Exhaled breath condensate markers of oxidative stress in male storekeepers of chemical stores in the Ariaria international market Aba Abia state Nigeria.
In most developing countries, stores, where chemical substances are sold, are poorly ventilated, and best practices are not followed. This can result in the contamination of the ambient air inside the stores with toxicological implications for the lungs. This work aimed at determining the risk of pulmonary disease in chemical storekeepers in the Ariaria international market Aba by the evaluation of exhaled breath condensate (EBC) biomarkers of oxidative stress. A gas monitor was used for gas sampling while an Aerocet analyzer was used for particulate matter determinations. Exposed filter paper was used for the sampling of heavy metals in the air, and the determination was done using atomic absorption spectrophotometry. The exhaled breath condensate was collected with a refrigerated condenser, and the markers of oxidative stress were determined spectrophotometrically. Concentrations of particulate matter (PM1, PM2.5, PM4, PM7, PM10) were elevated in all the chemical stores studied. Our findings also showed that the indoor air of the chemical stores studied was polluted with SO2, NO2, NH3 and H2S, as their concentrations were respectively higher than the WHO standard values. Concentrations of all the heavy metals present in the ambient air of the chemical stores were also higher than the Nigerian Environmental Standard and Regulation Enforcement Agency (NESREA) standard values. Chemical storekeepers at the Ariaria international market exhaled increased concentrations of thiobarbituric acid reactive substances (TBARS), H2O2, and lower concentrations of glutathione (GSH). The pH values of the exhaled breath condensates were decreased and slightly acidic. It therefore means that the storekeepers were exposed to polluted ambient air inside the stores. This resulted to airway oxidative stress in the storekeepers as reported herein. Therefore, storekeepers of chemical stores in the Ariaria international market, Aba Nigeria were at risk of pulmonary disease(s).


Homology modeling reveals the structural background of the striking difference in thermal stability between two related [NiFe]hydrogenases.
Hydrogenases are redox metalloenzymes in bacteria that catalyze the uptake or production of molecular hydrogen. Two homologous nickel-iron hydrogenases, HupSL and HydSL from the photosynthetic purple sulfur bacterium Thiocapsa roseopersicina, differ substantially in their thermal stabilities despite the high sequence similarity between them. The optimum temperature of HydSL activity is estimated to be at least 50 degrees C higher than that of HupSL. In this work, homology models of both proteins were constructed and analyzed for a number of structural properties. The comparison of the models reveals that the higher stability of HydSL can be attributed to increased inter-subunit electrostatic interactions: the homology models reliably predict that HydSL contains at least five more inter-subunit ion pairs than HupSL. The subunit interface of HydSL is more polar than that of HupSL, and it contains a few extra inter-subunit hydrogen bonds. A more optimized cavity system and amino acid replacements resulting in increased conformational rigidity may also contribute to the higher stability of HydSL. The results are in accord with the general observation that with increasing temperature, the role of electrostatic interactions in protein stability increases. Electronic supplementary material to this paper can be obtained by using the Springer Link server located at http://dx.doi.org/10.1007/s00894-001-0071-8.


Potential role of dopamine transporter in behavioral flexibility.
Behavioral flexibility is subserved by the prefrontal cortex and the basal ganglia. Orbitofrontal cortex (OFC) and dorsomedial striatum (DMS) form a functional frontocorticostriatal circuit crucial for the mediation of flexibility during reversal learning via dopamine (DA) neurotransmission. The regulatory control in maintaining DA homeostasis and function is provided by the dopamine transporter (DAT), which therefore likely plays a significant role in controlling the influence of DA on cognitive processes. Here we used a gene knockout mouse model to investigate the role of DAT in the performance on the Attentional Set-Shifting Task (ASST) stages dependent upon the OFC and the DMS. Additionally, behavior of mice after repeated administration of selective DAT inhibitor, GBR 12909, was examined. The animals were treated with the inhibitor to elicit a compensatory DAT up-regulation following withdrawal. Learning was slower and the number of errors during reversal learning and intra-dimensional shift stages was higher in DAT+/- mutant mice than in WT mice. GBR 12909-treated mice had deficits in reversal stages of the ASST. Neuronal activation in the OFC and DMS during the ASST was examined with early growth response proteins 1 and 2 (egr-1, egr-2) immunohistochemistry. Density of egr-2 labeled cells in the OFC was lower in mutant mice than in wild-types during reversal learning and the expression of the egr-1 was lower in mutant mice in the OFC and DMS during reversal and intra-dimensional shift stages. Mice with decreased DAT levels displayed behavioral difficulties that were accompanied by a lower task-induced activation of neurons in brain regions involved in the reversal learning. Altogether, these data indicate the role of the DAT in the behavioral flexibility.


Hybrid Materials and Nanocomposites as Multifunctional Biomaterials.
This review article provides an overview of hybrid and nanocomposite materials used as biomaterials in nanomedicine, focusing on applications in controlled drug delivery, tissue engineering, biosensors and theranostic systems. Special emphasis is placed on the importance of tuning the properties of nanocomposites, which can be achieved by choosing appropriate synthetic methods and seeking synergy among different types of materials, particularly exploiting their nanoscale nature. The challenges in fabrication for the nanocomposites are highlighted by classifying them as those comprising solely inorganic phases (inorganic/inorganic hybrids), organic phases (organic/organic hybrids) and both types of phases (organic/inorganic hybrids). A variety of examples are given for applications from the recent literature, from which one may infer that significant developments for effective use of hybrid materials require a delicate balance among structure, biocompatibility, and stability.


[X-ray computed tomography in venous pathology].
After presenting the tomodensitometric semiology of venous thromboses in various territories, the authors define its indications. It is essentially in deep territories, head, chest and abdomen that the CT-Scan is used to study and diagnose unrecognized thromboses as well as determine the venous repercussion of various neighboring ailments. The respective place of the CT-Scan, ultrasonography and various phlebographies is analyzed.


CORAL Software: Analysis of Impacts of Pharmaceutical Agents Upon Metabolism via the Optimal Descriptors.
The CORAL software has been developed as a tool to build up quantitative structure- activity relationships (QSAR) for various endpoints. The task of the present work was to estimate and to compare QSAR models for biochemical activity of various therapeutic agents, which are built up by the CORAL software. The Monte Carlo technique gives possibility to build up predictive model of an endpoint by means of selection of so-called correlation weights of various molecular features extracted from simplified molecular input-line entry system (SMILES). Descriptors calculated with these weights are basis for building up correlations "structure - endpoint". Optimal descriptors, which are aimed to predict values of endpoints with apparent influence upon metabolism are crytically compared in aspect of their robustness and heuristic potential. Arguments which are confirming the necessity of reformulation of basics of QSARs are listed: (i) each QSAR model is stochastic experiment. The result of this experiment is defined by distribution into the training set and validation set; (ii) predictive potential of a model should be checked up with a group of different splits; and (iii) only model stochastically stable for a group of splits can be estimated as a reliable tool for the prediction. Examples of the improvement of the models previously suggested are demonstrated. The current version of the CORAL software remains a convenient tool to build up predictive models. The Monte Carlo technique involved for the software confirms the principle "QSAR is a random event" is important paradigm for the QSPR/QSAR analyses.


The association between maternal perfluoroalkyl substances exposure and early attention deficit hyperactivity disorder in children: a systematic review and meta-analysis.
Some studies have shown that maternal exposure to perfluoroalkyl substances (PFASs) may be associated with early attention deficit hyperactivity disorder (ADHD) in children. The purpose of this systematic review and meta-analysis is to verify this association by reviewing existing studies and to provide a strong basis for preventing ADHD. The researchers searched electronic databases such as PubMed, Science Direct, Scopus, Google Scholar, Web of Science, and Embase for all studies published before October 2020. Finally, we included nine articles for analysis. Our meta-analysis showed that maternal exposure to PFASs was not significantly associated with the prevalence rate of early childhood ADHD (perfluorooctanoic acid (PFOA), odds ratio (OR) = 1.00, 95% confidence interval (95% CI) = 0.75-1.25; perfluorooctane sulfonate (PFOS), OR = 1.01, 95% CI = 0.88-1.14; perfluorohexane sulfonate (PFHxS), OR = 1.08, 95% CI = 0.80-1.09; perfluorononanoic acid (PFNA), OR = 1.13, 95% CI = 0.99-1.28; perfluorodecanoic acid (PFDA), OR = 1.23, 95% CI = 0.15-2.32). Due to significant heterogeneity, we subsequently performed subgroup analysis and sensitivity analysis. Through subgroup analysis, we found that PFOS concentration of children's blood and the prevalence rate of early childhood ADHD were statistically positively correlated, and there was also a positive correlation between PFOS exposure and the prevalence rate of early childhood ADHD in the America. Moreover, there was also a statistically positive correlation between PFNA concentration in maternal blood and the prevalence rate of early childhood ADHD. Sensitivity analysis showed that the final results did not change much, the sensitivity was low, and the results were relatively stable. In conclusion, a causal relationship between maternal PFASs exposure and ADHD in children was unlikely. Among them, PFOS, PFNA, and ADHD might have positive associations worthy of further investigation.


C-reactive protein and procalcitonin profile in ventilator-associated lower respiratory infections.
Ventilator-associated tracheobronchitis (VAT) has been suggested as an intermediate process between tracheobronchial colonization and ventilator-associated pneumonia (VAP) in patients receiving mechanical ventilation. The aim of this study was to evaluate the ability of C-reactive protein (CRP) and procalcitonin (PCT) to differentiate between VAT and VAP. Pre-planned analysis of the prospective multinational TAVeM database, performed on 2960 patients receiving mechanical ventilation for >48 h, including 689 patients with VA-LRTI. Patients with the diagnosis of VAT or VAP microbiologically documented and with one measurement of CRP and/or PCT on the day of diagnosis were included. Four hundred and four patients (mean age 63 years, 298 men, ICU mortality 40%) were studied, 207 with VAT and 197 with VAP. On the day of infection diagnosis, the median CRP was elevated in both groups but significantly higher in VAP (18 mg/dL vs. 14 mg/dL, p = .001). Median PCT was also significantly higher in VAP (2.1 ng/dL vs. 0.64 ng/d L, p < .001). Both biomarkers could not help distinguish between VAT and VAP. Although PCT and CRP presented lower values in VAT as compared to VAP, there was a marked overlap of both biomarkers values in both VA-LRTI not allowing adequate discrimination.


Differential responsiveness of RVLM sympathetic premotor neurons to hypoxia in rabbits.
To determine whether differential sympathetic nerve responses to hypoxia are explained by opposing effects of hypoxia upon sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM), the cardiac sympathetic nerve and the renal sympathetic nerve were recorded in anesthetized and vagotomized rabbits. Renal sympathetic nerve was activated by the injection of sodium cyanide solution close to the bifurcation of the common carotid artery and/or by inhalation of hypoxic gas (3% oxygen-97% nitrogen). On the other hand, cardiac sympathetic nerve was inhibited by these stimuli. Barosensitive (inhibited by the stimulation of baroreceptor afferents) reticulospinal (antidromically activated by the stimulation of the spinal cord) neurons in the RVLM were divided into three groups according to their responses to hypoxic stimulation: neurons (Type I, n = 25), the activity of which was inhibited by the injection of sodium cyanide solution close to the bifurcation of the common carotid artery and/or by inhalation of hypoxic gas, neurons (Type II, n = 99), the activity of which was facilitated by the same stimulation, and neurons (Type III, n = 11), the activity of which was not changed. These data indicated that the differential responses of cardiac and renal sympathetic nerves might be due to opposing effects of hypoxia on individual RVLM neurons.


Secretion of gastrin and calcitonin after ingestion of meat extract in patients with peptic ulcer.
Serum gastrin and calcitonin were determined after administration of meat extract to patients with peptic ulcer in order to investigate what role gastrin and calcitionin are playing in peptic ulcer. Serum gastrin levels were elevated after ingestion of meat extract in 9 out of 11 patients with peptic ulcer. Serum calcitonin (CT) levels were elevated rather gradually in 7 subjects. It was suggested that increased endogenous gastrin levels may have stimulated the release of CT. When salmon calcitonin (SCT) was admininstered intravenously at a dose of 100 MRCu before administration of meat extract, the rise of gastrin and CT was suppressed in 67% of cases as to gastrin and in 43% as to CT.


Computerized microassay of keratinocyte cell-plastic attachment and proliferation for assessing net stimulatory, inhibitory and toxic effects of compounds on nonimmortalized cell lines.
Testing of pharmacological agents that affect growth of epidermal keratinocytes (EK) requires a standardized assay. We have developed an assay measuring net effects of stimulatory (e.g. growth factors), inhibitory (e.g. methotrexate) or toxic (e.g. Triton X-100) compounds. The amount of crystal violet staining viable EK attached to the wells of standard 96-well microplates is measured in situ using an ELISA plate reader. Optical density readings are directly converted into cell counts by computer software. Counts obtained by this method strongly correlate with the results obtained using the [3H]thymidine uptake assay and direct cell counts. The assay standardizes measurements of nonimmortalized EK lines with different innate proliferative properties and allows accurate quantitation of EK numbers in the range of 2,500-500,000 EK/well.


Aerobic plate counts as a measure of hazard analysis critical control point effectiveness in a pork processing plant.
A hazard analysis critical control point (HACCP) system was designed to identify specific hazards so that preventive and control measures to ensure the safety of a food could be implemented. Microbiological data generated through sampling were used to characterize the hygienic performance and to validate and verify the various HACCP plans. Aerobic plate counts (APCs) often are chosen as an indicator of the effectiveness of HACCP plans, because data for all aerobic bacteria are more easily collected than are data for pathogens of concern or other indicator organisms. However, it is not clear whether APCs are useful in verifying that a HACCP plan is working satisfactorily. In this study, APC data were collected from one pork-cutting plant in Korea both before and after the company initiated its HACCP plan. These APC data were used to compare microbiological differences and to determine the effect of any changes before and after implementing the HACCP plan. For this pork plant, after the HACCP plan was implemented the proportion of samples exceeding the 3 log CFU/cm2 limit dropped from 73.39 to 4.29% for the overall process. These results indicate that this plant improved its hygienic performance considerably and that the HACCP plan was an effective and valuable tool for achieving this improvement. The APC data were sufficient for validation and verification of the HACCP system that was successfully implemented to improve hygienic performance.


Patterns of functional vision loss in glaucoma determined with archetypal analysis.
Glaucoma is an optic neuropathy accompanied by vision loss which can be mapped by visual field (VF) testing revealing characteristic patterns related to the retinal nerve fibre layer anatomy. While detailed knowledge about these patterns is important to understand the anatomic and genetic aspects of glaucoma, current classification schemes are typically predominantly derived qualitatively. Here, we classify glaucomatous vision loss quantitatively by statistically learning prototypical patterns on the convex hull of the data space. In contrast to component-based approaches, this method emphasizes distinct aspects of the data and provides patterns that are easier to interpret for clinicians. Based on 13 231 reliable Humphrey VFs from a large clinical glaucoma practice, we identify an optimal solution with 17 glaucomatous vision loss prototypes which fit well with previously described qualitative patterns from a large clinical study. We illustrate relations of our patterns to retinal structure by a previously developed mathematical model. In contrast to the qualitative clinical approaches, our results can serve as a framework to quantify the various subtypes of glaucomatous visual field loss.


Rheumatologic services in Central Asian countries: current state of development of rheumatology in Central Asia.
Rheumatologic and public health services of Central Asia's republics have suffered hugely as a result of social and economic declines following the dissolution of the Union of Soviet Socialist Republics (USSR) and transition of these republics to market economies. Between 1990 and 2000 there was a mass outflow of highly skilled rheumatologists and teachers and researchers in rheumatology to countries abroad, leading to significant deprivation of rheumatological service in Central Asian countries. During this time, there was continued growth of various rheumatic diseases (RDs) including rheumatic fever, and musculoskeletal and connective tissue disorders. The medical and social burden of RDs imposed on society was strongly underestimated until recent times. There is an urgent need to define the epidemiology of RDs and their impact on the quality of life of people afflicted by these conditions, and to improve the diagnostics and treatment of these conditions.


A Slow- Compared with a Fast-Release Form of Oral Arginine Increases Its Utilization for Nitric Oxide Synthesis in Overweight Adults with Cardiometabolic Risk Factors in a Randomized Controlled Study.
Oral l-arginine supplements can have a beneficial effect on nitric oxide (NO)-related functions when subjects have cardiovascular disease risk factors. The study was designed to determine the utilization for NO synthesis of oral l-arginine as a function of the cardiometabolic risk and the speed of absorption by comparing immediate-release arginine (IR-Arg), as in supplements, and sustained-release arginine (SR-Arg), which mimics the slow release of dietary arginine. In a randomized, single-blind, 2-period crossover, controlled trial (1 wk of treatment, >2 wk of washout), using [(15)N-(15)N-(guanidino)]-arginine for the first morning dose, we compared the bioavailability (secondary outcome) and utilization for NO synthesis (primary outcome) of 1.5 g IR- and SR-Arg 3 times/d in 12 healthy overweight [body mass index (BMI; in kg/m(2)): 25-30] adults with the hypertriglyceridemic waist phenotype [HTW; plasma triglycerides (TGs): >150 mg/dL; waist circumference: >94 cm (men) or >80 cm (women)] and 15 healthy control adults (CON; BMI: 18.5-25; no elevated TGs and waist circumference). Plasma oral arginine areas under the curve were lower after supplementation with SR-Arg than with IR-Arg (112 ± 52.3 and 142 ± 50.8 μmol ⋅ h/L; P < 0.01). The utilization of oral arginine for NO synthesis was 58% higher in HTW subjects than in CON subjects and higher with SR-Arg than with IR-Arg (P < 0.05 both), particularly in HTW subjects (group-by-treatment interaction, P < 0.05). In HTW subjects administered the SR form, utilization for NO synthesis was 32% higher than with the IR form and 87% higher than in CON subjects who were administered the SR form. In overweight adults with the HTW phenotype, a slow- compared with a fast-release form of oral arginine markedly favors the utilization of arginine for NO synthesis. The utilization of low-dose, slow-release arginine for NO synthesis is higher in overweight adults with the HTW phenotype than in healthy controls, suggesting that the sensitivity of NO synthesis to the dietary arginine supply increases with cardiometabolic risk. The trial was registered at clinicaltrials.gov as NCT02352740.


Myocardial infarction risk among patients with fractures receiving bisphosphonates.
To determine if bisphosphonates are associated with reduced risk of acute myocardial infarction (AMI). A cohort of 14,256 veterans 65 years or older with femoral or vertebral fractures was selected from national administrative databases operated by the US Department of Veterans Affairs and was derived from encounters at Veterans Affairs facilities between October 1, 1998, and September 30, 2006. The time to first AMI was assessed in relationship to bisphosphonate exposure as determined by records from the Pharmacy Benefits Management Database. Time to event analysis was performed using multivariate Cox proportional hazards regression. An adjusted survival analysis curve and a Kaplan-Meier survival curve were analyzed. After controlling for atherosclerotic cardiovascular disease risk factors and medications, bisphosphonate use was associated with an increased risk of incident AMI (hazard ratio, 1.38; 95% CI, 1.08-1.77; P=.01). The timing of AMI correlated closely with the timing of bisphosphonate therapy initiation. Our observations in this study conflict with our hypothesis that bisphosphonates have antiatherogenic effects. These findings may alter the risk-benefit ratio of bisphosphonate use for treatment of osteoporosis, especially in elderly men. However, further analysis and confirmation of these findings by prospective clinical trials is required.


Force and kinetic barriers to initiation of DNA unzipping.
A semimicroscopic model of the binding of the two nucleotide strands in a double-stranded DNA is used to describe the effects of applied tension on strand unpairing. We show that the model describes strand separation by elevated temperature, applied torque, and applied force. In particular, we show how the interactions responsible for stabilizing the double helix against thermal denaturation determine the approximately 12 pN force threshold for DNA strand separation. The larger rigidity of the strands when formed into double-stranded DNA, relative to that of isolated strands, gives rise to a potential barrier to unzipping. We show that this barrier results in a approximately 250 pN force barrier opposing the beginning of strand separation. The thermal-fluctuation-assisted "tunnelling" through the barrier is then analyzed using instanton calculations. The resulting kinetics of unzipping initiation is shown to be consistent with solution-phase strand dissociation experiments, and can explain results of two recent unzipping experiments done using atomic-force microscopy.


[Knowledge and opinions concerning legal and ethical issues with abortion among physicians working in emergency wards in Ribeirão Preto, São Paulo, Brazil].
This study focused on the knowledge and opinions of physicians regarding legal and ethical aspects of abortion. A self-administered questionnaire was filled out by 57 physicians working in the emergency rooms of two hospitals in Ribeirão Preto, São Paulo State, Brazil in 2001. The questionnaire had 38 questions on general knowledge, legislation, and attitudes towards abortion. Interviewees' mean age was 28.3, most were females, 52.6% were single, 42.1% were married, 54.4% were Catholic, and 21% were Spiritists. Although most of the physicians had a good level of overall knowledge on abortion (70%), one in five was not aware that abortion is the main cause of maternal mortality in Brazil. Most accepted the prevailing legal conditions for performing an abortion in Brazil but would also include fetal malformation incompatible with life, while opposing decriminalization of abortion on other grounds. Limited knowledge is revealed by misconceptions concerning enforcement of the prevailing legislation in practice. The study strongly suggests that many physicians lack knowledge or face difficulties in conforming to the Brazilian legislation on abortion.


Bombesin analogue-mediated delivery preferentially enhances the cytotoxicity of a mitochondria-disrupting peptide in tumor cells.
Tumor-homing peptides that recognize specific markers on tumor cells have shown potential as drug carriers for targeted cancer therapy. Bombesin receptors are frequently overexpressed or ectopically expressed in a wide range of human tumors. Bombesin and its analogues have been widely used as drug carriers for tumor imaging and tumor therapy. However, the cargos used in previous studies, including radioactive and chemotherapeutic agents, are usually small molecules. Mitochondrial-disrupting peptides depolarize the mitochondria and trigger apoptosis after entering tumor cells. We are interested in whether the bombesin analogue, Bn(6-14), which contains a bombesin receptor-binding motif, can specifically deliver the mitochondria-disrupting peptide, B28, to tumor cells. To this end, we created a chimeric peptide, B28Bn(6-14), by conjugating B28 to Bn(6-14) at its N-terminus. The cytotoxicity of B28Bn(6-14) in tumor cells was much stronger than unconjugated B28. The IC50 values of B28Bn(6-14) in tumor cells (1.7-3.5 µM) were approximately 10 times lower than B28. However, conjugation of B28 to Bn(2-7), which lacks the bombesin receptor-binding motif, did not increase its cytotoxicity. In addition, the IC50 values of B28Bn(6-14) in tumor cells (1.7-3.5 µM) was 3-10 times lower than in normal cells (10.8-16.8 µM). We found that selective binding of B28Bn(6-14) to tumor cells is Bn(6-14)-dependent. Upon entering the tumor cell, B28Bn(6-14) accumulated in the mitochondria and triggered caspase-dependent apoptosis. Intratumoral and intraperitoneal administration of B28Bn(6-14) substantially suppressed the growth of DU145 tumor xenografts in mice. These results demonstrate that Bn(6-14) is able to deliver the mitochondria-disrupting peptide to tumor cells, and B28Bn(6-14) should be further developed as novel anti-cancer agent.


Structure of protein solutions. Part 2. Solutions of total protein of yeast Saccharomyces cerevisiae.
Water systems formed by total protein of yeast Saccharomyces cerevisiae and model systems on the basis of unfractionated casein were studied by viscosimetry and electron microscopy. Methodologically, both methods offered a possibility of distinguishing several quantitatively different concentration intervals in protein solutions under different conditions. Viscosimetry gave the most informative results at the concentration intervals where the solutions approached the true ones, while electron microscopy did so when supermolecular formations prevailed. In comparing the data obtained by these two methods the following conclusions were drawn: At low temperatures (4-10 degrees C) yeast protein was in molecular-dissociated condition. Association in the system starts at 10 degrees C, and becomes enhanced with a rise in temperature. A temperature rise to 25-30 degrees C promotes a more compact packing of polypeptide chains; further heating leads to high-temperature denaturation. Lipids induce covering of polypeptide chains and prevent associations, thus leading to an increase in the system's thermostability.


Analyzing protein folding cooperativity by differential scanning calorimetry and NMR spectroscopy.
Some marginally stable proteins undergo microsecond time scale folding reactions that involve significant populations of partly ordered forms, making it difficult to discern individual steps in their folding pathways. It has been suggested that many of these proteins fold non-cooperatively, with no significant barriers to separate the energy landscape into distinct thermodynamic states. Here we present an approach for studying the cooperativity of rapid protein folding with a combination of differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR) relaxation dispersion experiments, and an analysis of the temperature dependence of amide (1)H and (15)N chemical shifts. We applied this method to the PBX homeodomain (PBX-HD), which folds on the microsecond time scale and produces a broad DSC thermogram with an elevated and steeply sloping native-state heat capacity baseline, making it a candidate for barrierless folding. However, by globally fitting the NMR thermal melt and DSC data, and by comparing these results to those obtained from the NMR relaxation dispersion experiments, we show that the native form of the protein undergoes two-state exchange with a small population of the thermally denatured form, well below the melting temperature. This result directly demonstrates the coexistence of distinct folded and unfolded forms and firmly establishes that folding of PBX-HD is cooperative. Further, we see evidence of large-scale structural and dynamical changes within the native state by NMR, which helps to explain the broad and shallow DSC profile. This study illustrates the potential of combining calorimetry with NMR dynamics experiments to dissect mechanisms of protein folding.


Postural Heart Rate Changes in Young Patients With Vasovagal Syncope.
Recurrent postural vasovagal syncope (VVS) is caused by transient cerebral hypoperfusion from episodic hypotension and bradycardia; diagnosis is made by medical history. VVS contrasts with postural tachycardia syndrome (POTS), defined by chronic daily symptoms of orthostatic intolerance with excessive upright tachycardia without hypotension. POTS has recently been conflated with VVS when excessive tachycardia is succeeded by hypotension during tilt testing. We hypothesize that excessive tachycardia preceding hypotension and bradycardia is part of the vasovagal response during tilt testing of patients with VVS. We prospectively performed head-up tilt (HUT) testing on patients with recurrent VVS (n = 47, 17.9 ± 1.1 y), who fainted at least 3 times within the last year, and control subjects (n = 15, 17.1 ± 1.0 y), from age and BMI-matched volunteers and measured blood pressure, heart rate (HR), cardiac output, total peripheral resistance, and end tidal carbon dioxide. Baseline parameters were the same in both groups. HR (supine versus 5 and 10 minutes HUT) significantly increased in control (65 ± 2.6 vs 83 ± 3.6 vs 85 ± 3.7, P < .001) and patients with VVS (69 ± 1.6 vs 103 ± 2.3 vs 109 ± 2.4, P < .001). HUT in controls maximally increased HR by 20.3 ± 2.9 beats per minute; the increase in patients with VVS of 39.8 ± 2.1 beats per minute was significantly greater (P < .001). An increase in HR of ≥40 beats per minute by 5 and 10 minutes or before faint with HUT, occurred in 26% and 44% of patients with VVS, respectively, but not in controls. Orthostasis in VVS is accompanied by large increases in HR that should not be construed as POTS.


Covid-19 vaccine acceptance and associated factors among pregnant women in Pennsylvania 2020.
Data on factors associated with vaccine acceptance among pregnant women are critical to the rapid scale up of interventions to improve vaccine uptake. When COVID-19 vaccines were still in the testing phases of research, we surveyed pregnant women accessing prenatal care at an academic medical institution in Central Pennsylvania, United States to examine factors associated with vaccine acceptance. Willingness to receive a COVID-19 vaccine once a vaccine became available was asked as part of an ongoing study on the COVID-19 pandemic and pregnancy (n = 196). Overall, 65% of women reported they would be willing or somewhat willing to receive the COVID-19 vaccine. Women who had received an influenza vaccine within the past year were more likely to be willing to receive the COVID-19 vaccine than women who had never received an influenza vaccine or those who received it over one year ago (aOR 4.82; 95% CI 2.17, 10.72). Similarly, women who were employed full-time were more willing to receive the COVID-19 vaccine than women who were not employed full time (aOR 2.22; 95% CI 1.02, 4.81), and women who reported feeling overloaded were more willing to receive the COVID-19 vaccine than women who did not feel overloaded (aOR 2.18; 95% CI 1.02, 4.68). Our findings support the need to increase vaccination education among pregnant women before vaccines are rolled out, especially those who have not received an influenza vaccine within the past year. Improved understanding of willingness to vaccinate among pregnant women will improve future pandemic responses and current vaccination efforts.


Gene × Environment Determinants of Stress- and Anxiety-Related Disorders.
The burgeoning field of gene-by-environment (G×E) interactions has revealed fascinating biological insights, particularly in the realm of stress-, anxiety-, and depression-related disorders. In this review we present an integrated view of the study of G×E interactions in stress and anxiety disorders, including the evolution of genetic association studies from genetic epidemiology to contemporary large-scale genome-wide association studies and G×E studies. We convey the importance of consortia efforts and collaboration to gain the large sample sizes needed to move the field forward. Finally, we discuss several robust and well-reproduced G×E interactions and demonstrate how epidemiological identification of G×E interactions has naturally led to a plethora of basic research elucidating the mechanisms of high-impact genetic variants.


Chlorophyll thermoluminescence of leaf discs: simple instruments and progress in signal interpretation open the way to new ecophysiological indicators.
Luminescence from photosynthetic material observed in darkness following illumination is a delayed fluorescence produced by a recombination of charge pairs stored in photosystem II, i.e. the back-reaction of photosynthetic charge separation. Thermoluminescence (TL) is a technique consisting of a rapid cooling followed by the progressive warming of a preilluminated sample to reveal the different types of charge pairs as successive emission bands, which are resolved better than the corresponding decay phases recorded at constant temperatures. Progress in thermoelectric Peltier elements and in compact light detectors made the development of simple, affordable and transportable instruments possible. These instruments take advantage of multifurcated light guides for combined TL, fluorescence and absorbance/reflectance measurements. Meanwhile, experiments on unfrozen leaf discs, with excitation by single turn-over flashes or far red light and infiltration by specific inhibitors/uncouplers, have led to a better understanding of in vivo TL signals. Much like chlorophyll fluorescence and in a complementary way, TL in the 0-60 degrees C temperature range not only informs on the state of photosystem II in leaf tissues and its possible alterations, but also gives a broader insight into the energetic state inside the chloroplast by probing (1) the light-induced or dark-stable thylakoid proton gradient through the protonation of the Mn oxygen-evolving complex, (2) the induction of cyclic/chlororespiratory electron flow towards the plastoquinone pool, (3) the [NADPH+ATP] assimilatory potential. By a different mechanism, warming above 60 degrees C without preillumination reveals chemiluminescence high temperature thermoluminescence (HTL) bands due to the radiative thermolysis of peroxides, which are indicators of oxidative stress in leaves.


Norman Cousins Lecture. Glia as the "bad guys": implications for improving clinical pain control and the clinical utility of opioids.
Within the past decade, there has been increasing recognition that glia are far more than simply "housekeepers" for neurons. This review explores two recently recognized roles of glia (microglia and astrocytes) in: (a) creating and maintaining enhanced pain states such as neuropathic pain, and (b) compromising the efficacy of morphine and other opioids for pain control. While glia have little-to-no role in pain under basal conditions, pain is amplified when glia become activated, inducing the release of proinflammatory products, especially proinflammatory cytokines. How glia are triggered to become activated is a key issue, and appears to involve a number of neuron-to-glia signals including neuronal chemokines, neurotransmitters, and substances released by damaged, dying and dead neurons. In addition, glia become increasingly activated in response to repeated administration of opioids. Products of activated glia increase neuronal excitability via numerous mechanisms, including direct receptor-mediated actions, upregulation of excitatory amino acid receptor function, downregulation of GABA receptor function, and so on. These downstream effects of glial activation amplify pain, suppress acute opioid analgesia, contribute to the apparent loss of opioid analgesia upon repeated opioid administration (tolerance), and contribute to the development of opioid dependence. The potential implications of such glial regulation of pain and opioid actions are vast, suggestive that targeting glia and their proinflammatory products may provide a novel and effective therapy for controlling clinical pain syndromes and increasing the clinical utility of analgesic drugs.


Hernia of the bladder through the broad ligament with renal agenesis and ipsilateral ureter blind ending.
Hernia through a defect of the broad ligament is extremely rare in children. These defects can result from a developmental defect or a spontaneous rupture of cystic formations remnants of mesonephric ducts or Müller. Genital anomalies associated with unilateral renal agenesis are more common in females. We report the case of a 13 months girl allowed for assessment of recurrent urinary tract infection; abdominal examination did not objectified palpable mass, the external genitalia were without abnormalities. Abdominal ultrasound revealed a left renal space is empty with a retrovesical cyst. Cystography was requested that objectified a large pelvic cystic mass retrovesical communicating with the bladder, there was also a left vesicoureteral reflux. Uro- MRI showed a cystic formation retrovesical communicating with the bladder, the right pelvic kidney; uterus is normal size for age. DMSA scintigraphy confirmed the absence of the left kidney with the right kidney that ensures 100% of total renal function. To surgical exploration we found a hernia of the bladder through the left broad ligament, the uterus was dislocated on the right side; left ovary was hypoplasic; the ipsilateral ureter was blind with renal agenesis, we performed by reduction of the bladder then closing the hernial orifice, dissection of the ureter with its ligation and section at the vesical stoma. The postoperative course was uneventful. Evolution is favorable. This observation illustrates a hernia of the bladder through the broad ligament associated with ovarian hypoplasia, renal agenesis and ipsilateral ureter blind ending; this association was not described to our knowledge in the literature.


[Lung cancer occurring in a left upper division which is mirror imaged to a right upper lobe].
A 55-year-old man was admitted to our hospital because of an abnormal shadow in the left upper division on chest computed tomography(CT). Virtual bronchoscopy revealed a displaced anomalous bronchus. Thin sliced CT revealed complete lobulation between the upper division and the lingula. Three dimensional (3D)-CT revealed abnormal distribution of the left pulmonary artery which descended without passing over the left main bronchus. The left upper division was evaluated to be mirror imaged to a right upper lobe. Video assisted thoracoscopic left upper divisionectomy was performed. The tumor was diagnosed as adenocarcinoma( pT1aN0M0:p-stage I A).


Inducing resistance to the misinformation effect by means of reinforced self-affirmation: The importance of positive feedback.
The misinformation effect is one of the major threats for the quality of witness testimony. It involves including of information that is inconsistent with the course of an event, and which originates from sources other than the event itself, into a witness's report of the event. In the present article research is presented aiming at reducing the tendency to rely on misinformation. After viewing a video clip, participants received a post-event narrative describing the events in the film which in the misled group included some incorrect information about the clip. They were then administered reinforced self-affirmation (RSA), a technique aiming at boosting self-confidence in order to increase the tendency to rely on own memory instead of external cues. This technique consists of self-affirmation by means of writing down one's greatest achievements in life and manipulated positive feedback. Feedback about memory, perception and independence of judgements was analyzed. All types of feedback effectively reduced the misinformation effect. Mediation analyzes confirmed that RSA operates via increased self-confidence or self-independence.


Early use of daptomycin versus vancomycin for methicillin-resistant Staphylococcus aureus bacteremia with vancomycin minimum inhibitory concentration >1 mg/L: a matched cohort study.
Recent reports have described decreased effectiveness with vancomycin treatment for methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) when the vancomycin minimum inhibitory concentration (MIC) is >1 µg/mL. This matched, retrospective cohort study compared the clinical effectiveness of daptomycin with that of vancomycin for the treatment of MRSAB with vancomycin MICs >1 µg/mL. The primary outcome was clinical failure, defined as a composite of 30-day mortality or bacteremia persisting for ≥7 days. One hundred seventy patients were matched 1:1 with respect to the antimicrobial administered. In the daptomycin group, all patients received <72 hours of vancomycin (median, 1.7 days [interquartile range, 1.1-2.3 days]) prior to switching to daptomycin. The rate of clinical failure at 30 days was significantly lower in the daptomycin arm compared to the vancomycin arm (20.0% vs 48.2%; P < 0.001). Both 30-day mortality and persistent bacteremia were significantly lower in the daptomycin group compared to the vancomycin group (3.5% vs 12.9% [P = .047] and 18.8% vs 42.4% [P = .001], respectively). Logistic regression confirmed the association between vancomycin treatment and increased risk of clinical failure (adjusted odds ratio, 4.5; 95% confidence interval, 2.1-9.8). This is the first matched study comparing early daptomycin versus vancomycin for the treatment of MRSAB when the vancomycin MIC is >1 µg/mL. Treatment with daptomycin resulted in significantly improved outcomes, including decreased 30-day mortality and persistent bacteremia. These results support the practice of switching early from vancomycin to daptomycin for the treatment of MRSAB when the vancomycin MIC is >1 µg/mL.


The role and application of enterococci in food and health.
The genus Enterococcus is the most controversial group of lactic acid bacteria. Studies on the microbiota of many traditional cheeses in the Mediterranean countries have indicated that enterococci play an important role in the ripening of these cheeses, probably through proteolysis, lipolysis, and citrate breakdown, hence contributing to their typical taste and flavour. Enterococci are also present in other fermented foods, such as sausages and olives. However, their role in these products has not been fully elucidated. Furthermore, the production of bacteriocins by enterococci is well documented. Moreover, enterococci are nowadays used as probiotics. At the same time, however, enterococci have been associated with a number of human infections. Several virulence factors have been described and the number of vancomycin-resistant enterococci is increasing. The controversial nature of enterococci has prompted an enormous increase in scientific papers and reviews in recent years, where researchers have been divided into two groups, namely pro and contra enterococci. To the authors' impression, the negative traits have been focused on very extensively. The aim of the present review is to give a balanced overview of both beneficial and virulence features of this divisive group of microorganisms, because it is only acquaintance with both sides that may allow their safe exploitation as starter cultures or co-cultures.


Pharmacokinetics of intraperitoneal cisplatin and doxorubicin.
Intraperitoneal chemotherapy, mainly when performed during HIIC after cytoreductive surgery, is considered potentially curative for the treatment of solid tumors with spread to the peritoneal surface. When selecting antiblastic agents to be administered intraperitoneally, it is important to bear in mind that a low lipophility and a high molecular weight are the ideal drug characteristics. Drugs with these features allow a favorable ratio to be achieved between peritoneal and plasma concentrations, due to the reduced tendency to diffuse through the plasma-peritoneal barrier, even after extensive removal of the peritoneum. Moreover, a low rate of diffusion through the tumor capillaries implies a low rate of drug clearance, with a higher intratumoral drug accumulation. Among the drugs used so far for intraperitoneal chemotherapy, the combination of CDDP and DXR appears to be one of the most effective available regimens with acceptable local-regional toxicity. CDDP has also been extensively employed as a single agent for ovarian and gastrointestinal cancers, under both normal and hyperthermic conditions, while intraperitoneally administered DXR appears to be of greater potential efficacy when associated with CDDP and hyperthermia (41.5 degrees C) following cytoreductive surgery. In our clinical experience with this drug combination, DXR showed a much more advantageous plasma/peritoneal AUC ratio than CDDP (162 +/- 113 and 20 +/- 6, respectively). On the other hand, it has been demonstrated that very high intraperitoneal concentrations of CDDP can be achieved without incurring significant systemic toxicity by using intravenous injection of sodium thiosulphate during HIIC. Penetration of the tumor mass by CDDP is greater than DXR. This phenomenon is enhanced by hyperthermia and by hypotonic solutions of sodium chloride used as the perfusate. Following experimental and clinical results of TNF alpha-based isolated limb perfusion for locally advanced soft tissue sarcoma or melanoma, greater efforts are being made to exploit the potential effect of this cytokine used in association with hyperthermia and other drugs (i.e., CDDP and DXR) suitable for intraperitoneal infusion/perfusion. However, it is not yet clear whether the observed effect of TNF alpha on the peritoneal-plasma barrier, which seems to favor the passage of both drugs into the systemic circulation, is overcome by the positive effect of this agent on drug penetration into tumor. Further pharmacologic studies should be undertaken to clarify whether or not these interactions will be of benefit to the patient. Likewise, liposomes, which in animal models seem to favor tumor uptake of encapsulated DXR, should now be tested in the clinical setting.


Development and clinical validation of inertial sensor-based gait-clustering methods in Parkinson's disease.
Gait symptoms and balance impairment are characteristic indicators for the progression in Parkinson's disease (PD). Current gait assessments mostly focus on straight strides with assumed constant velocity, while acceleration/deceleration and turning strides are often ignored. This is either due to the set up of typical clinical assessments or technical limitations in capture volume. Wearable inertial measurement units are a promising and unobtrusive technology to overcome these limitations. Other gait phases such as initiation, termination, transitioning (between straight walking and turning) and turning might be relevant as well for the evaluation of gait and balance impairments in PD. In a cohort of 119 PD patients, we applied unsupervised algorithms to find different gait clusters which potentially include the clinically relevant information from distinct gait phases in the standardized 4x10 m gait test. To clinically validate our approach, we determined the discriminative power in each gait cluster to classify between impaired and unimpaired PD patients and compared it to baseline (analyzing all straight strides). As a main result, analyzing only one of the gait clusters constant, non-constant or turning led in each case to a better classification performance in comparison to the baseline (increase of area under the curve (AUC) up to 19% relative to baseline). Furthermore, gait parameters (for turning, constant and non-constant gait) that best predict motor impairment in PD were identified. We conclude that a more detailed analysis in terms of different gait clusters of standardized gait tests such as the 4x10 m walk may give more insights about the clinically relevant motor impairment in PD patients.


Identification of fatty acids and aliphatic hydrocarbons in Sarcina lutea by gas chromatography and combined gas chromatography-mass spectrometry.
The composition and nature of the fatty acids and hydrocarbons of Sarcina lutea were elucidated by gas chromatography and by combined gas chromatography-mass spectrometry. The distribution of fatty acids found in S. lutea showed two families of pairs, or dyads, of saturated monocarboxylic acids (C12-C18) with and without methyl branching. These pairs of fatty acids showed a pattern of iso and anteiso structures for C13, C15, and C17, and iso and normal structures for C12, C14, and C16. Only the C18 showed unsaturation. The distribution of hydrocarbons in the range C22-C29 showed two families of tetrads of unsaturated aliphatic hydrocarbons all showing methyl branching. Each tetrad was composed of four isomers identified as two iso olefins and two anteiso olefins. The only difference between the tetrads pertaining to different families was found in the relative gas chromatographic retention times of the last two components of each group.


Association Of Serum Testosterone And Sex Hormone Binding Globulin Levels In Females With Acne Based On Its Severity.
Androgens are involved in the development of acne. The aim of this study was to find out if there was an association of serum testosterone and sex hormone binding globulin (SHBG) in females with acne based on its severity. It was a cross sectional study, conducted in Dermatology unit of Fauji Foundation Hospital (FFH), Rawalpindi. Duration of study was eight months. Adult females with acne were enrolled in the study. Patients were categorized into minor, mild, moderate groups. Blood samples were taken for serum testosterone and SHBG. Five hundred and thirty-one adult female were enrolled into the study. The mean age was 21.49±4.73 years. Acne was graded as minor in 78 (14.7%) cases, mild in 248 (46.7%) and moderate in 205 (38.6%). There was no statistically significant relationship between the levels of serum testosterone (p=0.776) and SHBG (p=0.711) with acne severity. There was no association of serum testosterone and sex hormone binding globulin levels in females with acne based on its severity.


Microglial P2X₇ receptor in the hypothalamic paraventricular nuclei contributes to sympathoexcitatory responses in acute myocardial infarction rat.
Several pieces of evidence indicate that the microglial P2X7 receptor (P2X7R) regulate cardiovascular activities. We explored the possible roles of microglial P2X7R in the PVN mediated sympathoexcitatory responses in acute myocardial infarction (AMI) rat. Sprague-Dawley rats underwent coronary artery ligation to induce AMI. The rats received intraperitoneal administration of the P2X7R antagonist Brilliant Blue-G (BBG, 25 or 50 mg kg(-1), once a day for 5 days) prior to myocardial ischemia. Other rats received bilateral microinjection of P2X7R-siRNA (0.015 or 0.03 nmol 0.1μl per side, once a day for 2 days) targeting P2X7R mRNA into the PVN prior to myocardial ischemia. First, we examined the ATP levels and protein expression P2X7R in the PVN in different ischemia time groups, and we found that the change of P2X7R was positive correlated with the ATP levels in a time-dependent manner. The double-immunofluorescence evidence showed that P2X7R was mainly co-localizated with the microglial marker Iba-1 in the PVN. Second, gene knockdown of P2X7R with P2X7-siRNA or inhibition of P2X7R with BBG reduce the mRNA and protein expression of IL-1β and TNF-α in the PVN of AMI rat. Third, microinjected P2X7-siRNA also suppressed the up-regulation of P2X7R, oxytocin and vasopressin in the PVN of AMI rats. Fourth, P2X7-siRNA and BBG also attenuated the renal sympathetic nerve activity (RSNA) in the AMI rats. Our results indicate that microglial P2X7R activation in PVN mediating the production of proinflammatory cytokines that activate oxytocinergic and vasopressinergic neuron, which augmented the RSNA in the AMI rat.


The fate of 17 beta-estradiol in the plasma of premenopausal and postmenopausal patients with cancer.
The patterns of radioactive estrogen metabolities in the plasma of patients with a variety of malignancies were determined after the injection of physiological amounts of 17 beta-estradiol-6,7-3H or of estrone-6,7-3H. The metabolites were separated and isolated from the plasma by the following procedures: a) alumina chromatography, b) modified Brown procedure, and c) gas liquid chromatography. This study showed that the conjugated state of the estrogens varied with the subjects's age. There was a dramatic decrease in the relative quantity of the plasma free estrogens which are converted to sulfates as the age of the patient increased. This change was noted just prior to menopause, suggesting that there are alterations in the conjugation of plasma estrogens which are detectable before clinical menopause.


Arthroscopy of the knee.
Arthroscopy of the knee is an essential diagnostic aid for difficult knee problems. It is safe and is indicated especially in the problem knee of adolescents, where it is most undesirable to remove a normal cartilage; in litigation cases; in the post-surgery knee problem; in planning surgical procedures; and in surgery on professional sportsmen.


Effects of antihypertensive therapy on left atrial function.
To investigate left atrial (LA) function as a reservoir, as a conduit and as a booster pump in essential hypertension (EH). LA volumes were echocardiographically measured in 28 untreated hypertensive patients and in 20 control subjects. LA makes a large contribution in left ventricular filling, especially in patients with impaired diastolic function. LA function is fundamental in left ventricular filling in hypertensive patients as hypertension results in left ventricular diastolic dysfunction. Diagnosis of EH (blood pressure > 140/90 mm Hg) was based on three repeated readings of blood pressure (BP). Patients with myocardial infarction, cardiomyopathy, valvular or congenital heart disease were excluded. Doppler diastolic early (E) and late (A) velocity of mitral inflow were measured. The following indexes were calculated: left ventricular mass index (LVMI) using the Penn convention; left ventricular stroke volume (LVSV); LA reservoir volume (LARV = LA maximal volume at mitral valve opening minus minimal volume); LA conduit volume (LACV = LVSV-LARV). Atrial systolic function was assessed by calculating the active emptying fraction (volume at onset of atrial systole minus minimal volume/volume at onset of atrial systole, the E/A ratio and the LA ejection force (0.5 rho A2 MOA, where rho = the density of blood, MOA = mitral orifice area from the parasternal short axis view). Measurements were obtained in all hypertensive patients before and after 16 weeks administration of either enalapril (10 or 20 mg) or enalapril +/- chlorthalidone (20/25 mg) once a day. After 16 weeks of treatment, BP was reduced significantly (from 172/110 to 137/86 mm Hg, P < 0.001). LVMI decreased significantly as well (from 141 to 123 g/m2) although it was higher compared to controls (94 g/m2, P < 0.001). LARV decreased significantly (from 35.4 to 29.3 cm3, P < 0.05) while LACV increased significantly (from 43.8 to 51.3 cm3, P < 0.05), LA active emptying fraction and E/A ratio did not change. LA ejection force decreased significantly (from 20.9 to 18.1 kdynes, P < 0.05) but it was greater than controls (16.7 kdynes, P < 0.01). There was a positive relationship of LVMI to LARV (P < 0.01) in controls (r = 0.77) which held true in hypertensive patients, before (r = 0.72) and after treatment (r = 0.69). There was a negative relationship of LVMI to LACV (P < 0.01) in controls (r = -0.65), and in hypertensive patients untreated (r = -0.74) and after treatment (r = -0.72). Our results showed that in hypertensive patients, LA reservoir function increases and LA conduit function decreases, while LA ejection force increases. Antihypertensive treatment with enalapril and/or thiazide, induces normalisation of the LA function in parallel to left ventricular hypertrophy regression.


Dystrophin-glycoprotein complex sequesters Yap to inhibit cardiomyocyte proliferation.
The regenerative capacity of the adult mammalian heart is limited, because of the reduced ability of cardiomyocytes to progress through mitosis. Endogenous cardiomyocytes have regenerative capacity at birth but this capacity is lost postnatally, with subsequent organ growth occurring through cardiomyocyte hypertrophy. The Hippo pathway, a conserved kinase cascade, inhibits cardiomyocyte proliferation in the developing heart to control heart size and prevents regeneration in the adult heart. The dystrophin-glycoprotein complex (DGC), a multicomponent transmembrane complex linking the actin cytoskeleton to extracellular matrix, is essential for cardiomyocyte homeostasis. DGC deficiency in humans results in muscular dystrophy, including the lethal Duchenne muscular dystrophy. Here we show that the DGC component dystroglycan 1 (Dag1) directly binds to the Hippo pathway effector Yap to inhibit cardiomyocyte proliferation in mice. The Yap-Dag1 interaction was enhanced by Hippo-induced Yap phosphorylation, revealing a connection between Hippo pathway function and the DGC. After injury, Hippo-deficient postnatal mouse hearts maintained organ size control by repairing the defect with correct dimensions, whereas postnatal hearts deficient in both Hippo and the DGC showed cardiomyocyte overproliferation at the injury site. In the hearts of mature Mdx mice (which have a point mutation in Dmd)-a model of Duchenne muscular dystrophy-Hippo deficiency protected against overload-induced heart failure.


Quantum chaos and operator fidelity metric.
We show that the recently introduced operator fidelity metric provides a natural tool to investigate the crossover to quantum chaotic behavior. This metric is an information-theoretic measure of the global stability of a unitary evolution against perturbations. We use random matrix theory arguments to conjecture that the operator fidelity metric can be used to discriminate phases with regular behavior from quantum chaotic ones. A numerical study of the onset of chaotic in the Dicke model is given in order to support the conjecture.


Carcinoma of the head of the pancreas.
Extended radical surgery might provide a survival advantage for patients with carcinoma of the head of the pancreas. Between January 1980 and December 1999, 144 patients with carcinoma of the head of the pancreas were treated in a community hospital setting, of whom 69 patients who underwent radical surgery were retrospectively reviewed. Surgical procedures included standard pancreaticoduodenectomy (27 patients), pylorus-preserving pancreaticoduodenectomy (27 patients), and total pancreatectomy (15 patients). Portal vein resection was performed for 15 patients. Retroperitoneal lymphadenectomy was performed for 35 patients. No patients received adjuvant chemotherapy or radiotherapy. The surgical resection rate was 47.9% with a surgical mortality rate of 4.3% during this period. The overall 5-year survival rate after radical surgery was 16.1% with a median survival of 12 months. Seven patients survived five years, making 16.3% of the patients available for a more than 5-year follow-up. Long-term survivors had less than two positive lymph nodes in the posterior pancreatic head. Fourteen of 15 patients undergoing portal vein resection died within 21 months. One patient having no portal vein invasion microscopically survived 27 months without recurrence. Extended radical surgery did not prolong survival for patients with carcinoma of the head of the pancreas.


Pregabalin and Radicular Pain Study (PARPS) for Cervical Spondylosis in a Multiracial Asian Population.
Pain from cervical spondylosis (CS) may result from degenerative spinal canal stenosis (cervical spondylotic myelopathy (CSM)) or lateral recesses compromise, leading to nerve root compression (cervical spondylotic radiculopathy (CSR)). Pregabalin was shown to be effective in randomized, placebo-controlled trials for post-herpetic neuralgia and diabetic neuropathy. We evaluate its efficacy in CS with underlying CSR or CSM in a prospective study comprising Asian patients for the first time. Patients with CS and CSR or CSM (clinical, MRI, or electrophysiological evidence) presenting with neuropathic pain were recruited. We excluded patients with diabetes, underlying neurological disease or who were previously on antiepileptics. Pregabalin 75 mg bd was administered for 4 weeks, after which dosage was increased to 150 mg bd for another 4 weeks if the visual analog scale (VAS) was not reduced by 50%. In addition, we monitored the short form McGill pain questionnaire (SFMPQ) at baseline, 4 weeks and 8 weeks. Mood changes were monitored using the hospital anxiety and depression score (HADS) with an identical timeline. We recruited 50 patients, of which 23 completed the trial. Of the 27 who withdrew, 12 (44%) were for somnolence. Thirteen patients' (54%) dosages remained at 75 mg and 11 patients' (46%) dosages were escalated to 150 mg bd. There were significantly reducing trends from baseline for VAS (ANOVA, F(1, 21) = 25.4, P < 0.0005), SFMPQ (sensory) (F(1, 22) = 11.2, P = 0.003), and SFMPQ (affective) (F(1, 21) = 10.9, P = 0.008). For VAS, there was significant reduction at 4 weeks (P = 0.001) and 8 weeks (P < 0.0005) compared to baseline. For SFMPQ (sensory), there was significant reduction at 4 weeks (P = 0.01) and 8 weeks (P = 0.006) in scores compared to baselines. For SFMPQ (affective), there was significant reduction at 4 weeks (P = 0.04) and 8 weeks (P = 0.008) in scores compared to baseline. No significant anxiety (F(1, 4) = 1.3, P = 0.32) or depression (F(1, 4) = 0.06, P = 0.82) changes were observed in the HADS. Pregabalin is efficacious in alleviation of pain symptoms related to CSR as a first-line single agent, evaluated by quantitative severity and other experiential scales. No significant mood changes reported in other studies were demonstrated. Somnolence was commonest adverse effect leading to high dropout rates, occurring early even at the lowest dose. The findings suggest the need for further studies of efficacy at lower dosages, particularly in the Asian population.


Benign cephalic histiocytosis.
A 2-year-old boy was seen because of an extensive asymptomatic papular eruption on the face, neck, and shoulders of 18-months' duration. A skin biopsy specimen revealed cellular infiltrates composed predominantly of histiocytes. Electron microscopy of biopsy material disclosed "comma-shaped" inclusion bodies in the cell cytoplasm, consistent with the findings described in benign cephalic histiocytosis. To the best of our knowledge, this is the first report of this clinical entity in the American literature.


New anthropometric indices or old ones: which perform better in estimating cardiovascular risks in Chinese adults.
Various anthropometric indices can be used to estimate obesity, and it is important to determine which one is the best in predicting the risk of coronary heart disease (CHD) and to define the optimal cut-off point for the best index. This cross-sectional study investigated a consecutive sample of 11,247 adults, who had lived in rural areas of China and were older than 35 years of age. Eight obesity indices, including the body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), abdominal volume index (AVI), body adiposity index (BAI), body roundness index (BRI) and a body shape index (ABSI) were investigated. The risk of CHD was evaluated by the 10-year coronary event risk (Framingham risk score). Receiver operating characteristic (ROC) curve analyses were used to evaluate the predictive ability of the obesity indices for CHD risk. Of the whole population, 3636 (32.32%) participants had a risk score higher than 10%. Those who suffered medium or high CHD risk were more likely to have higher mean anthropometric indices, except for BMI in males. In the multivariate-adjusted logistic regression, all these anthropometric measurements were statistically associated with CHD risk in males. After adjusting for all the possible confounders, these anthropometric measurements, except for ABSI, remained as independent indicators of CHD risk in females. According to the ROC analyses, ABSI provided the largest area under the curve (AUC) value in males, and BMI showed the lowest AUC value, with AUC varying from 0.52 to 0.60. WHtR and BRI provided the largest AUC value in female, and similarly, BMI showed the lowest AUC value, with AUC varying from 0.59 to 0.70. The optimal cut-off values were as follows: WHtR (females: 0.54), BRI (females: 4.21), and ABSI (males: 0.078). ABSI was the best anthropometric index for estimating CHD risk in males, and WHtR and BRI were the best indicators in females. Males should maintain an ABSI of less than 0.078, and females should maintain a WHtR of less than 0.54 or a BRI of less than 4.21.


Urticaria in children.
The etiologic factors responsible for urticaria were analyzed in 44 children seen in the Urticaria Clinic, a referral center of the Dermatology Department. Of these, 23 were girls and 21 boys. Nine (20.5%) had acute urticaria and 25 (79.5%) were diagnosed as having chronic urticaria. A definitive etiology factor was identified in 18 (40%) patients. Of these, 15 had physical urticarias; in 2 foods and in 1 drug was incriminated. Probable etiologic factors were identified in 19 (43%) patients, in 5 (11.3%) of whom more than one factor was identified. In 11 (25%) children, it was not possible to establish the cause. Our study suggests that etiologic factors of urticaria are more readily identifiable in children than in adults.


The irony of highly-effective bacterial therapy of a patient-derived orthotopic xenograft (PDOX) model of Ewing's sarcoma, which was blocked by Ewing himself 80 years ago.
William B. Coley developed bacterial therapy of cancer more than 100 years ago and had clinical success. James Ewing, a very famous cancer pathologist for whom the Ewing sarcoma is named, was Coley's boss at Memorial Hospital in New York and terminated Coley's bacterial therapy of cancer. A tumor from a patient with soft-tissue Ewing's sarcoma, who failed doxorubicin (DOX) therapy, was previously implanted in nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. In the present study, the Ewing's sarcoma PDOX was treated with tumor-targeting S. typhimurium A1-R expressing green fluorescent (GFP), alone and in combination with DOX. S. typhimurium A1-R-GFP was detected in the tumors after intratumor (i.t.) or intravenous (i.v.) injection. The combination of S. typhimurium A1-R and DOX significantly reduced tumor weight (37.8 ± 15.6 mg) compared to the untreated control (73.8 ± 10.1 mg, P < 0.01). S. typhimurium A1-R monotherapy-treated tumors tended to be smaller (50.9 ± 17.8 mg, P = 0.051). DOX monotherapy did not show efficacy (66.3 ± 26.4 mg, P = 0.82), as was the case with the patient. The PDOX model faithfully replicated the DOX resistance the Ewing's sarcoma had in the patient. S. typhimurium A1-R converted the Ewing's sarcoma from DOX resistant to sensitive. One can only wonder how bacterial therapy and immunotherapy of cancer would have developed over the past 80 years if Ewing did not stop Coley.


Treatment of herpes labialis with acyclovir. Review of three clinical trials.
Three trials with acyclovir in the treatment of recurrent herpes labialis in the same patient population are reviewed. In the first trial, oral acyclovir capsules, five times per day for five days, were shown to be of significant benefit for some parameters of cutaneous resolution in three successive episodes. Topical formulations were evaluated in two separate trials; 5 percent acyclovir in a modified aqueous cream base exhibited favorable trends, but 5 percent acyclovir in a polyethylene base was ineffective. A high dose of oral acyclovir may offer the most effective method of control of recurrent herpes labialis.


Ca2+ bursts occur around a local minimal concentration of attractant and trigger sperm chemotactic response.
Ca(2+) is known to have important roles in sperm chemotaxis, although the relationship between intracellular Ca(2+) concentration ([Ca(2+)](i)) and modulation of the swimming and chemotactic behavior of spermatozoa has not been elucidated. Using a high-speed Ca(2+) imaging system, we examined the chemotactic behavior and [Ca(2+)](i) in individual ascidian sperm cells exhibiting chemotactic responses toward sperm activating and attracting factor (SAAF), a chemoattractant released by eggs. In this study, we found that transient [Ca(2+)](i) increased in the flagellum (Ca(2+) bursts) concomitantly with a change in the swimming direction in an SAAF gradient field. During the initial phase of the Ca(2+) bursts, the flagellum of the spermatozoon exhibited highly asymmetric waveforms enabling the quick turning of the swimming path. However, the flagellum subsequently changed to symmetric beating, causing the spermatozoon to swim straight. Interestingly, during such responses, [Ca(2+)](i) remained higher than the basal level, indicating that the series of responses was not simply determined by Ca(2+) concentrations. Also, we found that Ca(2+) bursts were consistently evoked at points at which the spermatozoon attained around a temporally minimal value for a given SAAF concentration. We concluded that Ca(2+) bursts induced around a local minimal SAAF concentration trigger a sequence of flagellar responses comprising quick turning followed by straight swimming to direct spermatozoa efficiently toward eggs.


A switch of the oxidation state of graphene oxide on a surface plasmon resonance chip.
Controlling the assembly and manipulating the oxidation state of graphene nanosheets on surfaces are of essential importance for application of graphene-related optical and biosensing devices. In this study, we assemble a graphene oxide (GO) film on a surface plasmon resonance chip surface and then convert it to reduced graphene by an in situ electrochemical method. The mechanism and application of surface-enhanced Raman spectroscopy and DNA sensing from graphene-based substrates are investigated. The average thickness and dielectric constant of GO are varied significantly with the switch of its oxidation state. Electrochemical reduction decreases the distance between carbon atoms and the gold surface by removing the spacer of oxygen functional groups. The electromagnetic field of the graphene surface is therefore enhanced, resulting in an enhancement of the Raman signal. A p doping of electrochemically reduced GO (ERGO) that occurred from changes in the graphene electronic structure through interaction between gold and ERGO is also observed during electrochemical reduction. The GO and ERGO substrates perform different interaction abilities with single- and double-stranded DNA. This work may be valuable for graphene-related research works on optoelectronics and biosensors.


An initial explanatory model of a medical students' preferences for patient types.
Previous studies suggest that medical students and doctors may express a range of positive and negative attitudes and behaviours towards patients. As an initial attempt to understand how attitudes toward patients are formed, first-year medical students were asked to describe their feelings about six categories of patients. These reactions were then correlated with the students' social background, social values and perception of these conditions.


Cholinergic regulation of adrenal medullary blood flow.
To determine the relative role of nicotinic and muscarinic mechanisms in splanchnic nerve stimulation (NS)-induced adrenal catecholamine secretion and medullary vasodilation, 12 pentobarbital-anesthetized dogs were subjected to three identical stimulations. The first NS was performed before drug administration and served as a control. The second NS was performed after administration of either the muscarinic antagonist, atropine 0.5 mg/kg (group 1), or the nicotinic antagonist, hexamethonium 20 mg/kg (group 2). The third NS was performed after administration of both drugs. NS in the absence of drug resulted in 4-fold and greater than 200-fold increases in medullary blood flow (Q, measured with radiolabeled microspheres) and catecholamine secretion (assayed by high-pressure liquid chromatography), respectively. Atropine, when administered alone (group 1), had no effect on these responses. Subsequent administration of hexamethonium to group 1 animals resulted in complete blockade of NS-induced changes in medullary Q and secretion. Hexamethonium alone (group 2) reduced the catecholamine response to NS by 95% but had no effect on the medullary Q response. Addition of atropine further attenuated the increase in catecholamine secretion induced by NS and completely blocked the medullary Q increase. These data suggest the presence of redundant mechanisms to increase medullary Q during NS. One mechanism likely involves neurally released acetylcholine-stimulating vascular muscarinic receptors, whereas the second requires either chromaffin cell degranulation or nicotinic ganglionic transmission.


The intragastric milieu during gastric ulcer treatment with pirenzepine 50 mg b.i.d. or cimetidine 400 mg b.i.d.
In a double-blind randomised four-center trial 43 patients with gastric ulcer (20 men, 23 women; mean age 52.2 years) were treated with either pirenzepine (P) 50 mg b.i.d. (n = 24) or cimetidine (C) 400 mg b.i.d. (n = 19) during six weeks. In ten patients gastric juice was examined before and at the end of the treatment for concentration and type of the microbial flora, and for nitrite concentration. After six weeks 83% of the patients in both groups were either symptom-free or clearly improved. In 15/24 patients on P (62.6%) and in 13/18 on C (72.2%) the ulcer(s) were healed at the time of control endoscopy. In the ten patients investigated, intragastric concentrations of fungi, bacteria, and nitrite were not significantly changed by the treatment. In gastric ulcer, treatment with pirenzepine 50 mg b.i.d. or cimetidine 400 mg b.i.d. during six weeks does not result in significant microbial overgrowth or generation of nitrite.


[Observation on 104 senile chronic renal insufficiency patients treated with integrated traditional Chinese and Western medicine].
A clinical study on 104 cases of senile chronic renal insufficiency (SCRI) was conducted. In order to analyze the clinical features of SCRI and the efficacy of integrated TCM-WM treatment, all cases were treated by this combined therapy, except for the treatment of primary diseases and removing the aggravating factors. It was concluded that the effective rate reached 57% it had no significant difference with 61% of non-senile group, P > 0.05. The senile patients featured Kidney Yang Deficiency in TCM Syndrome Differentiation. It could guide the clinical treatment and thus the senile patient's Yang should be strengthened at usual time. When Kidney Qi was insufficient and frequent nocturia appeared, sufficient water supply as well as Warming Kidney Yang drugs should be given and that Yang Qi should be protected all the time. Also diuretics and purgatives should not be misused which might damage Yin and Yang.


Evaluation of pyroptosis in macrophages using cytosolic delivery of purified flagellin.
Pyroptosis is a molecularly controlled form of cell death that exhibits some features of apoptosis as well of necrosis. Pyroptosis is induced by inflammasome-activated caspase-1 or caspase-11 (caspase-4 in humans), as a result of distinct pathogenic or damage stimuli. Although pyroptosis displays some morphological and biochemical features of apoptosis, it has an inflammatory outcome due to the loss of plasma membrane integrity and the consequent release of intracellular contents, reminiscent to necrosis. Here, we use cytosolic delivery of purified flagellin as an experimental tool to trigger pyroptosis and describe potential methods to study this form of cell death. Finally, we discuss the advantages and limitations of these methods.


Impact of biological therapy on body composition of patients with Chron's disease.
Protein-energy malnutrition in Crohn's disease (CD) has been reported in 20 to 92% of patients, and is associated with increased morbidity and mortality and higher costs for the health system. Anti-TNF drugs are a landmark in the clinical management, promoting prolonged remission in patients with CD. It is believed that the remission of this disease leads to nutritional recovery. The effect of biological therapy on body composition and nutritional status is unclear. Prospective study of body assessment by bioelectrical impedance method in patients with moderate to severe CD undergoing treatment with infliximab. The main outcome was the body composition before and after 6 months of anti-TNF therapy. There was a predominance of females (52%) with a mean age of 42±12 years. Most patients were eutrophic at baseline and remained so. There was an increase in all parameters of body composition after anti-TNF treatment: BMI (22.9±3.2 versus 25±3.8; p=0.005), waist circumference (88.1±6.7 versus 93.9±7.7; p=0.002), lean mass index (17.5±2.2 versus 18.2±2.3; p=0.000) and fat mass index (5.5±2.3 versus 6.8±2.3; p=0.000). Phase angle remained unchanged (6.2 versus 6.8; p=0.94). After therapy with IFX, all components of body composition increased, except for phase angle. The substantial increase in fat mass index and waist circumference led to concern regarding cardiovascular risk and, thus, to the need for further studies.


Behavioral Regulation Sport Questionnaire: Gender and Sport Invariance in Portuguese Athletes.
This study aimed to analyze measurement invariance of the Behavioral Regulation Sports Questionnaire (BRSQ) across gender and four different sports. In addition, we examined nomological validity via basic psychological needs satisfaction. Participants totaled 1,812 Portuguese athletes (1,220 males and 592 females; aged 15-59 years, Mage = 17.72, SD = 5.51) from football ( n = 596), basketball ( n = 273), swimming ( n = 800), and parasport ( n = 143). The BRSQ measurement model was invariant across gender and these four sports. The scale confirmed nomological validity in that satisfaction of basic psychological needs positively predicted autonomous forms of motivation and negatively predicted more controlled motivation and amotivation as suggested by self-determination theory. In light of this evidence for BRSQ construct validity, composite reliability, nomological validity, and invariance across gender and four different sports, this scale is a useful tool for coaches of the aforementioned sports in their efforts to evaluate their athletes' motivation.


Can Total Wrist Arthroplasty Be an Option for Treatment of Highly Comminuted Distal Radius Fracture in Selected Patients? Preliminary Experience with Two Cases.
We present two case reports of successful primary shortening of the forearm and total wrist arthroplasty (TWA) using the new angle-stable Maestro Wrist Reconstructive System (WRS) for treatment of highly comminuted distal radius fracture in selected autonomous patients. In a 56-year-old male patient with adequate bone stock, insertion of the noncemented Maestro WRS was combined with ulnar shortening osteotomy. In an 84-year-old female patient with poor osteoporotic bone stock, insertion of the radial cemented Maestro WRS was combined with ulnar head resection. Both patients could resume their work without additional surgery after TWA. At the 1-year follow-up, there were no changes in position of either implant without signs of loosening, no impingement, and no instability of the distal radioulnar joint or the distal ulna stump. All clinical parameters (DASH score, pain through VAS, and grip strength) were satisfactory. Both patients reported that they would have the same procedure again. Further experience is needed to validate this concept.


Raman enhancement by plasmonic excitation of structurally-characterized metal clusters: Au8, Ag8, and Cu8.
The optical responses of metal clusters, M8 (M = Au, Ag and Cu), are investigated by the linear response theory based on the density functional theory. Unlike sodium clusters [Yasuike et al., Phys. Rev. A, 2011, 83, 013201], the plasmonic excitations in the present metal clusters are strongly reduced by the background d-electron excitations, i.e., Landau damping. To avoid the reduction of plasmon intensity, the control of cluster structures is one of the promising strategies. We demonstrate that the plasmonic excitations of the linear clusters are partially decoupled with the background d-electron excitations and their intensities are much stronger than those of the three-dimensional bicapped octahedral isomers. The linear isomer gives a strong enhancement of the Raman vibrational spectrum of a pyrazine molecule.


Dense cataract and microphthalmia--new spontaneous mutation in BALB/c mice.
We describe a new spontaneous mutation in BALB/c mice that causes abnormal phenotype, such as congenital cataract and microphthalmia. This abnormality was found to be inheritable because offspring with the same abnormality were produced by backcrossing the abnormal male to its normal female parent. Results of various crosses made to determine the mode of inheritance indicated that this abnormality is attributable to mutation of an autosomal recessive gene. Slit lamp examination of the mutant eyes revealed total lenticular opacity, disturbed typical iris pattern, and abnormal pupillary muscle development. Histologic changes in mutant eyes between gestation day 13 and postnatal day 1 indicated various eye and lens abnormalities, including microphthalmia; underdeveloped iris, optic stalk, cornea, and retina; degenerated lens fibers with lost fibrillar structure; and vacuoles of various sizes at the posterior border of the lens. Mild opacity of the lens was found to progress with age and became denser, resembling mature cataract, and occupying the lens completely at the age of six to eight weeks. We, therefore, temporarily designated this abnormality as dense cataract and microphthalmia, with the gene symbol dcm.


Uniform free-space cell shaping using diffractive-type beam diffusers for optical wireless links.
This Letter presents the design of a diffractive beam diffuser to homogenize the irradiance within optical free-space cells generated from multimode fibers in an indoor high-speed network environment. Native speckled beams with a Gaussian envelope are transformed into circular flat-top distributions to guarantee a constant signal-to-noise ratio at the wireless receiving stage. Design considerations followed by the device fabrication and test results are given, showing its ability to shape narrow line-of-sight optical wireless cells operating at the Gbps range.


The effect of nurse-led digital health interventions on blood pressure control for people with hypertension: A systematic review and meta-analysis.
Nurse-led digital health interventions (DHIs) for people with chronic disease are increasing. However, the effect of nurse-led DHIs on blood pressure control and hypertension self-management remains unclear. This study aimed to identify the characteristics of nurse-led DHIs for people with hypertension and compared the effect size of nurse-led DHIs with that of usual care to establish evidence for the development of effective nursing interventions using technologies. Systematic review and meta-analysis. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews of Intervention (PRISMA) guidelines and registered the protocol in PROSPERO. Studies published from 2000 to August 5, 2021, were searched using the international databases: PubMed; Embase; Cochrane Central Register of Controlled Trials; Web of Science; CINAHL; Korean databases: RISS, KISS, KMBASE; and NDSL. Risk of bias 2.0 was used for evaluating the quality of studies. The primary outcome was blood pressure control. The secondary outcomes were self-management, medication adherence, and diet adherence. Publication bias was assessed using the funnel plot and Egger's regression tests. The systematic review included 26 studies. A meta-analysis of 21 studies was conducted to calculate the effect size and identify heterogeneity among the included studies. In our meta-analysis, we observed that nurse-led DHIs reduced systolic blood pressure by 6.49 mmHg (95% confidence interval [CI]: -8.52 to -4.46, I2 = 75.4%, p < 0.05) and diastolic blood pressure by 3.30 mmHg (95% CI: -4.58 to -2.01, I2 = 70.3%, p < 0.05) when compared with usual care. Concerning secondary outcomes, the effect size on self-management, medication adherence, and diet adherence was 0.98 (95% CI: 0.58 to 1.37, I2 = 63.2%, p < 0.05), 1.05 (95% CI: 0.41 to 1.69, I2 = 92.5%, p < 0.05), and 0.80 (95% CI: 0.17 to 1.42, I2 = 80.5%, p < 0.05), respectively. Nurse-led DHIs were more effective in reducing blood pressure and enhancing self-management than usual care among people with hypertension. Therefore, as new technologies are being rapidly developed and applied in healthcare systems, further studies and policy support are needed to utilize the latest digital innovations with nursing interventions. This study could be used to identify that nurse-led interventions may take advantage of real-time communication by employing digital technologies for improving blood control and self-management behaviors such as medication adherence and diet adherence. Using nurse-led DHIs allows nurses to provide patient-centered interventions such as reflecting on patients' needs and shared decision-making without space constraints and limited treatment time.


[The contents of gamma-aminobutyric acid and glutamic acid in brain affected by coriaria lactone].
Capillary chromatography was applied to studying the contents of gamma-aminobutyric acid (GABA) and glutamic acid (Glu) in brain affected by coriaria lactone. The results showed that there was a significant increase in the content of Glu whereas no significant change in the content of GABA was noted. The precisions for GABA and Glu were 3.3% and 4.98% and the recoveries of them were 80.5% and 85.2%, respectively. Capillary chromatography is a good method for determining the contents of GABA and Glu in brain, which has the characteristics of rapid and high sensitivity.


Neurological manifestations of the oculodentodigital dysplasia syndrome.
Oculodentodigital dysplasia (ODDD) (MIM 164200) is a rare autosomal dominant inherited disorder affecting the development of the face, eyes, limbs and dentition. Neurological complications are thought to be occasional manifestations of the disorder. This report illustrates the neurological manifestations by a pedigree of two ODDD patients with spastic paraparesis, cerebral white matter hyperintensity and basal ganglia hypointensity. A systematic review of the English, French, German and Italian literature on ODDD is also provided to summarize the neurological manifestations of the disorder. 243 previously described ODDD cases presented a spectrum of neurological manifestation including spasticity (25), subcortical white matter lesions (9) and basal ganglia changes (6) on MRI. Additional findings consisted of gaze palsy and squinting (28), bladder and bowel disturbances (21), visual loss (20) and blindness (4), hearing loss (15), ataxia (11), nystagmus (9), muscle weakness (5) and paresthesias (3). Neurological manifestations, including spasticity associated with MRI changes, are an underrecognized feature in the ODDD phenotype. A clinical guide to the neurological manifestations of ODDD may assist in the assessment of patients with this condition.


Clinical efficacy of montelukast sodium combined with budesonide or combined with loratadine in treating children with cough variant asthma and influence on inflammatory factors in the serum.
Clinical efficacy of montelukast sodium combined with budesonide or combined with loratadine in children with cough variant asthma was investigated. A retrospective analysis of the medical records of 72 children with cough variant asthma who were treated in Xuzhou Children's Hospital, Xuzhou Medical University from April 2015 to August 2017 was performed and the 72 child patients were divided into two groups: 35 children were treated with montelukast sodium combined with budesonide in Group A, and 37 children were treated with montelukast sodium combined with loratadine in Group B. The clinical efficacy of the two groups was evaluated according to the lung function indexes [forced expiratory volume in the first second (FEV1), ratio of the forced expiratory volume in the first second to the forced vital capacity (FEV1/FVC), the peak expiratory flow (PEF)], the inflammation biomarkers [tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4)], the level of eosinophil granulocyte, and the level of IgE at three time-points: before treatment, the 4th week after treatment, and the 12th week after treatment as well as adverse reactions, recurrence of symptoms, and treatment compliance were recorded. After treatment, the levels of FEV1, FEV1/FVC, PEF, TNF-α and IL-4, eosinophil granulocyte and IgE in the two groups were significantly improved (P<0.05). The treatment compliance of Group A was significantly lower than that of Group B (P<0.05). In conclusion, the method of montelukast sodium combined with budesonide or loratadine are both worthy of clinical promotion because they have equivalent efficacy in the treatment of cough variant asthma to effectively improve the lung function and inflammatory response in patients and both bring less adverse reactions and lower recurrence rate.


Moderate hypofractionated helical tomotherapy for older patients with localized prostate cancer: long-term outcomes of a phase I-II trial.
Our previous study showed that two different regimens of moderate hypofractionated radiotherapy (HFRT) delivered with helical tomotherapy (HT) are well tolerated in older prostate cancer patients. We provide a longterm efficacy and toxicity after > 7 years of follow-up. The study recruited 33 patients from February 2009 to July 2011 (76 Gy/34F; Group-1); and 34 from July 2011 to February 2014 (71.6 Gy/28F; 50.4 Gy/25F for the risk of pelvic lymph nodes involvement (LNI) >15%; Group-2). The primary outcomes were biochemical failure (BF), biochemical failure and clinical disease failure (BCDF), progression-free survival (PFS), overall survival (OS), late genitourinary (GU) and gastrointestinal (GI) toxicity. The average ages of two groups were 80 and 77 years and the proportions of patients with LNI > 15% were 69.7% and 73.5%, respectively. At the final follow-up in February 2020, 27.3% and 20.6% cases experienced BF, with a median time until BF of 3.3 years. A total of 38.8% patients reached primary endpoints, in which 18 deaths were reported BCDF events (45.5% vs. 32.4%, p = 0.271). There was no significant difference in 7-year PFS (68.6% vs. 74.8%, p = 0.591), BCDF (45.5% vs. 32.4%, p = 0.271) and OS (71.9% vs. 87.5%, p = 0.376) for full set analysis and for subgroup analysis (all p > 0.05). The incidence of grade ≥ 2 late GU (6.2% vs. 6.3%, p = 0.127) and GI toxicities (9.4% vs. 15.6%, p = 0.554) was comparable. In older patients with localized prostate cancer, two moderate hypofractionated regimens were all well tolerated with similar, mild late toxicities and satisfactory survival, without necessity of prophylactic pelvic node irradiation.


Radiation-induced temporal lobe injury for nasopharyngeal carcinoma: a comparison of intensity-modulated radiotherapy and conventional two-dimensional radiotherapy.
To compare the radiation-induced temporal lobe injury (TLI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) or two-dimensional conventional radiotherapy (2D-CRT). 1276 cases of NPC treated with IMRT or 2D-CRT were retrospectively reviewed. A diagnosis of TLI was made on follow-up magnetic resonance imaging (MRI). The crude incidence of TLI was 7.5% and 10.8% (P = 0.048), and the actuarial 5-year incidence was 16% and 34.9% (P<0.001) for the IMRT and 2D-CRT groups, respectively. Multivariate analysis revealed both T stage (P<0.001) and radiation technique (P<0.001) as independent predictors. Patients with T1, T2 and T3 disease had a significantly higher risk when treated with 2D-CRT (P = 0.005, 0.016, <0.001, respectively). This trend was not evident for T4 patients (P = 0.680). The 2D-CRT group had a longer latency for the development of TLI (P<0.001). Those with T4 disease had a shorter median time to TLI (P = 0.006, 0.042, <0.001 when compared with T1, T2 and T3, respectively). IMRT is superior to 2DRT for the management of T1-T3 NPC in terms of sparing the temporal lobe. The high incidence of TLI in T4 disease needs to be addressed.


Correction: New tetranuclear manganese clusters with [MnII3MnIII] and [MnII2MnIII2] metallic cores exhibiting low and high spin ground state.
Correction for 'New tetranuclear manganese clusters with [MnII3MnIII] and [MnII2MnIII2] metallic cores exhibiting low and high spin ground state' by M. Sobocińska et al., Dalton Trans., 2016, 45, 7303-7311.


Role of NAD(P)H:(quinone acceptor) oxidoreductase (DT-diaphorase) in activation of mitomycin C under acidic conditions.
The quinone antitumor agent mitomycin C is preferentially toxic to some cells under hypoxic and acidic conditions. The two-electron reducing enzyme DT-diaphorase may be a major contributor to mitomycin C activation under aerobic conditions, but its role in drug activation under hypoxic and acidic conditions is unclear. In this study, we observed that mitomycin C produced increased DNA cross-linking and cytotoxicity in Chinese hamster ovary cells at pH 6.6, compared with pH 7.2, under aerobic conditions, but drug activity was similar at these pH values under hypoxic conditions. The DT-diaphorase inhibitor dicoumarol completely inhibited the enhanced activity of mitomycin C at acidic pH under aerobic conditions but had no effect on DNA cross-linking or cytotoxicity under hypoxic conditions. These finding suggest that the enhanced activity of mitomycin C at acidic pH, in air, is due to increased drug activation by DT-diaphorase. However, the role of DT-diaphorase in activating mitomycin C under hypoxic conditions appears to be limited, even at acidic pH.


Early chest X-ray in persons with presumptive tuberculosis increases Xpert® MTB/RIF diagnostic yield and efficiency.
Adult presumptive tuberculosis (TB) patients (n = 1690) were screened for TB using a questionnaire, chest X-ray (CXR) and sputum microscopy for acid-fast bacilli (AFB); Mycobacterium tuberculosis culture was performed for 74% of the patients and Xpert® MTB/RIF was done for 17.2%. Among patients recruited, 943 (55.8%) were diagnosed with TB, of whom 870 (92.3%) were bacteriologically confirmed and 73 (7.7%) were clinically diagnosed on the basis of CXR. Using CXR prior to culture or Xpert testing reduces the number needed to screen from 7.6 to 5.0. Using CXR to triage for culture or Xpert testing reduces the number of missed cases and increases the efficiency of culture and Xpert testing.