Increasing use of dose-escalated external beam radiation therapy for men with nonmetastatic prostate cancer.
To examine recent practice patterns, using a large national cancer registry, to understand the extent to which dose-escalated external beam radiation therapy (EBRT) has been incorporated into routine clinical practice for men with prostate cancer. We conducted a retrospective observational cohort study using the National Cancer Data Base, a nationwide oncology outcomes database in the United States. We identified 98,755 men diagnosed with nonmetastatic prostate cancer between 2006 and 2011 who received definitive EBRT and classified patients into National Comprehensive Cancer Network (NCCN) risk groups. We defined dose-escalated EBRT as total prescribed dose of ≥75.6 Gy. Using multivariable logistic regression, we examined the association of patient, clinical, and demographic characteristics with the use of dose-escalated EBRT. Overall, 81.6% of men received dose-escalated EBRT during the study period. The use of dose-escalated EBRT did not vary substantially by NCCN risk group. Use of dose-escalated EBRT increased from 70.7% of patients receiving treatment in 2006 to 89.8% of patients receiving treatment in 2011. On multivariable analysis, year of diagnosis and use of intensity modulated radiation therapy were significantly associated with receipt of dose-escalated EBRT. Our study results indicate that dose-escalated EBRT has been widely adopted by radiation oncologists treating prostate cancer in the United States. The proportion of patients receiving dose-escalated EBRT increased nearly 20% between 2006 and 2011. We observed high utilization rates of dose-escalated EBRT within all disease risk groups. Adoption of intensity modulated radiation therapy was strongly associated with use of dose-escalated treatment.


Microalgae-bacteria consortium for wastewater treatment and biomass production.
The diversity of microalgae and bacteria allows them to form a complementary consortium for efficient wastewater treatment and nutrient recovery. This review highlights the potential of wastewater-derived microalgal biomass as a renewable feedstock for producing animal feed, biofertilisers, biofuel, and many valuable biochemicals. Data corroborated from this review shows that microalgae and bacteria can thrive in many environments. Microalgae are especially effective at utilising nutrients from the water as they grow. This review also consolidates the current understanding of microalgae characteristics and their interactions with bacteria in a consortium system. Recent studies on the performance of only microalgae and microalgae-bacteria wastewater treatment are compared and discussed to establish a research roadmap for practical implementation of the consortium systems for various wastewaters (domestic, industrial, agro-industrial, and landfill leachate wastewater). In comparison to the pure microalgae system, the consortium system has a higher removal efficiency of up to 15% and shorter treatment time. Additionally, this review addresses a variety of possibilities for biomass application after wastewater treatment.


From urban neighbourhood environments to cognitive health: a cross-sectional analysis of the role of physical activity and sedentary behaviours.
There is a dearth of studies on the effects of the neighbourhood environment on adults' cognitive function. We examined how interrelated aspects of the built and natural neighbourhood environment, including air pollution, correlate with adults' cognitive function, and the roles of physical activity and sedentary behaviours in these associations. We used data from 4,141 adult urban dwellers who participated in the Australian Diabetes, Obesity and Lifestyle 3 study on socio-demographic characteristics, neighbourhood self-selection, physical activity and sedentary behaviours, and cognitive function. Neighbourhood environmental characteristics included population density, intersection density, non-commercial land use mix, and percentages of commercial land, parkland and blue space, all within 1 km residential buffers. We also calculated annual mean concentrations of NO2 and PM2.5. Generalised additive mixed models informed by directed acyclic graphs were used to estimate the total, direct and indirect effects of environmental attributes on cognitive functions and the joint-significance test was used to examine indirect effects via behaviours. In the total effects models, population density and percentage of parkland were positively associated with cognitive function. A positive association of PM2.5 with memory was also observed. All neighbourhood environmental attributes were directly and/or indirectly related to cognitive functions via other environmental attributes and/or physical activity but not sedentary behaviours. Engagement in transportation walking and gardening frequency partially mediated the positive effects of the neighbourhood environment on cognitive function, while frequency of transportation walking mediated the negative effects. In the context of a low-density country like Australia, denser urban environments with access to parkland may benefit residents' cognitive health by providing opportunities for participation in a diversity of activities. A more fine-grained characterisation of the neighbourhood environment may be necessary to tease out the negative and positive impacts of inter-related characteristics of urban neighbourhood environments on cognitive function.


Intraoperative Neuromonitoring Using a Single Transcartilage Needle Electrode During Thyroidectomy.
Application of transcartilage needle electrode for intraoperative neuromonitoring (IONM) during thyroidectomy has been considered an alternative method of electromyography (EMG) tube recording. However, needle electrodes must be inserted into both sides of the thyroid cartilage with exposure of the cartilage lamina. We sought to evaluate the feasibility of applying a single ipsilateral transcartilage needle electrode for IONM during unilateral hemithyroidectomy. Thirty-four patients underwent IONM during unilateral thyroidectomy. A dual disposable needle electrode was inserted obliquely into the inferior lower third of the ipsilateral lamina of the thyroid cartilage. Patients were classified as deep (≥ 5 mm) or superficial (< 5 mm) by the depth of the needle electrode inserted into the thyroid cartilage. Without using an EMG tube, IONM was done according to the standardized procedure using a single needle electrode only. IONM was successful in all nerves at risk. Amplitude of the EMG signal was stable during the surgery, with no cases presenting loss of signal. Amplitude of the signal from vagal and recurrent laryngeal nerve stimulation was significantly lower when needle insertion was superficial (< 5 mm). None of the patients showed postoperative vocal cord paralysis, and complications related to needle electrode were not identified. IONM using a single ipsilateral transcartilage needle electrode during unilateral hemithyroidectomy was feasible with no significant complications. It may serve as an alternative method of IONM with the advantage of minimal exposure of the thyroid cartilage lamina. 4 Laryngoscope, 131:448-452, 2021.


Genetic polymorphisms of cytochrome P450 in patients with hepatitis C virus-associated hepatocellular carcinoma.
The carcinogenic process can be modulated by exposure to endogenous or environmental substance(s) acting as carcinogens or protocarcinogens. Polymorphic enzymes of cytochrome P450 (CYP) that play a role in detoxication/toxication of such substances via metabolization may account for the interpatient variability of clinical course in cancers such as hepatocellular carcinoma (HCC). Many CYP genetic polymorphisms, which may change enzyme activity, are known to exist in Japanese. The aim of the present study was to compare the frequencies of CYP polymorphisms between hepatitis C virus (HCV)-related HCC patients and healthy subjects. Seven mutant alleles and related genotypes of CYP in 44 HCV-positive HCC patients were chosen as follows: *1C heterozygous, *1C homozygous and *1F homozygous for CYP1A2, *4A homozygous for CYP2A6, *2A or *3 heterozygous, *2A or *3 homozygous and *2A and *3 heterozygous for CYP2C19, and *10/*5 homozygous for CYP2D6. These mutant alleles have been reported to change the CYP enzyme activity in Japanese. The frequencies of the mutant alleles and genotypes were then compared with those reported in healthy Japanese. There is no statistically significant difference in genetic mutant alleles between the two groups, except for the genotype of CYP2A6*4A homozygous. The frequency of this genotype in the HCC patients (0.144) is significantly higher than that in healthy Japanese (0.034; P < 0.05; odds ratio 3.36). The clinical significance related to HCC is unknown. Further evaluation of CYP2A6*4A (deletion type) in HCV-related HCC patients is required.


A new approach to generate a safe double-attenuated Plasmodium liver stage vaccine.
Recently it has been shown in rodent malaria models that immunisation with genetically attenuated Plasmodium parasites can confer sterile protection against challenge with virulent parasites. For the mass production of live attenuated Plasmodium parasites for vaccination, safety is a prerequisite. Knockout of a single gene is not sufficient for such a strategy since the parasite can likely compensate for such a genetic modification and a single surviving parasite is sufficient to kill an immunised individual. Parasites must therefore be at least double-attenuated when generating a safe vaccine strain. Genetic double-attenuation can be achieved by knocking out two essential genes or by combining a single gene knockout with the expression of a protein toxic for the parasite. We generated a double-attenuated Plasmodium berghei strain that is deficient in fatty acid synthesis by the knockout of the pdh-e1α gene, introducing a second attenuation by the liver stage-specific expression of the pore-forming bacterial toxin perfringolysin O. With this double genetically attenuated parasite strain, a superior attenuation was indeed achieved compared with single-attenuated strains that were either deficient in pyruvate dehydrogenase (PDH)-E1 or expressed perfringolysin O. In vivo, both single-attenuated strains resulted in breakthrough infections even if low to moderate doses of sporozoites (2,000-5,000) were administered. In contrast, the double genetically attenuated parasite strain, given at moderate doses of 5,000 sporozoites, did not result in blood stage infection and even when administered at 5- to 20-fold higher doses, only single and delayed breakthrough infections were observed. Prime booster immunisation with the double genetically attenuated parasite strain completely protected a susceptible mouse strain from malaria and even a single immunisation conferred protection in some cases and lead to a markedly delayed onset of blood stage infection in others. Importantly, premature rupture of the parasitophorous vacuole membrane by liver stage-specific perfringolysin O expression did not induce host cell death and soluble parasite proteins, which are released into the host cell cytoplasm, have the potential to be processed and presented via MHC class I molecules. This, in turn, might support immunological responses against Plasmodium-infected hepatocytes.


FDA-regulated AI Algorithms: Trends, Strengths, and Gaps of Validation Studies.
To assess key trends, strengths, and gaps in validation studies of the Food and Drug Administration (FDA)-regulated imaging-based artificial intelligence/machine learning (AI/ML) algorithms. We audited publicly available details of regulated AI/ML algorithms in imaging from 2008 until April 2021. We reviewed 127 regulated software (118 AI/ML) to classify information related to their parent company, subspecialty, body area and specific anatomy type, imaging modality, date of FDA clearance, indications for use, target pathology (such as trauma) and findings (such as fracture), technique (CAD triage, CAD detection and/or characterization, CAD acquisition or improvement, and image processing/quantification), product performance, presence, type, strength and availability of clinical validation data. Pertaining to validation data, where available, we recorded the number of patients or studies included, sensitivity, specificity, accuracy, and/or receiver operating characteristic area under the curve, along with information on ground-truthing of use-cases. Data were analyzed with pivot tables and charts for descriptive statistics and trends. We noted an increasing number of FDA-regulated AI/ML from 2008 to 2021. Seventeen (17/118) regulated AI/ML algorithms posted no validation claims or data. Just 9/118 reviewed AI/ML algorithms had a validation dataset sizes of over 1000 patients. The most common type of AI/ML included image processing/quantification (IPQ; n = 59/118), and triage (CADt; n = 27/118). Brain, breast, and lungs dominated the targeted body regions of interest. Insufficient public information on validation datasets in several FDA-regulated AI/ML algorithms makes it difficult to justify clinical applications since their generalizability and presence of bias cannot be inferred.


Oxygen desaturation in adults following inhaled metaproterenol therapy.
Following bronchodilator therapy in asthmatic patients, a fall in arterial oxygen tension (PaO2) has been attributed to increased perfusion of persistently underventilated alveoli. We used continuous noninvasive pulse oximetry to evaluate the extent and timing of oxygen saturation (SaO2) decrease in adults following metaproterenol inhalation for acute bronchospasm. We also examined the effect of supplemental oxygen upon these factors. Baseline and peak drop in SaO2 after completion of the first bronchodilator therapy were measured and the percent change in SaO2 was calculated. A total of 47 patient visits were studied; 10 patients received supplemental oxygen. Mean age was 38 +/- 17.9 years. Baseline was SaO2 = 94.6 +/- 2.9%, peak drop SaO2 = 91.4 +/- 3.4%, and percent change in SaO2 = -3.4 +/- 2.5%. The mean time to peak drop was 24.4 +/- 15.4 minutes in the 40 patients, with an observed drop after initial treatment. The absolute change in SaO2 from baseline was significant both with and without oxygen (P less than .05 and less than .01, respectively). The group receiving oxygen had a significantly smaller percent drop and a larger proportion of patients showing no drop in SaO2 (P less than 0.01 and less than 0.03, respectively). Clinically significant oxygen desaturation can occur within 30 minutes of inhaled bronchodilator therapy. Supplemental oxygen (2-3 L/min) helps blunt the metaproterenol-induced drop in SaO2.


Behavioral vs beta-blocker therapy in patients with primary hypertension: effects on blood pressure, left ventricular function and mass, and the pressor surge of social stress anger.
We compared the relative effects of relaxation therapy, conventional hygienic techniques, and a beta-receptor blocker, atenolol, on control of arterial pressure, left ventricular mass, and diastolic function in patients with mild primary hypertension. Furthermore, we related these effects to baseline neural tone and its changes and assessed the efficacy of relaxation or the pressor surge of "social stress" anger. In group I left ventricular mass index was related to both systolic and diastolic blood pressure (r = 0.46; p less than 0.05). Plasma norepinephrine was related to age (r = 0.33; p less than 0.01). Slope was inversely related to both plasma norepinephrine (r = -0.29; p less than 0.05) and age (r = -0.31; p less than 0.05). Relaxation therapy reduced both supine systolic and diastolic blood pressures, 4.5% and 7.6%, respectively, but did not affect plasma norepinephrine. Hygienic informational therapy reduced plasma norepinephrine by 18%, (p less than 0.05) and did not change blood pressure. Blood pressure responders to nondrug therapy (i.e., diastolic blood pressure reduction of 7% or more) had a 7% reduction of left ventricular mass index (p less than 0.02). On the other hand, atenolol reduced systolic and diastolic blood pressure by 10% and 15%, respectively, (p less than 0.01) and improved left ventricular function by 17% (p less than 0.05) without a significant change in left ventricular mass index. Finally, relaxation therapy but not hygienic therapy reduced systolic blood pressures 4% and 6%, respectively (p less than 0.01), both before and during social stress anger.(ABSTRACT TRUNCATED AT 250 WORDS)


Mask Performance Rating Table for specific military tasks.
The Performance Rating Table (PRT) is introduced as a means to separate mask-wearer performance by causative factors. The PRT shows which mask factors require design attention and how the mask affects different users.


NMDA receptors and voltage-dependent calcium channels mediate different aspects of acquisition and retention of a spatial memory task.
Activity dependent calcium entry into neurons can initiate a form of synaptic plasticity called long-term potentiation (LTP). This phenomenon is considered by many to be one possible cellular mechanism underlying learning and memory. The calcium entry that induces this phenomenon can occur when N-methyl-D-aspartate receptors (NMDARs) and/or voltage-dependent calcium channels (VDCCs) are activated. While much is known about synaptic plasticity and the mechanisms that are triggered by activation of these two Ca(2+) channels, it is unclear what roles they play in learning. To better understand the role activation of these channels may play in learning we systemically administered pharmacological antagonists to block NMDARs, VDCCs, or both during training trials and retention tests in a radial arm maze task. Wistar rats injected with the NMDAR antagonist MK-801 (0.1mg/kg) were impaired in the acquisition of this task. In contrast, rats injected with verapamil (10mg/kg), an antagonist to VDCCs, acquired the task at the same rate as control animals, but were impaired on a 10-day retention test. A group of animals injected with both antagonists were unable to learn the task. The results suggest that each of the calcium channels and the processes they trigger are involved in a different stage of memory formation or expression.


Subacute cutaneous lupus erythematosus: a paraneoplastic dermatosis?
Subacute cutaneous lupus erythematosus (SCLE) is characterized by clinical, laboratory and immunological features different from those of systemic lupus erythematosus (SLE). We describe the case of a patient with a 2-year history of SCLE that demonstrated a close temporal relationship with a squamous cell malignancy of the head and neck. This association has not been previously reported. We also review the evidence for SCLE as a 'paraneoplastic dermatosis' and discuss the criteria for diagnosis and possible pathogenesis.


Enhancing performance of ZnO dye-sensitized solar cells by incorporation of multiwalled carbon nanotubes.
A low-temperature, direct blending procedure was used to prepare composite films consisting of zinc oxide [ZnO] nanoparticles and multiwalled carbon nanotubes [MWNTs]. The mesoporous ZnO/MWNT films were fabricated into the working electrodes of dye-sensitized solar cells [DSSCs]. The pristine MWNTs were modified by an air oxidation or a mixed acid oxidation treatment before use. The mixed acid treatment resulted in the disentanglement of MWNTs and facilitated the dispersion of MWNTs in the ZnO matrix. The effects of surface property and loading of MWNTs on DSSC performance were investigated. The performance of DSSCs was found to depend greatly on the type and the amount of MWNTs incorporated. At a loading of 0.01 wt%, the acid-treated MWNTs were able to increase the power conversion efficiency of fabricated cells from 2.11% (without MWNTs) to 2.70%.


Instability of the carbon dioxide stimulus under the "mixed venous isocapnic" conditions advocated for testing the ventilatory response to hypoxia.
Meaningful and reproducible ventilatory responses to hypoxia cannot be obtained from the mixed venous isocapnic test reported by Rebuck and Campbell if it is not recognized that the CO2 drive increases progressively for at least 6 to 10 min after the PCO2 step.


Unilateral cleft lip repair. Z-plasty.
All unilateral clefts of the lip are not alike. The deficiencies that exist, especially in the lateral lip element, can vary considerably. Because of these differences, it is unreasonable to expect one technique of repair to satisfy all situations. In more difficult complete unilateral cleft lip deformity, the Z-plasty repairs described in this article better satisfy the goals of this surgery.


Adsorption of the organic salt TAB(HCl)4 on Cu(111) studied using STM and XPS.
Sublimation of Tetra-Amino Benzene (TAB) in its tetrahydrochlorinated form onto Cu(111) leads to the formation of long range ordered structures consisting of TAB molecules with partially protonated amino groups interspersed with Cl species.


Pupilloplasty for pupil size attenuation to prevent pupillary capture: Theory of quintet in glued IOL.
We describe a pupilloplasty procedure to prevent a captive iris and to narrow the pupillary aperture and its associated complications. We also describe 5 surgical techniques in combination-vertical glued IOL, peripheral iridectomy, anterior sclerotomy, pupilloplasty, and application of a trocar anterior chamber maintainer-performed in eyes with a large WTW diameter; that is, the quintet in glued IOL. Neither author has a financial or proprietary interest in any material or method mentioned.


Incorporation of individual-patient data in network meta-analysis for multiple continuous endpoints, with application to diabetes treatment.
Availability of individual patient-level data (IPD) broadens the scope of network meta-analysis (NMA) and enables us to incorporate patient-level information. Although IPD is a potential gold mine in biomedical areas, methodological development has been slow owing to limited access to such data. In this paper, we propose a Bayesian IPD NMA modeling framework for multiple continuous outcomes under both contrast-based and arm-based parameterizations. We incorporate individual covariate-by-treatment interactions to facilitate personalized decision making. Furthermore, we can find subpopulations performing well with a certain drug in terms of predictive outcomes. We also impute missing individual covariates via an MCMC algorithm. We illustrate this approach using diabetes data that include continuous bivariate efficacy outcomes and three baseline covariates and show its practical implications. Finally, we close with a discussion of our results, a review of computational challenges, and a brief description of areas for future research.


[Quarterly occurrence of selected types of birth defects in the Czech Republic in the 1994-2005 twelve-year period].
An analysis of quarterly occurrence of selected types of birth defects in the Czech republic in the 1994 - 2005 twelve-year period. Evaluation of possible changes of occurrence of selected types of birth defects along with standard deviations from mean values calculated from 1974 - 1993 period data. Retrospective analysis of quarterly data from the National Birth Defect Register in 1994 - 2005 period. Mean incidences of birth defects from the previous 1974-2003 period (per 10,000 live births) were calculated and compared to current data from each particular quarter. A calculation of observed/expected rates (O/E ratio) for particular selected birth defects was performed. Further, results are presented by means of figures and are widely discussed. In 1994-2005 period, totally 1,132,567 children were born in the Czech Republic. Out of this number, 38 298 children were born with one or more birth defects. The mean incidence of birth defects was 338.15 per 10,000 live birth in the period under the study. Our results make clear, that incidences of particular defects as well as incidences as a whole are influenced by several factors making possible incidences increase. These factors are extremely difficult to assess individually and separately, therafore a particular period and a particular population is to be considered. Incidences of 11 selected types of birth defects and their time-changes are analyzed. Current registration of birth defects and their incidences analysis as a vital part of a environmental factors assessment is underlined.


The two pathophysiologies of focal brain ischemia: implications for translational stroke research.
Brain injury after focal ischemia evolves along two basically different pathophysiologies, depending on the severity of the primary flow reduction and the dynamics of postischemic recirculation. In permanent and gradually reversed focal ischemia as after thromboembolic occlusion, primary core injury is irreversible but the expansion of the core into the penumbra can be alleviated by hemodynamic and molecular interventions. Such alleviation can only be achieved within 3 hours after the onset of ischemia because untreated core injury expands to near maximum size during this interval. In promptly reversed transient ischemia as after mechanical vascular occlusion, primary core injury may recover but a secondary delayed injury evolves after a free interval of as long as 6 to 12 hours. This injury can be alleviated throughout the free interval but the longer window is without clinical relevance because transient mechanical vascular occlusion is not a model of naturally occurring stroke. As this difference is widely ignored in stroke research, most clinical trials have been designed with a far too long therapeutic window, which explains their failure. Transient mechanical vascular occlusion models should, therefore, be eliminated from the repertoire of preclinical stroke research.


The CYP1A2-164A-->C polymorphism (CYP1A2*1F) is associated with the risk for colorectal adenomas in humans.
Colorectal cancer (CRC) is believed to be related to the intake of processed meat and the formed heterocyclic aromatic amines (HCA) herein, which are metabolically activated by the enzymes cytochrome P4501A2 (CYP1A2) and N-acetyltransferase 2 (NAT2). The influence of genotypic and phenotypic variations for CYP1A2 and NAT2 on the risk for colorectal adenomas was investigated in 94 individuals at different risk of developing CRC. Significant associations were found between the CYP1A2-164A-->C polymorphism (CYP1A2*1F) and the risk of colorectal adenomas, suggesting that the studied polymorphism plays an important role in CRC risk in humans.


C5a is not involved in experimental autoimmune myasthenia gravis pathogenesis.
C5 deficient mice are highly resistant to experimental autoimmune myasthenia gravis (EAMG) despite intact immune response to acetylcholine receptor (AChR), validating the pivotal role played by membrane attack complex (MAC, C5b-9) in neuromuscular junction destruction. To distinguish the significance of C5a from that of C5b in EAMG pathogenesis, C5a receptor (C5aR) knockout (KO) and wild-type (WT) mice were immunized with AChR to induce pathogenic anti-AChR antibodies. In contrast with C5 deficient mice, C5aR KO mice were equally susceptible to EAMG as WT mice and exhibited comparable antibody and lymphocyte proliferation response to AChR implicating that C5a is not involved in EAMG development.


Use of the point of origin code from a universal billing form, UB-04, to efficiently identify hospitalized patients admitted from other health care facilities.
Recent exposure to health care facilities is a risk factor for carriage of multidrug-resistant organisms, but identification of hospitalized patients admitted from other health care facilities is often inefficient. At an acute care hospital, we utilized a standard point of origin code from a universal billing form (UB-04) to categorize hospitalized patients as admitted from any health care facility (long-term care facility vs acute care facility). In a prospective study, the point of origin code and information obtained from physician-documented history were validated against patient self-report. Admission source for 523 patients was assessed. For identifying admission from any health care facility, the point of origin code had 86% sensitivity (95% confidence interval [CI]: 77-92) and 98% specificity (95% CI: 97-99). Physician-documented history had 75% sensitivity (95% CI: 65-84) and 98% specificity (95% CI: 96-99). For identifying patients from long-term care facilities, the sensitivities of the point of origin code and physician history were 50% (95% CI: 23-77) and 71% (95% CI: 42-92), respectively. For identifying patients admitted from acute care facilities, the sensitivities of the point of origin code and physician history were 93% (95% CI: 84-98) and 76% (95% CI: 64-85), respectively. The point of origin code is an accurate method of identifying patients admitted from another health care facility that is comparable with physician-documented history.


Captopril and its dimer captopril disulfide: photodegradation, aerobic biodegradation and identification of transformation products by HPLC-UV and LC-ion trap-MS(n).
In some countries effluents from hospitals and households are directly emitted into open ditches without any further treatment and with very little dilution. Under such circumstances photo- and biodegradation in the environment can occur. However, these processes do not necessarily end up with the complete mineralization of a chemical. Therefore, the biodegradability of photoproduct(s) by environmental bacteria is of interest. Cardiovascular diseases are the number one cause of death globally. Captopril (CP) is used in this study as it is widely used in Egypt and stated as one of the essential drugs in Egypt for hypertension. Three tests from the OECD series were used for biodegradation testing: Closed Bottle test (CBT; OECD 301 D), Manometric Respirometry test (MRT; OECD 301 F) and the modified Zahn-Wellens test (ZWT; OECD 302 B). Photodegradation (150 W medium-pressure Hg-lamp) of CP was studied. Also CBT was performed for captopril disulfide (CPDS) and samples received after 64 min and 512 min of photolysis. The primary elimination of CP and CPDS was monitored by LC-UV at 210 nm and structures of photoproducts were assessed by LC-UV-MS/MS (ion trap). Analysis of photodegradation samples by LC-MS/MS revealed CP sulfonic acid as the major photodegradation product of CP. No biodegradation was observed for CP, CPDS and of the mixture resulting from photo-treatment after 64 min in CBT. Partial biodegradation in the CBT and MRT was observed in samples taken after 512 min photolysis and for CP itself in MRT. Complete biodegradation and mineralization of CP occurred in the ZWT.


Syphilitic hepatitis as a manifestation of secondary syphilis.
Syphilis is a multisystem disease caused by the spirochete Treponema pallidum. Among various organs affected, liver involvement is seen infrequently and can be missed. Here we present a case of hepatitis due to secondary syphilis that completely resolved with penicillin G therapy.


A proton-electron sequential transfer mechanism: theoretical evidence about its biological relevance.
Density functional theory calculations, using the SMD continuum model, indicate that hydrogen transfer from totally protonated uric to a tryptophanyl radical in proteins corresponds to a sequential mechanism. Modeling in methyl butanoate indicates that this mechanism is more important in a hydrophobic medium than in water.


Cuproptosis-related miRNAs signature and immune infiltration characteristics in colorectal cancer.
A novel form of cell death termed cuproptosis was proposed recently. miRNAs play important roles in colorectal cancer (CRC). However, their relationships have not been reported. miRNAs that negatively regulate 16 cuproptosis regulators were predicted using Targetscan database. The univariate Cox, LASSO, and multivariate Cox regression analyses were performed to select cuproptosis-related miRNAs. GSEA and ssGSEA analysis was carried out for functional enrichment analysis. The immune cell proportion score (IPS) and the efficiencies of multiple chemotherapy drugs were compared between different risk groups. The CCK8, cell colony, edu, and flow cytometry assays were performed to validate the roles of miRNA. Luciferase reporter assay confirmed the regulatory mechanism of miRNA on cuproptosis. Six cuproptosis-related miRNAs (hsa-miR-653, hsa-miR-216a, hsa-miR-3684, hsa-miR-4437, hsa-miR-641, and hsa-miR-552) were screened out for model construction. The risk score could act as an independent prognostic indicator in CRC (p < 0.001, 95% HR = 1.243 (1.129-1.369)). The nomogram could efficiently predict the overall survival rate (AUC = 0.836). Then, the level of immunosuppressive pathways, immunosuppressive cells, stromal-activated genes, and stromal score was higher in the high-risk group. The IPS analysis showed a better response to immunotherapy in the low-risk group. Also, the risk score was closely correlated with efficiencies of multiple chemotherapy drugs. Furthermore, miR-653 was highly expressed in CRC tissues (p < 0.001), closely correlated with T stage (p < 0.001), metastasis (p < 0.001), and tumor stage (p < 0.001). High expression of miR-653 predicted a shorter overall survival (p = 0.0282) and disease-free survival (p = 0.0056). In addition, miR-653 promoted cell proliferation, inhibited apoptosis, and negatively regulated the expression of DLD through directly binding to the 3'-UTR of DLD mRNA. We constructed a cuproptosis-related miRNA signature for the prediction of CRC patient survival and immunotherapy sensitivity. miR-653 was highly expressed in CRC tissues, promoted cell proliferation, and inhibited apoptosis by negatively regulating the expression of DLD.


Coordinating the delivery of vaccinations and other preventive health care recommendations for adolescents.
Although recommendations for annual preventive care for adolescents have been in place for decades, the need to bring adolescents to the medical setting for newly recommended vaccines has placed this issue in the public health spotlight. Aggressive efforts have been ongoing to increase adolescent adherence to new vaccine recommendations--a measured outcome variable, and the hope has been that enhanced adherence to comprehensive health care visits will follow. Evidence indicates that the implementation of more comprehensive preventive health care elements among adolescents may be improving; however, a passive approach to bringing more adolescents to preventive health visits using vaccine as an incentive may not be effective for all youth. This paper reviews the history of recommendations for new vaccines as well as comprehensive health care visit recommendations for adolescents, how these recommendations may synergistically improve preventive care for adolescents, and how we may need to continue to think creatively to further access all youth for preventive health care using vaccination implementation as a model for reaching out beyond the providers' office walls.


Aging effects on the visually driven part of vergence movements.
To examine gain, speed, and temporal characteristics of initial and closed-loop components of vergence eye movements in young and elderly subjects. Vergence eye movements in 13 elderly and 10 young adults were examined. A table with light-emitting diodes was used to elicit vergence starting from near (convergence, 40-20 cm; divergence, 20-40 cm) or from far (convergence, 150-40 cm; divergence, 40-150 cm). Vergence eye movements were recorded with a video eye tracker or an infrared eye movement device. There were no aging effects on the gain or peak velocity of vergence. Vergence duration was longer in elderly than in young adults, but only for the second, closed-loop components, driven by visual feedback. Elderly and young adults showed higher peak velocity and gain for convergence than for divergence. This observation is discussed in the context of physiological evidence of a robust convergence, rather than a divergence, generator at the brain stem level. Such a specific effect of aging on the duration of the closed-loop component is attributed to the reduced capacity of cortical processing of visual binocular disparity; slowing of vergence would allow good final accuracy.


Self-assessed and directly measured occupational physical activities--influence of musculoskeletal complaints, age and gender.
This study compares questionnaire assessed physical activity with direct technical measurements among cleaners and office workers, stratified regarding age, gender and self-reported neck/shoulder complaints. During two full working days number of steps was recorded by a pedometer, sitting/standing positions by a posimeter and heart rate by a Sport-Tester. In addition the subjects kept a work task diary for 10 days. There were high intra-individual variations in exposure between the days. Subjects with complaints rated their exposure higher than those without, although they in fact showed lower direct measured exposure. This may imply underestimation of exposure-effect relationships. Rate of perceived exertion showed low correlation with heart rate ratio within the two occupational groups, but high, 0.64 when the two groups were combined. Age and complaints explained 31% of the variance for the cleaners.


Effect of cadmium on lung lysosomal enzymes in vitro.
Labilization of lysosomal enzymes is often associated with the general process of inflammation. The present study investigated the effect of the pneumotoxin cadmium on the release and activity of two lung lysosomal enzymes. Incubation of rat lung lysosomes with cadmium resulted in the release of beta-glucuronidase but not acid phosphatase. The failure to "release" acid phosphatase appears to be the result of a direct inhibitory effect of cadmium on this enzyme. The K1 for cadmium was determined to be 26.3 microM. The differential effect of cadmium on these two lysosomal enzymes suggests that caution should be exercised in selecting the appropriate enzyme marker for assessing lysosomal fragility in the presence of this toxicant. Furthermore, the differential basal release rate of the two enzymes from lung lysosomes may reflect the cellular heterogeneity of the lung.


Synthesis, cytotoxicity and docking studies (with SARS-CoV-2) of water-soluble binuclear Ru-p-cymene complex holding indole thiosemicarbazone ligand.
A water-soluble binuclear organometallic Ru-p-cymene complex [Ru(η6-p-cymene)(η2-L)]2 (1) was prepared from (E)-2-((1H-indol-3-yl)methylene)-N-phenylhydrazine-1-carbothioamide (HL) and [RuCl2(p-cymene)]2 in methanol at room temperature under inert atmosphere. The structure of binuclear complex was analyzed by UV-Visible, FT-IR, NMR and mass spectroscopic methods. The solid-state structure of the complex was ascertained by single crystal X-ray diffraction technique. The complex exhibited pseudo-octahedral (piano-stool) geometry around Ru(II) ion. The cytotoxic property of the ligand and complex along with cisplatin was investigated against A549-lung, MCF-7-breast, HeLa-cervical, HepG-2-liver, T24-urinary bladder and EA.hy926-endothelial cancer cells, and Vero-kidney epithelial normal cells. The complex exhibited superior activity than cisplatin against A549, HeLa and T24 cancer cells with the IC50 values of 7.70, 11.2, and 5.05 µM, respectively. The complexes were cytotoxic specifically to the cancer cells. Molecular docking studies showed good binding potential of the ligand and complex with the spike protein and main protease of SARS-CoV-2, indicating the promising role of these compounds as antiviral compounds.


Structure and function of auditory cortex: music and speech.
We examine the evidence that speech and musical sounds exploit different acoustic cues: speech is highly dependent on rapidly changing broadband sounds, whereas tonal patterns tend to be slower, although small and precise changes in frequency are important. We argue that the auditory cortices in the two hemispheres are relatively specialized, such that temporal resolution is better in left auditory cortical areas and spectral resolution is better in right auditory cortical areas. We propose that cortical asymmetries might have developed as a general solution to the need to optimize processing of the acoustic environment in both temporal and frequency domains.


Arachidonic acid induces calcium-dependent mitochondrial formation of species promoting strand scission of genomic DNA.
Both the phospholipase A(2) activator melittin and reagent arachidonic acid (AA) are poor inducers of DNA single strand breaks in U937 cells. These responses, however, were dramatically increased by the calcium-mobilizing agent caffeine (Cf) or by the respiratory substrate pyruvate via a mechanism that involved enforced mitochondrial Ca(2+) accumulation and that was sensitive to lipoxygenase inhibitors. In permeabilized cells, the DNA damage generated by AA in combination with either Cf, L-malate or CaCl(2) was blunted by catalase. AA generated DNA strand scission also in HeLa cells supplemented with pyruvate via a mechanism identical to that observed in U937 cells. This response was associated with an enforced formation of free radical species. These results demonstrate that mitochondria play a pivotal role in the DNA-damaging response evoked by AA and provide the bases for a calcium-dependent mechanism whereby the AA produced during inflammatory processes may affect various pathologic conditions, including carcinogenesis.


Lithium ion intercalation of 3-D vertical hierarchical TiO2 nanotubes on a titanium mesh for efficient photoelectrochemical water splitting.
In this communication, we report for the first time the demonstration of a lithium ion intercalation strategy to significantly enhance the photoelectrochemical water splitting performance on 3-dimensional vertical hierarchical top-porous-bottom-tubular TiO2 nanotubes on a fabricable titanium mesh.


Bilateral laparoscopic adrenalectomy for corticotrophin-dependent Cushing's syndrome: a review of the Mayo Clinic experience.
There has been a rapid shift from open to laparoscopic approaches in adrenal surgery, but the safety and efficacy of bilateral laparoscopic adrenalectomy (BLA) in patients with corticotrophin (ACTH)-dependent Cushing's syndrome continues to be defined. Review outcomes in the largest series of patients reported to date undergoing BLA for ACTH-dependent Cushing's syndrome. Retrospective review study. Between January of 1995 and October of 2006, BLA was attempted in 68 patients with ACTH-dependent Cushing's syndrome (26 ectopic ACTH syndrome; 42 persistent pituitary-dependent Cushing's syndrome following pituitary surgery). Review of peri-operative morbidity and mortality, biochemical parameters and patient-reported symptom response from chart review and mailed questionnaire. BLA was successfully completed in 59 of 68 patients (87%); nine (13%) required conversion to open adrenalectomy (OA). Intra-operative complications occurred in three patients (4.4%) (two BLA, one OA), and non-operative complications occurred in 11 (16%) patients (eight BLA, three OA). There were no peri-operative deaths. Median hospitalization was 5.5 days (range, 3-28) and 11.9 days (range, 4-29) for the BLA and OA groups, respectively. In patients with follow-up data available, all achieved biochemical resolution and at least partial clinical resolution of signs and symptoms associated with hypercortisolism. Resolution of hypertension, diabetes and obesity was achieved in 64%, 29% and 35% of patients carrying those diagnoses prior to surgery, respectively. This study further supports the role of BLA as an effective treatment option for patients with ACTH-dependent Cushing's syndrome.


Association of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, mean platelet volume with the risk of gestational diabetes mellitus.
In the present study, we aimed to investigate the correlation of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, mean platelet volume with the risk of gestational diabetes mellitus. The study enrolled 120 pregnant women who were the 24th and 28th weeks of gestation, including GDM group (n = 58), the control group (n = 62). The NLR, PLR and MPV levels were measured. NLR, PLR and MPV were significantly higher in GDM compared with control group. Logistic regression analysis showed that elevated WBC, NLR, PLR and MPV was an independent variable for predicting GDM in pregnancy. The OR and 95% CI was (OR: 1.6, 95% CI: 1.2-2.5), (OR: 4.1, 95% CI: 1.3-13.1), (OR: 5.5, 95% CI: 1.5-20.0), (OR: 4.0, 95% CI: 1.2-12.0), respectively. Increased WBC, PLR, NLR, MPV were independent predictors of GDM.


Synaptotagmin-4 promotes dendrite extension and melanogenesis in alpaca melanocytes by regulating Ca2+ influx via TRPM1 channels.
Synaptotagmin-4 (SYT4) is a membrane protein that regulates membrane traffic in neurons in a calcium-dependent or calcium-independent manner. In melanocytes, the intracellular free calcium ion (Ca2+ ) may be important for dendrite growth and melanogenesis. Mammalian melanocytes originating from neural crest cells produce melanins. Therefore, we predicted that SYT4 might play a role in melanogenesis and the dendrite morphology of melanocytes. To investigate whether SYT4 is involved in melanocyte physiology, SYT4 was overexpressed in alpaca melanocytes and B16-F10 cells. The results showed that SYT4 overexpression resulted in a phenotype consistent with melanogenesis and dendrite extension. At the molecular level, SYT4 interacted with extracellular regulated MAP kinase (ERK) to decrease p-ERK activity, which negatively regulated CREB expression. Furthermore, cyclic AMP-responsive element-binding protein (CREB) was upregulated and caused the downregulation of the expression of melanogenic regulatory proteins, including microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein-1 (TYRP1), dopachrome tautomerase (DCT), and transient receptor potential melastatin 1 (TRPM1). Intracellular free Ca2+ promoted the upregulation of calcium/calmodulin dependent protein kinase IV (CAMK4) expression, which phosphorylated CREB (p-CREB). In turn, p-CREB participated in the transcription of MITF. These results demonstrated that SYT4 promoted melanogenesis through dendrite extension and tyrosinase activity, during which the regulation of Ca2+ influx via the TRPM1 channel was a key factor. SIGNIFICANCE OF THE STUDY: Intracellular Ca2+ is important for the function and survival of melanocytes and melanoma cells. SYT4 stimulated melanogenesis through calcium. These results provide evidence that SYT4 regulates Ca2+ influx through TRPM1 to cause melanogenesis and axonal elongation in alpaca melanocytes and further suggesting that the growth and metastasis of melanoma is controlled by the inhibited expression of SYT4 in melanoma cells.


Brain potentials related to seeing one's own name.
Subjects were assigned an assumed name and then shown a series of statements of the form, "My name / is / X", where X was the assumed name, their own first name, or one of a set of other false names. Their task was to respond positively to the "assumed" name and reject as false all other names, including their own. An N380 feature of the averaged task-related brain potentials, considered to be inversely related to the degree of contextual priming, was greatly enhanced for the false names compared to the assumed name. The N380 to one's own name was more similar to that of the false than the assumed name, indicating that the sentence context's priming of various names was under the subjects' attentional control, and that the late negativity could be modulated by this attention. In contrast, a large P510 feature distinguished one's own name from the false name, and this difference was unaffected by practice. Even in cases, then, where the context allows anticipation of one verbal event (here, the assumed name), a highly overlearned and salient stimulus such as one's own name continues to produce a distinctive neural response.


Cross-cultural Adaptation and Validation of the Exercise-Induced Leg Pain Questionnaire for English- and Greek-Speaking Individuals.
Clinical measurement. To translate the German version of the Exercise-Induced Leg Pain Questionnaire (EILP-G) to Greek and English and evaluate the psychometric properties of the Greek version. The EILP-G was developed to evaluate the severity of symptoms and sports ability in individuals with exercise-induced leg pain (EILP). Translation of the questionnaire to other languages will provide a standard outcome measure across populations. The EILP-G questionnaire was cross-culturally adapted to Greek and English, according to established guidelines. The validity and reliability of the Greek version were assessed in 40 patients with EILP, 40 patients with other lower extremity injuries, 40 track-and-field athletes with no history of EILP, and 40 young adults without pathology. Participants completed the questionnaire at baseline and again after 7 to 10 days. The expert committee and the participants considered the questionnaire to have good face and content validity. Concurrent validity as assessed using the Schepsis score was almost perfect (rho = 0.947, P<.001). Dimensionality analysis revealed a 1-factor solution, explaining 83.8% of the total variance. Known group validity was demonstrated by significant differences between patients compared with the asymptomatic groups (P<.001). The Greek version exhibited excellent test-retest reliability (intraclass correlation coefficient = 0.995 for the EILP group) and internal consistency (Cronbach α = .942 for the EILP group). Finally, no ceiling or floor effects were found, as none of the individuals with EILP scored the maximum or minimum possible values on the questionnaire. The Greek version, adapted from the original EILP-G, is a valid and reliable questionnaire, and its psychometric properties are comparable with the original version.


Human ex vivo dentin-pulp complex preservation in a full crown model.
Currently, there is lack of human in vitro full tooth models that hold the odontoblast layer with pulp tissue in their native environment. The appearance of new in vitro and in vivo models has provided new understanding of the potential of tissue engineering in dental pulp regeneration. However, the development of new in vitro full tooth models will allow us to get closer to in vivo conditions. Thus, the aim of this study is to preserve a living dentin-pulp complex, in a novel in vitro full crown model, after tooth extraction. Twenty intact third molars, after preparation, were divided into four groups, with five samples each. We placed the negative control samples (C) in saline, and the tested groups were placed (T) in supplemented DMEM, at two different times: 1 and 7 days. The specimens were processed for light microscopy observation. Contrary to C-groups, T-groups showed a functional dentin-pulp complex. The treated dentin-pulp complex presents normal histological appearance. This study showed that it is possible to preserve a living dentin-pulp complex after tooth extraction during 7 days.


Interactions of cyclic and non-cyclic naphthalene diimide derivatives with different nucleic acids.
Recently, strategy based on stabilization of G-quadruplex telomeric DNA by small organic molecule has been realized by naphthalene diimide derivatives (NDIs). At the same time NDIs bind to DNA duplex as threading intercalators. Here we present cyclic derivative of naphthalene diimide (ligand 1) as DNA-binding ligand with ability to recognition of different structures of telomeric G-quadruplexes and ability to bis-intercalate to double-stranded helixes. The results have been compared to non-cyclic derivative (ligand 2) and revealed that preferential binding of ligands to nucleic acids strongly depends on their topology and structural features of ligands.


Cytotoxic effects exerted by pentachlorophenol by targeting nodal pro-survival signaling pathways in human pancreatic cancer cells.
Pancreatic adenocarcinoma is one of the deadliest human solid tumors in the developed countries characterized by high resistance toward chemotherapeutic treatment. We have previously shown that silencing of the pro-survival protein kinase CK2 by RNA interference contributes to enhance the cytotoxicity of the chemotherapeutic agent 2',2'-difluoro 2'-deoxycytidine (gemcitabine). Initial experiments showed that pentachlorophenol (PCP) inhibits CK2 and induces cell death in human pancreatic cancer cell lines. We report here evidence that exposure of this type of cells to PCP induces caspase-mediated apoptosis, inhibition of the lysosome cysteine protease cathepsin B and mitochondrial membrane depolarization. Beside cellular inhibition of CK2, the analysis of signaling pathways deregulated in pancreatic cancer cells revealed that PCP causes decreased phosphorylation levels of NF-κB/p65, suppresses its nuclear translocation and leads to activation of JNK-mediated stress response. Surprisingly, exposure to PCP results in increased phosphorylation levels of AKT at the canonical S473 and T308 activation sites supporting previous data showing that AKT phosphorylation is not predictive of tumor cell response to treatment. Taken together, our study provides novel insights into the effects induced by the exposure of pancreatic cancer cells to chlorinated aromatic compounds posing the basis for more advanced studies in vivo.


Chemical compositions extracted from Wikstroemia indica and their multiple activities.
The rhizome of Wikstroemia indica (L.) C. A. Mey (Thymelaeaceae) is widespread in China which has been widely used in China as folk medicine for the treatment of syphilis, arthritis, whooping cough, and cancer. Due to its multiactivities, its extract has an attractive potential as a promising natural agent in the pharmaceutical industries. Aims of this study were to optimize the extraction process of the flavonoids from W. indica, and evaluate its multiple activities. An orthogonal test design was employed to optimize the extraction procedure of flavonoids from W. indica. And multichromatography and spectroscopy were used to study the chemical compounds of W. indica, while several bioactivity assays were used to evaluate the antibacterial, anti-inflammatory, and antitumor activities of W. indica. Optimal extraction conditions were determined: ethanol concentration was 60%; extraction time was 60 min; liquid-solid ratio was 16:1 and the power of ultrasonic instrument was 160 W. Four compounds: daphnoretin, chrysophanol, myricitrime and rutin were purified from W. indica, and chrysophanol was identified from this plant for the first time. The extract of W. indica displayed significant antimicrobial and anti-inflammatory activities. Daphnoretin showed a significant inhibition effect on CNE cells and HeLa cells lines at the concentrations ranging from 15.6 to 125 μg/mL, the tendency of antitumor effect was displayed in a concentration-dependent manner. Extracts of W. indica could potentially be used as a promising natural agent in the pharmaceutical industries.


Production of lymphokines by murine cortisone-resistant thymocytes, stimulated by concanavalin A. II. Kinetics of interleukin-2 and interferon production in vitro.
The results presented in this study indicate that cortisone-resistant thymocytes stimulated with concanavalin A produce interferon and interleukin-2. The kinetic studies show that the peak of interleukin-2 activity precedes the maximal level of interferon activity which occurs later and does not show as rapid decline as the activity of interleukin-2.


The importance of flow pulsatility for the rate of transvascular fluid filtration in lungs.
1. The rate of transvascular fluid filtration has been studied with a gravimetric technique in isolated perfused rabbit lungs during periods of elevated left atrial pressure (PLA). 2. Fluid filtration was expressed as the filtration coefficient, Kf (g/min x 100 g bloodless lung x mmHg PLA) and determined during alternately pulsatile and non-pulsatile perfusion in six zone III and three zone II/I lung preparations. Perfusion pattern was changed without interruption of flow. Mean in- and outflow pressures were kept constant. 3. In all the lungs it was found that Kf was higher during pulsatile than during non-pulsatile flow (P less than 0.01). Mean Kf (+/- S.E. of mean) for the zone III preparations was 0.42 (+/- 0.089) and 0.27 (+/- 0.057) for pulsatile and non-pulsatile perfusion, respectively. The corresponding figures for the zone II/I preparations were 0.11 (+/- 0.035) and 0.04 (+/- 0.030). 4. We suggest that the difference is due to a larger filtration area and/or a higher mean microvascular hydrostatic pressure during pulsatile than during non-pulsatile flow and not to a rise in hydraulic conductivity due to pressure pulsations ('stretched pores'). 5. When the water-exchange function of the lung is considered, flow pattern should be taken into account as an entity in its own right in addition to the steady state or the mean component of blood flow.


Human pegivirus 2 exhibits minimal geographic and temporal genetic diversity.
We applied an NGS based target capture approach to amplify HPgV-2 sequences from metagenomic libraries and enable full genome characterization. Despite expanded geographical sampling, sequence variability remains low, with diversity concentrated in approximately 3.3% of all amino acids. Serial samples from one HPgV-2 positive individual co-infected with comparable titers of HIV, HCV, and GBV-C showed that HPgV-2 remains highly stable over several weeks compared to other RNA viruses, despite a similarly error-prone polymerase. The consistent epidemiological association with and structural similarities to HCV, and the weak positive correlation of HCV and HPgV-2 titers shown here, suggests it may benefit from co-infection. While minimal selective pressure on HPgV-2 to evolve could suggest fitness, the rarity of HPgV-2 and the tight phylogenetic clustering of global strains likely indicates origination from a common source and a virus that is ill-suited to its host. Sporadic infections may explain the limited genetic diversity observed worldwide.


Hospital-prepared low-dose atropine eye drops for myopia progression control using atropine sulfate injection diluted in normal saline and lubricants.
As low-dose atropine eye-drops for myopia progression control prepared in-house by diluting the commercial 0.1% atropine eye-drop with sterile water or normal saline has been a common practice whereas atropine injection is readily available and could be a more feasible alternative, this study aimed to assess the properties of the in-house low-dose atropine eye-drops prepared by diluting the atropine injection in two solvents and tested in two temperature conditions. The 0.01% atropine eye-drops contains no bacteria, fungi, or particulate matter. The levels of atropine sulfate on all samples were comparable to the freshly prepared samples at the 12th week, regardless of the solvents used or storage conditions. The low-dose atropine eye-drops prepared from readily available atropine sulfate injection at healthcare facilities could be an alternative to commercial products.


Differential regulation of gonadotropin receptors by bone morphogenetic proteins in the zebrafish ovary.
Follicle-stimulating hormone receptor (fshr) and luteinizing hormone/choriogonadotropin receptor (lhcgr) exhibit differential temporal expression patterns during zebrafish folliculogenesis with fshr being dominant during vitellogenic growth and lhcgr increasing its expression dramatically before maturation. The dynamic and distinct expression patterns of fshr and lhcgr suggest that they are under tight regulatory control. However, the underlying mechanisms for the differential expression of the two receptors remain unknown. We have recently demonstrated that members of bone morphogenetic protein (BMP) family are largely expressed in the oocyte, while their receptors are exclusively localized on the follicle cells, suggesting a potential paracrine signaling from the oocyte to the follicle cells by BMPs. In this study, we investigated the effects of zebrafish BMP2b (zfBmp2b) and BMP4 (zfBmp4) on the expression of fshr and lhcgr using a novel co-culture approach. The recombinant zfBmp2b or zfBmp4-producing CHO cells were co-cultured with the zebrafish follicle cells followed by real-time qPCR analysis of fshr and lhcgr expression. Our results showed that zfBmp2b and zfBmp4 both down-regulated fshr, while up-regulated lhcgr expression at 24 h of co-culturing. This finding, together with the high expression level of BMP receptors in the follicle cells prior to oocyte maturation, strongly suggests a potential role for BMPs in the differential expression of fshr and lhcgr, especially in the full-grown follicles before maturation. As BMPs are largely expressed in the oocyte, this also implies an important role for the oocyte in orchestrating the differentiation and function of the follicle cells.


Cholecystokinin-octapeptide constricts guinea-pig and human airways.
1. Cholecystokinin-octapeptide (CCK-OP, 10(-10)-3 x 10(-6) M) produced a concentration-dependent contractile response in guinea-pig trachea which was enhanced by both the mechanical removal of the epithelium and by indomethacin (10(-5) M), with an EC50 of 6.18 +/- 0.10 x 10(-8) M. 2. Sub-threshold concentrations of CCK-OP, which did not alter the resting tone of the smooth muscle, did not alter responses produced to electrical field stimulation (EFS) or to vagal nerve stimulation in an intact tracheal tube preparation. Atropine (2 x 10(-6) M) did not alter the concentration-response curve to CCK-OP, indicating that CCK-OP contraction is not mediated by cholinergic mechanisms. 3. The inhibition of neutral endopeptidase (endopeptidase-24.11) by phosphoramidon (10(-5) M) gave a leftward shift in the CCK-OP concentration-response curve in tissues with intact epithelium obtained from normal animals, but had no effect in tissues denuded of epithelium or in tissues obtained from animals which had been actively sensitized and challenged with ovalbumin (OA). 4. CCK-OP-induced contractile responses were antagonized by the CCK-receptor antagonists dibutyryl cyclic guanosine monophosphate (pA2 = 4.3) and L-364,718 (pA2 = 9.6). 5. CCK-OP induced bronchoconstriction in large, but not small, human airways and was antagonized by the CCK-receptor antagonist L-364,718. CCK-OP had no effect on cholinergic neural responses elicited by EFS in human airways.


Female urethral strictures: successful management with long-term clean intermittent catheterization after urethral dilatation.
To report our experience in the diagnosis and treatment of urethral stricture in women. A retrospective review of records and video-urodynamics identified women treated for urethral stricture between 1999 and 2004 at one institution by one surgeon. Urethral stricture was defined as a fixed anatomical narrowing between the bladder neck and distal urethra of <14 F preventing catheterization, and the diagnosis was confirmed by cysto-urethroscopy, and/or video-urodynamics. Women with a history of external beam radiotherapy to the pelvis, or of gynaecological, urethral or bladder malignancy, were excluded, and the women had a urethral biopsy to exclude a malignant cause of the stricture. Initial treatment consisted of urethral dilatation to > or = 30 F. After a period of indwelling catheterization, the women were placed on clean intermittent self-catheterization (CISC) at least once daily, and monitored every 3-6 months. At each follow-up, the urethra was catheterized to exclude recurrence. American Urological Association (AUA) symptom scores were obtained at presentation and at the initial 3 month follow-up. Seven women met the criteria for urethral stricture, and were followed for a mean (range) of 21 (6-34) months. All were initially maintained on daily CISC, and some were gradually reduced to weekly CISC for the duration of follow-up. No patient had a recurrent stricture while on CISC, and none has had a urethral reconstruction to manage their condition. AUA symptom scores improved in all of the women by a mean of 10.7 points. No complications related to catheterization were noted. Urethral stricture is rare in women. Long-term CISC in these women is safe and effective, and can avoid the need for major reconstructive surgery.


Ultra-high-field MRI using composite RF (STEP) pulses.
Ultra-high field MRI offers many opportunities to expand the applications of MRI. In order for this to be realized, the technical problems associated with MRI at field strengths of 7 T and greater need to be solved or mitigated. This paper explores the use of new variations of composite RF pulses, named serial transmit excitation pulses (STEP), in contrast to parallel pulse techniques, in order to remove and/or mitigate the effects of non-uniform B1 excitation fields associated with the subject (eg the human brain). Several techniques based on STEP sequences are introduced and their application to human brain imaging is presented and evaluated.


Primary DNA damage but not mutagenicity correlates with ciprofloxacin concentrations in German hospital wastewaters.
Recently, we showed for the wastewater of a large Swiss university hospital that primary DNA damage, assessed by a bacterial SOS repair assay (umuC test), could be largely assigned to a specific class of antibiotics, the fluoroquinolones (FQs) (Hartmann et al. [1998] Environ Toxicol Chem 17:377-382). In an attempt to confirm the significance of FQs for the bacterial DNA damaging effects in native hospital wastewaters, 25 samples from five German clinics were screened in this study by the umuC test. The results were compared to HPLC-derived concentrations of ciprofloxacin, an important member of the FQs. Ten samples (40%) were umuC-positive and ciprofloxacin concentrations ranged from 0.7 to 124.5 microg/L (n = 24). Primary DNA damage, as indicated by the umuC test, correlated strongly with ciprofloxacin concentrations in a logistic, dose-dependent manner (r2 = 0.896), almost irrespective of the use of S9 metabolic activation. The lowest observed effect concentration (LOEC) for ciprofloxacin was 5.2 microg/L (+S9) and 5.9 microg/L (-S9). Similar to our previous findings, these results indicate that positive umuC results in hospital wastewater are strongly dependent on the presence of fluoroquinolone antibiotics. In a second part of the study, previously generated Ames and V79 chromosomal aberration data of the same samples (Gartiser and Brinker [1995] in Umweltbundesamt Texte 74/95) were compared with the newly generated results. Neither the mutagenic effects detected by the Ames assay (8%, n = 25) nor the positive V79 results (46% n = 13) seemed to be caused by ciprofloxacin. Therefore, the Ames and V79 results suggest the presence of additional mutagens that are yet to be identified.


Evaluation of non-coding variation in GLUT1 deficiency.
Loss-of-function mutations in SLC2A1, encoding glucose transporter-1 (GLUT-1), lead to dysfunction of glucose transport across the blood-brain barrier. Ten percent of cases with hypoglycorrhachia (fasting cerebrospinal fluid [CSF] glucose <2.2mmol/L) do not have mutations. We hypothesized that GLUT1 deficiency could be due to non-coding SLC2A1 variants. We performed whole exome sequencing of one proband with a GLUT1 phenotype and hypoglycorrhachia negative for SLC2A1 sequencing and copy number variants. We studied a further 55 patients with different epilepsies and low CSF glucose who did not have exonic mutations or copy number variants. We sequenced non-coding promoter and intronic regions. We performed mRNA studies for the recurrent intronic variant. The proband had a de novo splice site mutation five base pairs from the intron-exon boundary. Three of 55 patients had deep intronic SLC2A1 variants, including a recurrent variant in two. The recurrent variant produced less SLC2A1 mRNA transcript. Fasting CSF glucose levels show an age-dependent correlation, which makes the definition of hypoglycorrhachia challenging. Low CSF glucose levels may be associated with pathogenic SLC2A1 mutations including deep intronic SLC2A1 variants. Extending genetic screening to non-coding regions will enable diagnosis of more patients with GLUT1 deficiency, allowing implementation of the ketogenic diet to improve outcomes.


Preparation of a shikonin-based pH-sensitive color indicator for monitoring the freshness of fish and pork.
A novel intelligent pH-responsive color indicator was prepared by adsorbing a natural naphthoquinone pigment, shikonin, onto cellulose paper. FTIR results indicated that shikonin was crosslinked with the cellulose of the indicator paper. The addition of shikonin increased antioxidant activity, thermal stability, and water resistance properties of the paper. The indicator changed the color from red to dark blue, depending on the pH of buffer solutions. Also, the indicator showed high stability after 4 months of storage and maintained high sensitivity to pH changes. This indicator was used to monitor fish and pork freshness during storage at room temperature, and the results showed a high correlation between the color change of the indicator and the pH change of the sample. The shikonin-adsorbed indicator with stable and sensitive color change depending on pH can be used in the intelligent food packaging applications to monitor the quality of packaged food in real-time.


Duodenal mucosal resurfacing combined with glucagon-like peptide-1 receptor agonism to discontinue insulin in type 2 diabetes: a feasibility study.
Duodenal mucosal resurfacing (DMR) is an endoscopic intervention in which the duodenal mucosa is ablated by hydrothermal energy. DMR improves glycemic control in patients with type 2 diabetes (T2D), most likely by altered duodenal signaling leading to insulin sensitization. We studied whether we could discontinue insulin use in T2D patients by combining DMR with glucagon-like peptide-1 receptor agonist (GLP-1RA) and lifestyle counseling. In this single-arm, single-center feasibility study in 16 insulin-treated patients with T2D (hemoglobin A1c [HbA1c] ≤8.0%, basal insulin <1 U/kg/day, C-peptide ≥.5 nmol/L), patients underwent a single DMR followed by a 2-week postprocedural diet, after which GLP-1RA (liraglutide) was introduced. Lifestyle counseling was provided per American Diabetes Association guidelines. The primary endpoint was percentage of patients without insulin with an HbA1c ≤7.5% (responders) at 6 months. Secondary endpoints were changes in multiple glycemic and metabolic parameters and percentage of responders at 12 and 18 months, respectively. All 16 patients underwent successful DMR without procedure-related serious adverse events. At 6 months, 69% of patients were off insulin therapy with an HbA1c ≤7.5%. At 12 and 18 months 56% and 53% remained off insulin, respectively. All patients significantly improved in the glycemic and metabolic parameters of homeostatic model assessment for insulin resistance, body mass index, weight, and liver fat fraction. In this feasibility study, the combination of a single DMR and GLP-1RA, supported by lifestyle counseling, eliminated the need for insulin therapy in most patients with T2D through 18 months postprocedure, with adequate beta-cell capacity, while improving glucose regulation and metabolic health in all patients. A randomized-sham controlled trial is currently initiated based on these results. (Clinical trial registration number: EudraCT 2017-00349-30.).


Outcomes after acute coronary syndrome in patients with inflammatory bowel disease.
Patients with chronic inflammatory conditions are at an increased risk of developing atherothrombotic events. We aimed to assess the 1-year prognosis after myocardial infarction (MI) in patients with inflammatory bowel disease (IBD). From the PMSI (Program de Medicalisation des Systèmes d'informatique) database, 246 out of 39,835 consecutive MI patients, hospitalized between 2012 and 2017, were diagnosed with IBD and followed up for 1 year after discharge. A matched cohort was built matching each MI patient with IBD to patient without IBD using age and sex (n = 1,470, matching ratio 1:5). Compared with MI patients without IBD, MI patients with IBD were younger (aged 69 vs. 70.8 years, p = 0.04) with a higher rate of increased body mass index (BMI) (21.5% vs 15%, p = 0.004), previously diagnosed ischemic cardiopathy (18.3% vs 12.6%, p < 0.0008) and chronic renal disease (8.9% vs 5.6%, p = 0.02). In our age- and sex-matched cohort, we found that all-cause mortality (9% vs 8.3, p = 0.729), stroke (0.8% vs 0.6%, p = 0.656) and hospitalization resulting from heart failure (3ool, .3% vs 3.5%, p = 0.846) did not significantly differ between the IBD and non-IBD groups within the first year after initial admission whereas the risk of recurrent MI was increased by 50% (2.9% vs 1.9%, p = 0.33) in the IBD group without reaching statistical significance. Moreover, a significant increase in the blood transfusion rate at the 1-year follow-up was observed in MI patients with IBD compared with MI patients without IBD (15.1% vs 9.4%, p < 0.001). Our findings suggest that both residual MI risk and bleeding events should be carefully monitored in MI patients diagnosed with chronic inflammation such as that observed in IBD.


Pathophysiological characterization of the Townes mouse model for sickle cell disease.
A deeper pathophysiologic understanding of available mouse models of sickle cell disease (SCD), such as the Townes model, will help improve preclinical studies. We evaluated groups of Townes mice expressing either normal adult human hemoglobin (HbA), sickle cell trait (HbAS), or SCD (HbS), comparing younger versus older adults, and females versus males. We obtained hematologic parameters in steady-state and hypoxic conditions and evaluated metabolic markers and cytokines from serum. Kidney function was evaluated by measuring the urine protein/creatinine ratio and urine osmolality. In vivo studies included von Frey assay, non-invasive plethysmography, and echocardiography. Histopathological evaluations were performed in lung, liver, spleen, and kidney tissues. HbS mice displayed elevated hemolysis markers and white blood cell counts, with some increases more pronounced in older adults. After extended in vivo hypoxia, hemoglobin, platelet counts, and white blood cell counts decreased significantly in HbS mice, whereas they remained stable in HbA mice. Cytokine analyses showed increased TNF-alpha in HbS mice. Kidney function assays revealed worsened kidney function in HbS mice. The von Frey assay showed a lower threshold to response in the HbS mice than controls, with more noticeable differences in males. Echocardiography in HbS mice suggested left ventricular hypertrophy and dilatation. Plethysmography suggested obstructive lung disease and inflammatory changes in HbS mice. Histopathological studies showed vascular congestion, increased iron deposition, and disruption of normal tissue architecture in HbS mice. These data correlate with clinical manifestations in SCD patients and highlight analyses and groups to be included in preclinical therapeutic studies.


Sorptivity of water in enamel for categorizing caries lesions.
The aim of this research was to determine the association between sorptivity of water and the state of mineralization in carious enamel of different stages of severity. As a preliminary work, water droplets of 1.5 μL were placed on the surfaces of hydroxyapatite (HA) discs of different densities. The water droplet profile was dynamically recorded every second over a period of 10 s using a contact angle meter to determine the relationship between sorptivity and density. To measure and calculate sorptivity on enamel surfaces, varnish was painted on the labial surface of 96 extracted caries-free human teeth, leaving two 1.4 ± 0.1 mm diameter circular exposed test sites. The specimens were randomly divided into 6 groups (n = 16) and subjected to 0(G0), 7(G7), 14(G14), 21(G21), 28(G28) and 35(G35) days of pH cycling, respectively. A 0.7 μL water droplet was placed on each exposed site and Optical Coherence Tomography was used to measure its height every 10 seconds for 2 min. Sorptivity was computed by considering sorption equations and Washburn's analysis of capillary kinetics and correction for evaporation was also performed. Micro-Computed Tomography scans of the specimens were obtained and delta Z (ΔZ) is the parameter used to measure mineral loss. ΔZ at 10 μm (ΔZ10) and 50 μm (ΔZ50) from the surface were calculated. One-way ANOVA and Post-hoc Tukey tests were used to compare sorptivity between groups and bivariate correlations were used to analyze the association between sorptivity and ΔZ. Sorptivity was found to be inversely and linearly correlated with HA density with R2 value of 0.95. With enamel, there is a general trend of increase in mean sorptivity from G0 to G35, except for a decrease in G21. The same trends were observed for both ΔZ10 and ΔZ50. The decrease in sorptivity in G21 coincided with the presence of a surface hypermineralized layer in G21 samples. Post-hoc Tukey showed significant differences in mean sorptivity between G0 and G14, G0 and G21 as well as G14 and G21. Post-hoc Dunnett's T3 showed significant differences for ΔZ10 between G0 and G14 as well as G14 and G21. Significant correlation between mean sorptivity and ΔZ10 was detected with Pearson correlation coefficient of 0.461. For ΔZ50, post-hoc Tukey showed significant differences between G0 and G14 but no significant difference was detected between G14 and G21. No correlations were detected between mean sorptivity and ΔZ50. Sorptivity was found to be inversely and linearly correlated with HA density with R2 value of 0.95. With enamel, there is a general trend of increase in mean sorptivity from G0 to G35, except for a decrease in G21. The same trends were observed for both ΔZ10 and ΔZ50. The decrease in sorptivity in G21 coincided with the presence of a surface hypermineralized layer in G21 samples.


Mutations in influenza A virus (H5N1) and possible limited spread, Turkey, 2006.
We report mutations in influenza A virus (H5N1) strains associated with 2 outbreaks in Turkey. Four novel amino acid changes (Q447L, N556K, and R46K in RNA polymerase and S133A in hemagglutinin) were detected in virus isolates from 2 siblings who died.


Efficacy, Safety And Feasibility Of Antiemetic Prophylaxis With Fosaprepitant, Granisetron And Dexamethasone In Pediatric Patients With Hemato-Oncological Malignancies.
Chemotherapy-induced nausea and vomiting (CINV) are a major burden for patients undergoing emetogenic chemotherapy. International guidelines recommend an antiemetic prophylaxis with corticosteroids, 5-HT3R-antagonists and NK1R-antagonists. The NK1R-antagonist fosaprepitant has shown favorable results in pediatric and adult patients. There is little pediatric experience with fosaprepitant. This non-interventional observation study analyzed 303 chemotherapy courses administered to 83 pediatric patients with a median age of 9 years (2-17 years), who received antiemetic prophylaxis either with fosaprepitant and granisetron with or without dexamethasone (fosaprepitant group/FG; n=41), or granisetron with or without dexamethasone (control group/CG; n=42), during moderately (CINV risk 30-90%) or highly (CINV risk>90%) emetogenic chemotherapy. The two groups' results were compared with respect to the safety and efficacy of the antiemetic prophylaxis during the acute (0-24hrs after chemotherapy), delayed (>24-120hrs after chemotherapy) and both CINV phases. Laboratory and clinical adverse events were compared between the two cohorts. Adverse events were not significantly different in the two groups (p>0.05). Significantly fewer vomiting events occurred during antiemetic prophylaxis with fosaprepitant in the acute (23 vs 142 events; p<0.0001) and the delayed (71 vs 255 events; p<0.0001) CINV phase. In the control group, the percentage of chemotherapy courses with vomiting was significantly higher during the acute (24%/FG vs 45%/CG; p<0.0001) and delayed CINV phase (28%/FG vs 47%/CG; p=0.0004). Dimenhydrinate (rescue medication) was administered significantly more often in the CG, compared to the FG (114/FG vs 320/CG doses; p<0.0001). Likewise, in the control group, dimenhydrinate was administered in significantly more (p<0.0001) chemotherapy courses during the acute and delayed CINV phases (79 of 150; 52.7%), compared to the fosaprepitant group (45 of 153; 29.4%). Antiemetic prophylaxis with fosaprepitant and granisetron with or without dexamethasone was well tolerated, safe and effective in pediatric patients. However, larger prospective trials are needed to evaluate these findings.


Associations between retail food store exterior advertisements and community demographic and socioeconomic composition.
This paper examines the association between the prevalence of various types of outdoor food and beverage advertising found on the building exteriors and properties of retail food outlets and community racial/ethnic and socioeconomic composition in a nationwide sample of food outlets in the U.S. Our major finding from multivariable analysis is that food stores in low-income communities have higher prevalence of all food and beverage ads, including those for unhealthy products such as regular soda, controlling for community racial/ethnic composition and other covariates. This adds to growing research pointing to socioeconomic disparities in food and beverage marketing exposure.


Effect of dissolved oxygen concentration on performance and mechanism of simultaneous nitrification and denitrification in integrated fixed-film activated sludge sequencing batch reactors.
Integrated fixed-film activated sludge (IFAS) is a superior system for achieving simultaneous nitrification and denitrification (SND), however, the impact of dissolved oxygen (DO) has not been fully elucidated. Therefore, this study investigated the effect of DO concentration on performance and mechanism of SND in IFAS system. Results showed that IFAS outperformed control systems and achieved optimal SND performance at a DO concentration of 0.5 mg/L, with an SND efficiency of 88.51% and total nitrogen removal efficiency of 82.78%. Typical cycles analysis demonstrated limited-DO promoted SND performance. Further analysis implied biofilms exhibited high biomass and denitrification activity with decreasing DO. Microbial community analysis revealed low DO concentrations were responsible for abundant functional groups and genes associated with SND and promoted unconventional nitrogen removal pathways. Moreover, co-occurrence network analysis elucidated microbial interactions, responses to DO, and keystone genera. This study helps understanding the roles of DO for enhanced SND in IFAS.


Cantharide acantholysis: endogenous protease activation leading to desmosomal plaque dissolution.
Using a method which allowed us to study the morphological consequences of the expression and the inhibition of proteases in living tissues, we demonstrated that the primary detectable cellular event in cantharide acantholysis is the dissolution of the dense plaque, leading to the detachment of tonofilaments from desmosomes. This process is inhibited by neutral serine protease inhibitors. This suggests that the desmosome-tonofilament complex, more precisely the desmosomal dense plaque, is the primary target of activated proteases during cantharide acantholysis, and can be disrupted by a specific epidermal protease-anti protease system. Cantharide acantholysis may be useful model for studying desmosomal turnover.


An unusual cause of necrosis and nasal septum perforation after septoplasty: Enterobacter cloacae.
A 20-year-old man with nasal obstruction underwent septoplasty due to nasal septal deviation. Nasal packs were inserted at the end of surgery and removed 48 hours after surgery. Twenty-four hours after removal of nasal packs, there was necrosis in both sides of septal mucosa and in bilateral inferior turbinates. Nasal swab culture was performed from both nasal cavities. Enterobacter cloacae was isolated from samples. Two weeks after surgery, nasal septum perforation was unavoidable. To our knowledge, this is the first case in literature describing septal mucosal necrosis caused by this pathogen after septoplasty. Mucosal necrosis and perforation as septoplasty complications should be kept in mind, the result of causes both common and, as in the present case, unusual.


A platelet inhibitor protein with cytochalasin-like activity against actin polymerization in vitro.
We have obtained an inhibitor fraction containing cytochalasin-like activity from human platelets. Using a procedure involving DEAE-cellulose, hydroxyapatite and gel filtration column chromatography, we obtained a fraction from human platelets which apparently can compete with 3H--cytochalasin B for binding to spectrin-actin complexes from human erythrocytes. The inhibitor activity is nondialyzable, sensitive to heat and to trypsin and has a Stoke's radius of 40 A. This fraction stops nuclei-induced actin polymerization in 0.4 mM MgCl2 and reduces the viscosity of F actin to that of G actin, which suggests depolymerization of the filaments. These results suggest that the inhibitor fraction contains a protein which interacts with actin filaments and nuclei in a manner similar to that of cytochalasin B. It is possible that such a protein is involved in the control of cell motility by affecting assembly and disassembly of actin-containing microfilaments in vivo.


Electrophysiological correlates of categorization: P300 amplitude as index of target similarity.
Two experiments examined event-related potentials (ERPs) and behavioral correlates of categorizing stimuli varying in perceptual similarity to targets. Participants performed a target-detection task in which non-target stimuli varied in target similarity but occurred with equivalent probability. The stimuli were variations of a schematic human face comprised of eight distinct features: two eyes, two eyebrows, one nose, one mouth, and two ears. Non-target stimuli that were perceptually similar to targets produced larger P300-like neurophysiological responses than did other non-target stimuli. These effects emerged whether participants' target was relatively complex (eight features) or quite simple (zero features). Accordingly, the presence of many constituent elements of a test stimulus does not appear necessary to trigger increases in categorical processing of non-targets that are similar to a target. The data further suggest that the P300 amplitude may be used as a good index of perceptual similarity between target and non-target stimuli.


The importance of screening for functional neurological disorders in patients with persistent post-concussion symptoms.
Functional neurological disorder (FND) may commonly co-occur with persistent symptoms following a psychological trauma or physical injury such as concussion. To explore the occurrence of FND in a population with persistent post-concussion symptoms (PPCS) and the associations between FND and depression as well as anxiety in participants with PPCS. Sixty-three individuals with PPCS presenting to a specialized brain injury clinic completed the following questionnaires: screening for somatoform disorder conversion disorder subscale (SOM-CD), Rivermead post-concussion symptom questionnaire (RPQ), patient health questionnaire-9 (PHQ-9), and generalized anxiety disorder questionnaire- 7 (GAD-7). Both multiple linear regression and logistic regression were conducted to evaluate the relationship between questionnaires and adjust for covariates. We found that total RPQ score (βˆ= 0.27; 95% CI = [0.16, 0.38]), GAD-7 score (βˆ= 0.71; 95% CI = [0.50, 0.92]) and PHQ-9 score (βˆ= 0.54; 95% CI = [0.32, 0.76]) were positively associated with SOM-CD score individually, after consideration of other covariates. Participants meeting the criteria for severe FND symptoms were 4.87 times more likely to have high PPCS symptom burden (95% CI = [1.57, 22.84]), 8.95 times more likely to have severe anxiety (95% CI = [3.31, 35.03]) and 4.11 times more likely to have severe depression symptom burden (95% CI = [1.77, 11.53]). The findings of this study indicate an association between FND and post-concussion symptoms as well as an association between FND and symptoms of depression and anxiety in patients with PPCS. Patients with PPCS should be screened for FND to provide a more targeted treatment approach that includes somatic-focused interventions.


[Treatment of intractable epilepsy with hemispherectomy].
To explore the clinical effectiveness of hemispherectomy for patients with intractable epilepsy. Thirty-six patients with intractable epilepsy were treated by modified hemispherectomy and their clinical results were followed up after operation. The seizures of the 36 patients were effectively controlled and 34 (94.4%) were thoroughly controlled. Meanwhile, the dysfunction of the central nervous system in 30 patients (83.3%) was aggravated, and 5 patients (13.9%) showed better improvement than before. Neuropsychological assessment revealed much improvement in the patients. Modified hemispherectomy is advisable for patients with wide-range lesion of the half-brain associated with intractable epilepsy.


Inverted reamer technique for bone grafting of the acetabulum: technical note.
Socket fixation with bone grafting for dysplastic hips is technically demanding, and inadequate coverage of the socket may cause poor results in patients with severely dysplastic hips. An accurate technique to form a bone graft to fit into the defect is necessary. We aim to introduce the simple method of bone grafting, "inverted reamer technique" in cemented total hip arthroplasty (cTHA). After acetabular preparation with a normal acetabular reamer, the bone graft was prepared from the resected femoral head with the inverted reamer. The graft can be press-fit into the defect of the acetabulum with good compatibility through this method. Then, the bone graft was fixed with 1-3 screws and the socket was implanted with bone cement. The "inverted reamer technique" can easily and automatically create a well-fit graft. This method is simple and technically less demanding; it can be performed by every surgeon, including trainee and inexperienced surgeons. This method can improve the outcome of cTHA for dysplastic hips by preserving bone stock and increasing bone coverage of the socket implanted in the anatomic position.


Semi-quantitative RT-PCR analysis of fat metabolism genes in mammary tissue of lactating and non-lactating water buffalo (Bubalus bubalis).
Understanding the mechanism of milk fat synthesis and secretion is important for dairy industry, as the nature of the cream fraction influences the manufacturing properties and organoleptic qualities of milk and dairy products. So, there is a need to understand the mechanism of milk fat synthesis and to elucidate the key genes regulating milk fat synthesis by studying the expression of genes involved in milk fat synthesis. Present manuscript reports the expression of genes involved in milk fat synthesis and metabolism in buffalo mammary tissue. The expression of lipogenic genes was studied in lactating and non-lactating mammary tissue of water buffalo by semi-quantitative reverse transcription PCR expression analysis. The genes studied were acetyl-CoA carboxylase (ACACA), stearoyl-CoA desaturase (SCD), 3 hydroxybutyrate dehydrogenase (BDH), LIPIN, lipoprotein lipase (LPL), peroxisome proliferator-activated receptor gamma (PPARG), and sterol regulatory element binding protein (SREBF). The expression of ACACA, BDH, LIPIN, PPARG, LPL, and SREBF was higher in lactating as compared to non-lactating buffalo whereas no difference was found in the expression of SCD between both the stages.


Effect of neurophysin on enzymatic maturation of oxytocin from its precursor.
We examined the extent to which rates of enzymatic conversion of the oxytocin biosynthetic precursor to mature peptide are modulated by intramolecular and intermolecular assembly of precursor and polypeptide intermediates. The biosynthesized precursor contains hormone and neurophysin sequences linked by a Gly-Lys-Arg sequence and undergoes enzymatic processing reactions which include endoproteolytic cleavage at the Lys-Arg dibasic sequence, carboxypeptidase B-like exoproteolytic cleavage, and enzymatic amidation. We evaluated the effect of neurophysin on such processing reactions using semisynthetic precursors of oxytocin/bovine neurophysin I and synthetic oxytocinyl precursor intermediates as substrates. Neurophysin I at high concentration (0.7 mM) reduced the rates of carboxy-peptidase B-like conversion of oxytocinyl-Gly-Lys-Arg to oxytocinyl-Gly and the enzymatic amidation of oxytocinyl-Gly to mature (C-terminal amidated) oxytocin. The dependence of rate suppression on the concentrations of peptide substrate and neurophysin I suggested that suppression is due to intermolecular formation of hormone-neurophysin complexes which are aggregated at least to dimers. An analogous intramolecular neurophysin effect was found for endoproteolytic processing of semisynthetic precursors. Endoproteinase Lys-C cleaved the Lys11-Arg12 peptide bond in a native-like semisynthetic precursor at a significantly slower rate than it did an assembly-deficient precursor analogue. The difference in semisynthetic precursor endoproteolysis rates is most substantial at the high concentrations at which the native-like precursor would form dimers but the assembly-deficient analogue would not. The native-like semisynthetic precursor was more stable than the assembly-deficient precursor analogue to tryptic digestion. The concentration-dependent effects of neurophysin, both intramolecularly as a precursor domain and intermolecularly as an interacting protein, are likely to occur in the secretory granules in which the biosynthetic precursors are packaged. The molecular organization of both hormone/neurophysin precursors and the noncovalently complexed hormone-neurophysin intermediates can be expected to play a role in modulating enzymatic processing reactions that lead to mature neurohypophysial hormones.


Paraneoplastic and non-paraneoplastic retinopathy and optic neuropathy: evaluation and management.
Paraneoplastic syndromes involving the visual system are a heterogeneous group of disorders occurring in the setting of systemic malignancy. Timely recognition of one of these entities can facilitate early detection and treatment of an unsuspected, underlying malignancy, sometimes months before it would have otherwise presented, and gives the patient an increased chance at survival. We outline the clinical features, pathogenesis, and treatment strategies for the retinal- and optic nerve-based paraneoplastic syndromes: cancer-associated retinopathy; melanoma-associated retinopathy; paraneoplastic vitelliform maculopathy; bilateral diffuse uveal melanocytic proliferation; paraneoplastic optic neuropathy; and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome. Distinguishing these disorders from their non-paraneoplastic counterparts (e.g., autoimmune-related retinopathy and optic neuropathy, and acute zonal occult outer retinopathy) and determining appropriate systemic evaluation for the responsible tumor can be challenging. In addition, we discuss the utility and interpretation of autoantibody testing.


Laser therapies for glaucoma: new frontiers.
Glaucoma is a long-term ocular neuropathy defined by optic disc or retinal nerve fiber structural abnormalities and visual-field defects. Treatment for glaucoma consists of reducing intraocular pressure (IOP) to an acceptable target range to prevent further optic-nerve damage. Currently available treatments include topical drug (single then multidrug combinations) followed, for those patients on maximal tolerated medical therapy who still need additional IOP reduction, by laser treatments. These included laser iridotomy, laser trabeculoplasty, laser iridoplasty, laser cyclophotocoagulation. Although the various types of laser enjoyed great success as glaucoma therapy for many years, recently the excimer laser trabeculotomy is a promising IOP-lowering technique.


Cell membrane patches are supported by proteoglycans.
A cell membrane patch isolated on a patch clamp pipette incorporates in addition to the phospholipid bilayer, an extracellular matrix and cytoskeletal components. The significance of the extracellular matrix for the patch formation was studied in aortic smooth muscle and cerebellar granule cells grow in the presence of an inhibitor of proteoglycan synthesis, beta-D-xyloside. The xyloside improved the seal success rate, and after patch excision membrane vesicles were formed instead of inside-out patches. When amphotericin B was included in the pipette solution, perforated outside-out vesicles were formed in 96% of cells. The findings suggest, that membrane patches are supported by the extracellular matrix or by structures that relate to this matrix.


Refocusing the debate: evidence-based clinical cancer research versus marketplace reality.
The continued development and licensing of modestly beneficial high-priced treatments, and the potential for widening disparities in cancer care, warrant a renewed focus on how we measure and define benefits and cost.