continuity of the vector field across all zones, and we show that we can obtain a homoclinic bifurcation in the fast subsystem. We use the recently developed canard theory for PWL systems in order to reproduce the spike-adding canard explosion feature of the HR model as studied, e.g., in Desroches et al., Chaos 23(4), 046106 (2013).


Sarcolipin retention in the endoplasmic reticulum depends on its C-terminal RSYQY sequence and its interaction with sarco(endo)plasmic Ca(2+)-ATPases.
Sarcolipin (SLN) and phospholamban (PLN) are effective inhibitors of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA). These homologous proteins differ at their N and C termini: the C-terminal Met-Leu-Leu in PLN is replaced by Arg-Ser-Tyr-Gln-Tyr in SLN. The role of the C-terminal sequence of SLN tagged N-terminally with the FLAG epitope (NF-SLN) in endoplasmic reticulum (ER) retention was investigated by transfecting human embryonic kidney-293 cells with cDNAs encoding NF-SLN or a series of NF-SLN mutants in which C-terminal amino acids were deleted progressively. Immunofluorescence and immunoblotting of transfected cells by using anti-FLAG antibodies indicated that NF-SLN and PLN tagged at its N terminus with the FLAG epitope, even when overexpressed, were restricted to the ER. However, C-terminal truncation deletions of SLN, which lacked RSYQY, were not localized to ER and did not inhibit Ca(2+)-dependent Ca2+ uptake by SERCA. The shortest deletion constructs, NF-SLN 1-22 and NF-SLN 1-23, did not express stable protein products. However, all NF-SLN cDNA constructs, including NF-SLN 1-22 and NF-SLN 1-23, were expressed stably and localized to the ER when they were coexpressed with SERCA2a. These results show that NF-SLN subcellular distribution depends on SERCA coexpression and on its luminal, C-terminal RSYQY sequence. By using immunoprecipitation and MS, glucose-regulated protein 78/BiP and glucose-regulated protein 94 were identified as proteins that interact with NF-SLN through the RSYQY sequence. Thus, in the absence of SERCA, retention of NF-SLN in the ER is mediated through its association with other components through the C-terminal RSYQY sequence.


Oral sulodexide reduces albuminuria in microalbuminuric and macroalbuminuric type 1 and type 2 diabetic patients: the Di.N.A.S. randomized trial.
Diabetic nephropathy may be effectively prevented and treated by controlling glycemia and administering angiotensin-converting enzyme (ACE) inhibitors. However, strict metabolic control can be difficult, and ACE inhibitors may be poorly tolerated and only partially effective, particularly in diabetes mellitus type 2 (DM2), warranting the search for ancillary treatment. Sulodexide is a glycosaminoglycan, a new class of drug that has demonstrated nephroprotective activity in experimental investigations. The Di.N.A.S. study was a randomized, double-blind, placebo-controlled, multicenter, dose-range finding trial to evaluate the extent and duration of the hypoalbuminuric effect of oral sulodexide in diabetic patients. A total of 223 microalbuminuric and macroalbuminuric DM1 and DM2 patients with serum creatinine < or =150 micromol/L and stable BP and metabolic control were recruited. They were randomly allocated to one of four groups: 50 mg/d, 100 mg/d, or 200 mg/d sulodexide daily or placebo for 4 mo (T0 to T4), with 4 mo of follow-up after drug suspension (T4 to T8). Treatment with 200 mg/d sulodexide for 4 mo significantly reduced log albumin excretion rate (logAER) from 5.25 +/- 0.18 at T0 to 3.98 +/- 0.11 at T4 (P < 0.05), which was maintained till T8 (4.11 +/- 0.13; P < 0.05 versus T0). Moreover, the sulodexide-induced percent reductions in AER at T4 were significantly different from the placebo value at T4 and approximately linear to dose increments (30% [confidence limits, 4 to 49%], P = 0.03; 49% [30 to 63%], P = 0.0001; and 74% [64 to 81%], P = 0.0001 in the sulodexide 50, 100, and 200 mg/d groups, respectively. At T8, the sulodexide 200 mg/d group maintained a 62% (45 to 73%) AER significant reduction versus placebo (P = 0.0001). Subanalysis by type of diabetes (DM1 versus DM2, microalbuminuric versus macroalbuminuric, or on concomitant ACE inhibitors versus not on ACE inhibitors) demonstrated similar findings. These effects were obtained without any significant variation in metabolic control and BP or serum creatinine. Very few adverse events were reported; none were serious. In conclusion, a 4-mo course of high doses of sulodexide significantly and dose-dependently improves albuminuria in DM1 and DM2 patients and micro- or macroalbuminuric patients with or without concomitant ACE inhibition. The effect on albuminuria is long-lasting and seemingly additive to the ACE inhibitory effect.


Ultrasonographic assessment of early leakage in intestinal sutures in dogs.
Intestinal suture dehiscence is one of the most feared complications following gastrointestinal surgery in both human and veterinary medicine, increasing the morbidity and mortality of these patients. Clinical and laboratory early signs of septic peritonitis are not always easily identifiable while prompt treatment should help decrease postoperative morbidity and mortality. The aim of this study is to describe the ultrasonographic (US) features of confirmed leakage of intestinal sutures (LIS) and to evaluate if this imaging technique can be useful as noninvasive tool for the early diagnosis of LIS. Seven dogs developed LIS in a range of three-four days after gastrointestinal surgery and four of these developed a second dehiscence. On B-mode ultrasonography, all intestinal surgical sites were identified and characterized by a bowel focal thickening with reduced or absent wall layering and the presence of hyperechoic, double-walled foci at regular intervals (suture material). Furthermore, hyperechoic linear interfaces associated with dirty acoustic shadowing and comet-tail artifacts crossing the intestinal wall to free-float in peritoneal cavity or in a saccate collection have been documented. On the basis of these preliminary results, canine abdominal ultrasound seems to be a useful diagnostic technique for post-operative monitoring of patients undergoing intestinal surgery, allowing early detection of signs of a LIS, before the patient develops clinical signs of septic peritonitis.


Microvascular Reconstruction of Free Jejunal Graft in Larynx-preserving Esophagectomy for Cervical Esophageal Carcinoma.
Losing the ability to speak severely affects the quality of life, and patients who have undergone laryngectomy tend to become depressed, which may lead to social withdrawal. Recently, with advancements in chemoradiotherapy and with alternative perspectives on postoperative quality of life, larynx preservation has been pursued; however, the selection of candidates and the optimal reconstructive procedure remain controversial. In this study, we retrospectively reviewed our experience with free jejunal graft for larynx-preserving cervical esophagectomy (LPCE), focusing on microvascular reconstruction. Seven patients underwent LPCE for cervical esophageal carcinoma, and defects were reconstructed by free jejunal transfer subsequently. We collected preoperative and postoperative data of the patients and assessed the importance of the procedure. We mostly used the transverse cervical artery as the recipient, and a longer operative time was required, particularly for the regrowth cases. The operative field for microvascular anastomosis was more limited and deeper than those in the laryngectomy cases. Two graft necrosis cases were confirmed at postoperative day 9 or 15, and vessels contralateral from the graft were chosen as recipients in both patients. Microvascular reconstruction for free jejunal graft in LPCE differed in several ways from the procedure combined with laryngectomy. Compression from the tracheal cartilage to the pedicle was suspected as the reason of the necrosis clinically and pathologically. Therefore, we should select recipient vessels from the ipsilateral side of the graft, and careful and extended monitoring of the flap should be considered to make this procedure successful.


Practical routes to (SiH₃)₃P: applications in group IV semiconductor activation and in group III-V molecular synthesis.
The (SiH₃)₃P hydride is introduced as a practical source for n-doping of group IV semiconductors and as a highly-reactive delivery agent of -(SiH₃)₂P functionalities in exploratory synthesis. In contrast to earlier methods, the compound is produced here in high purity quantitative yields via a new single-step method based on reactions of SiH₃Br and (Me₃Sn)₃P, circumventing the need for toxic and unstable starting materials. As an initial demonstration of its utility we synthesized monosubstituted Me₂M-P(SiH₃)₂ (M = Al, Ga, In) derivatives of Me₃M containing the (SiH₃)₂P ligand for the first time, in analogy to the known Me₂M-P(SiMe₃)₂ counterparts. A dimeric structure of Me₂M-P(SiH₃)₂ is proposed on the basis of spectroscopic characterizations and quantum chemical simulations. Next, in the context of materials synthesis, the (SiH₃)₃P compound was used to dope germanium for the first time by building a prototype p(++)Si(100)/i-Ge/n-Ge photodiode structure. The resultant n-type Ge layers contained active carrier concentrations of 3-4 × 10¹⁹ atoms cm⁻³ as determined by spectroscopic ellipsometry and confirmed by SIMS. Strain analysis using high resolution XRD yielded a Si content of 4 × 10²⁰ atoms cm⁻³ in agreement with SIMS and within the range expected for incorporating Si₃P type units into the diamond cubic Ge matrix. Extensive characterizations for structure, morphology and crystallinity indicate that the Si co-dopant plays essentially a passive role and does not compromise the device quality of the host material nor does it fundamentally alter its optical properties.


Hospital medicine: understanding and drawing on the patient's perspective.
Poor communication and distance may result when the perspectives of clinicians and patients differ. Individual interviews, focus groups, and surveys of patients can inform health professionals about patient expectations and experiences with care. Hospital medicine will advance by learning from patients and their families and involving them in efforts to monitor and improve care.


Ciprofloxacin-Loaded Poly(N-isopropylacrylamide-co-acrylamide)/Polycaprolactone Nanofibers as Dual Thermo- and pH-Responsive Antibacterial Materials.
Nanofibers are an attractive option in drug release, especially as antibacterial materials. However, there is no universal antibacterial material and little attention has been devoted to bacteria-nanofiber attachment. Poly(N-isopropylacrylamide-co-acrylamide) is particularly interesting due to its dual thermo- and pH-responsive nature. Here, we prepared stimuli-responsive antibacterial nanofibers by the blend electrospinning of polycaprolactone (PCL), various concentrations of PNIPAm-co-AAm and ciprofloxacin (CIP). The lower critical solution temperature (LCST) of PNIPAm-co-AAm was determined by refractometry in distilled water and buffer solutions at pH 4 and 7.4. Based on the results obtained, we performed release tests, which indicated that the amount of released CIP and its release kinetics were dependent on nanofiber composition. Moreover, the nanofibers showed enhanced release at temperatures below LCST and, in turn, this led to enhanced antibacterial activity, as demonstrated by disk diffusion tests on Staphylococcus epidermidis and Escherichia coli. In addition, both bacterial strains demonstrated much lower attachment to CIP-loaded PCL/PNIPAm-co-AAm compared with CIP-loaded PCL nanofibers. Furthermore, cytocompatibility tests, performed using primary human dermal fibroblasts, produced similar good cell spreading regardless of PNIPAm-co-AAm concentration. Collectively, our results show that the proposed nanofibers have considerable potential as materials, which promote wound healing and significantly decrease the probability of bacterial infection.


The pitfalls of proteomics experiments without the correct use of bioinformatics tools.
The elucidation of the entire genomic sequence of various organisms, from viruses to complex metazoans, most recently man, is undoubtedly the greatest triumph of molecular biology since the discovery of the DNA double helix. Over the past two decades, the focus of molecular biology has gradually moved from genomes to proteomes, the intention being to discover the functions of the genes themselves. The postgenomic era stimulated the development of new techniques (e.g. 2-DE and MS) and bioinformatics tools to identify the functions, reactions, interactions and location of the gene products in tissues and/or cells of living organisms. Both 2-DE and MS have been very successfully employed to identify proteins involved in biological phenomena (e.g. immunity, cancer, host-parasite interactions, etc.), although recently, several papers have emphasised the pitfalls of 2-DE experiments, especially in relation to experimental design, poor statistical treatment and the high rate of 'false positive' results with regard to protein identification. In the light of these perceived problems, we review the advantages and misuses of bioinformatics tools - from realisation of 2-DE gels to the identification of candidate protein spots - and suggest some useful avenues to improve the quality of 2-DE experiments. In addition, we present key steps which, in our view, need to be to taken into consideration during such analyses. Lastly, we present novel biological entities named 'interactomes', and the bioinformatics tools developed to analyse the large protein-protein interaction networks they form, along with several new perspectives of the field.


Vocal mechanisms in birds and bats: a comparative view.
Vocal signals play a very important role in the life of both birds and echolocating bats, but these two unrelated groups of flying vertebrates have very different vocal systems. They nevertheless must solve many of the same problems in producing sound. This brief review examines avian and microchiropteran motor mechanisms for: 1) coordinating the timing of phonation with the vocal motor pattern that controls its acoustic properties, and 2) achieving respiratory strategies that provide adequate ventilation for pulmonary gas exchange, while also facilitating longer duration songs or trains of sonar pulses.


Epidemiological and clinical observations on patients with dengue in Puerto Rico: results from the first year of enhanced surveillance--June 2005-May 2006.
From June 2005 to May 2006, a clinic-based enhanced surveillance system for dengue was implemented in a Puerto Rican municipality to provide a population-based measure of disease incidence and clinical outcomes. We obtained demographic and clinical information from suspected cases and performed serologic and virologic testing. We used World Health Organization (WHO) criteria to classify cases and applied a simplified case definition for severe dengue illness. There were 7.7 laboratory-positive cases of dengue per 1,000 population. The highest incidence, 13.4 per 1,000, was among 10 to 19 year olds. Of the 156 laboratory-positive cases, three patients (1.9%) met WHO criteria for dengue hemorrhagic fever, and 30 patients (19.2%) had at least one severe clinical manifestation of dengue infection. Our data suggest that in a community with endemic dengue, enhanced surveillance is useful for detecting symptomatic infections. Furthermore, the simplified case definition for severe dengue may be useful in clinic-based surveillance.


Route of infection and hematological effect of Metarhizium anisopliae (Metsch.) Sorokin on Dysdercus cingulatus (Fab.) adult.
The primary objective of this work was to identify, under laboratory conditions, the route of infection and hemogram of Dysdercus cingulatus (Fab.) adults by Metarhizium anisopliae. The infection process in D. cingulatus by M. anisopliae involved the conidia adherence to the host cuticle and germination after 24 h post-infection, accompanied by falling of bristles. The subsequent step, within 24-48 h post-infection, comprised penetration of fungus through spiracles, root of bristles, hemolymph, and the three dorsal sacs. Subsequently, within 72-96 h post-infection, the fungus penetrated into trachea and sacs, then emerged on cuticular surface and was found to be maximum in hemolymph. A great decrease in hemocytes count was observed within 96 h from infection. The hemosomic index (HSI) decreased gradually as the incubation period increased. As far as we know, this is the first study to know the mechanism of action of M. anisopliae to D. cingulatus.


Bilateral familial carotid body paragangliomas. Report of a case with DNA flow cytometric and cytogenetic analyses.
A case study of bilateral familial carotid body paragangliomas with DNA flow cytometric and cytogenetic analyses is presented. Analysis of tumor cell nuclear DNA content by flow cytometry revealed aneuploid cell populations in both tumors. Standard cytogenetic analysis (Giemsa-banding technique used) of the right carotid body paraganglioma showed no evidence of numerical or structural abnormalities. We describe parameters currently used to "predict" biological behavior in these tumors.


Dexpramipexole is ineffective in two models of ALS related neurodegeneration.
Treatment options for people living with amyotrophic lateral sclerosis (ALS) are limited and ineffective. Recently, dexpramipexole (RPPX) was advanced into human ALS clinical trials. In the current studies, we investigated RPPX in two parallel screening systems: 1) appropriately powered, sibling-matched, gender-balanced survival efficacy screening in high-copy B6-SJL-SOD1G93A/Gur1 mice, and 2) high-content neuronal survival screening in primary rat cortical neurons transfected with wild-type human TDP43 or mutant human TDP43. In both cases, we exposed the test systems to RPPX levels approximating those achieved in human Phase II clinical investigations. In SOD1G93A mice, no effect was observed on neuromotor disease progression or survival. In primary cortical neurons transfected with either mutant or wild-type human TDP43, a marginally significant improvement in a single indicator of neuronal survival was observed, and only at the 10 µM RPPX treatment. These systems reflect both mutant SOD1- and TDP43-mediated forms of neurodegeneration. The systems also reflect both complex non-cell autonomous and neuronal cell autonomous disease mechanisms. The results of these experiments, taken in context with results produced by other molecules tested in both screening systems, do not argue positively for further study of RPPX in ALS.


Induction of c-fos and c-jun proto-oncogenes in target cells of the lung and pleura by carcinogenic fibers.
To study mechanisms of cell proliferation by asbestos and nonasbestos fibers, we examined the effects of these agents on the mRNA levels of c-fos and c-jun and ornithine decarboxylase (ODC) in hamster tracheal epithelial (HTE) cells and rat pleural mesothelial (RPM) cells, the progenitor cells of bronchogenic carcinoma and mesothelioma, respectively. In comparison with crocidolite asbestos, increases in c-jun mRNA were less striking in HTE cells after exposure to man-made vitreous fiber-10 (MMVF-10) or refractory ceramic fiber-1 (RCF-1). No c-fos mRNA was detected in HTE cells after exposure to particulates, but exposure of HTE cells to H2O2 caused striking increases in c-fos and c-jun, which preceded increases in ODC mRNA. Increases in ODC mRNA were also observed in HTE cells after exposure to nonasbestos fibers, whereas only crocidolite asbestos caused elevations in ODC mRNA in RPM cells. In RPM cells, crocidolite and chrysotile asbestos caused increases in mRNA levels of both c-fos and c-jun. No increases in proto-oncogene induction were observed using MMVF-10 or RCF-1 at nontoxic concentrations (< or = 5 micrograms/cm2 dish). Moreover, erionite, a fiber extremely potent in the causation of mesothelioma in humans, caused more dramatic elevations in c-fos and c-jun. Nonfibrous particles (riebeckite, polystyrene beads) did not alter proto-oncogene expression in these cell types, suggesting that the fibrous geometry of particulates is critical in the induction of c-fos and c-jun.


Green polymer chemistry VIII: synthesis of halo-ester-functionalized poly(ethylene glycol)s via enzymatic catalysis.
Halo-ester-functionalized poly(ethylene glycol)s (PEGs) are successfully prepared by the transesterification of alkyl halo-esters with PEGs using Candida antarctica lipase B (CALB) as a biocatalyst under the solventless conditions. Transesterifications of chlorine, bromine, and iodine esters with tetraethylene glycol monobenzyl ether (BzTEG) are quantitative in less than 2.5 h. The transesterification of halo-esters with PEGs are complete in 4 h. (1) H and (13) C NMR spectroscopy with MALDI-ToF and ESI mass spectrometry confirm the structure and purity of the products. This method provides a convenient and "green" process to effectively produce halo-ester PEGs.


Pulmonary echinococcal cyst with a filamentous fungus co-infection.
Fungal infections are known to colonize the pre-existing lung cavities formed as a result of diseases like tuberculosis, sarcoidosis, bronchiectasis and cavitatary neoplasia, mostly encountered in immunocompromised patients. Pulmonary echinococcal cysts have been reported coexistent with cryptococcosis and other saprophytic mycosis, but the coexistence of aspergillosis and echinococcal cyst is extremely rare and occasionally been reported in English literature. Active invasion and proliferation of the fungi in the laminated ectocyst of the echinococcal cyst is very unusual. We report a case of 60 years old immunocompetent female, presented with cough, chest pain and shortness of breath. The chest X-ray showed a large thick walled cavity in the lower and mid zone of right lung with positive water lily sign. Surgical enucleation of the echinococcal cyst revealed aspergilloma involving the cavity with massive invasion of laminated ectocyst by filamentous fungus, morphologically resembling an Aspergillus species and was further treated with Itraconazole for 3 months. This unique coexistence of active pulmonary echinococcosis and aspergillosis is being reported because of its rarity and clinical importance for its management.


Structure of potato inhibitor complex of carboxypeptidase A at 5.5-A resolution.
The complex of the 39-amino inhibitor (potato) of bovine carboxypeptidase A (carboxypeptidase; peptidyl-L-amino-acid hydrolase, EC 184.108.40.206) was crystallized in space group P32. There are two protein-inhibitor complexes in the asymmetric unit. These crystals exhibited pseudo-P3221 symmetry due to twinning about the a3 axis. Heavy atom difference Patterson maps and rotation functions indicated, however, that the noncrystallographic twofold axis that relates these two complexes is nearly coincident with the a3 axis. Consequently, to a good approximation at low resolution, the space group of the complex is P3221 and the effects of twinning may be ignored. The structure was solved by using multiple isomorphous replacement and molecular replacement techniques. At 5.5-A resolution, the multiple isomorphous replacement map was readily interpretable in terms of the known native carboxypeptidase A structure plus extra density around the active site. The position of this extra density is consistent with the binding mode for extended substrate proposed from earlier model building studies with the native enzyme (Lipscomb, W.N., Hartsuck, J.A., Reeke, G.N., Quiocho, F.A. Bethge, P.H., Ludwig, M.L., Steitz, T.A., Muirhead, H. & Coppola, J.C. (1968) Brookhaven Symp. Biol. 21, 24-90).


Different mechanisms of recognition of bacteriophage Q beta plus and minus strand RNAs by Q beta replicase.
Our earlier work on the recognition of Q beta plus strand RNA by replicase had shown by RNase degradation and by electron microscopic techniques that specific binding interactions occurred at two internal sites, the S-site and the M-site, but not at the 3'-end, i.e. the site of initiation of synthesis. Using essentially similar methods, we have found now for binding complexes of replicase with the minus strand a completely different pattern, namely considerable terminal binding, whereas binding to internal sites was without detectable specificity. In the case of plus strand complexes, simultaneous binding at the two internal sites and at a terminal site could be demonstrated by electron microscopy after initiation of RNA synthesis in the presence of host factor, GTP and ATP. A variant plus strand RNA containing a 490 nucleotide duplication near the 5'-end resulted in similar double-looped complexes, however with an elongated free arm, showing that the protein-bound terminal site was the 3'-end of the RNA. Interestingly, the same two-looped structures were also found for complexes consisting of plus strand RNA and host factor without replicase. This suggests that the role of the host factor on the plus strand template is to bring the 3'-end into the proximity of the S-site/M-site domain, where replicase can initiate on it. In contrast, the 3'-end of the minus strand appears to be directly available to the enzyme.


ATR protects ongoing and newly assembled DNA replication forks through distinct mechanisms.
The ATR kinase safeguards genomic integrity during S phase, but how ATR protects DNA replication forks remains incompletely understood. Here, we combine four distinct assays to analyze ATR functions at ongoing and newly assembled replication forks upon replication inhibition by hydroxyurea. At ongoing forks, ATR inhibitor (ATRi) increases MRE11- and EXO1-mediated nascent DNA degradation from PrimPol-generated, single-stranded DNA (ssDNA) gaps. ATRi also exposes template ssDNA through fork uncoupling and nascent DNA degradation. Electron microscopy reveals that ATRi reduces reversed forks by increasing gap-dependent nascent DNA degradation. At new forks, ATRi triggers MRE11- and CtIP-initiated template DNA degradation by EXO1, exposing nascent ssDNA. Upon PARP inhibition, ATRi preferentially exacerbates gap-dependent nascent DNA degradation at ongoing forks in BRCA1/2-deficient cells and disrupts the restored gap protection in BRCA1-deficient, PARP-inhibitor-resistant cells. Thus, ATR protects ongoing and new forks through distinct mechanisms, providing an extended view of ATR's functions in stabilizing replication forks.


ωB97M-V: A combinatorially optimized, range-separated hybrid, meta-GGA density functional with VV10 nonlocal correlation.
A combinatorially optimized, range-separated hybrid, meta-GGA density functional with VV10 nonlocal correlation is presented. The final 12-parameter functional form is selected from approximately 10 × 10(9) candidate fits that are trained on a training set of 870 data points and tested on a primary test set of 2964 data points. The resulting density functional, ωB97M-V, is further tested for transferability on a secondary test set of 1152 data points. For comparison, ωB97M-V is benchmarked against 11 leading density functionals including M06-2X, ωB97X-D, M08-HX, M11, ωM05-D, ωB97X-V, and MN15. Encouragingly, the overall performance of ωB97M-V on nearly 5000 data points clearly surpasses that of all of the tested density functionals. In order to facilitate the use of ωB97M-V, its basis set dependence and integration grid sensitivity are thoroughly assessed, and recommendations that take into account both efficiency and accuracy are provided.


Influence of the thromboxane synthetase inhibitor HOE 944, prostacyclin and indomethacin on reperfusion arrhythmias, cardiodynamics and metabolism in isolated ischemic rat hearts.
We investigated the influence of the thromboxane (TX) synthetase inhibitor HOE 944 (6-(5-Methylimidazol-1-yl)methyl-2-naphthoic acid-Hydrochloride), prostacyclin (PGI2) and indomethacin on reperfusion arrhythmias in isolated perfused ischemic rat hearts. HOE 944, PGI2 and indomethacin were perfused in a concentration of 1 x 10(-6), 5 x 10(-8) and 1 x 10 (-6) mol/l respectively (in vitro). In another set up rats were pretreated p.o. with a daily dose of 30 mg/kg for 7 days (ex vivo). Acute regional myocardial ischemia was induced in isolated working rat hearts by occlusion of the left coronary artery. Reperfusion commenced upon release of this occlusion which was invariably associated with ventricular fibrillations (VF). Perfusion with 1 x 10(-6) mol/l HOE 944 did not affect these arrhythmias. In contrast hearts from HOE 944 pretreated rats were protected against fibrillations (p less than 0.01). PGI2 perfusion was also protective against VF (p less than 0.01) whereas indomethacin perfusion aggravated VF. In the ischemic period cardiodynamics like left ventricular pressure (LVP), dp/dt max and coronary flow (CF) were improved in HOE 944 pretreated rat hearts. In the venous effluent the enzyme activities of lactate dehydrogenase (LDH) and creatine kinase (CK) as well as lactate production were decreased in the ischemic and reperfusion period. Myocardial tissue levels of ATP were distinctly increased and lactate levels decreased in HOE 944 pretreated rats, whereas glycogen and creatine phosphate did not change.(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluation of calgranulin B in stools from the patients with colorectal cancer.
Calprotectin (heterodimer of calgranulin A and B) has been previously studied as a candidate stool marker for detecting colorectal cancer. We assessed the clinical usefulness of calgranulin B as a stool marker for colorectal cancer in a pilot study of patients with colorectal cancer. We performed 2-DE-based proteomics to screen stool markers for colorectal cancer. We checked the calgranulin B in stools from 77 colorectal cancer patients and from 75 controls by western blot and enzyme-linked immunosorbent assay. We measured calgranulin A using the same methods, and stool hemoglobin by immunologic fecal occult blood test. Fecal calgranulin A did not show any difference, but stool calgranulin B of colorectal cancer patients was significantly higher than controls [50.6 ng/mg stool protein (SD, 34.8) vs. 20.2 ng/mg stool protein (SD,24.0), respectively, P < 0.001). At the cut off level 24.4 ng/mg stool protein, the sensitivity was somewhat higher than fecal occult blood test (72.0 percent vs. 62.3 percent) but the specificity was much lower than fecal occult blood test (77.1 percent vs. 98.7 percent). Calgranulin B was increased in stools of colorectal cancer patients but our results suggest that colorectal cancer screening by determination of stool calgranulin B would not be better than conventional fecal occult blood test.


Effect of electrochemical treatment of oleic acid on anaerobic digestion.
Electrochemical pre-treatment of oleate on anaerobic digestion was investigated using two anaerobic filters (AF and AFm) working, respectively, with increasing concentrations of electrochemically pre-treated oleate and oleate. Influents containing 25% and 50% of chemical oxygen demand (COD) of these substrates did not cause relevant alterations in either digester's performance. Comparatively, the pre-treated oleate unit (AF) showed a higher gas production but a lower COD removal than AFm (2.0 vs 1.5 m(3) CH4 m(-3) d(-1) 76-85 vs 91-93% COD removal). The raised AFm COD removal together with the larger proportion of VSS in its effluent than in AF (5.69 vs 0.26 kg m(-3)) indicate that the biomass washout can be a consequence of the encapsulated solids by lipidic compounds that were not fairly degraded. Further increases of oleate in AFm feed (75 and 100% COD) led to decreases of biogas production to half and COD removal from values higher than 90% to 83-75%. The simultaneous increase of effluent VSS concentrations to 10-12 kg m(3) emphasizes the oleate negative effect. The use of pretreated oleate as the only carbon source did not influence negatively the AF behaviour in terms of methane production. COD removal was maintained at values higher than 80% and the effluent VSS at low concentrations (0.15 kg m(-3)). The significantly higher methane yield achieved by AF than AFm indicates a higher accumulation of oleate than pre-treated oleate. Therefore, electrochemical process stands for a suitable pre-treatment for lipid rich effluents, allowing the application of higher organic loads keeping a higher methane yield.


Manganese-Based Nanogels as pH Switches for Magnetic Resonance Imaging.
pH-responsive nanogels (NGs) were used to prepare high-efficiency magnetic resonance imaging dual T1/T2 contrast agents for pH imaging. The polymeric NG matrix acts as a strong polydentate ligand that chelates the Mn cations in its inner cavity generating a hybrid NG structure. The Mn chelate NG is sensitive to pH changes, such that protonation induces a change of the polymer hydration state and consequent swelling. The swollen nanogel allows water molecules to enter and interact with the Mn chelate, shortening the relaxation time (switch ON) and giving rise to positive or negative contrast on T1- or T2-weighted magnetic resonance images.


[Virologic detection of arboviruses in greater cormorants].
Cormorants (Phalacrocorax carbo, Pelecaniformes) caught in southern Moravia (Czech Republic) in 1989-1990 were examined for arbovirus infections. Isolation experiments were carried out using blood samples of 56 birds. The results were negative. Serological examinations of 31 birds were performed by haemagglutination-inhibition test (HIT) using 5 arboviral antigens of the genera Alphavirus (Sindbis--SIN) and Flavivirus (tick-borne encephalitis--TBE, West Nile--WN) and of the family Bunyaviridae (Tahyna--TAH, Calovo--CVO). Antibodies were detected only to viruses SIN, WN and TAH at different frequencies: 9.7%, 9.7% and 22.6%. The titres ranged from 1:20 to 1:80.


An AFLP marker tightly linked to apomixis reveals hemizygosity in a portion of the apomixis-controlling locus in Paspalum simplex.
A mapping population of Paspalum simplex segregating for apomixis (asexual reproduction through seeds) was screened with AFLPs to find apomixis-linked markers. Four AFLPs linked to apomixis in coupling phase were found. Three of them did not show recombinants among the 87 individuals of the mapping population, whereas the other was more loosely linked. Integrating the AFLP data with those obtained previously with rice RFLP anchor markers, a map was drawn for the chromosome region of P. simplex encompassing apomixis. We cloned the three AFLPs tightly linked with apomixis into plasmid vectors and used them as probes to hybridize the restriction digested DNA of the mapping population. Two of them revealed RFLP bands linked to apomixis together with other alleles, whereas one was proven to belong to a hemizygous portion of the apomixis locus. The total picture resulting from AFLP and RFLP analyses was that a cluster of markers tightly linked with apomixis was detected in P simplex together with two other markers that were more loosely linked. These two markers enclosed a relatively large chromosome segment characterized by strong repression of recombination. The block of recombination may have caused sequence divergence and, therefore, hemizygosity of some regions belonging to the apomixis-controlling chromosome segment of P. simplex. The potential of developing an apomixis-specific sequence for screening large-fragment libraries for the physical isolation of the locus encompassing apomixis is discussed.


Steinernema taiwanensis n. sp. (Rhabditida: Steinernematidae), a new entomopathogenic nematode from Taiwan.
A new isolate of the entomopathogenic nematode, Steinernema taiwanensis n. sp., was isolated from soil in Pingtung County, Taiwan. This new species could be characterized and distinguished from other related species by its morphological characters, morphometrics, and phylogenetic analysis. The body length and distance from anterior end to nerve ring of infective juveniles is 1012 (983-1045) µm and 124 (120-127) µm, lateral field formula 2, 6, 7, 8, 2, and the tail length 90 (79-96) µm without dorsal constriction in tail region. The first generation males of S. taiwanensis n. sp. are characterized by spicule shape, smooth blade tip, 23 genital papillae (11 pairs and 1 single papilla), spicule length of 94 (89-99) µm and gubernaculum length of 68 (65-70) µm. Females from the first generation of S. taiwanensis n. sp. have no epiptygmata and a slightly developed post-anal swelling. Phylogenetic analysis of ITS and D2D3 regions of rDNA showed that S. taiwanensis n. sp. belongs to the Longicaudum-clade and comprises a monophyletic group with S. guangdongense and S. longicaudum. The new isolate is described as a novel species according to morphological and phylogenetic analyses.


Potential of Coffee Fruit Extract and Quinic Acid on Adipogenesis and Lipolysis in 3T3-L1 Adipocytes.
This study was to assess the impact of different colors of coffee fruit (green, yellow and red) on adipogenesis and/or lipolysis using 3T3-L1 adipocytes. Characterization of chemical constituents in different colors of coffee fruit extracts was determined by ESI-Q-TOF-MS. The cytotoxicity of the extracts in 3T3-L1 preadipocytes were evaluated by MTT assay. Oil-red O staining and amount of glycerol released in 3T3-L1 adipocytes were measured for lipid accumulation and lipolysis activity. All coffee fruit extracts displayed similar chromatographic profiles by chlorogenic acid > caffeoylquinic acid > caffeic acid. Different colors of raw coffee fruit possessed inhibitory adipogenesis activity in 3T3-L1 adipocytes, especially CRD decreased lipid accumulation approximately 47%. Furthermore, all extracts except CYF and their major compounds (malic, quinic, and chlorogenic acid) increased glycerol release. Our data suggest that different colors of coffee fruit extract have possessed anti-adipogenic and lipolytic properties and may contribute to the anti-obesity effects.


Endovascular treatment for large-core ischaemic stroke: a meta-analysis of randomised controlled clinical trials.
Current guidelines recommend endovascular treatment (EVT) for acute ischaemic stroke (AIS), due to large-vessel occlusion and an Alberta Stroke Program Early CT Score (ASPECTS) of ≥6. High-quality evidence resulting from randomised controlled clinical trials (RCTs) regarding EVT among large-core AIS has recently become available, justifying an updated meta-analysis aiming to evaluate efficacy and safety of EVT in this clinical setting. We conducted a systematic review and meta-analysis including all available RCTs that compared EVT in addition to best medical treatment (BMT) versus BMT alone for large-core AIS (defined by ASPECTS 2-5 or volumetric methods). The primary outcome was reduced disability at 3 months (≥1-point reduction across all Modified Rankin Scale (mRS) grades). Secondary outcomes included independent ambulation at 3 months (mRS score 0-3), good functional outcome at 3 months (mRS score 0-2), excellent functional outcome at 3 months (mRS score 0-1), symptomatic intracranial haemorrhage (sICH) and any intracranial haemorrhage (ICH) and mortality at 3 months. The random-effects model was used. Four RCTs were included comprising a total of 662 patients treated with EVT vs 649 patients treated with BMT. Compared with BMT, EVT was significantly associated with reduced disability (common OR 1.70, 95% CI 1.39 to 2.07; I2=0%), independent ambulation (risk ratio (RR) 1.69, 95% CI 1.33 to 2.14; I2=39%) and good functional outcome (RR 2.33, 95% CI 1.76 to 3.10; I2=0%), but not with excellent functional outcome (RR 1.46, 95% CI 0.91 to 2.33; I2=39%) at 3 months. Although rates of sICH (RR 1.98, 95% CI 1.07 to 3.68; I2=0%) and any ICH (RR 2.13, 95% CI 1.70 to 2.66; I2=37%) were higher in the EVT group, 3-month mortality (RR 0.98, 95% CI 0.83 to 1.15; I2=0%) did not differ between the two groups. EVT appears to be effective and safe and may be considered for the treatment of large-core AIS, as assessed by ASPECTS of 2-5 or volumetric methods. CRD42022334417.


Nonequilibrium 1/f noise in rectifying nanopores.
We report a single rectifying conically shaped nanopore system with ion current fluctuations whose 1/f noise characteristics observed at low frequencies are voltage dependent. Switching the voltage polarity allows one to switch between a system that produces equilibrium and nonequilibrium 1/f ion current fluctuations. The nonequilibrium fluctuations in the high-conductance state of the device are characterized by exponential dependence of the normalized power spectrum on voltage. The asymmetric 1/f noise is found characteristic for rectifying polymer nanopores and absent in pores with Ohmic current-voltage curves.


Articulatory settings and L2 English coronal consonants.
Background/aims: We explore the potential contribution of Articulatory Settings (AS) theory to L2 speech production research, testing the hypothesis that L2 segmental speech learning should involve a gradual, overall shift in both place and constriction degree, simultaneously affecting all consonants of a series as opposed to a set of parallel but unrelated changes in learners' production of individual sounds. Methods: We conducted an electropalatography study of four francophone learners' production of French and English word-initial and -medial /t d s z n l/ via carrier-sentence reading tasks. Results: L1-L2 differences in tongue shape are more common than those in constriction location, first and foremost for sonorants, and, thus, our results are not completely consistent with AS theory's claims. Conclusions: AS theory provides a potentially rich framework for exploring the L2 speech learning of consonantal phenomena including low-level L1-L2 differences in place of articulation. We propose that the observed lack of systematic between-language articulatory differences could be attributed to a number of factors to be explored in future research, such as the targeting of voicing and manner differences before the adjustment of small place differences as well as individual patterns of entrenchment of L1 articulatory routines.


Spatial surrogate for domestic combustion's air emissions: A case study from Silesian Metropolis, Poland.
The aim of this study is improving currently applied methodology for spatial disaggregation, as well as mapping air emission inventories by taking into account the auxiliary spatial data on population density. District heating infrastructure occurring in more populated areas changes distinctly the spatial distribution of estimated air emission; however, it does not change the initial estimate. That means the total, disaggregated value is constant. Considered sources of domestic combustion are located in the central part of the Silesian Metropolis, in the southern part of Poland. A large part of this area is strongly urbanized and supplied with heat (hot water) from the district heating system. Data on population density help to determine the area within which the dwellers use heat energy and hot water supplied by the heating infrastructure, apart from heating with small domestic boilers and stoves. This causes the domestic combustion's emission impact within the distinguished area to be significantly lower in comparison to the official guidelines on air emission inventories. The important differences in spatial air emissions distributions calculated using a top-down approach are found for strongly urbanized areas supplied partly with heat and hot water from the district heating network. This fact should be taken into account when preparing detailed, high-resolution emission inventories for air regional and local quality modeling. The spatial issues connected with elaboration of the high-resolution emission inventories are presented for the example of the populated area of the Silesian Metropolis (Poland). Spatial distribution of the population density is used to determine the area supplied with heat and hot water from the district heating system. It changes distinctly the spatial distribution of the air emission from small residential combustion sources.


Application of a tissue receptor assay to measurement of serum follitropin (FSH).
A rat testes tubule receptor assay, employing 125I-hFSH as the radioligand, has been applied to measurement of human serum follitropin (FSH). Highly purified hFSH LER-1575C was used as the reference preparation. Problems related to interference with uptake of radioligand by receptor, presumably due to non-hormonal serum factors, were minimized by dialysis of the serum prior to TRA. Results obtained by TRA were compared with those obtained by radioimmunoassay (RIA). The mean index of discrimination (TRA/RIA) for a series of 11 postmenopausal sera (PM) was 5.4 and the mean index of precision was 0.063. Sensitivity of the TRA was 9 ng hFSH/ml. Postmenopausal serum averaged 81 ng/ml, PM on estrogen therapy averaged less than 9 ng/ml, Turners Syndrome was 40 ng/ml. No FSH was detected in hypophysectomized serum, in normal male serum or in blood bank serum. PM levels by TRA were similar to those obtained by others with RIA after multiplying by the conversion factor of 5.4.


Improvement of mitochondrial function by celastrol in palmitate-treated C2C12 myotubes via activation of PI3K-Akt signaling pathway.
Compelling evidences posited that high level of saturated fatty acid gives rise to mitochondrial dysfunction and inflammation in the development of insulin resistance in skeletal muscle. Celastrol is a pentacyclic triterpenoid derived from the root extracts of Tripterygium wilfordii that possesses potent anti-inflammatory properties in a number of animal models with metabolic diseases. However, the cellular mechanistic action of celastrol in alleviating obesity-induced insulin resistance in skeletal muscle remains largely unknown. Therefore, the present investigation evaluated the attributive properties of celastrol at different concentrations (10, 20, 30 and 40nM) on insulin resistance in C2C12 myotubes evoked by palmitate. We demonstrated that celastrol improved mitochondrial functions through significant enhancement of intracellular ATP content, mitochondrial membrane potential, citrate synthase activity and decrease of mitochondrial superoxide productions. Meanwhile, augmented mitochondrial DNA (mtDNA) content with suppressed DNA oxidative damage were observed following celastrol treatment. Celastrol significantly enhanced fatty acid oxidation rate and increased the level of tricarboxylic acid (TCA) cycle intermediates in palmitate-treated cells. Further analysis revealed that the improvement of glucose uptake activity in palmitate-loaded myotubes was partly mediated by celastrol via activation of PI3K-Akt insulin signaling pathway. Collectively, these findings provided evidence for the first time that the protection from palmitate-mediated insulin resistance in C2C12 myotubes by celastrol is likely associated with the improvement of mitochondrial functions-related metabolic activities.


Mode-independent thermo-optic switch based on the total-internal-reflection effect.
A broadband mode-independent thermo-optic (TO) switch using the total-internal-reflection (TIR) effect is proposed and experimentally demonstrated on a polymer waveguide platform. By optimizing geometric parameters of the TIR switch, a mode-independent TO switching function with a large bandwidth and extinction ratio can be realized for E11, E12, and E21 modes. The measurement results show an extinction ratio larger than 18.1 dB with a driving power of 160 mW for each mode over the wavelength range of 1500-1620 nm. The designed structure can also be cascaded to form a 1 × N switch network for mode-division multiplexing (MDM) systems, which greatly improves the network flexibility.


Recovery and Detection of Enteric Viruses from Non-Traditional Irrigation Water Sources.
The variability of environmental water samples impacts the allowance of one method to be universally ideal for all water types and volumes. Surface and reclaimed waters can be used for crop irrigation and may be referred to as non-traditional irrigation waters as these water types may be associated with a higher risk of microbial contamination compared to groundwater. These waters are typically more microbially and chemically complex than groundwater and have a higher risk of viral contamination. To detect viruses in these water types, an infinite number of variations can be made to traditional recovery methods. This protocol was developed based on a commonly used virus adsorption and elution (VIRADEL) method. Additional steps were included to simplify and efficiently reduce particulates in the viral concentrate and remove DNA from eluted nucleic acids prior to detection. Method alterations allow for volumes up to 40 liters to be processed with consistent recovery of enteric viruses including Aichi virus, hepatitis A virus, and noroviruses belonging to genogroups GI and GII. No inhibition was observed among either surface or reclaimed water samples. This protocol could be utilized in the monitoring of a wide array of irrigation water sources throughout irrigation processes.


Molecular aspects of growth factor action: receptors and intracellular signals.
An increasing number of factors have been described which influence the proliferative responses of normal and neoplastic cells. A review of such moieties, their occurrence and possible mechanisms of their action and interaction is presented together with a discussion of their potential importance in the genesis and progression of neoplasms.


DNA double-strand break and chromosomal rejoining defects with misrejoining in Nijmegen breakage syndrome cells.
NBS1-deficient cells exhibit pronounced radiosensitivity and defects in chromosome integrity after ionizing radiation (IR) exposure, yet show only a minor defect in DNA double-strand break (DSB) rejoining, leaving an as yet unresolved enigma as to the nature of the radiosensitivity of these cells. To further investigate the relationship between radiosensitivity, DSB repair, and chromosome stability, we have compared cytological and molecular assays of DSB misrejoining and repair in NBS1-defective, wild type, and NBS1-complemented cells after IR damage. Our findings suggest a subtle defect in overall DSB rejoining in NBS1-defective cells and uniquely also reveal reduced ability of NBS1-defective cells to rejoin correct ends of DSBs. In agreement with published results, one of two different NBS1-defective cell lines showed a slight defect in overall rejoining of DSBs compared to its complemented counterpart, whereas another NBS line did not show any difference from wild type cells. Significant defects in the correct rejoining of DSBs compared to their respective controls were observed for both NBS1-defective lines. The defect in DSB rejoining and the increased misrejoining detected at the molecular level were also reflected in higher levels of fragments and translocations, respectively, at the chromosomal level. This work provides both molecular and cytological evidence that NBS1-deficient cells have defects in DSB processing and reveals that these molecular events can be manifest cytologically.


Oral Medications to Treat Toenail Fungal Infection.
Which oral antifungal medication is associated with the highest clinical (ie, normal appearance of the toenail) and mycological (negative culture, microscopy, or both) cure rates vs placebo or other antifungals when used to treat fungal infections? Both terbinafine and azole-based medications were associated with higher clinical and mycological cure rates compared with placebo (high-quality evidence). Azoles were associated with lower cure rates than terbinafine when compared directly.


Effects of oral florfenicol and azithromycin on gut microbiota and adipogenesis in mice.
Certain antibiotics detected in urine are associated with childhood obesity. In the current experimental study, we investigated two representative antibiotics detected in urine, florfenicol and azithromycin, for their early effects on adipogenesis, gut microbiota, short-chain fatty acids (SCFAs), and bile acids in mice. Thirty C57BL/6 mice aged four weeks were randomly divided into three groups (florfenicol, azithromycin and control). The two experimental groups were administered florfenicol or azithromycin at 5 mg/kg/day for four weeks. Body weight was measured weekly. The composition of the gut microbiota, body fat, SCFAs, and bile acids in colon contents were measured at the end of the experiment. The composition of the gut microbiota was determined by sequencing the bacterial 16S rRNA gene. The concentration of SCFAs and bile acids was determined using gas chromatography and liquid chromatography coupled to tandem mass spectrometry, respectively. The composition of the gut microbiota indicated that the two antibiotics altered the gut microbiota composition and decreased its richness and diversity. At the phylum level, the ratio of Firmicutes/Bacteroidetes increased significantly in the antibiotic groups. At the genus level, there were declines in Christensenella, Gordonibacter and Anaerotruncus in the florfenicol group, in Lactobacillus in the azithromycin group, and in Alistipes, Desulfovibrio, Parasutterella and Rikenella in both the antibiotic groups. The decrease in Rikenella in the azithromycin group was particularly noticeable. The concentration of SCFAs and secondary bile acids decreased in the colon, but the concentration of primary bile acids increased. These findings indicated that florfenicol and azithromycin increased adipogenesis and altered gut microbiota composition, SCFA production, and bile acid metabolism, suggesting that exposure to antibiotics might be one risk factor for childhood obesity. More studies are needed to investigate the specific mechanisms.


High glucose-induced oxidative stress impairs proliferation and migration of human gingival fibroblasts.
Delayed gingival wound healing is widely observed in periodontal patients with diabetes. However, the molecular mechanisms of the impaired function of gingival fibroblasts in diabetes remain unclear. The purpose of this study was to investigate changes in the properties of human gingival fibroblasts (HGFs) under high-glucose conditions. Primary HGFs were isolated from healthy gingiva and cultured with 5.5, 25, 50, and 75 mM glucose for 72 h. In vitro wound healing, 5-ethynyl-2'-deoxyuridine (EdU), and water-soluble tetrazolium salt (WST-8) assays were performed to examine cell migration and proliferation. Lactase dehydrogenase (LDH) levels were measured to determine cytotoxicity. The mRNA expression levels of oxidative stress markers were quantified by real-time PCR. Intracellular reactive oxygen species (ROS) were also measured in live cells. The antioxidant N-acetyl-l-cysteine (NAC, 1 mM) was added to evaluate the involvement of ROS in the glucose effect on HGFs. As a result, the in vitro wound healing assay showed that high glucose levels significantly reduced fibroblast migration and proliferation at 6, 12, 24, 36, and 48 h. The numbers of cells positive for EdU staining were decreased, as was cell viability, at 50 and 75 mM glucose. A significant increase in LDH was proportional to the glucose concentration. The mRNA levels of heme oxygenase-1 and superoxide dismutase-1 and ROS levels were significantly increased in HGFs after 72 h of exposure to 50 mM glucose concentration. The addition of NAC diminished the inhibitory effect of high glucose in the in vitro wound healing assay. The results of the present study show that high glucose impairs the proliferation and migration of HGFs. Fibroblast dysfunction may therefore be caused by high glucose-induced oxidative stress and may explain the delayed gingival wound healing in diabetic patients.


Coexpression of intermediate-sized filaments in sialadenoma papilliferum and other salivary gland neoplasms.
The neoplastic cells present in a sialadenoma pappiliferum were found by immunoperoxidase method and immunofluorescent staining technique to co-express 3 different types of intermediate-sized filaments (IFs) defined by monoclonal antibodies to cytokeratin, vimentin and desmin. When other salivary gland tumors such as 18 pleomorphic adenomas, 15 adenolymphomas, 2 oxyphilic adenomas, 7 mucoepidermoid tumors, 5 acinic cell tumors, 8 adenoid cystic carcinomas and 6 adenocarcinomas were examined immunohistochemically for the expression of IFs, no tumors with all 3 types of IFs observed in sialadenoma papilliferum were found.


Assessing cognitive performance in dairy calves using a modified hole-board test.
The hole-board test has been used to assess working and reference memory in a variety of species, but not in cattle. We developed and applied a modified hole-board test for dairy calves. Fifteen bottles were evenly spaced along three walls of a test arena; 11 of these were empty and 4 were 'baited' with milk. Calves were exposed daily (over an 11-day learning period) to the test arena with the location of the baited bottles held constant; the location of the 4 baited bottles was then changed and calves were re-trained on these new locations (over a 7-day re-learning period). Working memory (no. of revisits to the baited set), general working memory (no. of revisits to the whole set), and reference memory (avoidance of non-baited bottles) were assessed daily. Performance significantly improved during the learning period for reference and general working memory. Working memory tended to improve, albeit non-significantly. The change in bottle location initially reduced all performance measures, but these subsequently improved during the 7-day re-learning period. These results indicate that a modified hole-board test can be used to assess calf cognition, and thus may be helpful in future research designed to investigate the effects of housing and rearing conditions on cognition.


Effects of immunization against two inhibin antigens on daily sperm production and hormone concentrations in ram lambs.
The gonadal hormone inhibin regulates daily sperm production (DSP) indirectly through negative feedback control of FSH secretion and may also affect DSP via direct actions within the testis. Studies attempting to increase DSP through the immunization against inhibin have yielded equivocal results. The current study compared 2 inhibin antigens for effects on DSP and hormone secretion. Hampshire ram lambs (BW = 42 +/- 2 kg; age = 113 +/- 3 d) were assigned randomly to 3 groups: 1) control (n = 4); 2) alpha-peptide conjugate (PTC, n = 6); and 3) alpha-subunit (SUB, n = 6). Antigen PTC consisted of an alpha-inhibin, N-terminal, 25-amino acid peptide conjugated to ovalbumin. Antigen SUB was the complete inhibin alpha-subunit. Lambs were immunized on d 0 (June 19, 2006), 18, 38, and 63. Body weight was recorded on immunization days and scrotal circumference on d 63. Blood samples were collected on d 0, 7, 14, 18, 28, 35, 38, 49, 56, 63, and 70. Rams were slaughtered on d 71. Testes were weighed, and parenchyma was obtained for DSP determination. Plasma alpha-inhibin antibody titer and LH, FSH, and testosterone concentrations were measured. alpha-Inhibin antibody titer was first detectable on d 14 in both PTC- and SUB-immunized ram lambs and generally increased thereafter. Mean DSP per gram of testis (DSP/g) was increased (P < 0.01) 26% in PTC- and SUB-immunized ram lambs over that in control ram lambs. Total DSP per ram lamb and testes weight did not differ among the 3 treatment groups. Variation in DSP per ram lamb and testes weight were greater (P = 0.05) in PTC- and SUB-immunized ram lambs than in control ram lambs. Plasma FSH concentrations were similar in PTC- and SUB-immunized ram lambs. Immunization against either alpha-inhibin antigen did not alter LH, testosterone, BW, or scrotal circumference. Findings indicate that 1) the 2 alpha-inhibin antigens increase DSP/g to similar extents; 2) alpha-inhibin antibody may act at least in part through an intratesticular mechanism because DSP/g was increased in some animals without concomitant increases in FSH; and 3) immunization against alpha-inhibin may affect testes weight by actions independent of those that regulate DSP/g.


Impact of a statewide home visiting program to prevent child abuse.
To assess the impact of a voluntary, paraprofessional home visiting program in preventing child maltreatment and reducing the multiple, malleable psychosocial risks for maltreatment for which families had been targeted. This collaborative, experimental study focused on 6 Healthy Families Alaska (HFAK) programs; 325 families were enrolled in 2000-2001, randomized to intervention and control groups, and interviewed to measure baseline attributes. Follow-up data were collected when children were 2 years old (85% follow-up rate). Outcomes included maltreatment reports, measures of potential maltreatment and parental risks, for example, poor mental health, substance use, and partner violence. HFAK records were reviewed to measure home visiting services. Home visitors were surveyed to measure perceived effectiveness and training adequacy. Parental risks were common at baseline, and one-sixth of families had a substantiated child protective services report in the child's first 2 years of life. There was no overall program effect on maltreatment reports, and most measures of potential maltreatment. Home visited mothers reported using mild forms of physical discipline less often than control mothers. The groups were similar in their use of more severe forms of physical discipline. There was no program impact on parental risks. There was no impact on outcomes for families with a 'high dose' of home visiting. Home visitors often failed to address parental risks and seldom linked families with community resources. Contradictions in the model compromised effectiveness. The program did not prevent child maltreatment, nor reduce the parental risks that had made families eligible for service. Research is needed to develop and test strategies to improve the effectiveness of home visiting.


Comparative studies on reproductive traits of natural populations of Eisenia andrei Bouché, 1972 from Zagros Mountain, Iran (Annelida: Oligochaeta).
Comparative studies were carried out on growth and reproduction patterns of eight populations of Eisenia andrei (Bouché, 1972) from different parts of western Iran along the Zagros Mountains, considered to lie within the natural range of this species. Parameters were gain in body weight, number of cocoon production, hatching success, number of hatchlings, hatchlings growth and survival. There were significant differences in mean numbers of viable cocoons, incubation time, reproductive rate, growth rate and final weight between different populations. The resulting groupings did only partially coincide with genetic clusters established in a previous study. It is nonetheless suggested to include life cycle parameters as an additional set of data to understand the micro-taxonomic structure of variable species.


[Application and prospect of digital technology in the field of orthodontics].
The three-dimensional(3D)digital technology has brought a revolutionary change in diagnostic planning and treatment strategy of orthodontics. Acquisition of 3D image data of the hard and soft tissues of the patients, diagnostic analysis and treatment prediction, and ultimately the individualized orthodontic appliance, will become the development trend and workflow of the 3D orthodontics. With the development of 3D digital technology, the traditional plaster model has been gradually replacing by 3D digital models. Meanwhile, 3D facial soft tissue scan and cone-beam CT scan have been gradually applied to clinical orthodontics, making it possible to get 3D virtual anatomical structure for patients. With the help of digital technology, the diagnostic process is much easier for orthodontist. However how to command the whole digital workflow and put it into practice in the daily work is still a long way to go. The purpose of this article is to enlighten the orthodontists interested in digital technology and discuss the future of digital orthodontics in China.


The contraceptive practice of abortion patients.
An analysis is made of the contraceptive practice of 100 women prior to abortion. Half the women were not using any method during the month they became pregnant. Problems with the pill, risk-taking behaviour and fears of infertility, were the commonest reasons for non-use. In the 50 percent who were using a method, failure was most commonly due to human error and to the use of less reliable methods. Psychological and social factors were seen to be important determinants of behaviour. This study emphasises the need for remedial action.


[Bone adaptation changes mechanical stress in the femur--a prospective two years follow up after Hüft-TEP implantation].
Periprosthetic adaptive bone remodeling after total hip arthroplasty (THA) has been frequently simulated in computer models, combining bone remodeling theory with finite element analysis. Unfortunately, there is still a lack of clinical validation data. The collection of prospective volumetric bone density data with a clinical computerized tomography study after THA was previously conducted. The objective of the study presented here is an additional evaluation of femoral strain. In a prospective clinical trial with 7 female patients after THA computerized tomography (CT) and finite element (FE) modeling was patient specifically combined immediately after surgery, as well as at three and 24 months postoperatively. Mechanical strain was expressed by strain energy density. Corresponding to a bone density decrease, a decrease of the femoral strain energy density was observed during the two year follow-up after surgery (approximately 20 %). The predominant change occurred within the first three months and was found to be distally stronger than proximally. As far as we are aware, this is the first combination of fully prospective 3D CT density data in vivo with patient-specific finite element modeling. The assessment of mechanical strain data during a follow-up trial should be a new approach for analyzing hip stems in clinical biomechanics. A future confirmative study based on a statistical case number calculation would increase the evidence of the results presented here.


Continuous culture studies of xylose-fermenting Zymomonas mobilis.
The continuous cofermentation performance of xylose-fermenting Zymomonas mobilis at 30 degrees C and pH 5.5 was characterized using a pure-sugar feed solution that contained 8 g/L glucose and 40 g/L xylose. Successful chemostat start up resulted in complete utilization of glucose and greater than 85% utilization of xylose, but was only reproducibly achieved using initial dilution rates at or less than 0.04/h; once initiated, cofermentation could be maintained at dilution rates of 0.04 to 0.10/h. Whereas xylose and cell-mass concentrations increased gradually with increasing dilution rate, ethanol concentrations and ethanol yields on available sugars remained approximately constant at 20-22 g/L and 80-90% of theoretical, respectively. Volumetric and specific ethanol productivities increased linearly with increasing dilution rate, rising from approx 1.0 each (g/L/h or g/g/h) at a dilution rate of 0.04/h to approx 2.0 each (g/L/h or g/g/h) at a dilution rate of 0.10/h. Similarly, specific sugar-utilization rates increased from approx 2.0 g/g/h at dilution rate 0.04/h to approx 3.5 g/g/h at dilution rate of 0.10/h. The estimated values of 0.042 g/g for the maximum Z. mobilis cell-mass yield on substrate and 1.13 g/g/h for the minimum specific substrate utilization rate required for cellular maintenance energy are within the range of values reported in the literature. Results are also presented which suggest that long-term adaptation in continuous culture is a powerful technique for developing strains with higher tolerance to inhibitory hemicellulose hydrolyzates.


Straight until proven gay: A systematic bias toward straight categorizations in sexual orientation judgments.
Perceivers achieve above chance accuracy judging others' sexual orientations, but they also exhibit a notable response bias by categorizing most targets as straight rather than gay. Although a straight categorization bias is evident in many published reports, it has never been the focus of systematic inquiry. The current studies therefore document this bias and test the mechanisms that produce it. Studies 1-3 revealed the straight categorization bias cannot be explained entirely by perceivers' attempts to match categorizations to the number of gay targets in a stimulus set. Although perceivers were somewhat sensitive to base rate information, their tendency to categorize targets as straight persisted when they believed each target had a 50% chance of being gay (Study 1), received explicit information about the base rate of gay targets in a stimulus set (Study 2), and encountered stimulus sets with varying base rates of gay targets (Study 3). The remaining studies tested an alternate mechanism for the bias based upon perceivers' use of gender heuristics when judging sexual orientation. Specifically, Study 4 revealed the range of gendered cues compelling gay judgments is smaller than the range of gendered cues compelling straight judgments despite participants' acknowledgment of equal base rates for gay and straight targets. Study 5 highlighted perceptual experience as a cause of this imbalance: Exposing perceivers to hyper-gendered faces (e.g., masculine men) expanded the range of gendered cues compelling gay categorizations. Study 6 linked this observation to our initial studies by demonstrating that visual exposure to hyper-gendered faces reduced the magnitude of the straight categorization bias. Collectively, these studies provide systematic evidence of a response bias in sexual orientation categorization and offer new insights into the mechanisms that produce it. (PsycINFO Database Record


Primary prevention of myocardial infarction: aspirin is not as useful as it seems.
Aspirin has not been reliably shown to reduce all-cause and cardiovascular mortality but can prevent symptomatic myocardial infarction. However, silent myocardial infarction (SMI) is not uncommon in clinical practice. No meta-analysis has compared the effect of aspirin administration on primary prevention of all myocardial infarctions, including SMI. We systematically searched PubMed, Embase, Web of Science, Cochrane Library and Google Scholar for randomized double-blind controlled trials evaluating the effect of aspirin on primary prevention of all myocardial infarctions, including SMI. The current meta-analysis included 9 trials involving 67,486 patients and 67,557 controls on aspirin primary prevention of all myocardial infarctions. When SMI was included in the total number of myocardial infarctions, the aspirin effect on the primary prevention of myocardial infarction was not as significant as expected [risk ratio (RR): 0.883; 95% confidence interval (CI): 0.780 to 1.001; P=0.052]. Aspirin may not provide a primary preventive effect in all myocardial infarction patients. Previously demonstrated reductions in myocardial infarction are not present when SMI is included.


Drosophila melanogaster, Vicia faba and Arabidopsis thaliana short-term bioassays in genotoxicity evaluation of air and soil samples from sites surrounding two industrial factories in the Czech Republic.
The Somatic Mutation and Recombination Test (SMART) in wing cells of Drosophila melanogaster, the Vicia faba cytogenetic tests-Sister Chromatid Exchange (SCE) and Micronucleus Test (MN), and the Müller test for gametic mutations in Arabidopsis thaliana were used for genotoxicity testing of environmental samples of pollutants from the surroundings of LACHEMA chemical factory (Brno, Czech Republic) and DEZA factory in Valasské Mezirící (Moravia, Czech Republic). Tested soil and air samples were taken from the near vicinity of both factories. The surroundings of both sites are heavy loaded by exhalation of chemicals from the factories. Chemical analyses of the 16 Polycyclic Aromatic Hydrocarbons (PAHs) according to the United States Environmental Protection Agency (US EPA) list of priority pollutants and heavy metals were performed in both soil and air samples. The Drosophila wing spot test was positive in 70.6% of the tested samples, the Vicia sister chromatid exchange test in 62.5%, and the Arabidopsis Müller test in 58.9%. The micronucleus Vicia faba test was quite insensitive in tested environmental samples. The concordance between SMART and SCE was 62.5%, between SMART and Müller test 76.5%, and between Müller test and SCE 100%. Total concordance of these three tests was 79.7%. Müller test for gametic mutation in Arabidopsis thaliana and cytogenetic SCE test in Vicia faba seem to be quite sensitive and convenient plant bioassays for assessing the mutagenic potential of environmental agents, when compared to the SMART test in Drosophila melanogaster.


Suppression of the osmoinduced proline response of rapeseed leaf discs by polyamines.
Rapeseed leaf discs (RLD) subjected to upshock osmotic stress accumulate proline (Pro). Di- and polyamines (PA) supplied to the external medium suppressed Pro accumulation. These effects were dependent not only on diamine and PA concentrations but also on their cationic charge. The suppression of Pro accumulation required that diamine and PA be taken up and further accumulated in the leaf tissues. Glycine betaine (GB) also inhibited Pro accumulation, with the effects of GB and PA being additive. Experiments to elucidate the mechanism(s) responsible for the inhibitory effect of spermine (Spm) indicated that it could be simulated with methionine sulfoximine (MSO), a potent inhibitor of glutamine synthetase. The inhibitory effects of Spm and MSO were both alleviated by supplying glutamine to the RLD. In addition, Spm as well as MSO increased glutamate content, indicating that these compounds could inhibit the conversion of glutamate to proline. A comparison of the changes in chlorophyll and protein content of RLD osmotreated with or without added Spm indicates that this PA behaves as an antisenescent compound, preventing chlorophyll breakdown and proteolysis and hence the conversion of amino acids to Pro. Since the PA concentrations used in this work were much higher than the endogenous concentrations in RLD, the significance of PA under osmotic stress remains unclear. This study shows, however, that PA can suppress Pro accumulation.


Radioactive Iodine for the Treatment of Subclinical Thyrotoxicosis Grade 1 and 2: Outcome of up to 18-Year Follow Up.
Subclinical thyrotoxicosis (SCT) is associated with significant morbidity and mortality, specifically increased risk of atrial fibrillation and cardiovascular death. The management is ill-defined due to the scarcity of randomised controlled studies. Some clinicians recommend radioiodine (RAI) treatment however its long-term outcome is unknown. Therefore, further data is needed to provide robust evidence-based guidelines. A prospective, single-protocol analysis of the outcome of SCT patients (Grade 1; 0.1-0.4 mIU/L and Grade 2; <0.1 mIU/L) treated with mean dose of 427 MBq of I131, followed up for up to 18 years. Thyroid function tests were measured at 4-6 weeks, 3-, 6-, and 12-months post-RAI, and annually thereafter. Cure was defined as achieving a euthyroid/hypothyroid state. Seventy-eight patients with a median age of 68 years (range 36-84) and varying aetiology [55 toxic multinodular goitre (TMNG), 10 toxic nodule (TN) and 13 Graves' disease (GD)] were followed up for a median period of 7.5 years (range 1-18). The cure rate was 100%. The rates of hypothyroidism in TMNG, TN and GD were 23.6%, 30% and 38.5% respectively. The median time to hypothyroidism was 6 and 12 months in GD and TMNG/TN respectively. No differences in outcome between Grade 1 versus Grade 2 were observed. RAI using single mean dose of 427 MBq is effective and safe, irrespective of aetiology or grade of TSH suppression. GD patients become hypothyroid within the first year, whilst TMNG/TN for up to 9-years. Thus after 12 months of follow up, annual thyroid function monitoring is advised.


The Shared Mechanism and Candidate Drugs of Multiple Sclerosis and Sjögren's Syndrome Analyzed by Bioinformatics Based on GWAS and Transcriptome Data.
This study aimed to explore the shared mechanism and candidate drugs of multiple sclerosis (MS) and Sjögren's syndrome (SS). MS- and SS-related susceptibility genes and differentially expressed genes (DEGs) were identified by bioinformatics analysis based on genome-wide association studies (GWAS) and transcriptome data from GWAS catalog and Gene Expression Omnibus (GEO) database. Pathway enrichment, Gene Ontology (GO) analysis, and protein-protein interaction analysis for susceptibility genes and DEGs were performed. The drugs targeting common pathways/genes were obtained through Comparative Toxicogenomics Database (CTD), DrugBank database, and Drug-Gene Interaction (DGI) Database. The target genes of approved/investigational drugs for MS and SS were obtained through DrugBank and compared with the common susceptibility genes. Based on GWAS data, we found 14 hub common susceptibility genes (HLA-DRB1, HLA-DRA, STAT3, JAK1, HLA-B, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB5, HLA-DPA1, HLA-DPB1, TYK2, IL2RA, and MAPK1), with 8 drugs targeting two or more than two genes, and 28 common susceptibility pathways, with 15 drugs targeting three or more than three pathways. Based on transcriptome data, we found 3 hub common DEGs (STAT1, GATA3, PIK3CA) with 3 drugs and 10 common risk pathways with 435 drugs. "JAK-STAT signaling pathway" was included in common susceptibility pathways and common risk pathways at the same time. There were 133 overlaps including JAK-STAT inhibitors between agents from GWAS and transcriptome data. Besides, we found that IL2RA and HLA-DRB1, identified as hub common susceptibility genes, were the targets of daclizumab and glatiramer that were used for MS, indicating that daclizumab and glatiramer may be therapeutic for SS. We observed the shared mechanism of MS and SS, in which JAK-STAT signaling pathway played a vital role, which may be the genetic and molecular bases of comorbidity of MS with SS. Moreover, JAK-STAT inhibitors were potential therapies for MS and SS, especially for their comorbidity.