Enumeration of microparticles on a gridded filter using a stratified random sampling tool.
Quantifying microplastics and other microparticles is a matter of interest in the field of environmental science. Stereomicroscopy is one of the most common methods to identify and enumerate micro-size particles. However, the process of enumerating an entire environmental sample can be tedious and time-consuming, especially when target particles are abundant. Here we present a method to develop a subsampling strategy and spreadsheet-based tool to speed up the process of microparticle enumeration while maintaining particle count accuracy. We first identified the pattern in which tire road wear particles (TRWPs) from environmental samples were distributed on a filter when vacuum-plated, then used particle abundance within relatively homogeneous subsection arrangements to establish stratified random subsampling schemes. We describe a repeated sampling experiment using count data to test the stratified design and illustrate the relationship between the fraction of the filter counted (sample size) with accuracy and variance in the extrapolated total sample count and the corresponding analyst time savings when applied to analyzing TRWPs isolated from sediments. Based on the results, a particle enumeration tool was created in Microsoft Excel Visual BasicⓇ configured using a 47 mm gridded filter, and the source is available for free modification under the same open license.•Vacuum-plated microparticles are often highly abundant and not homogenously distributed across a filter.•A random sampling selection data tool was created using knowledge of particle distribution.•Method describes how to structure and use partial filter counts to extrapolate for total particle enumeration.


Pharmacokinetics and pharmacodynamics of propranolol stereoisomers in hyperthyroid patients.
The disposition of propranolol stereoisomers after administration of a single oral dose of the racemic drug was investigated in seven hyperthyroid patients before and after antithyroid drug therapy. The possibility of hypersensitivity to propranolol in the patients was evaluated by constructing plasma propranolol concentration -- beta-blocking effect curves. There was no statistically significant difference in elimination half-life (t1/2) between (+/-)- and (-)-propranolol before and after antithyroid drug therapy. However, the plasma clearance (Vp) of (-)-propranolol was smaller than that of (+/-)-propranolol, and the difference was statistically significant after antithyroid drug therapy. Vp decreased or did not change in young patients after therapy. No significant difference was observed in the relationship between the tilt-induced pulse rate response and plasma propranolol concentration when treated patients became euthyroid compared to their response in the hyperthyroid state.


Prescription Opioid Use Among Seriously Mentally Ill Veterans Nationally in the Veterans Health Administration.
Frequent prescription opioid use has been recognized as a growing problem but there have been no studies specifically among veterans with serious mental illness (SMI). National data from the Veterans Health Administration (VHA) during Fiscal Year 2012 show that VHA patients with SMI receive more opioid prescriptions than other veterans. Additionally, high numbers of opioid prescriptions is associated with greater use of anxiolytics/sedative-hypnotics, drug dependence and COPD-all of which pose an increased risk of respiratory depression and falls and warrant substantial caution and improved coordination between mental health and non-mental health prescribers to evaluate risk-benefit tradeoffs.


Cryptocarya species--substitute plants for Ocotea bullata? A pharmacological investigation in terms of cyclooxygenase-1 and -2 inhibition.
In response to the serious scarcity of Ocotea bullata (Burch.) Baillon (Lauraceae), an important medicinal plant in South Africa, Cryptocarya species (Lauraceae) are frequently used as substitute plants. Our investigation was aimed at a pharmacological comparison of O. bullata and the Cryptocarya species C. latifolia Sonder, C. myrtifolia Stapf., C. transvaalensis Burtt Davy, C. woodii Engl. and C. wyliei Stapf., in terms of in vitro cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibition, as an indication of O. bullatas' repute as a remedy against headache. Furthermore, we also compared bark and leaf extracts of the species investigated in order to address the problem of destructive ring-barking. The utilization of leaves instead of bark would help in the management of threatened medicinal plants. All Cryptocarya species were superior to O. bullata with regard to bark extracts. C. woodii bark extracts showed outstanding equipotent activity towards COX-1 and COX-2. The activity of extracts of fresh leaves was comparable to the activity of the respective bark extracts. Drying the leaves before extraction resulted in a loss of activity, with the exception of C. wyliei. Extracts of dried C. wyliei leaves exhibited high inhibitory activity, with a COX-2/COX-1 ratio of 5.8.


Computerised fetal heart rate analysis in labour--effect of sampling rate.
To study the effect of sampling rate on the accuracy of fetal heart rate recording in labour. Prospective observational study. The fetal heart rate was obtained from 153 fetuses in labour. The heart rate data was sampled at a rate of 0.5 Hz (every 2 s) and the means and standard deviations of 5-min segments compared against the mean and standard deviation for all beats in the same time interval. There was a highly significant correlation between the means (r = 0.994, p < 0.001) and standard deviations (r = 0.957, p < 0.001) of FHR sampled on successive beats compared with 2 s sampling. Two second sampling of the fetal heart rate in labour will allow a highly complex analytical algorithm to process the signal in near real time for objective analysis.


Aztreonam: worldwide overview of the treatment of patients with gram-negative infections.
Multicenter trials were conducted to determine the safety and efficacy of aztreonam in the treatment of patients with gram-negative bacterial infections. A total of 2,821 patients were treated; 2,117 received aztreonam and 704 received control antibiotics. All patients were evaluated for safety and 1,180 of those treated with aztreonam and 428 treated with the control drugs met the criteria for efficacy evaluation. The number of patients treated with aztreonam who were evaluable for efficacy and their microbiologic response rates were: urinary tract infections, 443 (82 percent); lower respiratory tract infections, 217 (79 percent); septicemia, 63 (98 percent); skin/skin structure infections, 136 (88 percent); intra-abdominal infections, 47 (85 percent); postpartum/gynecologic infections, 21 (100 percent); bone and joint infections, 12 (100 percent); acute uncomplicated gonorrhea, 209 (97 percent); and acute uncomplicated cystitis, 56 (84 percent). Adverse reactions were qualitatively similar to those reported for beta-lactam antibiotics, i.e., mild gastrointestinal upset, rash, eosinophilia, or transient increase in hepatic enzyme parameters. There was an apparent lack of adverse effects on kidney, inner ear, and blood coagulation system. The most frequent adverse effect was phlebitis at infusion site (2.4 percent of patients). Superinfections and colonization with new organisms occurred in 9.4 percent of aztreonam-treated patients and in 7.4 percent of control drug-treated patients; only 40 percent of patients in each group, approximately 4 percent of all patients receiving aztreonam and 3 percent of those receiving control antibiotics, required specific therapy for the superinfection. Overall, results indicated that aztreonam is a safe and effective antibiotic in the treatment of aerobic gram-negative infections, when used either as monotherapy or in combination with other antibiotics.


Optimization of the environmental performance of food diets in Peru combining linear programming and life cycle methods.
The improvement of diets from a nutritional and health perspective has been a critical policy objective in developing nations for the past few decades. However, the current stress that human populations are exerting on the planet has made it important to assess diets using environmental indicators, such as greenhouse gas (GHG) emissions. Therefore, the main objective of the current study was to propose a methodology in which Life Cycle Assessment results linked to dietary patterns in Peru were combined with nutritional and economic data to optimize diets. For this, a linear programming model was built in which the environmental, nutritional and economic information on a set of 25 dietary patterns in Peru were optimized in order to achieve the environmentally best-performing diet that complies with economic and nutritional standards. The result of the proposed linear program allowed understanding the amount of each individual food product that should be consumed in each city that satisfies all the restrictions included in the model in order to attain the lowest GHG emissions possible. Results demonstrated that GHG reductions in food diets can be attained through optimization. For instance, in the case of Lima the obtained reduction was 6%, lowering the annual per capita footprint linked to food diets to 690 kg CO2eq, as compared to the current value of 736 kg CO2eq. From an economic perspective, results show that there are important disparities between cities in terms of increasing or decreasing prices of the market basket. Considering that in most areas of the country food purchase accounts for approximately 50% of household expenditure, it is plausible to assume that food choice is a main carrier to achieve GHG emission mitigations. In this context, the method constitutes a useful tool for policy-makers to push forward joint regulations to improve health-related issues linked to the food diet and food choice together with recommendations to lower the climatic impact of diets.


Tracheostomy or delayed extubation after maxillofacial free-flap reconstruction?
Tracheostomy is commonly done to secure the airway after free-flap reconstruction in the head and neck, but it can have serious complications. We reviewed the outcomes of 78 patients who had microvascular free-flap reconstruction for maxillofacial pathology. Twenty-five had primary tracheostomy and 53 delayed extubation 24-48hours after operation. Both groups had similar operations, and the duration of stay in the intensive therapy unit (ITU) was almost identical. However, the overall hospital stay was significantly longer (27.2 days) in the tracheostomy group than in the delayed extubation group (20.4 days, p=0.03). Three patients who had a tracheostomy had serious complications related to the procedure (12%), including cardiorespiratory arrest when the tracheostomy tube was obstructed. Only one patient in the delayed extubation group required a delayed (secondary) tracheostomy for persistent oedema of the airway and failed delayed extubation (2%), and a further two had a tracheostomy for other reasons (4%). Of those who had delayed extubation, 50 (94%) did not ultimately require a tracheostomy, which is consistent with other studies. We have used our data to develop an algorithm to help clinicians decide when tracheostomy is needed. In general, primary tracheostomy should be considered for patients who have maxillofacial free-flap reconstruction and bilateral neck dissection, or those with oropharyngeal tumours who need additional access procedures. Delayed extubation is safe after free-flap reconstruction and unilateral neck dissection in patients who do not have conditions such as obstructive sleep apnoea or poor lung function.


Urinary myoglobin quantification by high-performance liquid chromatography: An alternative measurement for exercise-induced muscle damage.
This study investigated a means of quantifying urinary myoglobin using a novel reverse-phase high-performance liquid chromatography (RP-HPLC) method that is an alternative measure of exercise-induced muscle damage. It also investigated the effect of storage and alkalization on urinary myoglobin stability issues. An RP-HPLC method was validated by precision and repeatability experiments. Myoglobin stability was determined through spiked urine samples stored at various temperatures over an 8-week period using alkalization and dilution in a pH 7.0 buffer. The method was validated with urine collected from mixed martial arts fighters during a competition and training session. The method produced linearity from 5 to 1000 μg/ml (R(2) = 0.997), intra- and inter-assay coefficients of variation from 0.32 to 2.94%, and a lower detection limit of 0.2 μg/ml in the final dilution and 2 μg/ml in the original urine sample. Recovery ranged from 96.4 to 102.5%, myoglobin remained stable at 4 °C when diluted in a pH 7.0 buffer after 20 h, and a significant increase (P < 0.01) and an identifiable peak were observed following a mixed martial arts contest and training session. Storage length and conditions had significant effects (P < 0.05) on stability. The method's simplicity and noninvasive nature means it can be used as an alternative muscle damage assay following exercise and trauma.


Blood donation among women in Nigeria: Motivators, barriers and appealing incentives.
Women are grossly under-represented among blood donors in Nigeria. We, therefore, determined the barriers, motivators and appealing incentives to blood donation among women in Nigeria. This was an internet-based cross-sectional study among women aged 18-65 years. A well-structured questionnaire was used to determine sociodemographic characteristics, motivation, barriers and appealing incentives. Motivational and barrier differences in some sociodemographic characteristics were determined using the chi-squared test. A p-value of 0.05 was considered statistically significant. The most common motivators among blood donors were 'when family or friend is in need of blood', 'health benefits' and 'reminders to donate'. One-time donors who were willing to become regular donors were more motivated by reminders to donate than those not willing (p = 0.000). The most common barriers among non-donors were 'poor attitude of hospital staff' and 'fear of contracting infections'. Younger women and those of the Hausa tribe were more debarred by 'lack of privacy during blood donation exercise' than older women and those of the other tribes (p-values of 0.008 and 0.006, respectively). The most appealing incentives for blood donation were medical consultation and a blood donation certificate. Women's participation in blood donation in Nigeria can be improved by sending regular reminders to donors, especially one-time donors and by infrastructural adjustments to improve privacy at the blood donation sites. Specific and targeted capacity-building initiatives should also be put in place to drive a paradigm shift in the attitude of hospital staff to work in Nigeria.


Syntheses of substituted 3-methyleneisoindolin-1-ones by a palladium-catalyzed Sonogashira coupling-carbonylation-hydroamination sequence in phosphonium salt-based ionic liquids.
Two efficient approaches for the synthesis of isoindolin-1-one derivatives in phosphonium salt ionic liquids are described. The palladium-catalyzed carbonylation-hydroamination reaction of 1-halo-2-alkynylbenzene with amines afforded the substituted 3-methyleneisoindolin-1-ones in good yields and high selectivities in favor of the Z-isomers. The target molecules could also be synthesized by the Sonogashira coupling-carbonylation-hydroamination one-pot reaction of dihalides, alkynes, and amines. Both processes can be conducted under mild conditions and tolerate a wide array of functionalized substrates.


[Primary structure of DNA complementary to mRNA of murine oncoprotein p53].
Nucleotide sequencing of cDNA clone specific for murine oncoprotein p53 from the SVTZ all line has revealed nucleotide changes as compared with previously published structures of p53 cDNA originated from other cell lines.


Band-selective excited ultrahigh resolution PSYCHE-TOCSY: fast screening of organic molecules and complex mixtures.
Precise assignments of (1) H atomic sites and establishment of their through-bond COSY or TOCSY connectivity are crucial for molecular structural characterization by using (1) H NMR spectroscopy. However, this exercise is often hampered by signal overlap, primarily because of (1) H-(1) H scalar coupling multiplets, even at typical high magnetic fields. The recent developments in homodecoupling strategies for effectively suppressing the coupling multiplets into nice singlets (pure-shift), particularly, Morris's advanced broadband pure-shift yielded by chirp excitation (PSYCHE) decoupling and ultrahigh resolution PSYCHE-TOCSY schemes, have shown new possibilities for unambiguous structural elucidation of complex organic molecules. The superior broadband PSYCHE-TOCSY exhibits enhanced performance over the earlier TOCSY methods, which however warrants prolonged experimental times due to the requirement of large number of dwell increments along the indirect dimension. Herein, we present fast and band-selective analog of the broadband PSYCHE-TOCSY, which is useful for analyzing complex organic molecules that exhibit characteristic yet crowded spectral regions. The simple pulse scheme relies on band-selective excitation (BSE) followed by PSYCHE homodecoupling in the indirect dimension. The BSE-PSYCHE-TOCSY has been exemplified for Estradiol and a complex carbohydrate mixture comprised of six constituents of closely comparable molecular weights. The experimental times are greatly reduced viz., ~20 fold for Estradiol and ~10 fold for carbohydrate mixture, with respect to the broadband PSYCHE-TOCSY. Furthermore, unlike the earlier homonuclear band-selective decoupling, the BSE-PSYCHE-decoupling provides fully decoupled pure-shift spectra for all the individual chemical sites within the excited band. The BSE-PSYCHE-TOCSY is expected to have significant potential for quick screening of complex organic molecules and mixtures at ultrahigh resolution. Copyright © 2015 John Wiley & Sons, Ltd.


In vitro validation of gamma-secretase inhibitors alone or in combination with other anti-cancer drugs for the treatment of T-cell acute lymphoblastic leukemia.
Activating NOTCH1 mutations are common in T-cell acute lymphoblastic leukemia. Inhibition of NOTCH1 signaling with gamma-secretase inhibitors causes cell cycle block, but only after treatment for several days. We further documented the effects of gamma-secretase inhibitor treatment on T-cell acute lymphoblastic leukemia cell lines and tested whether combining gamma-secretase inhibitors with other anti-cancer drugs offers a therapeutic advantage. The effect of gamma-secretase inhibitor treatment and combinations of gamma-secretase inhibitors with chemotherapy or glucocorticoids was assessed on T-cell acute lymphoblastic leukemia cell lines. We sequenced NOTCH1 in T-cell acute lymphoblastic leukemia cases with ABL1 fusions and tested combinations of gamma-secretase inhibitors and the ABL1 inhibitor imatinib in a T-cell acute lymphoblastic leukemia cell line. gamma-secretase inhibitor treatment for 5-7 days reversibly inhibited cell proliferation, caused cell cycle block in sensitive T-cell acute lymphoblastic leukemia cell lines, and caused differentiation of some T-cell acute lymphoblastic leukemia cell lines. Treatment for 14 days or longer was required to induce significant apoptosis. The cytotoxic effects of the chemotherapeutic agent vincristine were not significantly enhanced by addition of gamma-secretase inhibitors to T-cell acute lymphoblastic leukemia cell lines, but gamma-secretase inhibitor treatment sensitized cells to the effect of dexamethasone. NOTCH1 mutations were identified in all T-cell acute lymphoblastic leukemia patients with ABL1 fusions and in a T-cell acute lymphoblastic leukemia cell line expressing NUP214-ABL1. In this cell line, the anti-proliferative effect of imatinib was increased by pre-treatment with gamma-secretase inhibitors. Short-term treatment of T-cell acute lymphoblastic leukemia cell lines with gamma-secretase inhibitors had limited effects on cell proliferation and survival. Combinations of gamma-secretase inhibitors with other drugs may be required to obtain efficient therapeutic effects in T-cell acute lymphoblastic leukemia, and not all combinations may be useful.


Surface Crystal Growth of Perovskite Nanocrystals via Postsynthetic Lead(II) Bromide Treatment to Increase the Colloidal Stability and Efficiency of Light-Emitting Devices.
The surface modification of metal halide perovskite nanocrystals (NCs) significantly impacts their optical properties and colloidal stability. This subsequently affects the performance of light-emitting devices (LEDs). Therefore, numerous surface passivation techniques like ligand exchange and metal halide doping have been explored to passivate the surface defects of perovskite NCs and obtain highly efficient LEDs. In this study, we demonstrated the postsynthetic metal halide doping treatment using lead(II) bromide (PbBr2) to passivate the surface defects of the CsPbBr3 NCs at a moderate reaction temperature of 80 °C. The alkyl quaternary ammonium salt, didodecyldimethylammonium bromide (DC12AB), enabled the complete dissolution of PbBr2 in a nonpolar solvent, toluene. Because of surface crystal growth, the particle sizes of the PbBr2-doped CsPbBr3 NCs were higher than those of the as-synthesized CsPbBr3 NCs. The photoluminescence quantum yield of the CsPbBr3 NCs drastically increased from 26.8 to 83.9% after the PbBr2 doping treatment. Moreover, the PbBr2-doped CsPbBr3 NCs possessed long-term colloidal stability of more than 2 months that indicates the strong bonding between the NCs and ligands. We observed that the alkyl chain length of the quaternary alkyl ammonium salts affected the luminance and device stability during operations. In this study, a promising strategy was devised to achieve highly luminescent perovskite NCs with excellent colloidal stability that can enhance the performance of LEDs.


Suppression of Epstein-Barr nuclear antigen 1 (EBNA1) by RNA interference inhibits proliferation of EBV-positive Burkitt's lymphoma cells.
Epstein-Barr virus (EBV) is associated with the development of several lymphoid and epithelial malignancies, including Burkitt's lymphoma. The EBV latent protein, EBV Nuclear Antigen 1 (EBNA1), is detectable in almost all types of EBV-associated tumors and is essential for replication and maintenance of the latent episome of EBV. We here examined whether the RNA interference (RNAi) technique could be employed to suppress expression of EBNA1 in EBV-positive Burkitt's lymphoma cells. A Raji cell line expressing small hairpin RNAs (shRNAs) against EBNA1 was established and EBNA1 mRNA level was determined by real-time RT-PCR analysis. We investigated the effects of EBNA1 silence on lymphoma cell growth and cell cycle progression. Transfection of an EBNA1 RNAi plasmid resulted in substantial loss of EBNA1 mRNA and significantly inhibited proliferation of Raji cells relative to the control plasmid case. Suppression of EBNA1 was also associated with downregulation of EBV oncogene EBNA2, a decreased PCNA labeling index and increased G0/G1 fraction in cell cycle analysis. These findings point to potential therapeutic applications for vector-mediated siRNA delivery to control EBV-associated malignant disorders.


Predictors of contralateral-bilateral nodal disease in oropharyngeal cancer: A National Cancer Data Base Study.
Oropharyngeal squamous cell carcinoma (SCC) frequently presents with cervical metastasis. Roles of human papillomavirus (HPV) status, among other factors, on laterality are elusive. The National Cancer Database was reviewed for oropharyngeal SCC diagnosed from 2010-2014. Predictors of clinically evident contralateral or bilateral nodal disease were identified. A total of 15 517 patients with oropharyngeal SCC met criteria. The majority was HPV-positive. Histologically poorly differentiated tumors were more frequent in the HPV-positive group (55.7% vs 37.6%; P < .001). By incidence, there was no statistical difference in contralateral or bilateral nodal disease between HPV-positive and HPV-negative patients (14.2% vs 14.5%, respectively; P = .769). On multivariable analysis, notable predictors of contralateral or bilateral nodal disease included HPV-positivity (odds ratio [OR] 1.26; 99% confidence interval [CI] 1.10-1.44), base of tongue (BOT) location (OR 2.15; 99% CI 1.88-2.45), poorly differentiated tumor (OR 1.72; 99% CI 1.20-2.46), and T4 classification (OR 6.65; 99% CI 5.34-8.28). Patients with HPV-associated oropharyngeal SCC have increased likelihood of contralateral or bilateral nodal disease. Tumor grade, tumor location, and tumor size are also independent predictors.


Effect of food on the pharmacokinetics and therapeutic efficacy of 4-phenylbutyrate in progressive familial intrahepatic cholestasis.
Progressive familial intrahepatic cholestasis (PFIC), a rare inherited disorder, progresses to liver failure in childhood. We have shown that sodium 4-phenylbutyrate (NaPB), a drug approved for urea cycle disorders (UCDs), has beneficial effects in PFIC. However, there is little evidence to determine an optimal regimen for NaPB therapy. Herein, a multicenter, open-label, single-dose study was performed to investigate the influence of meal timing on the pharmacokinetics of NaPB. NaPB (150 mg/kg) was administered orally 30 min before, just before, and just after breakfast following overnight fasting. Seven pediatric PFIC patients were enrolled and six completed the study. Compared with postprandial administration, an approved regimen for UCDs, preprandial administration significantly increased the peak plasma concentration and area under the plasma concentration-time curve of 4-phenylbutyrate by 2.5-fold (95% confidential interval (CI), 2.0-3.0;P = 0.003) and 2.4-fold (95% CI, 1.7-3.2;P = 0.005). The observational study over 3 years in two PFIC patients showed that preprandial, but not prandial or postprandial, oral treatment with 500 mg/kg/day NaPB improved liver function tests and clinical symptoms and suppressed the fibrosis progression. No adverse events were observed. Preprandial oral administration of NaPB was needed to maximize its potency in PFIC patients.


Information needs and information-seeking behaviors of on-call radiology residents.
The authors performed a baseline analysis of the information needs and information-seeking behaviors of on-call radiology residents to learn how to better serve their on-call information needs in the future. Print, electronic, and human information resources were made conveniently available to on-call radiology residents. A prospective, descriptive study was performed by using a modification of the critical incident technique to gather data from the residents every morning after being on call. Residents were asked to recall questions that arose, whether they sought answers to the questions, where they searched for answers, whether their search was successful, and whether they believed that patient care was affected. The residents had 182 questions that encompassed all organ systems, imaging modalities, and aspects of radiologic practice. Residents sought answers to 138 of the 182 questions (76%) by using a wide variety of resources, with staff members and textbooks being the most common. They found answers to 114 of 138 questions (83%); 100 of the 114 (88%) answered questions affected patient care. The ideal way to meet the information needs of on-call radiology residents is to devise an authoritative information resource that is compatible with their information-seeking behaviors.


A healthy individual with a homozygous PTCH2 frameshift variant: Are variants of PTCH2 associated with nevoid basal cell carcinoma syndrome?
Variants in PTCH2 have been described to be associated with Nevoid Basal Cell Carcinoma Syndrome (NBCCS). We report a family with a healthy female who is homozygous for a frameshift variant, c.269delG, p.(Gly90Alafs*4), in PTCH2 and her heterozygous daughter. The variant predicts a frameshift and a premature stop codon. A summary of reported heterozygous individuals with germline PTCH2 variants along with the existence of a healthy homozygous individual question whether variants in PTCH2 are associated with NBCCS.


Visual Discomfort While Viewing Three-dimensional Television as a Screening Tool for Pediatric Eye Diseases in Children.
To investigate the efficacy of evaluating 3D asthenopia and 3D perception difficulty for screening of binocular vision abnormalities in children. Patients aged 6-12 years with abnormal binocularity, including strabismus, amblyopia, and anisometropia, were included. Age-matched normal subjects without any ophthalmologic abnormality other than a refractive error were also recruited. The best-corrected visual acuity, refractive error, angle of strabismus, and stereopsis were measured. Presenting visual acuity (PVA) was measured as the uncorrected visual acuity for subjects without glasses and spectacle-corrected visual acuity for those with glasses. After watching 3D TV for 30 min, a survey was administered to evaluate the 3D perception and 3D asthenopia. Receiver operation characteristic (ROC) curve analysis was conducted to evaluate the efficacy of the survey for detecting abnormal binocularity and poor PVA. One hundred subjects were enrolled in this study. Among them, 59 had abnormal binocularity (strabismus, anisometropia, or amblyopia), and 41 were normal control. Among the entire subjects, the number of subjects with a PVA of 20/40 or worse in one or both eyes was 24 (7 from the normal control and 17 with abnormal binocularity). ROC curve analysis revealed that the survey did not effectively detect strabismus, anisometropia, or amblyopia. However, for detection of PVA 20/40 or worse in the subjects with abnormal binocularity, the total score of the survey yielded an area of 0.714 under the ROC curve (p = 0.010). The sensitivity was 88.2% and specificity was 61.9% with a cutoff at 0.50. The degree of 3D asthenopia and 3D perception while watching 3D TV were not effective for screening of abnormal binocularity. However, evaluation of the severity of 3D asthenopia and the quality of 3D perception can help screen of decrease in PVA that requires correction.


Enzymology of gallotannin and ellagitannin biosynthesis.
Gallotannins and ellagitannins, the two subclasses of hydrolyzable tannins, are derivatives of 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose. Enzyme studies with extracts from oak leaves (Quercus robur, syn. Quercus pedunculata; Quercus rubra) and from staghorn sumac (Rhus typhina) revealed that this pivotal intermediate is synthesized from beta-glucogallin (1-O-galloyl-beta-D-glucopyranose) by a series of strictly position-specific galloylation steps, affording so-called 'simple' gallotannins, i.e., mono- to pentagallyoylglucose esters. Besides its role as starter molecule, beta-glucogallin was also recognized as the principal energy-rich acyl donor required in these transformations. Subsequent pathways to 'complex' gallotannins have recently been elucidated by the isolation of five different enzymes from sumac leaves that were purified to apparent homogeneity. They catalyzed the beta-glucogallin-dependent galloylation of pentagallyoylglucose to a variety of hexa- and heptagalloylglucoses, plus several not yet characterized higher substituted analogous galloylglucoses. With respect to the biosynthesis of ellagitannins, postulates that had been formulated already decades ago were proven by the purification of a new laccase-like phenol oxidase from leaves of fringe cups (Tellima grandiflora) that regio- and stereospecifically oxidized pentagallyoylglucose to the monomeric ellagitannin, tellimagrandin II. This compound was further oxidized by a similar but different laccase-like oxidase to yield a dimeric ellagitannin, cornusiin E.


Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study.
Longer-term outcomes with the anti-CD38 antibody isatuximab in combination with carfilzomib-dexamethasone (Isa-Kd) were evaluated in the randomized Phase 3 trial IKEMA (NCT03275285), in a prespecified, follow-up analysis of progression-free survival (PFS, primary study endpoint), final complete response (CR) using Hydrashift Isa immunofixation assay, minimal residual disease (MRD) negativity, and safety. Enrolled patients had relapsed/refractory multiple myeloma (1-3 prior treatment lines). Isa 10 mg/kg was administered intravenously weekly in cycle 1 then biweekly. Efficacy analyses were performed in the intent-to-treat population (Isa-Kd: n = 179, Kd: n = 123) and safety evaluated in treated patients (Isa-Kd: n = 177, Kd: n = 122). Consistent with the primary interim analysis, the addition of Isa to Kd prolonged PFS (HR 0.58, 95.4% CI: 0.42-0.79; median PFS 35.7 [95% CI: 25.8-44.0] vs 19.2 [95% CI: 15.8-25.0] months). PFS benefit was observed with Isa-Kd across subgroups, including patients with poor prognosis. The stringent CR/CR rate was 44.1% vs 28.5% (odds-ratio: 2.09, 95% CI: 1.26-3.48), the MRD negativity rate 33.5% vs 15.4% (odds-ratio: 2.78, 95% CI: 1.55-4.99) and the MRD negativity CR rate 26.3% vs 12.2%, with Isa-Kd vs Kd. The safety profile of Isa-Kd was similar to that reported in the prior interim analysis. These findings further support Isa-Kd as a standard-of-care treatment for relapsed multiple myeloma patients.Clinical trial information: ClinicalTrials.gov, NCT03275285.


Dynamic electromyographic evaluation of adolescents with traumatic cervical injury after biceps to triceps transfer: the role of phasic contraction.
To characterize the EMG firing pattern of the biceps after transfer to the triceps. Seven subjects (12 arms), 18.0 +/- 1.7 years old, consented to fine wire EMG assessment of the biceps, averaging 23.0 +/- 10.0 months (range: 9 to 45 months) after transfer. Subjects were tested under 3 conditions: (1) single flexion and extension, (2) self-selected alternating elbow flexion and extension, and (3) isometric flexion and extension. A strain gauge electrogoniometer measured elbow movement. Using root-mean-squared values of biceps EMG, ratios of extension/flexion activity were calculated for each muscle. Conventional manual muscle testing grades were obtained before and after surgery. Median manual muscle testing for elbow extension was 0 before surgery and 4- (range: 3- to 4) following surgery. For each of the 3 conditions tested, the biceps reversed its action to an elbow extensor (p < .05). Our findings show that the biceps, after transfer to the triceps in patients with C5 or C6 spinal cord injury, can be trained to activate preferentially during elbow extension, a reversal of its ordinary action as an elbow flexor.


Interaction of TACC proteins with the FHL family: implications for ERK signaling.
The Transforming acidic coiled coil (TACC) proteins play a conserved role in normal development and tumorigenesis through interactions with multiple complexes involved in transcription, translation, and centrosomal dynamics. However, despite significant work on the function of TACC3 in the control of centrosomal mechanics, relatively little functional data is known about the family's founding member, TACC1. From a continued analysis of clones isolated by an unbiased yeast two-hybrid assay, we now show direct physical interactions between the TACC1 and the FHL (Four and a Half LIM-only) family of proteins. The authenticity of these interactions was validated both in vitro and in cellular systems. The FHLs exhibit diverse biological roles such as the regulation of the actin cytoskeleton and are promiscuous coregulators for several transcription factors. The interaction of the endogenous TACC-FHL proteins is primarily localized to the nucleus. However, similar to FHL2, overexpression of TACC1A in HEK293 is able to sequester serum activated ERK to the cytoplasm. This has the effect of reducing the serum induced transcriptional response of the c-fos and c-jun genes. The observation that TACCs can interact with the FHLs and alter their serum induced activities raises the possibility that the TACCs participate in crosstalk between cell signaling pathways important for cancer development and tumor progression. The transforming acidic coiled coil genes are known to be important prognostic indicators for breast, ovarian and lung cancer. In this manuscript, we identify a novel interaction between the TACCs and the FHL protein family. This interaction has an affect on ERK and may in part explain the variable associations and changes in subcellular locations of each family with specific subtypes of malignancy.


The role of microstructural integrity of major language pathways in narrative speech in the first year after stroke.
Left hemisphere stroke often results in a variety of language deficits due to varying patterns of damage to language networks. The Cookie Theft picture description task, a classic, quick bedside assessment, has been shown to quantify narrative speech reliably. In this study, we utilized diffusion tensor imaging (DTI) to assess language network white matter tract correlates of lexical-semantic and syntactic impairments longitudinally. Twenty-eight patients with mild to severe language impairments after left hemispheric lobar and/or subcortical ischemic stroke underwent the Cookie Theft picture description test and DTI up to three different time points: within the first three months, six months and twelve months after stroke. Dorsal and ventral stream language pathways were segmented to obtain DTI integrity metrics of both hemispheres. Multivariable regression models and partial correlation analyses adjusted for age, education, and lesion load were conducted to evaluate the temporal DTI profile of the white matter microstructural integrity of the language tracts as neural correlates of narrative speech within the first year after stroke. Among all the major language white matter pathways, the integrity of the left arcuate (AF), inferior fronto-occipital, and inferior longitudinal fasciculi (ILF) were related to picture description performance. After FDR correction, left ILF fractional anisotropy correlated with syntactic cohesiveness (r=0.85,p=0.00087) within the first three months after stroke, whereas at one year post-stroke, the strongest correlations were found between lexical-semantic performance and left AF radial diffusivity (r = -0.71, p = 0.00065). Our study provides a temporal profile of associations between the integrity of the main language pathways and lexical semantics and syntactic impairments in left hemispheric strokes.


Electrical stimulation of the sural nerve partially compensates effects of central fatigue.
Depression of motor evoked potentials (MEPs) following transcranial magnetic stimulation (TMS) may be a sign of central motor fatigue. Abnormal fatigue can be observed in MS patients. We have examined whether post-exercise MEP depression can be compensated by application of sensory stimuli prior to TMS. We studied 15 healthy volunteers (aged 21 to 28 years) who were required to perform an exercise protocol of ankle dorsiflexion until force fell below 66% of maximum force. MEPs were recorded from the right tibialis anterior muscle. Prior to TMS, electrical stimuli were applied to the ipsilateral sural nerve with an individual interstimulus interval between 50 to 80 ms. MEP areas decreased after exercise. When a sensory stimulus was administered MEPs did not change. We conclude that the effects of central fatigue may be--at least partially compensated--by application of sensory stimuli. Sensory stimulation (e.g. by implantation of a neurostimulator) might be a useful therapy for abnormal central fatigue.


Neurophysiological assessment of brachioradial pruritus patients.
Pruritus is a common complaint in dermatology. Wartenberg, in 1943, associated pruritus with neuropathy, relating it to the "posterior antebrachial cutaneous nerve neuropathy". In 1968, Waisman described patients with frequent pruritus complaints in the upper limb during the summer, which he named "brachioradial summer pruritus". Currently, this pruritus is named brachioradial pruritus (BRP). BRP is characterized by a chronic pruritus, usually localized, with a long duration, and without apparent cutaneous abnormalities. Neurological disorders both from the central and peripheral nervous systems, including multiple sclerosis, are associated with pruritus. To investigate correlations between symptomatic dermatomes and alterations in the myotomes, as evidenced by electroneuromyography (ENMG). Forty-six patients with BRP dermatological diagnoses were subjected to upper limb ENMG. Among 46 patients with C5 to C8 dermatomal pruritus, we evaluated 113 symptomatic dermatomal areas. Overall, 39 (85%) patients had radicular involvement and 28 (60%) had agreement between complaint and the ENMG findings (p=0.015). A total of 80% of the patients with complaints at C7 and 47% at C6 had radicular involvement at the same level. Among the patients who presented complaints, 47 and 80%, respectively, had ENMG alterations in the C6 and C7 myotomes. We conclude that peripheral nervous system involvement is associated with BRP.


Boric acid modified S and N co-doped graphene quantum dots as simple and inexpensive turn-on fluorescent nanosensor for quantification of glucose.
A new fluorescent nanosensor based on S and N co-doped graphene quantum dots (S,N-GQDs) modified by boric acid was designed for glucose detection. First, the S,N-GQDs was prepared via one pot hydrothermal process utilizing citric acid and thiourea as precursors. Then, S,N-GQDs was modified by boric acid to fabricate (B)/S,N-GQDs. The excitation dependent photoluminescence spectra of (B)/S,N-GQDs confirmed the heteroatom (S,N) dopant effect on GQDs emission. FT-IR and energy dispersive X-ray (EDX) spectroscopies confirmed the modification of S,N-GQDs with boric acid. The optical and electrochemical band gaps of the obtained (B)/S,N-GQDs were found to be 2.7 and 2.5 eV, respectively. The boric acid functionalized S,N-GQDs exhibited fluorescent enhancement at 455 nm upon addition of glucose. Such fluorescence response was used for glucose quantification with a detection limit of 5.5 μM which is comparable with previous boronic acid based fluorescent sensing systems. However, compared with earlier reported expensive boronic acid based glucose sensors, this modified system is simpler, more economical, and efficient. A mechanism was proposed for fluorescence enhancement based on the reaction of cis-diol units of glucose with the boric acid groups of (B)/S,N-GQDs which creates rigid (B)/S,N-GQDs-glucose structures, restricting the non-radiative intramolecular motions and results in the fluorescent enhancement.


Epinephrine affects gene expression levels and has a complex effect on biofilm formation in M icrococcus luteus strain C01 isolated from human skin.
In this study, the effect of epinephrine on the biofilm formation of Micrococcus luteus C01 isolated from human skin was investigated in depth for the first time. This hormone has a complex effect on biofilms in various systems. In a system with polytetrafluoroethylene (PTFE) cubes, treatment with epinephrine at a physiological concentration of 4.9 × 10-9 M increased the total amount of 72-h biofilm biomass stained with crystal violet and increased the metabolic activity of biofilms, but at higher and lower concentrations, the treatment had no significant effect. On glass fiber filters, treatment with the hormone decreased the number of colony forming units (CFUs) and changed the aggregation but did not affect the metabolic activity of biofilm cells. In glass bottom plates examined by confocal microscopy, epinephrine notably inhibited the growth of biofilms. RNA-seq analysis and RT-PCR demonstrated reproducible upregulation of genes encoding Fe-S cluster assembly factors and cyanide detoxification sulfurtransferase, whereas genes encoding the co-chaperone GroES, the LysE superfamily of lysine exporters, short-chain alcohol dehydrogenase and the potential c-di-GMP phosphotransferase were downregulated. Our results suggest that epinephrine may stimulate matrix synthesis in M. luteus biofilms, thereby increasing the activity of NAD(H) oxidoreductases. Potential c-di-GMP pathway proteins are essential in these processes.


Subcutaneous and Transvenous Defibrillators in Arrhythmogenic Right Ventricular Cardiomyopathy: A Comparison of Clinical and Quality-of-Life Outcomes.
There is limited evidence guiding the selection between subcutaneous and transvenous implantable cardioverter-defibrillators (ICDs) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) at risk for sudden death. This study aimed to compare clinical and quality-of-life outcomes between transvenous and subcutaneous ICDs among patients with ARVC. Patients with a subcutaneous ICD (n = 57) were matched to patients with a transvenous ICD (n = 88) based on sex, proband status, primary prevention or secondary prevention, monomorphic ventricular tachycardia before implantation, and year of implantation. Appropriate therapy for ventricular arrhythmia, inappropriate shocks, and complications were compared. Quality-of-life surveys were conducted annually. The matched cohort (median age of 35 years, 43% men, 78% proband, and 37% secondary prevention device) were prospectively followed for 5.1 ± 2.5 years. No significant difference was observed in the rate of appropriate ICD shocks. The subcutaneous group had more inappropriate shocks (23% vs 10%) and fewer procedure-related complications (4% vs 14%) than the transvenous group (P < 0.05). The association between ICD type and the composite of inappropriate shock and complication was not statistically significant (subcutaneous vs transvenous adjusted HR: 1.43; 95% CI: 0.72-2.84). A subcutaneous ICD was associated with more body image concerns and range of motion than a transvenous ICD (P < 0.05). In patients with ARVC receiving an ICD, the risk of inappropriate shocks from a subcutaneous ICD should be balanced against the significant vascular complication risk from a transvenous ICD. Patients with a subcutaneous ICD had more concerns for body image and range of motion.


[Etiology and genetics of Alzheimer disease].
Alzheimer's disease (AD) constitutes more than 50% of all dementias. The diagnosis is mainly based on clinical criteria and a definitive diagnosis of AD is made post-mortem with identification of amyloid plaques and neurofibrillary tangles. A small proportion of the patients are under the age of 60 at diagnosis, known as early-onset AD, and most of these cases have an evident genetic component. Aging is the most important risk factor for developing late-onset AD, but also genetic polymorphisms and many environmental conditions play a part in the development of this multifactorial disease. The Medline database was searched for "Alzheimer's and genetics". Histologic data were kindly provided from our hospital's department of pathology. We consider most of the proved etiological factors, especially the three genetic loci which have been shown to be associated with early-onset AD: amyloid precursor protein (APP) gene, presenilin (PS)-1 and PS-2 genes. Mutations in the PS-1 gene at chromosome 14 are by far the most frequent genetic cause of AD. However, the large number of mutations makes genetic screening difficult. We also discuss the impact of the different ApoE alleles in developing late-onset AD, in addition to other mutations and polymorphisms.


Polyethylene pipes exposed to chlorine dioxide in drinking water supply system: A critical review of degradation mechanisms and accelerated aging methods.
Polyethylene (PE) pipes have been widely used in drinking water distribution systems across the world. In many cases, chlorine dioxide (ClO2) is used to maintain a residual disinfectant concentration in potable water. Practical experiences have shown that the lifetime of PE pipes is significantly reduced due to exposure to drinking water with ClO2. Recently, many companies have proposed new PE pipes with a modified formulation, which are more resistant to chlorine dioxide. However, a standardized test method for evaluating the long-term performances of PE pipes is still missing. This literature review was performed to provide a description of chlorine dioxide uses and degradation mechanisms of polyethylene pipes in real water distribution systems. Current accelerated aging methods to evaluate long-term performances of PE pipes exposed to ClO2 are described and discussed along with the common technics used to characterize the specimens. Accelerate aging methods can be distinguished in immersion aging tests and pressurized pipe loop tests. Wide ranges of operational conditions (chlorine dioxide concentration, water pressure, water temperature, etc.) are applied, resulting in a great variety of results. It was concluded that pressurized looping tests applying semi-realistic operational conditions could better replicate the aging mechanisms occurring in service. Despite this, the acceleration and the evaluation of the long-term performance are still difficult to determine precisely. Further experimentation is needed to correlate chemical-mechanical characterization parameters of PE pipes with their lifetime in service.


Skin cancer in organ transplant recipients: dynamics in the incidence and clinical predictors for the first and subsequent post-transplant non-melanoma skin cancer.
Risk factors for primary non-melanoma skin cancer (NMSC) in organ transplant recipients (OTR) have been well described. Data for subsequent NMSC and dynamics in their occurrence in OTR are limited. To study long-term risks of primary and subsequent NMSC and associated risk factors in OTR. A retrospective single-centre cohort study analysing medical records from a dermato-oncological specialty clinic. Of 464 OTR 110 (23.7%) developed at least one, 73 (15.7%) two and 51 (11%) three NMSC during a median follow-up of 9.6 years. Cumulative incidences at 5, 10 and 15 years were 14.7%, 23.5% and 34.5% for the first and 75.8%, 86.5% and 93.3% for the second. Median time-to-diagnosis declined from 22 years (95% CI 19-25) to 2 years (1-3) and about 1 year (0-2) for the first, second and third NMSC. Risk for subsequent NMSC only partially related to risk factors for the primary NMSC. Histologic type of the first NMSC predicted subtype and time-to-diagnosis of the subsequent NMSC. A first post-transplant NMSC, particularly a SCC, confers a high risk for subsequent NMSC arising with accelerated dynamics. Risk-adapted dermato-oncologic surveillance is advisable for all OTR.


Extracellular polymeric substances of a marine bacterium mediated synthesis of CdS nanoparticles for removal of cadmium from aqueous solution.
Microbial extracellular polymeric substances (EPS) are natural metal adsorbent and effective bio-reductant. In the biosynthesis of CdS NPs, functional groups of EPS act as capping and stabilizing agents. The NPs enriched EPS have enhanced adsorption capacity of cadmium ions, which may be due to increased adsorptive sites. The current study demonstrates, an efficient biosynthesis method to prepare CdS NPs using EPS extracted from a marine bacterium Pseudomonas aeruginosa JP-11 and its comparison with chemical method using D-glucose. The synthesized NPs were characterised by Ultraviolet-visible spectroscopy, ATR-FTIR spectrometry, X-ray diffraction, Field emission scanning electron microscopy and Transmission electron microscopy. Atomic absorption spectroscope (AAS) was used to study adsorption capacity of pristine EPS, functionalized EPS and NPs incorporated functionalized EPS. Spherical CdS NPs of 20-40nm diameter were synthesized with high crystallinity confirmed by XRD, FESEM and TEM analysis. The ATR-FTIR peaks within 2300-2600cm(-1) range showed a prominent shift in sulphydryl group (SH). The cadmium removal efficiency by CdS NPs incorporated functionalized EPS (88.66%) was higher than functionalized EPS (80.81%) and pristine EPS (61.88%) after 48h of incubation. The experimental data of adsorption thermodynamics and kinetics of Cd by NPs incorporated functionalized EPS was fitted in Langmuir isotherm model.


Placement of the VenaTech LP caval filter in the elderly: feasibility and clinical benefits of insertion via the arm.
To evaluate routine use of access sites in the arm for percutaneous caval filter placement (PCFP) in elderly patients. Neck arthritis, patient anxiety, access site thrombosis or fecal/urinary incontinence complicating jugular or femoral access may require alternative access sites in this population. Access via the right arm was chosen for PCFP (VenaTech LP). The indication for PCFP was deep vein thrombosis, a history of pulmonary embolism, and a contraindication to anticoagulant therapy. Ultrasound-guided puncture was performed after diameter measurement of the arm veins (ØAV). The filter was inserted with standard imaging procedures. Procedural difficulty was graded and compared with ØAV and the angle from the arm vein to the superior vena cava (alphaAV/SVC). Over 2 years, 16 patients (14 women, 2 men) with an average age of 90 years (range 79-97 years) were included in the study. The average ØAV value of the basilic or brachial veins was 4.2 mm (range 3.0-5.1 mm). The minimal ØAV for successful access was determined after the first 15 patients. No hematoma occurred at the puncture sites. The average alphaAV/SVC value was 62 degrees (range 29 degrees -90 degrees ). Arm access was possible in 12 of 16 patients (75%) with ØAV >or= 3.5 mm and alphaAV/SVC >or= 29 degrees . Every procedure via the arm was graded "easy" by the operator, regardless of angulation values. Femoral access was used in one case due to the impossibility of traversing the heart (patient no. 2), and jugular access was used in 3 of 16 (19%) patients due to puncture failure (patient no. 4), small ØAV (3 mm) (patient no. 6), and stenosis of the distal right subclavian vein (patient no.16), respectively. PCFP via the arm can be routinely accomplished in patients older than 75 years, provided ØAV >or= 3.5 mm, and alphaAV/SVC >or= 29 degrees .


Procedure for the quantitative evaluation of motor disturbances in cerebellar ataxic patients.
Cerebellar ataxia is a complex motor disturbance that involves the planning and execution of movements and reduces movement accuracy and co-ordination. The quantification of ataxic signs is commonly realised through visual examination of motor tasks performed by the patient and assignment of scores to specific items composing the international co-operative ataxia rating scale (ICARS). The present work studied an experimental procedure to characterise specific aspects of motor disturbances in ataxia objectively. Four tests belonging to the ICARS were considered: walking, knee-tibia test, finger-to-nose and finger-to-finger test. Through a kinematic analysis performed during the above tests, specific indices were defined to quantify velocity, linearity, asymmetry, tremor, instability and smoothness of movement or posture. The procedure was applied to five patients with cerebellar ataxia and to ten healthy adult subjects. Results demonstrated that the patients moved significantly more slowly than the healthy subjects (0.67 against 0.97m s(-1) and 0.81 against 1.02 m s(-1), respectively, for straight walk and finger-to-nose tests) and showed poorer linearity and smoothness behaviour. Velocity, linearity, tremor, smoothness and instability indices showed moderate to good correlation with the corresponding ICARS score. Some of these indices can separately evaluate aspects that are combined in single ICARS subscores. It is concluded that the combination of clinical assessments and instrumental evaluations allows a better insight into ataxic patients' motor disturbances and is a useful tool for the definition and follow-up of rehabilitation programmes.


Sediment-bound trace metals in Golfe-Juan Bay, northwestern Mediterranean: Distribution, availability and toxicity.
The concentration, potential mobility, cation exchange capacity and toxicity of eight sediment-bound metals in Golfe-Juan Bay, France were examined. Results revealed significant spatial gradient of metal contamination along Golfe-Juan coast. The distribution and concentration of the metals appear to be influenced by the geochemical properties of the sediment, proximity to anthropogenic sources and general water circulation in the bay. The portion of trace metals found in the exchangeable, carbonate, oxidizable and reducible fractions of the sediment constitute 31%-58% of the total sediment-bound trace metal content, suggesting significant potential for remobilization of metals into the water column. Pb and Ni content of the sediment exceed the limits of the French marine sediment quality. Whole sediment extracts showed acute toxicity to marine rotifers. This study concludes that monitoring and management of sediment-bound trace metals in Golfe-Juan Bay are important so as not to underestimate their availability and risk to the marine ecosystems.


Plasmodium infection in Kerteszia cruzii (Diptera: Culicidae) in the Atlantic tropical rain forest, southeastern Brazil.
In Southeastern Brazil, Kerteszia cruzii (former Anopheles cruzii), a bromeliad mosquito species, is considered an efficient human Plasmodium spp. vector. In this region, recent studies showed asymptomatic or sub-patent Plasmodium falciparum infection. In areas of the Atlantic coast in Rio de Janeiro, Plasmodium simium infection was recently reported in both human and howler monkey. Considering that (1) few malaria cases are reported each year in areas across the tropical Atlantic rain forest in southeastern Brazil; (2) malaria elimination in Atlantic forest is challenged by circulation of P. falciparum and P. simium in humans; (3) the complexity of malaria epidemiology in this region; and (4) the public health importance of Kerteszia cruzii as a sylvatic vector; the major goal of this study is to evaluate Plasmodium infection in Ke. cruzii. Mosquito sampling collections were conducted in Esteiro do Morro and Sítio Itapuan, in Cananeia municipality, and Tapiraí municipality in Ribeira Valley, southeastern São Paulo state, Brazil. Influence of climate and landscape factors in Plasmodium infection in Ke. cruzii was addressed. Among the 1719 mosquitoes tested, 3 females collected in Sítio Itapuan and three from Tapiraí were found infected with either P. vivax or P. simium. Results of statistical analyses did not demonstrate association between Plasmodium infection in mosquito and the landscape. Mosquito infection was found in two landscape clusters, with Plasmodium detected in forest fringe mosquitoes. This finding shows that Ke. cruzii can facilitate transmission among human and non-human primates. Plasmodium falciparum was not identified in the samples analyzed. Spatiotemporal variation in local malaria incidence, low prevalence of Plasmodium, variations in humidity and temperature can explain the absence of mosquitoes infected with P. falciparum in the study.


[Community viral pneumonia in the adult population: a prospective multicenter study of 62 cases. The Pneumonia Study Group of the Community of Valencia].
The present work prospectively analyzes, in a multicentric study, viral pneumonias acquired in the community during one year. Were studied 510 patients diagnosed of pneumonia in hospital, or whom 62 (12.1%) had a viral origin. Influenza virus A and B were the most common causative agents (47.6% and 20.6% respectively). Smoking habit was present in 44% of patients, previous OCFA in 45% and other previous pathology in 64.4%. The greatest number of registered cases was during December. The most frequent radiologic finding was alveolar pattern. Evolution in general, was favourable with a low mortality rate (one case).


Microencapsulation of avocado oil by spray drying using whey protein and maltodextrin.
Cold pressed avocado oil was microencapsulated by spray drying in four different wall systems consisting of whey protein isolate (WPI) alone or in combination with maltodextrin (MD) DE 5 at various ratios (90 : 10, 50 : 50 and 10 : 90). The WPI only or WPI/MD (90 : 10) powders were spherical and smooth, whereas the WPI/MD (50 : 50 and 10 : 90) powders exhibited pronounced surface collapse. Increasing the MD ratio resulted in higher bulk density and wettability, probably due to more compact physical structure and hydrophilic wall matrix. Surface free oil contents and microencapsulation efficiencies of powders were 11-16% and 45-66%, respectively, and no significant differences were observed between the samples. The crude avocado oil used in this study appeared to be stable against oxidation at cold and ambient temperatures, irrespective of microencapsulation. However, at high temperature of 60 degrees C, the oxidative stability decreased significantly in all cases but it was improved to some extent by microencapsulation.


Spectrum of congenital anomalies of the kidney and urinary tract (CAKUT) including renal parenchymal malformations during fetal life and the implementation of prenatal exome sequencing (WES).
Congenital malformations of the kidney and urinary tract (CAKUT) have a prevalence of 4-60 in 10,000 livebirths and constitute for 40-50% of all end stage pediatric kidney disease. CAKUT can have a genetic background due to monogenetic inherited disease, such as PKD or ciliopathies. They can also be found in combination with extra-renal findings as part of a syndrome. Upon detection of genitourinary malformations during the fetal anomaly scan the question arises if further genetic testing is required. The purpose of this study was to determine the phenotypic presentation of CAKUT cases and the results of exome analysis (WES). This is a retrospective analysis of 63 fetal cases with a diagnosis of CAKUT or DSD at a single center between August 2018 and December 2022. A total of 63 cases (5.6%) out of 1123 matched CAKUT phenotypes including renal parenchyma malformations. In 15 out of 63 WES analysis a pathogenic variant was detected (23.8%). In fetuses with isolated CAKUT the rate of detecting a pathogenic variant on exome sequencing was five out of 44 (11.4%). Ten out of 19 fetuses (52.6%) that displayed extra-renal findings in combination with CAKUT were diagnosed with a pathogenic variant. WES provides an increase in diagnosing pathogenic variants in cases of prenatally detected CAKUT. Especially in fetuses with extra-renal malformations, WES facilitates a gain in information on the fetal genotype to enhance prenatal counselling and management.


Understanding causal paths between mental illness and violence.
The stigma associated with mental illness is a major concern for patients, families, and providers of health services. One reason for the stigmatization of the mentally ill is the public perception that they are violent and dangerous. Although, traditionally, mental health advocates have argued against this public belief, a recent body of research evidence suggests that patients who suffer from serious mental conditions are more prone to violent behaviour than persons who are not mentally ill. It is a point of contention, however, whether the relationship between mental illness and violence is only one of association, or one of causality; that mental illness causes violence. A proven causal association between mental illness and violence will have major consequences for the mentally ill and major implications for caregivers, communities, and legislators. This paper outlines the key methodological barriers precluding casual inferences at this time. The authors suggest that a casual inference about mental illness and violence may yet be hasty. Because a premature statement advocating a causal relationship between mental illness and violence could increase stigma and have devastating effects on the mentally ill the authors urge researchers to consider the damage that may be produced as a result of poorly substantiated causal inferences.


Integrin-targeting disulfide-crosslinked micellar docetaxel eradicates lung and prostate cancer patient-derived xenografts.
Actively targeted nanomedicines though conceptually attractive for tumor therapy are extremely hard to realize due to problems of premature drug leakage, excessive liver accretion, inadequate tumor uptake, and/or retarded drug release inside tumor cells. Here, we systemically studied the influence of disulfide crosslinking on the in vitro and in vivo performance of integrin-targeting micellar docetaxel (t-MDTX). Of note, t-M5DTX with a high disulfide content was clearly advantageous in terms of stability, intracellular drug release, anti-tumor activity toward αVβ3-overexpressing A549 cells, blood circulation and therapeutic efficacy in orthotopic A549-luc lung tumor-bearing mice. t-MDTX induced extraordinary tumor targetability with tumor-to-normal tissue ratios of 1.7-8.3. Further studies indicated that t-M5DTX could effectively eradicate αVβ3-overexpressing lung and prostate cancer patient-derived xenografts (PDX), in which ca. 80% mice became tumor-free. This integrin-targeting disulfide-crosslinked micellar docetaxel emerges as a promising actively targeted nanoformulation for tumor therapy. STATEMENT OF SIGNIFICANCE: Nanomedicines have a great potential in treating advanced tumor patients; however, their tumor-targeting ability and therapeutic efficacy remain unsatisfactory. In addition to PEGylation and ligand selection, particle size, stability and drug release behavior are also critical to their performance in vivo. In this paper, we find that small and cRGD-guided disulfide-crosslinked micellar docetaxel (t-MDTX) induces superior tumor uptake and retention but without increasing liver burden, leading to extraordinary selectivity and inhibition of αvβ3 overexpressing lung tumors. t-MDTX is further shown to effectively treat αvβ3-positive patient-derived tumor models, lending it a high potential for clinical translation.


Evolution and dynamics of protein interactions and networks.
The central role of protein-protein interactions (PPIs) in biology has stimulated colossal efforts to identify thousands of them in several organisms. The resulting PPI maps are commonly represented as graphs, where nodes denote proteins and edges represent physical interactions. However, the methods used to generate PPI data on a large scale do not readily allow one to discriminate features such as interaction strength (affinity), type (protein-protein or protein-peptide interaction) or spatiotemporal existence (where and when the proteins are present and interact). Yet, in recent years, a number of studies have tackled these limitations by projecting additional information onto PPIs, revealing novel properties in terms of their evolution and dynamics. In this review we examine these properties both at the binary interaction level and at the network level. We suggest that the diverse and sometimes contradictory results described by different research groups are mostly due to incomplete data coverage and limited data types. Finally, we discuss recently developed methods that will improve this picture in the future.


The accuracy of measurements of ovarian follicular scanning by inexperienced observers using real-time sector scanning.
Three inexperienced operators (2 midwives and one obstetric registrar) were given ten sessions of training in ovarian follicular scanning. During each session, five patients were examined jointly. Once the inexperienced observers had received sufficient training the prospective study was started. Twenty measurements by each inexperienced observer were compared to measurements made by an experienced observer. In 17% of measurements the error was greater than 3 mm, the errors being evenly distributed among the three observers. After a further five sessions of instructions, another set of sixty measurements was generated: 93% of these measurements correlated exactly among the inexperienced operators and between the inexperienced and the experienced operator. This study suggests that after a supervised training of 15 sessions, obstetricians and midwives with prior obstetric scanning experience can produce reliable ovarian follicular measurements.


[Myths and Legends: Electrocardiographic Position Control of Central Venous Catheters - Where Does the P Come from?]
Misplacement of central venous accesses can be associated with deleterious iatrogenic complications. Electrocardiography is often used to guide the placement of central venous catheters and to confirm the correct position of the catheter tip. A characteristically peaked p-wave is traditionally considered to indicate the entrance of the catheter tip into the right atrium. However, recent data show that intraarterial and even extravascular localisation might result in an increased amplitude. The peaked p-wave most likely detects the pericardial reflection rather than a right atrial catheter position, hence real-time ultrasound is to be recommended as a superior technique to confirm a correct catheter position.


Effect of serum albumin on estrogen metabolism in human cancer cell lines.
The observation that charcoal-treated fetal bovine serum (ctFBS) was able to modify one of main pathways of estrogens in cancer cells in culture, prompted us to initiate the present study. The active component of serum was isolated using native preparative polyacrylamide gel electrophoresis (PAGE). Under analysis with SDS-PAGE, a M(W) of 68 kDa and mobility of authentic bovine serum albumin (BSA) was observed. The addition of BSA to the serum free culture medium of HEC 1A human endometrial cancer cell line, resulted in an alteration of estradiol (E2) metabolism similar to that observed in the presence of ctFBS. BSA in fact, much enhanced 16 alpha-hydroxylation and significantly reduced 2-hydroxylation of E2 in HEC 1A cells. Comparable results were obtained with different endometrial (Ishikawa) and mammary (MCF-7) tumor cell lines having a different metabolic conversion rate of E2. Several albumin preparations from either bovine or human serum had the same effect; besides, BSA activity was unaffected by treatment with dextran-charcoal or heat. In the light of the present results, the inclusion of serum albumin (SA) in the formulation of media for studies evaluating steroid metabolism in cultured cells should be carefully considered.


Two yeast nuclear genes, CBS1 and CBS2, are required for translation of mitochondrial transcripts bearing the 5'-untranslated COB leader.
Mutations in one of the yeast nuclear genes CBS1 or CBS2 both prevent the excision of the maturase-coding introns bI2, bI3 and bI4 from the mitochondrial COB precursor transcript. Mutant strain MK2 (cbs1-1) has recently been reported to be primarily defective in the translation of COB transcripts, as it can be suppressed by a fusion of the COB structural gene with the 5' untranslated leader of the mitochondrial OLI1 gene (G. Rödel, A. Körte and F. Kaudewitz, Curr Genet 9: 641-648). Here I report that the effect of mutation cbs2-1, too, is suppressed by this gene rearrangement. CBS2 is the second nuclear gene identified which is involved in the translation of mitochondrial transcripts bearing the 5' untranslated COB leader. Gene specific translation control appears to be a major mode of regulation of mitochondrial gene expression in Saccharomyces cerevisiae.


Delayed pentobarbital therapy of acute focal cerebral ischemia.
The efficacy of pentobarbital in the delayed treatment of acute cerebral ischemia was investigated in cats. Cerebral ischemia was produced by left middle cerebral artery (LMCA) ligation. Ten cats received 50 mg/kg of pentobarbital prior to ligation; a second group of 10 cats received the same dose of pentobarbital 2 hrs after ligation, and the control group of 7 cats received no pentobarbital. Brains were removed after spontaneous or induced death and the volume infarction was determined histologically. It was found that the volume of brain infarction in the group receiving pentobarbital 2 hrs after ligation was significantly less than that of the control group, which received no pentobarbital; but the volume of infarction in the former group was significantly greater than that found in the experimental group, which received pentobarbital prior to ligation. However, the mortality after LMCA ligation was higher in the 2 experimental groups, which received pentobarbital therapy, than in the control group, which did not receive pentobarbital. An hypothesis was advanced, which speculated that secondary adrenal insufficiency and altered cardiovascular function accounted for the increased mortality after pentobarbital treatment of patients with ischemic stroke.


Comparison of the Efficacy of Homeopathic Drug Arnica and Ibuprofen on Postextraction Pain in Children: A Triple-blind Randomized Controlled Trial.
To compare the homeopathic drug Arnica with ibuprofen as an analgesic for postextraction pain control in children. Forty-four healthy children between 8 and 12 years of age requiring two clinical sessions of tooth extraction in two different quadrants of the oral cavity were selected for the study. All the children received both the drugs in this crossover trial with a washout of 10 days. Patient-rated and operator-assessed pain was compared to a 10-point validated Visual Analog Scale at baseline, 24, 48, and 72 hours using the paired t-test. Acceptance to taste and frequency of dosing was recorded at the end of three days using a five-point Likert scale and were compared using the Chi-squared test. Kappa statistics were performed to assess intraoperator variability. Pain reduction by Ibuprofen was significantly more than Arnica only at 48 hours with respect to both patient-reported and operator-assessed pain [(t = 3.567, p < 0.05), (t = 2.834, p < 0.05)]. As the age of the child increased, patient-reported pain significantly decreased. Children preferred the taste of Arnica over that of Ibuprofen (x 2 = 56.76, p < 0.0001). There was no difference between Arnica and Ibuprofen in the postextraction pain management in 8-12-year-old children. The results of this study suggest that Arnica may be considered as an alternative to ibuprofen in managing postextraction pain in 8-12-year-old children, especially those with asthma, COPD, or known allergy to ibuprofen. Thakur JH, Katre AN. Comparison of the Efficacy of Homeopathic Drug Arnica and Ibuprofen on Postextraction Pain in Children: A Triple-blind Randomized Controlled Trial. Int J Clin Pediatr Dent 2022;15(3):332-337.


Atopy and depression: results from the Northern Finland 1966 Birth Cohort Study.
Several studies have suggested an association between IgE-mediated atopic allergies and depression. The present study extends our understanding about putative gender differences of this association and provides further epidemiological evidence for our previous finding that the association between atopy and depression may be characteristic for females only. In order to clearly determine the presence of atopic disorders and depression, we used more valid tools than had been employed earlier and we had access to a database (the Northern Finland 1966 Birth Cohort), in which individuals were followed up prospectively until the age of 31 years. The information on allergic symptoms, verified by skin-prick tests and comprising data of 5518 individuals, was used to ascertain the presence of atopy. Depression was assessed with the help of Hopkins' Symptom Checklist-25 and self-reported doctor-diagnosed depression. After adjusting for a father's social class, mother's parity, and place of residence, logistic regression analyses showed that the risk of developing depression increased in parallel with the increasing severity of depression and, when compared with nonatopic subjects, was 3.0 to 4.7-fold up in atopic females and statistically significant. In atopic males, the association between atopy and depression was statistically significant only in the highest depression scores, the odds ratio being 6.3-fold. The results indicate that females suffering from atopic diseases might possess an elevated risk of developing depression already during early adulthood. In males, the association between these two disorders is evident only among the most severe manifestations of depression. Possible background theories, that is, genetic abnormalities in serotonin metabolism, HPA-axis dysfunction, and histamine theory are discussed.


Associations Between Motor Competence and Physical Activity, Physical Fitness and Psychosocial Characteristics in Adolescents: A Systematic Review and Meta-analysis.
Motor competence is an integral component of the health and performance of youth. Numerous studies support the hypothesis that motor competence interacts with perceived motor competence and physical fitness during childhood to induce positive (e.g. healthy weight status) or negative (e.g. reduced physical activity engagement) trajectories. Yet, while adolescence is a key period of rapid growth and maturation, no systematic reviews and meta-analyses have examined the association between motor competence and physical activity, physical fitness and psychosocial characteristics solely within adolescents. This study aimed to (1) analyse the scientific literature evaluating associations between motor competence and physical activity, physical fitness and/or psychosocial characteristics amongst adolescents; (2) evaluate the associations between motor competence and physical activity, physical fitness characteristics and/or psychosocial characteristics amongst adolescents; and (3) investigate the impact of moderator variables (i.e., age, sex, type of motor competence assessment) on the associations. A systematic search of electronic databases was conducted, followed by a qualitative synthesis of study methods. Random-effects meta-analyses were performed to establish the magnitude and orientation of pooled correlation coefficients between motor competence and physical activity, physical fitness and psychosocial characteristics of adolescents, whilst considering potential moderators (i.e., age, sex, type of motor competence assessment). Sixty-one studies were included, totalling 22,256 adolescents. Twenty-seven different assessments of motor competence were used, with 31 studies utilising product-orientated (i.e. outcome) motor competence assessments. Meta-analyses of 43 studies showed that motor competence was positively associated with physical activity (r = 0.20 to 0.26), some physical fitness characteristics (e.g. muscular strength, cardiovascular endurance; r = 0.03 to 0.60) and psychosocial characteristics (r = 0.07 to 0.34), and inversely associated with weight status (r = - 0.36 to - 0.10), speed (r = - 0.31) and agility (r = - 0.37 to 0.41). Associations with flexibility were unclear. The results of this systematic review and meta-analysis support the hypothesised interactions of motor competence with physical activity (positive), physical fitness (positive except for weight status, speed and agility) and psychosocial characteristics (positive) in adolescence. However, methodological approaches vary considerably (e.g. variety of motor competence assessments utilised), with limitations of the current literature including an inadequate assessment of motor competence, a lack of longitudinal observations and a failure to account for biological maturation. Future research assessing associations between motor competence and physical activity, physical fitness and psychosocial characteristics of adolescents should include longitudinal observations of a combined motor competence assessment (i.e. process and product) and account for biological maturation. Improved evaluation using these recommendations could provide more accurate data, leading to more targeted interventions to improve adolescents' physical and psychosocial outcomes. CRD42021233441 (PROSPERO ID).


Giant plasma cells with multiple immature nuclei in a young woman with newly diagnosed multiple myeloma.
Multiple myeloma with giant multinucleated plasma cells is a very rare entity and mostly reported cases are dated. This plasma cell morphology has been observed after monoclonal antibody treatments, such as daratumumab, and patients have experienced a worse prognosis with partial responses and a high rate of relapse. Here, we showed a newly diagnosed multiple myeloma with giant plasma cells with multiple (up to 13) immature nuclei who achieved a complete remission after a first line therapy and underwent to autologous hematopoietic stem cell transplantation, as per international guidelines.


Long term follow up and analysis of long term survivors in patients treated with paclitaxel-based concurrent chemo/radiation therapy for locally advanced non-small cell lung cancer.
For patients with locally advanced non-small cell lung cancer (LANSCLC), concurrent chemotherapy/radiation therapy (RT) has become the standard of care. Three multi-institutional phase II studies with paclitaxel-based chemotherapeutic regimen given concurrently with RT for patients with LANSCLC were performed from March of 1994 to May of 1997. We sought to determine mature data from this database of patients, as well as to perform analysis of a cohort of patients who have achieved long term survival (LTS) when treated with this regimen. Database of these patients was analyzed retrospectively upon longer follow up, with median follow up for the three studies being 498 days (range 11-2905 days, average 780 days). Weight loss limitation for the three studies was liberal: weight loss <10% and <15% 3 months preceding diagnosis (LUN-27 and LUN-63, respectively), and no weight loss limitation for LUN-56. The 4-year overall survival (OS) for the three trials was 16.3%, and 2-year progression free survival (PFS) was 25.7%. Statistical analysis of the long term survivors (OS > 4 years) was performed, and performance status (PS) was found to be a significant factor predictive of LTS. PS of 0 compared to 1 yielded a 2.5-fold increased likelihood of LTS (p = .04). There was also a trend (p = .067) for responders (complete or partial response) to yield a five-fold likelihood of LTS compared to non-responders (stable or progressive disease). Our results support the efficacy of combined modality therapy (CMT) for patients with LANSCLC even despite our more liberal weight loss eligibility criteria. Furthermore, our analysis indicates that LTS is more likely to be achievable in patients with PS = 0 compared to 1 when treated with CMT for LANSCLC.


Isolation and partial characterization of an 80,000-dalton protein kinase from the microvessels of the porcine brain.
A novel serine/threonine-specific protein kinase was isolated from the microvessels of porcine brains. The molecular mass of the protein is 80,000 daltons, as judged by gel electrophoresis under denaturing conditions, or 122,000 daltons, on high-resolution gel permeation chromatography in the native state. The activity of this enzyme is stimulated by various histones or polyamines, like spermine or spermidine, but not by any of the common second messengers. The amino-terminal sequence data show no homologies to any of the published kinases, but rather to a heat-shock protein of unknown function.


The prevalence of type 2 diabetes and gestational diabetes mellitus in an inner city multi-ethnic population.
Zeeburg', a multiethnic town borough in the Amsterdam-East region, has one of the city's highest rates of immigrants. In the total population of 19,825 Surinam (mainly Creole), Turkish, Moroccan, and Dutch adults the prevalence of known type 2 diabetes in 1994 and of gestational diabetes mellitus (GDM) between January 1992 and January 1997 was investigated. Based on World Health Organization (WHO) criteria of 1985, the age-standardized prevalence of type 2 diabetes was similar in men (6.4%; 95% confidence interval [CI]: 5.6-7.2) and women (6.4%: 95% CI: 5.8-7.0) for all ethnic groups combined. However, the age- and sex-standardized prevalence of type 2 diabetes was significantly greater in the non-Dutch inhabitants than in the Dutch inhabitants (17.3% [95% CI: 12.9-21.6] in Surinam inhabitants, 10.9% [95% CI: 9.7-12.2] in Turkish inhabitants, 12.4% [95% CI: 9.7-15.0] in Moroccan inhabitants, and 3.6% [95% CI: 3.2-3.9] in Dutch inhabitants). The odds ratios for type 2 diabetes for the separate immigrant groups relative to the Dutch group were 5.88 (95% CI: 4.54-7.69) for Surinam inhabitants, 4.00 (95% CI: 2.86-5.55) for Turkish inhabitants, and 4.17 (95% CI: 3.03-5.55) for Moroccan inhabitants. GDM was present in 2.59% of women of non-Dutch origin compared with 0.62% of women of Dutch origin. A significant positive association was found between the non-Dutch origin and the occurrence of GDM (chi2 = 6.7; p < 0.01). The study highlights a high prevalence of known type 2 diabetes and GDM in the immigrant inhabitants and emphasizes that appropriate interventions are necessarily with implications for health targets and capitation based budgets.


[Chronic suppurative bronchopathy and motility defect of neutrophils: evaluation of an immunomodulating treatment].
Five patients with recurrent infections of the lower respiratory tract, chronic bronchial suppuration and significant defect of polymorphonuclear granulocyte (PMN) motility were studied. Clinical evaluation and in vitro studies of PMN motility were performed before, during and after the treatment with levamisole chlorhydrate (2.5 mg/Kg twice a week). Clinical improvement was obtained in all the patients, together with a significant increase in the chemotactic response of PMN. No side effects were reported. After a follow-up of 7-18 months PMN chemotaxis remained normal in all the patients and a reappearance of respiratory symptoms was observed only in one subject.


The Role of Microbiome-Based Therapeutics in Clostridioides difficile Infection: Durable, Long-Term Results of RBX2660.
A recently published manuscript described findings from a phase 2 open label study of the microbiota-based live biotherapeutic product RBX2660 in patients with two or more previous recurrent Clostridioides difficile infection (rCDI) episodes, and described long-term safety and sustained treatment success through 24 months. As previous studies have typically focused on short-term clinical outcomes, these new data provide insight into the tolerability, safety, and efficacy of RBX2660 over the long term. When microbiota-based products were first evaluated, the long-term efficacy and safety were principal concerns of the United States Food and Drug Administration. Microbiota-based live biotherapeutic products (LBPs) represent an emerging approach to the management of CDI and perhaps other gastrointestinal and medical conditions whose pathogenesis is defined by microbial dysbiosis. RBX2660 is a human-derived, broad consortium microbiota-based LBP that consists of a population of microbes obtained from healthy stool donors and may reflect the symbiotic nature of a healthy colonic microbiome. RBX2660 is rectally administered and does not require sedation or special preparation of the recipient. Potential advantages of the rectal administration of RBX2660 include the ease of administration and lack of need for any bowel preparation, which may benefit those who are frail, have swallowing issues, or cannot take bowel laxative preparations. In this multicenter prospective trial of rCDI, patients who achieved treatment success 8 weeks after receiving RBX2660 continued to have a sustained clinical response over the course of long-term follow-up, with more than 90% of treatment responders remaining CDI-free at 6, 12, and 24 months. Following receipt of RBX2660, the gut microbiota of those with treatment success were restored from a dysbiotic state to become more diverse and similar to RBX2660 composition. The restoration of the microbiota occurred as early as 7 days after RBX2660 administration and remained stable through the 24-month analysis. No new adverse outcomes were observed during the prospective assessment, and the safety profile of RBX2660 was consistent with previous studies. Based on the clinical studies, RBX2660 will most likely benefit those with ≥ 1 rCDI episode or those who are at a high risk of subsequent rCDI, such as patients who have comorbid conditions including renal disease, heart disease, or inflammatory bowel disease, or who are immunosuppressed. The role of microbiome-based therapeutics in 47 Clostridioides difficile infection: Durable, long-term results of RBX2660 (MP4 511833 KB).


Effect of continuous positive airway pressure on nocturnal urine production in patients with obstructive sleep apnea syndrome.
The aim of this study was to identify the clinical features of patients with obstructive sleep apnea syndrome (OSAS) and investigate the impact of continuous positive airway pressure (CPAP) treatment on nocturnal urine volume. This study enrolled 53 patients with moderate-to-severe OSAS and an apnea-hypoxia index of >20/hr. Data were collected on serum brain natriuretic peptide (BNP) level, International Prostate Symptom Score-Quality of Life (IPSS-QOL) score, Overactive Bladder Symptom Score (OABSS), International Consultation on Incontinence Modular Questionnaire-Nocturia QOL (ICIQ-NQOL) score, Epworth Sleepiness Scale (ESS) score, and the frequency volume chart. Only patients who continued CPAP treatment for 3 months were included in the analysis. In total, 40 patients (33 men and 7 women) completed the study (75.5%). The mean age was 56.9 years. The night-time frequency to void was significantly decreased from 2.1 to 1.2 after CPAP treatment (P < 0.01). The mean scores as assessed by ESS, IPSS-QOL, OABSS, and ICIQ-NQOL significantly improved after CPAP (P < 0.01). The mean diastolic blood pressure significantly decreased after CPAP treatment. However, there was no significant change in the BNP level before and after CPAP treatment. In the frequency volume chart, hours of undisturbed sleep, total nocturnal voided volume, and nocturnal polyuria index significantly improved after CPAP treatment (P < 0.05). However, 24-hr voided volume and mean voided volume during night-time did not change after CPAP treatment. CPAP treatment decreases night-time urinary frequency by reducing nocturnal urine production and improves QOL in patients with OSAS. Neurourol. Urodynam. 36:376-379, 2017. © 2015 Wiley Periodicals, Inc.


The preparation of liposomes bearing human (HLA) transplantation antigens.
The incorporation of HLA antigens into liposomes is described. At and above the lipidphase-transition temperature, between 50 and 80% of the added antigenic activity may be incorporated into liposomes in the form of multilamellar vesicles. The antigen appears to be asymmetrically orientated with respect to the lipid bilayer.


The FA2 gene of Chlamydomonas encodes a NIMA family kinase with roles in cell cycle progression and microtubule severing during deflagellation.
The NIMA kinases are one of several families of kinases that participate in driving the eukaryotic cell cycle. NIMA-related kinases have been implicated in G2/M progression, chromatin condensation and regulation of the centrosome cycle. Here we report the identification of a new member of this family, FA2, from Chlamydomonas reinhardtii. FA2 was originally discovered in a genetic screen for deflagellation-defective mutants. We have previously shown that FA2 is essential for basal-body/centriole-associated microtubule severing. We now report that the FA2 NIMA-related kinase also plays a role in cell cycle progression in Chlamydomonas. This is the first indication that members of the NIMA family might exert their effects through the regulation of microtubule severing.


Healthcare in the New Vietnam: comparing patients' satisfaction with outpatient care in a traditional neighborhood clinic and a new, western-style clinic in Ho Chi Minh City.
As Vietnam opens its economy to privatization, its system of healthcare will face a series of crucial tests. Vietnam's system of private healthcare--once comprised only of individual physicians holding clinic hours in their homes--has come to also include larger customer-oriented clinics based on an American business model. As the two models compete in the expanding private market, it becomes increasingly important to understand patients' perceptions of the alternative models of care. This study reports on interviews with 194 patients in two different types of private-sector clinics in Vietnam: a western-style clinic and a traditional style, after-hours clinic. In bivariate and multivariate analyses, we found that patients at the western style clinic reported both higher expectations of the facility and higher satisfaction with many aspects of care than patients at the after-hours clinic. These different perceptions appear to be based on the interpersonal manner of the physician seen and the clinic's delivery methods rather than perceptions of the physician's technical skill and method of treatment. These findings were unaffected by the ethnicity of physician seen. These findings suggest that patients in Vietnam recognize and prefer more customer-oriented care and amenities, regardless of physician ethnicity and perceive no significant differences in technical skill between the private delivery models.


Testicular function following the treatment of Hodgkin's disease in childhood.
Testicular function was studied in 40 males treated in childhood for Hodgkin's disease at St Bartholomew's Hospital, and the Hospital for Sick Children, London, between 1971-1985. All patients were 16 years or over at evaluation, and off treatment more than 6 years. Basal FSH, LH and testosterone levels were measured. Testicular size was measured using a Prader orchidometer, and all patients were offered a seminal analysis. Twenty-eight patients were treated with chemotherapy, usually ChlVPP. Twenty-one also had radiotherapy, five below the diaphragm. Twelve patients were treated with radiotherapy alone (five below the diaphragm). Twenty-six of 28 patients treated with chemotherapy and three of five patients treated with radiotherapy alone below the diaphragm have elevated basal FSH levels, and 18 of these also have elevated basal LH levels. Median testicular volume is 11 ml (range 5-25 ml). Eleven of 13 patients investigated are azoospermic. All patients have normal testosterone levels, and normal secondary sexual characteristics. There is no biochemical evidence of healing of the damaged germinal epithelium with elevated FSH levels persisting up to 17 years from the end of therapy. These results indicate a high incidence of damage to the germinal epithelium in patients treated with ChlVPP chemotherapy and/or radiotherapy below the diaphragm. Appropriate counselling of these patients with regard to their reproductive capabilities is essential.


Cryptosporidiosis in perspective.
In this review I have examined the vast literature which has accumulated on Cryptosporidium, particularly in the past 3 years, in an attempt to highlight areas in which progress has been made in relation to the organism and the disease, and to indicate areas in which knowledge is still lacking. Since 1982, a global effort by scientists and clinicians has been directed towards determining the nature of the disease in humans and the relative contribution of cryptosporidiosis to gastroenteritis. From published data, the incidence of diarrhoea is 1-5% in most developed countries, and 4-7% in less developed countries, when measured throughout the year and in all age groups. The frequency of cryptosporidiosis is highest in children aged between 6 months and 3 years, and in particular locations (e.g., day-care centres) and at particular times of the year. Although susceptibility to infection is life-long, one suspects that the lower prevalence among older children and adults is due to immunity acquired from frequent exposure. Other important factors contributing to higher prevalence are the season--it is more frequent in a wet, warm climate--association with travel to particular destinations, poor hygiene, intimate contact with certain animals, and congregation of large numbers of young previously unexposed children in day-care centres. The association between cryptosporidiosis and giardiasis presumably results from the existence of a common source of infection. The immune status of the host appears to be a major determinant of whether the infection is self-limiting or persistent. It is clear that both branches of the immune system are required for complete recovery, since T-lymphocyte dysfunction or hypogammaglobulinaemia can both lead to persistent illness. Chronic diarrhoea and malabsorption attributed to cryptosporidiosis also occur in the absence of evidence of immune defect. The importance of respiratory tract infection in humans, other than in the terminal stages of chronic illness, requires investigation. The infection has now been identified in all classes of vertebrates; it has been observed in all domestic animals including pets, and a wide range of wildlife including birds. Cryptosporidiosis seems to cause diarrhoea in young ruminants, less frequently in pets. In birds the parasite has been observed in the gastrointestinal tract, without ill effect, and in the respiratory tract, in which clinical symptoms of variable severity have been described. The mucosal response of the gastrointestinal tract to infection appears to vary among mammals and may be the key to the variable clinical manifestations observed.(ABSTRACT TRUNCATED AT 400 WORDS)


Glutamine-containing "turn-on" fluorescence sensor for the highly sensitive and selective detection of chromium (III) ion in water.
In this study, we reported a new fluorescence sensor for chromium (III) ion, dansyl-L-glutamine (1). The sensor displayed a unique selective fluorescence "turn-on" response to Cr(3+) over other common metal ions in water. Notably, 1 still showed a ratiometric response to Cr(3+) in UV-vis absorption spectra. The binding mechanism of 1 to Cr(3+) was further clarified by using NMR and ESI-MS spectra. The experiment results indicated that the dual-responses of 1 to Cr(3+) should attribute to the coordination of deprotonated sulfonamide group with Cr(3+) and the protonation of the dimethylamino group due to the coordination of Cr(3+) for 1. In addition, two chloride ions also coordinated to the complex of sensor-chromium (III) ion, which further strengthened the conformation of 1-Cr(3+).