Efficacy and Safety of Remote Cardiac Rehabilitation in the Recovery Phase of Cardiovascular Diseases: Protocol for a Multicenter, Nonrandomized, Single-Arm, Interventional Trial.
Conventional group-based outpatient cardiac rehabilitation through monitoring and center-based approaches for patients in the recovery phase has shown strong evidence for the prevention of cardiovascular diseases. However, there are some cases in which maintaining attendance of center-based cardiac rehabilitation is difficult. This study aims to ascertain the safety and efficacy of remote cardiac rehabilitation (RCR) in the recovery phase in patients with cardiovascular disease. Patients satisfying the study criteria will be recruited from multiple institutions (approximately 30) across Japan. In total, 75 patients (approximately 2 or 3 patients from each institution) are proposed to be recruited. Patients enrolled in the RCR group will be lent devices necessary for RCR (including calibrated ergometers and tablets). Patients will perform anaerobic exercise at home using ergometer for 30-40 minutes at least 3 times weekly. During exercise, an instructor will monitor the patient in real time (using interactive video tools and monitoring tools for various vital data). Moreover, educational instructions will be given 3 times weekly using e-learning methods. The primary endpoint is the peak oxygen uptake 2-3 months from the start of exercise or 6-min walk test. The extracted data will be compared between RCR patients and controls without RCR. The establishment of the system of RCR proposed in this study will lead to the development of more extensive applications, which have been insufficient through conventional interventions. University Hospital Medical Information Network-Clinical Trials Registry UMIN-CTR UMIN000042942; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000048983. DERR1-10.2196/30725.


Structural insight into the biological functions of Arabidopsis thaliana ACHT1.
The Arabidopsis thaliana atypical Cys His-rich thioredoxins (ACHTs) are a small class of atypical thioredoxins (TRXs) located in chloroplasts thylakoids and are characterized by a noncanonical motif at their redox active site, C (G/S)(S/G)C. Previous studies have reported that ACHT1 can interact with A. thaliana 2-Cys peroxiredoxins (2-Cys Prxs, including PrxA and PrxB) to transmit oxidation signals in response to illumination with normal light intensity. In this study, we reported the crystal structure of ACHT1 and show that ACHT1 adopts a canonical TRX fold. Comparison of the structures of ACHT1 in both reducing and oxidizing environments revealed that while the redox environment did not influence the overall structure of ACHT1, it did change the conformation of its catalytic residues. We found that the catalytic C125 of ACHT1 is the target residue for PrxA in vitro. In addition, we found that ACHT1 can reduce the peroxidase activity of PrxA, and further confirmed that the ability of ACHT1 to restore the peroxidase function of PrxA was due to the interaction between the two. Our results provide a structural basis for studying the function of atypical TRXs and the oxidative regulation mechanism of ACHT1 and 2-Cys Prxs in chloroplasts.


Prolonged dry periods between rainfall events shorten the growth period of the resurrection plant Reaumuria soongorica.
The resurrection plant Reaumuria soongorica is widespread across Asia, southern Europe, and North Africa and is considered to be a constructive keystone species in desert ecosystems, but the impacts of climate change on this species in desert ecosystems are unclear. Here, the morphological responses of R. soongorica to changes in rainfall quantity (30% reduction and 30% increase in rainfall quantity) and interval (50% longer drought interval between rainfall events) were tested. Stage-specific changes in growth were monitored by sampling at the beginning, middle, and end of the growing season. Reduced rainfall decreased the aboveground and total biomass, while additional precipitation generally advanced R. soongorica growth and biomass accumulation. An increased interval between rainfall events resulted in an increase in root biomass in the middle of the growing season, followed by a decrease toward the end. The response to the combination of increased rainfall quantity and interval was similar to the response to increased interval alone, suggesting that the effects of changes in rainfall patterns exert a greater influence than increased rainfall quantity. Thus, despite the short duration of this experiment, consequences of changes in rainfall regime on seedling growth were observed. In particular, a prolonged rainfall interval shortened the growth period, suggesting that climate change-induced rainfall variability may have significant effects on the structure and functioning of desert ecosystems.


Higher catalytic efficiency of N-7-methylation is responsible for processive N-7 and 2'-O methyltransferase activity in dengue virus.
Methyltransferases (MTases) from the genus Flavivirus encode both N-7 and 2'-O activities needed for type 1 (m(7)GpppNm) cap structure formation. We performed kinetic studies to understand the mechanisms of its progressive N-7 and 2'-O methylations. Sequential N-7 to 2'-O methylation occurred via a random bi bi and processive mechanism that does not involve enzyme-RNA dissociation. Analyses of steady state kinetic parameters showed that N-7 precedes 2'-O methylation as it turnovers RNA faster (k(cat)) resulting in 2.4-fold higher catalytic efficiency. Michaelis constants for S-adenosyl-methionine (AdoMet) in both reactions were about 10-fold lower than for their respective RNA substrates, suggesting that the rate-limiting steps in methylase reactions were associated with RNA templates. In the context of long viral RNA sequences, and compared to S-adenosyl-homocysteine, sinefungin was about 60- and 12-folds more potent against dengue N-7 and 2'-O MTase activity, exhibiting IC(50) values of 30 and 41nM, respectively.


Mechanism of immune evasion in breast cancer.
Breast cancer (BC) is the most common malignant tumor among women, with high morbidity and mortality. Its onset, development, metastasis, and prognosis vary among individuals due to the interactions between tumors and host immunity. Many diverse mechanisms have been associated with BC, with immune evasion being the most widely studied to date. Tumor cells can escape from the body's immune response, which targets abnormal components and foreign bodies, using different approaches including modification of surface antigens and modulation of the surrounding environment. In this review, we summarize the mechanisms and factors that impact the immunoediting process and analyze their functions in detail.


[Mediation Effect of Self-Efficacy on the Relationship between Perceived Self-Management Support and Health-Related Quality of Life among Cancer Survivors].
This study aimed to examine the levels of perceived self-management support, self-efficacy for self-management, and health-related quality of life (HRQoL) in cancer survivors, and to identify the mediating effect of self-efficacy in the relationship between perceived self-management support and HRQoL. This study used a descriptive correlational design. Two hundred and four cancer survivors who had completed treatment participated in the study. Measurements included the Patient Assessment of Chronic Illness Care Scale, the Korean version of the Cancer Survivors' Self-Efficacy Scale, and the Medical Outcomes Study Short Form-36. Data were analyzed using descriptive statistics, Pearson's correlation coefficient analysis, and multiple regression analysis using Baron and Kenny's method for mediation. The mean score for perceived self-management support was 3.35 out of 5 points, self-efficacy was 7.26 out of 10 points, and HRQoL was 65.90 out of 100 points. Perceived self-management support was significantly positively correlated with self-efficacy (r=.29, p<.001) and HRQoL (r=.27, p<.001). Self-efficacy was also significantly correlated with HRQoL (r=.59, p<.001). Furthermore, self-efficacy (β=.55, p<.001) had a complete mediating effect on the relationship between perceived self-management support and HRQoL (Z=3.88, p<.001). The impact of perceived self-management support on HRQoL in cancer survivors was mediated by self-efficacy for self-management. This suggests that strategies for enhancing self-efficacy in cancer survivors should be considered when developing self-management interventions for improving their HRQoL.


Pronator Quadratus Muscle Flap for Prevention of Flexor Tendon Rupture after Distal Radius Volar Plating.
Flexor tendon rupture is a serious but rare complication that can occur after volar plating of distal radius fractures. This study aims to introduce a novel surgical technique that uses a pronator quadratus (PQ) muscle flap transposition to protect the flexor tendons from rupture or irritation and evaluate its outcomes. A retrospective review was conducted on 204 patients with unstable distal radius fractures who underwent a standard volar flexor carpi radialis approach with extended release of the PQ muscle during exposure. A PQ muscle flap was harvested and transposed over the distal edge of the plate after open reduction and internal fixation of the distal radius. Postoperatively, patients were evaluated for flexor tendon irritation and rupture. Patients who had this injury before the use of the PQ flap were compared with the patients who received the PQ flap. Of the 204 patients, 119 received the PQ flap, and 85 did not. The mean follow-up time was 30.4 months. Among the patients who did not receive the PQ flap, five (5.9%) required plate removal or conservative treatment for tendon irritation or rupture. In contrast, only one patient (0.8%) who received the PQ flap required plate removal for flexor tendon irritation. The PQ muscle flap is a quick and effective surgical technique that reduces the risk of flexor tendon rupture or irritation during distal radius fracture fixation. The PQ muscle flap acts as a buffer between the plate and tendon and is more effective than not transposing the muscle.


Suppression of tumor-forming ability and related traits in MCF-7 human breast cancer cells by fusion with immortal mammary epithelial cells.
Somatic cell hybrids between MCF-7 human breast cancer cells and normal immortalized human mammary epithelial cells have been obtained by polyethylene glycol-mediated cell fusion. The hybrid cells are suppressed in their ability to form tumors in nude mice, as well as in traits specific to the tumorigenic MCF-7 parent: growth factor independence, tumor necrosis factor sensitivity, and pS2 gene expression. In addition, they display other characteristics of the "normal" parent, including increased expression relative to the MCF-7 cells of the genes for the extracellular matrix component fibronectin, the intermediate filament keratin 5, and the angiogenesis inhibitor thrombospondin. The levels of keratins 8 and 18 also resemble those of the nontumorigenic parent. These results provide evidence for the existence of tumor suppressor gene products in immortal mammary epithelial cells. We propose a characteristic "suppressed" tumor cell phenotype, which encompasses altered cytoarchitecture, angiogenesis capabilities, and growth factor requirements.


Improving public health nursing education: recommendations of local public health nurses.
This paper reports recommendations for improving public health nursing (PHN) undergraduate, graduate, and continuing education (CE) made by staff-level public health nurses working in local health departments (LHDs). Implications for academia and practice are discussed. A cross-sectional written survey was used to collect data from 424 public health nurses in 76 LHDs in Wisconsin (68% response rate) in 2003. Recommendations for improving undergraduate, graduate, and CE were made through responses to open-ended survey questions. Content analysis was conducted to identify major themes among responses. Major themes emerging from the recommendations for undergraduate education included the need for more clinical public health experiences and population-focused practice content. Graduate education improvement recommendations included addressing access barriers and increasing organizational incentives. Improved access and more public health content were the major recommendations for improving CE. Implications for academia focus on increasing opportunities for students to experience population-focused PHN and to learn organizational and collaborative practice skills, supporting PHN preceptors and building evidence for PHN intervention through research. Implications for practice include the need to expand opportunities for students with LHDs and to collaborate with academic partners for education and research.


The change of anterior chamber angle parameters after cataract surgery in diabetic patients.
The purpose of this study is to investigate the change of anterior chamber angle morphology after cataract surgery in patients with type 2 diabetes mellitus (DM2) using anterior segment optical coherence tomography (AS-OCT). In this prospective and comparative study, 57 eyes of the patients with cataract were investigated. The patients were divided into two groups. The DM2 group included cataractous type 2 diabetic patients without diabetic retinopathy (n = 30) and the non-DM2 group included nondiabetic participants with cataract (n = 27). The AS-OCT examinations were performed at baseline and 1 month after the cataract surgery. The corrected distance visual acuity (CDVA), intraocular pressure (IOP), angle-opening distance at 500 µm (AOD-500) and trabecular iris space area at 500 µm (TISA-500), and scleral spur angle (SSA) in temporal quadrant were analyzed. The mean age, sex, and axial length values were similar in both groups (p > 0.05 for all). The CDVA was significantly improved in both groups (p < 0.001). The mean AOD-500, TISA-500, and SSA were increased and the mean IOP was decreased after cataract surgery in both groups (p < 0.001 for all). There were not any statistically significant intergroup differences in CDVA, IOP, and AS-OCT measurements between the DM2 and non-DM2 groups (p > 0.05 for all). Cataract surgery showed significant increases in mean anterior chamber angle parameters and reductions in IOP values in both diabetic and nondiabetic patients without intergroup significant differences. These results suggested the safety and effectiveness of cataract surgery, especially regarding anterior chamber angle parameters and so IOP changes.


The caspase pathway in noise-induced apoptosis of the chinchilla cochlea.
We previously reported that intense noise exposure causes outer hair cell (OHC) death primarily through apoptosis. Here we investigated the intracellular signal pathways associated with apoptotic OHC death. Chinchillas were exposed to a 4 kHz narrowband noise at 110 dB SPL for 1 h. After the noise exposure, the cochleas were examined for the activity of each of three caspases, including caspase-3, -8, or -9 with carboxyfluorescein-labeled fluoromethyl ketone (FMK)-peptide inhibitors. The cochleas were further examined for cytochrome c release from mitochondria by immunohistology and for DNA degradation by the TUNEL method. The results showed that the noise exposure triggered activation of caspase-3, an important mediator of apoptosis. The noise exposure also caused the activation of caspase-8 and caspase-9, each of which is associated with a distinct signaling pathway that leads to activation of caspase-3. Caspase activation occurred only in the apoptotic OHCs and not in the necrotic OHCs. These results indicate that multiple signaling pathways leading to caspase-3 activation take place simultaneously in the apoptotic OHCs. In addition to caspase activation, noise exposure caused the release of cytochrome c from mitochondria, resulting in a punctate fluorescence in the cytosol. In contrast to activation of caspases, the release of cytochrome c took place in both apoptotic and necrotic OHCs. Moreover, the release of cytochrome c in a subpopulation of OHCs took place early in the cell death process, prior to any outward signs of necrosis or apoptosis. These data suggest that in this subpopulation there exists a common step that is shared by cell death pathways before entering either necrosis or apoptosis. Lastly, use of the TUNEL assay in combination with PI labeling provides a more accurate discrimination between apoptosis and necrosis.


High prevalence of metabolic syndrome in a middle-aged and elderly population with prehypertension in Tianjin.
Prehypertension has been reported as being correlated with future cardiovascular risk and end-organ damage in middle-aged and elderly persons, and also playing an important role in metabolic syndrome (MetS). The association between prehypertension and MetS has rarely been reported among urban adults in Tianjin, China. In this cross-sectional study, a total of 1176 participants aged 40-70 years (524 males and 652 females) were enrolled after excluding participants with hypertension or treated hypertension. Participants were divided into two groups [optimal blood pressure (BP) and prehypertension] based on the classification of BP from the JNC-7. The definition of MetS was as per the International Diabetes Federation standard. An adjusted logistic regression model was used to assess relationships between prehypertension and MetS. The prehypertension group had a significantly higher odds ratio (OR) than the optimal BP group for abnormal waist circumference (WC), fasting plasma glucose (FPG) and triglycerides (TG). In addition, the prehypertension group had a higher OR (3.12; 95% confidence interval 2.34-4.18) for having MetS after adjusting for potential confounders. The risk of having MetS was significantly associated with prehypertension in middle-aged and elderly persons in Tianjin. Stricter control of BP in this age group is warranted.


Post-traumatic growth and its predictors among Syrian refugees in Istanbul: A mental health population survey.
The negative mental health effects of exposure to trauma are well-documented. However, some individuals are theorized to undergo post-traumatic growth (PTG) after exposure to trauma, potentially experiencing positive psychological change across five domains: appreciation for life, relationships with others, new possibilities in life, personal strength, and spiritual change. PTG is less studied in forcibly displaced populations in low- and middle-income countries. This study aimed to explore levels of PTG and associated factors among Syrian refugee adults living in Istanbul, Turkey. A cross-sectional survey was conducted with 1678 respondents. This study analyzed PTG data from 768 individuals as measured by the Post-Traumatic Growth Inventory (PTGI). Descriptive analysis and univariate and multivariate least squares linear regression modeling were used. Factor analysis and Cronbach's alpha tests assessed the psychometric properties of the PTGI. The sample exhibited a moderate level of PTG at 55.94 (SD=22.91, range 0-105). Factor analysis of PTGI revealed only four factors instead of five, and the PTGI yielded high internal reliability (Cronbach's α=0.90). PTG and post-traumatic stress disorder (PTSD) had a curvilinear relationship, with the highest PTG levels experienced by those with moderate PTSD levels. Five other variables were significantly associated with PTG: older age, less education, somatic distress, and history of an overnight stay at a health facility for mental health care were associated with lower PTG, while more years of education were associated with higher PTG. This study identified the role of the sociodemographic and psychological determinants that influence post-traumatic growth among Syrian refugees in Istanbul. These findings could be used to inform future research and programs seeking to understand PTG in refugees.


Isolation and characterization of rabbit H of the alternative complement pathway.
Rabbit factor H, a control protein of the alternative complement pathway, was isolated from rabbit serum by polyethylene glycol precipitation, DEAE-Sephacel chromatography, and gel chromatography on Sephadex G200. The protein migrated as a single-chain polypeptide with a molecular weight of 160,000 on sodium dodecyl sulfate-gel electrophoresis with Laemmli's buffer system, but hardly migrated into the gel with Fairbanks' buffer system. Physical and chemical properties of rabbit H were similar to those of human H, except that fragments produced by limited tryptic digestion from rabbit H had different molecular sizes from those produced from human H. Significant species-specificity was observed in the functional activity of factor H; activation of the alternative complement pathway was inhibited more efficiently with homologous H than with heterologous H. In contrast, factor H inhibited the hemolysis of homologous erythrocytes less than that of heterologous erythrocytes.


Comparison of follicular fluid amphiregulin and EGF concentrations in patients undergoing IVF with different stimulation protocols.
Epidermal growth factor (EGF)-like growth factors, such as amphiregulin (AR) and EGF, have emerged as mediators to propagate Luteinizing hormone (LH) stimulus for the oocyte maturation throughout the preovulatory follicle, because cumulus cells and oocytes express few or no LH receptors. This study was to compare AR and EGF concentrations in follicular fluid (FF) among four controlled ovary stimulation (COS) protocols and to investigate the relationship between FF EGF-like growth factors and COS outcomes. Ninety-five patients who underwent in vitro fertilization-embryo transfer (IVF-ET) were treated by four different COS protocols, including gonadotropin-releasing hormone agonist (GnRH-a) long protocol, GnRH-a ultra-long protocol, GnRH-a short protocol, and GnRH antagonist protocol. FF was taken on oocyte retrieval day. FF AR and EGF concentrations were measured and their correlations with COS outcomes were analyzed. FF AR concentration was significantly different from each other among four COS protocol groups (GnRH-a ultra-long protocol group, 186.12 ng/ml; GnRH-a long protocol group, 128.35 ng/ml; GnRH antagonist protocol group, 108.23 ng/ml; GnRH-a short protocol group, 77.13 ng/ml, p < 0.05). FF AR concentrations were higher in GnRH-a ultra-long and long protocol groups, while number of oocytes retrieval, available embryos, and good quality embryos in these two groups were also significantly higher than GnRH-a short protocol group and GnRH antagonist protocol group. FF AR concentration was positively correlated with available embryos, but negatively correlated with serum LH level on hCG day. FF EGF concentration had no relationship with COS parameters. Different COS protocols might have variable effects on AR synthesis. FF AR might be a good indicator to predict the number of oocytes and embryos. FF AR elevation may result in increasing the number of oocyte retrieval and embryo generation, consequently increased cumulative pregnancy rate.


Spontaneous mutations in diploid Saccharomyces cerevisiae: another thousand cell generations.
Previously we performed a 1012-generation mutation accumulation (MA) study in yeast and found that a surprisingly large proportion of fitness-altering mutations were beneficial. To verify this result and assess the impact of sampling error in our previous study, we have continued the MA experiment for an additional 1050 cell generations and re-estimated mutation parameters. After correcting for biases due to selection, we estimate that 13% of the mutations accumulated during this study are beneficial. We conclude that the high proportions of beneficial mutations observed in this and our previous study cannot be explained by sampling error. We also estimate the genome-wide mutation rate to be 13.7x10-5 mutations per haploid genome per cell generation and the absolute value of the average heterozygous effect of a mutation to be 7.3%.


Consciousness, the brain and what matters.
Grant Gillett argues that it is consciousness which makes a human or other being the 'locus of ethical value'. Since cortical functioning is, in Gillett's view, necessary for conscious activity, an individual whose neocortex is permanently non-functional is no longer a locus of ethical value and cannot be benefited or harmed in a morally relevant sense. This means that there is no obligation to continue treating those who have suffered neocortical death.


Bupropion improved apathy in behavioral variant frontotemporal dementia: a case report.
Apathy is a common neurobehavioral sign in cases of behavioral variant frontotemporal dementia. However, there is still no established sustained effective treatment. We present the case of a 65-year-old man with behavioral variant frontotemporal dementia who suffered from severe apathy, but his apathy improved after a 10-month period of bupropion treatment. His single photon emission computed tomography report also showed slight improvement. To the best of our knowledge, such a case with imaging evidence has never been reported. Further studies to correlate the effects of bupropion on apathy in behavioral variant frontotemporal dementia patients are clearly needed.


Practical considerations of the vascular surgical "out-patients".
Continuity in vascular patient control is important. Physiological methods useful in diagnosis and follow-up of vascular surgical out-patients are discussed. Measurement of systolic blood pressure in the big toe gave good assessment of their peripheral perfusion pressure and helped in selecting patients for vascular reconstruction. Walking capacity was measured on a treadmill together with simultaneous ECG. We recommended that all our patients stop smoking.


Successful treatment of uterine artery pseudoaneurysm with laparoscopic temporary clamping of bilateral uterine arteries, followed by hysteroscopic surgery.
Surgical strategies for the treatment of uterine artery pseudoaneurysm (UAP) include transarterial embolization and ultrasound-guided low-dose thrombin injection. Such strategies, however, have limitations and include the risk of ischemic damage to the uterus. We report a case of UAP treated with a new hysteroscopic and laparoscopic technique. A 29-year-old G1P0 woman with spontaneous abortion was transferred to the present institution because of hemorrhagic shock. We diagnosed ruptured UAP on transvaginal ultrasound with color Doppler. Emergency laparoscopic temporary clamping of the bilateral uterine arteries was done to reduce the bleeding, and transcervical resection to stop the hemorrhaging and to collect the pseudoaneurysm tissue. After surgery, blood flow to the myometrium was monitored on ultrasound. By postoperative day 48, normal menstruation had restarted, and no intrauterine adhesions were observed. On pathology of the UAP, a dilated spiral artery without its characteristic elastic fibers was identified. This surgical approach may help preserve fertility and allow for pathological diagnosis of UAP.


The dinoflagellates Durinskia baltica and Kryptoperidinium foliaceum retain functionally overlapping mitochondria from two evolutionarily distinct lineages.
The dinoflagellates Durinskia baltica and Kryptoperidinium foliaceum are distinguished by the presence of a tertiary plastid derived from a diatom endosymbiont. The diatom is fully integrated with the host cell cycle and is so altered in structure as to be difficult to recognize it as a diatom, and yet it retains a number of features normally lost in tertiary and secondary endosymbionts, most notably mitochondria. The dinoflagellate host is also reported to retain mitochondrion-like structures, making these cells unique in retaining two evolutionarily distinct mitochondria. This redundancy raises the question of whether the organelles share any functions in common or have distributed functions between them. We show that both host and endosymbiont mitochondrial genomes encode genes for electron transport proteins. We have characterized cytochrome c oxidase 1 (cox1), cytochrome oxidase 2 (cox2), cytochrome oxidase 3 (cox3), cytochrome b (cob), and large subunit of ribosomal RNA (LSUrRNA) of endosymbiont mitochondrial ancestry, and cox1 and cob of host mitochondrial ancestry. We show that all genes are transcribed and that those ascribed to the host mitochondrial genome are extensively edited at the RNA level, as expected for a dinoflagellate mitochondrion-encoded gene. We also found evidence for extensive recombination in the host mitochondrial genes and that recombination products are also transcribed, as expected for a dinoflagellate. Durinskia baltica and K. foliaceum retain two mitochondria from evolutionarily distinct lineages, and the functions of these organelles are at least partially overlapping, since both express genes for proteins in electron transport.


Core-shell magnetic mesoporous N-doped silica nanoparticles: solid base catalysts for the preparation of some arylpyrimido[4,5-b]quinoline diones under green conditions.
Nowadays, the application of solid base catalysts as a perfect replacement for homogenous basic catalysts has attracted the attention of researchers. In this study, core-shell magnetic mesoporous N-doped silica nanoparticles N(x wt%)-MSN, as a heterogeneous base catalyst, were synthesized. The N(x wt%)-MSN composite was fabricated by adding different amounts of diethanolamine as a source of nitrogen, besides using tetraethylorthosilicate as a precursor of silica. The as-prepared catalyst was employed efficiently for the synthesis of some arylpyrimido[4,5-b]quinoline-dione derivatives under green conditions. The highly efficient catalyst N(1.3 wt%)-MSN was characterized via XRD, FESEM, HRTEM, BET and XPS techniques, and the results of these analyses proved that the nitrogen was doped into the silica structure. Also, the results demonstrated the core-shell structure of the as-synthesized composite.


Effect of the RF cavity temperature on low-energy injection at HLS.
The resonant frequency shift caused by the temperature of the RF cavity at the Hefei Light Source has been measured and the results analysed. The effect of this frequency shift on low-energy injection with a low cavity voltage is discussed, and a new injection mode is proposed.


Extraction Method Development for Quantitative Detection of Silver Nanoparticles in Environmental Soils and Sediments by Single Particle Inductively Coupled Plasma Mass Spectrometry.
For understanding the environmental behavior and toxicity of Ag nanoparticles (Ag-NPs), a quantitative method for characterizing the AgNPs in soils and sediments is urgently needed. In this study, we validated a previously developed extraction method by optimizing the extraction of silver nanoparticles from soil and sediment samples to which engineered AgNPs had been added. The samples were analyzed by single particle inductively coupled plasma mass spectrometry (SP-ICP-MS). Initially, different extraction conditions were evaluated to validate the optimal extraction procedure. Then the optimal extraction procedure was applied to environmental soil and sediment samples spiked with AgNPs. The extraction data for Ag-NPs with sizes below 30 nm was not shown due to the particle size detection limit of the SP-ICP-MS method (∼20 nm). The number concentrations of Ag particles extracted from different environmental soils and sediments matrices were in the range of (12 ± 1-23 ± 1) × 107 particles/g soil. Similarly, 53.4-100.0% of the particulate Ag mass was recovered. For the relatively low Ag mass recovery of Guiyu agricultural soil, the Ag mass recovery shows great improvement (from 53.4 to 105.8%) by the soil dilution using SiO2. The optimal method was validated to be feasible for extracting Ag-NPs from environmental soils and sediments, except for the soil with high soil organic matter (SOM) content. The SiO2 dilution of soil provides a promising way to promote the extraction of Ag-NPs in soil (or sediment) with high SOM content, which could further promote the study on the environmental behavior and toxicity of Ag-NPs in soil and sediment environment.


Nonverbal dialogue with the brain-damaged elderly.
In a population of twelve 63- to 89-year-old residents of a nursing home, rank-ordered scores of copying errors on the revised Benton visual retention test were found to be significantly correlated with the rotational shifts in the Minnesota percepto-diagnostic test. Residents on both ends of the continuum of brain damage could paint interesting, expressive and/or original pictures, in spite of the fact that the first eight residents were on psychotropic medication and the last four were occasionally handicapped by constructional apraxia. Ten adjudicators ranked pairs of figure drawings for each resident in decreasing order of 'aesthetic pleasingness' and 'originality'. Degree of brain damage was found unrelated to both measures. Interadjudicator agreement was stronger on 'originality' than on 'aesthetic pleasingness'. Some of the beneficial and provocative results of art therapy with the elderly are elaborated ans a plea made for accepting their observed creative performance as part of the realm of legitimate art.


Gangliosides of murine T lymphocyte subpopulations.
Gangliosides from murine T lymphoblasts were analyzed by high-performance thin-layer chromatography followed by in situ neuraminidase treatment and immunostaining of the resulting asialogangliosides and compared with those from thymocytes and cloned T lymphocytes with defined functions. The ganglioside IVNeuGc/Ac-GgOse5Cer (GalNAc-GM1b), a marker for T lymphoblasts [Müthing, J., Egge, H., Kniep, B., & Mühlradt, P. F. (1987) Eur. J. Biochem. 163, 407-416], was found only in small amounts as the N-acetylated species in gangliosides from thymocytes and a cytolytic T cell clone. Two helper clones expressed this ganglioside like T blasts. The structures of the two major disialogangliosides from T blasts, IVNeuAc,IIINeuAc-GgOse4Cer (GD1 alpha type) with C24:0/24:1 and C16:0 fatty acids, were elucidated by neuraminidase treatment and immunostaining and by fast atom bombardment mass spectrometry. Gangliosides of this type were detected in thymocytes only in minor amounts, whereas GM1b-type gangliosides prevailed in cells from this organ. Analysis of the T lymphoblast gangliosides from six genetically unrelated mouse strains showed that terminally sialylated GgOse4Cer (GM1b), IVNeuAc-GgOse5Cer (GalNAc-GM1b), and IVNeuAc,IIINeuAc-GgOse4Cer (GD1 alpha) were conserved structures in all strains examined. We conclude that maturation or stimulation of T cells may be correlated with elongation of a common GM1b-type precursor structure resulting in GalNAc-GM1b or GD1 alpha-type gangliosides.


Exploratory study of 18F-fluciclovine pet/ct for response assessment to docetaxel in patients with metastatic castration-resistant prostate cancer.
Monitoring therapeutic response in patients with metastatic castration-resistant prostate cancer (mCRPC) can be challenging. We set out to determine if 18F-fluciclovine PET/CT could be a useful imaging biomarker for response to docetaxel chemotherapy in patients with mCRPC. Seven patients with mCRPC had 18F-fluciclovine PET/CT scheduled at baseline and after 1 and 6 cycles of chemotherapy. The sum of SUVmax from the prostate/bed and up to 5 metastatic bone and soft tissue/visceral lesions were recorded. The SUVpeak of the hottest lesion (PERCIST-like) was also recorded. In comparison to the baseline scan, a decrease of ≥30% was considered response; new lesions or >30% increase was progressive disease; change of <30% was stable disease. Bone scintigraphy and CT were acquired at baseline and after the 6th cycle. Response assessment was based on the Prostate Cancer Clinical Trial Working Group 3 recommendations. All (7/7) enrolled patients completed the 1st and 2nd scans, while 4/7 patients completed all 3 scans. PET response correlated with PSA response in 3/7 (42.9%) patients after 1 cycle of docetaxel, and 3/4 (75%) patients after 6 cycles of docetaxel, respectively. Bone scan and CT correlated with PSA response in 1/4 (25%) patients. There was no significant correlation between baseline 18F-fluciclovine PET parameters or changes in PET parameters and time to PSA progression. In conclusion, this exploratory study showed that 18F-fluciclovine PET/CT has better correlation with PSA response than CT or bone scan in patients with mCRPC treated with docetaxel. 18F-fluciclovine PET/CT however did not predict time to PSA progression.


cyCombine allows for robust integration of single-cell cytometry datasets within and across technologies.
Combining single-cell cytometry datasets increases the analytical flexibility and the statistical power of data analyses. However, in many cases the full potential of co-analyses is not reached due to technical variance between data from different experimental batches. Here, we present cyCombine, a method to robustly integrate cytometry data from different batches, experiments, or even different experimental techniques, such as CITE-seq, flow cytometry, and mass cytometry. We demonstrate that cyCombine maintains the biological variance and the structure of the data, while minimizing the technical variance between datasets. cyCombine does not require technical replicates across datasets, and computation time scales linearly with the number of cells, allowing for integration of massive datasets. Robust, accurate, and scalable integration of cytometry data enables integration of multiple datasets for primary data analyses and the validation of results using public datasets.


Assessment of degree of health of the stomach by concomitant measurement of serum pepsinogen and serum Helicobacter pylori antibodies.
The stomach was assessed by measuring serum pepsinogen (PG) and Helicobacter pylori (Hp) antibodies by immunoassay, based on the findings of upper gastrointestinal endoscopy performed on the same day. The assessment involved 1,636 individuals who visited the hospital for general medical checkups. Those negative for Hp antibodies and PG were grouped in group A, Hp-positive/PG-negative subjects were included in group B, and PG-positive subjects in group C. Group A comprised 660 subjects (40.3%), group B 514 (31.4%), and group C 462 (28.2%). Gastric cancer was detected in 0.87% (4/462) in group C, 0.19% (1/514) in group B, and 0% (0/660) in group A. All four patients with gastric adenoma were in group C. Hyperplastic polyps were detected most frequently in group C followed by group B, while there were no cases in group A. By contrast, most fundic gland polyps were found in group A. The detection rate of peptic ulcers was highest in group B, while that of reflux esophagitis was highest in group A. These findings suggest that the "degree of health" of the stomach can be assessed by measuring serum PG and Hp antibodies.


Invasion-inhibitory antibodies inhibit proteolytic processing of apical membrane antigen 1 of Plasmodium falciparum merozoites.
Apical membrane antigen 1 (AMA-1) is a promising vaccine candidate for Plasmodium falciparum malaria. Antibodies against AMA-1 of P. falciparum (PfAMA-1) interrupt merozoite invasion into RBCs. Initially localized within the apical complex, PfAMA-1 is proteolytically processed and redistributed circumferentially on merozoites at about the time of their release and invasion into RBCs. An 83-kDa precursor form of PfAMA-1 is processed to 66-kDa and then to 48- and 44-kDa products. We show that, even at low concentrations, IgG antibodies against correctly folded recombinant PfAMA-1 cross-linked and trapped the 52-, 48-, and 44-kDa proteolytic products on merozoites. These products are normally shed into the culture medium. At higher concentrations antibodies inhibited invasion into RBCs and caused a reduction in the amount of 44- and 48-kDa products, both on merozoites and in the culture medium. A corresponding increase also occurred in the amount of the 66- and 52-kDa forms detected on the merozoites. These antibodies also prevented circumferential redistribution of AMA-1. In contrast, monovalent invasion-inhibitory Fab fragments caused accumulation of 66- and 52-kDa forms, with no cross-linking, trapping, or prevention of redistribution. Antibodies at low concentrations can be used as trapping agents for intermediate and soluble forms of AMA-1 and are useful for studying proteolytic processing of AMA-1. With this technique, it was confirmed that protease inhibitor chymostatin and Ca2+ chelators can inhibit the breakdown of the 66-kDa form. We propose that antibodies to AMA-1 capable of inhibiting erythrocyte invasion act by disrupting proteolytic processing of AMA-1.


Effect of muscle strength training in children and adolescents with spastic cerebral palsy: A systematic review and meta-analysis.
This systematic review and meta-analysis investigates the effects of strength training program in children and adolescents with cerebral palsy to improve function, activity, and participation. Five electronic databases (MEDLINE-Pubmed, Cochrane Library, PEDro, CINAHL, and SPORTDiscus) were systematically searched for full-text articles published from inception to 30 June 2021. Randomized controlled trials were included, who compared: (i) child population with spastic cerebral palsy population between 0 and 22 years; (ii) studies in which a muscle strength training program was performed and included dosing information; (iii) studies comparing strength training with other physical therapy technique(s) or untreated control group. Studies with similar outcomes were pooled by calculating standardized mean differences. Risk of bias was assessed with Cochrane Collaboration's tool for assessing the risk of bias and PROSPERO's registration number ID: CRD42020193535. Twenty-seven studies, comprising 847 participants with spastic cerebral palsy. The meta-analyses demonstrated significant standardized mean differences in favor of strength training program compared to other physical therapy technique(s) or untreated control group(s) for muscle strength at the knee flexors, at the knee extensor, at the plantarflexors, maximum resistance, balance, gait speed, GMFM (global, D and E dimension) and spasticity. A strength training program has positive functional and activity effects on muscle strength, balance, gait speed, or gross motor function without increasing spasticity for children and adolescents with cerebral palsy in Gross Motor Function Classification System levels I, II, and III when adequate dosage and specific principles are utilized.


Menoctone Resistance in Malaria Parasites Is Conferred by M133I Mutations in Cytochrome b That Are Transmissible through Mosquitoes.
Malaria-related mortality has slowly decreased over the past decade; however, eradication of malaria requires the development of new antimalarial chemotherapies that target liver stages of the parasite and combat the emergence of drug resistance. The diminishing arsenal of anti-liver-stage compounds sparked our interest in reviving the old and previously abandoned compound menoctone. In support of these studies, we developed a new convergent synthesis method that was facile, required fewer steps, produced better yields, and utilized less expensive reagents than the previously published method. Menoctone proved to be highly potent against liver stages of Plasmodium berghei (50 percent inhibitory concentration [IC50] = 0.41 nM) and erythrocytic stages of Plasmodium falciparum (113 nM). We selected for resistance to menoctone and found M133I mutations in cytochrome b of both P. falciparum and P. berghei The same mutation has been observed previously in atovaquone resistance, and we confirmed cross-resistance between menoctone and atovaquone in vitro (for P. falciparum) and in vivo (for P. berghei). Finally, we assessed the transmission potential of menoctone-resistant P. berghei and found that the M133I mutant parasites were readily transmitted from mouse to mosquitoes and back to mice. In each step, the M133I mutation in cytochrome b, inducing menoctone resistance, was confirmed. In summary, this study is the first to show the mechanism of resistance to menoctone and that menoctone and atovaquone resistance is transmissible through mosquitoes.


Serum amoxycillin levels following oral loading dose prior to outpatient general anaesthesia for dental extractions.
Serum amoxycillin levels were measured 4 h after oral administration of a 3 g loading dose given prior to outpatient dental treatment under general anesthesia. A mean level of 8.49 mg/l +/- (1 S.D.) 5.07 mg/l of amoxycillin was obtained, which is adequate at the time of bacteraemia to protect patients susceptible to bacterial endocarditis. A second identical dose of amoxycillin was given following recovery from anaesthesia (mean 18.7 min) and was tolerated by 97.6% of patients.


Absolute Instability near the Band Edge of Traveling-Wave Amplifiers.
Applying the Briggs-Bers "pole-pinch" criterion to the exact transcendental dispersion relation of a dielectric traveling wave tube (TWT), we find that there is no absolute instability regardless of the beam current. We extend this analysis to the circuit band edges of a linear beam TWT by approximating the circuit mode as a hyperbola in the frequency-wave-number (ω-k) plane and consider the weak coupling limit. For an operating mode whose group velocity is in the same direction as the beam mode, we find that the lower band edge is not subjected to absolute instability. At the upper band edge, we find a threshold beam current beyond which absolute instability is excited. The nonexistence of absolute instability in a linear beam TWT and the existence in a gyrotron TWT, both at the lower band edge, is contrasted. The general study given here is applicable to some contemporary TWTs such as metamaterial-based and advanced Smith-Purcell TWTs.


Association Between Insomnia and Mental Health and Neurocognitive Outcomes Following Traumatic Brain Injury.
We previously described five trajectories of insomnia (each defined by a distinct pattern of insomnia severity over 12 months following traumatic brain injury [TBI]). Our objective in the present study was to estimate the association between insomnia trajectory status and trajectories of mental health and neurocognitive outcomes during the 12 months after TBI. In this study, participants included N = 2022 adults from the Federal Inter-agency Traumatic Brain Injury Repository database and Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. The following outcome measures were assessed serially at 2 weeks, and 3, 6, and 12 months post-injury: Insomnia Severity Index, Patient Health Questionnaire, Post-Traumatic Stress Disorder (PTSD) Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), Patient Reported Outcomes Measurement Information System-Pain, and Quality of Life After Brain Injury-Overall Scale. Neurocognitive performance was assessed at 2 weeks, and 6 and 12 months using the Wechsler Adult Intelligence Scales Processing Speed Index and the Trails Making Test Parts A and B. Results indicated that greater insomnia severity was associated with greater abnormality in mental health, quality of life, and neuropsychological testing outcomes. The pattern of insomnia over time tracked the temporal pattern of all these outcomes for all but a very small number of participants. Notably, severe insomnia at 3 or 6 months post-TBI was a risk factor for poor recovery at 12 months post-injury. In conclusion, in this well-characterized sample of individuals with TBI, insomnia severity generally tracked severity of depression, pain, PTSD, quality of life, and neurocognitive outcomes over 12 months post-injury. More intensive sleep assessment is needed to elucidate the nature of these relationships and to help inform best strategies for intervention.


Late replication domains are evolutionary conserved in the Drosophila genome.
Drosophila chromosomes are organized into distinct domains differing in their predominant chromatin composition, replication timing and evolutionary conservation. We show on a genome-wide level that genes whose order has remained unaltered across 9 Drosophila species display late replication timing and frequently map to the regions of repressive chromatin. This observation is consistent with the existence of extensive domains of repressive chromatin that replicate extremely late and have conserved gene order in the Drosophila genome. We suggest that such repressive chromatin domains correspond to a handful of regions that complete replication at the very end of S phase. We further demonstrate that the order of genes in these regions is rarely altered in evolution. Substantial proportion of such regions significantly coincide with large synteny blocks. This indicates that there are evolutionary mechanisms maintaining the integrity of these late-replicating chromatin domains. The synteny blocks corresponding to the extremely late-replicating regions in the D. melanogaster genome consistently display two-fold lower gene density across different Drosophila species.


Parental estimate of child's developmental level in a high-risk population.
Forty-six children referred for developmental assessment underwent formal testing of language and intellectual development, and for each child a formal developmental quotient (FDQ) was obtained. Each child's mother was asked to provide a subjective estimate of her child's level of function, which was converted to a developmental quotient by dividing by the child's chronological age. The correlation coefficient between this derived parental developmental quotient estimate (DPDQE) and the FDQ was .85 (P less than .001). The DPDQE displayed 75% sensitivity and 100% specificity in detecting children with an FDQ of 69 or less. The DPDQE may be useful as one component of the routine office examination for preschool children.


Impacts of Nitrogen Deficiency on Wheat (Triticum aestivum L.) Grain During the Medium Filling Stage: Transcriptomic and Metabolomic Comparisons.
Nitrogen (N) supplementation is essential to the yield and quality of bread wheat (Triticum aestivum L.). The impact of N-deficiency on wheat at the seedling stage has been previously reported, but the impact of distinct N regimes applied at the seedling stage with continuous application on filling and maturing wheat grains is lesser known, despite the filling stage being critical for final grain yield and flour quality. Here, we compared phenotype characteristics such as grain yield, grain protein and sugar quality, plant growth, leaf photosynthesis of wheat under N-deficient and N-sufficient conditions imposed prior to sowing (120 kg/hm2) and in the jointing stage (120 kg/hm2), and then evaluated the effects of this continued stress through RNA-seq and GC-MS metabolomics profiling of grain at the mid-filling stage. The results showed that except for an increase in grain size and weight, and in the content of total sugar, starch, and fiber in bran fraction and white flour, the other metrics were all decreased under N-deficiency conditions. A total of 761 differentially expressed genes (DEGs) and 77 differentially accumulated metabolites (DAMs) were identified. Under N-deficiency, 51 down-regulated DEGs were involved in the process of impeding chlorophyll synthesis, chloroplast development, light harvesting, and electron transfer functions of photosystem, which resulted in the SPAD and Pn value decreased by 32 and 15.2% compared with N-sufficiency, inhibited photosynthesis. Twenty-four DEGs implicated the inhibition of amino acids synthesis and protein transport, in agreement with a 17-42% reduction in ornithine, cysteine, aspartate, and tyrosine from metabolome, and an 18.6% reduction in grain protein content. However, 14 DEGs were implicated in promoting sugar accumulation in the cell wall and another six DEGs also enhanced cell wall synthesis, which significantly increased fiber content in the endosperm and likely contributed to increasing the thousands-grain weight (TGW). Moreover, RNA-seq profiling suggested that wheat grain can improve the capacity of DNA repair, iron uptake, disease and abiotic stress resistance, and oxidative stress scavenging through increasing the content levels of anthocyanin, flavonoid, GABA, galactose, and glucose under N-deficiency condition. This study identified candidate genes and metabolites related to low N adaption and tolerance that may provide new insights into a comprehensive understanding of the genotype-specific differences in performance under N-deficiency conditions.


Patterns of online information use prior to middle-ear surgery: a retrospective cohort study.
This study aimed to identify what proportion of middle-ear surgery patients utilise the internet for information and to characterise which resources and media formats are used and for what durations. A single-arm, retrospective cohort study was performed using an online survey of English-speaking patients who underwent middle-ear surgery over a three-year period across two otology practices. Of 260 invitees, 165 responded. A total of 122 used online resources: 9.8 per cent used online resources for less than 15 minutes, 27.0 per cent used them for 15 to 29 minutes, 27.0 per cent used them for 30 to 59 minutes and 36.1 per cent used them for 60 minutes or more. Of online users with complete responses (108 of 122), the most used resources (used for 12 minutes or more) were: written information (73.1 per cent); surgeons' websites (55.6 per cent); pictures, diagrams or photos (42.6 per cent); videos (37.0 per cent); and social media (10.2 per cent). At least 46.9 per cent of patients undergoing elective ear surgery use online resources. Most time is spent using written information, pictures, diagrams, photos and videos. Therefore, it is increasingly essential that accurate and informative resources in these formats are readily available online.


Compliance with Tobacco Promotion and Sale Laws in School Neighbourhoods in India
Objective: Regulation of sale of tobacco has given sufficient attention in India and little information exists about the impact of bans near schools. Our study aim was to check the levels of tobacco promotion, advertising and sales in school neighborhoods' of Central Delhi. Methods: Using multistage random sampling 15 schools were selected in Central Delhi. Areas 100 meters around each were mapped using a map tool and screened using a self designed questionnaire consisting of 26 questions, both closed and open ended, to determine the details of outlets, sales of tobacco and tobacco products, advertising, promotions, school roles, and children seeking tobacco. The data were subjected to statistical analysis. Results: The response rate was 65%. Outlet licenses were present in only 6 (3.47%). The point sale of tobacco was most frequently in tea stalls and a total of 173 (41.2%) outlets had some form of tobacco sale. The brands of smokeless tobacco sold more were shikar (50%) and classic citrus (30%). Advertisement or promotion of sales was mainly in the form of signs and displays (53%). Major schools did not have any no tobacco boards displayed. Conclusion: Sale of tobacco continues in central Delhi with a lack of compliance with the rules of COPTA. The implications of this non compliance in the Capital region is of major significance for the rest of the country.


Developing and evaluating nurse led discharge in acute medicine.
To develop and evaluate nurse-led discharge criteria for a clinical decision unit in a large NHS Foundation Trust Criteria for nurse led discharge were developed for patients presenting to hospital via the emergency department with chest pain, headache and deliberate self poisoning. Data on length of stay on CDU and readmission were collected for these patient groups during a 2 month period, during which the nurse-led criteria were introduced. Following introduction of the criteria a survey was conducted to evaluate staff opinions of the new system. A trend towards reduced length of stay was noted during the month after introduction of nurse-led discharge (18.26 hrs vs 20 hours p=0.582). Our staff survey indicated that the process was popular and has been continued since the study period. Nurse-led discharge using defined criteria is feasible and popular with staff in an acute medical setting.


Influence of the mechanical and geometrical parameters on the cellular uptake of nanoparticles: A stochastic approach.
Nanoparticles (NPs) are used for drug delivery with enhanced selectivity and reduced side-effect toxicity in cancer treatments. Based on the literature, the influence of the NPs mechanical and geometrical properties on their cellular uptake has been studied through experimental investigations. However, due to the difficulty to vary the parameters independently in such a complex system, it remains hard to efficiently conclude on the influence of each one of them on the cellular internalization of a NP. In this context, different mechanical / mathematical models for the cellular uptake of NPs have been developed. In this paper, we numerically investigate the influence of the NP's aspect ratio, the membrane tension and the cell-NP adhesion on the uptake of the NP using the model introduced in1 coupled with a numerical stochastic scheme to measure the weight of each one of the aforementioned parameters. The results reveal that the aspect ratio of the particle is the most influential parameter on the wrapping of the particle by the cell membrane. Then the adhesion contributes twice as much as the membrane tension. Our numerical results match the previous experimental observations.


Gastric specimens for diagnosing tuberculosis in adults unable to expectorate in Rawalpindi, Pakistan.
Setting: Adult pulmonary tuberculosis (TB) patients unable to expectorate quality sputum represent a diagnostic challenge. A private hospital in Pakistan routinely performs gastric aspiration in adults with difficulties expectorating. Objective: To assess the usefulness of gastric specimens (GS) in diagnosing pulmonary TB (PTB) and drug-resistant TB in adult presumptive TB patients unable to expectorate, and to compare the diagnostic yield and sensitivity of smear, culture and the Xpert® MTB/RIF assay. Design: This was a comparative cross-sectional study based on retrospective record review. Results: Of 900, 885 and 877 GS tested by smear, Xpert and culture, respectively, interpretable results were obtained for respectively 900 (100%), 859 (97.1%) and 754 (86.0%), with a diagnostic yield of respectively 23.6%, 30.3% and 24.9%. The yield was significantly higher for Xpert in previously treated patients. There were 313 patients with definite TB, defined as positive on Xpert and/or culture. The 82.8% sensitivity of Xpert was significantly higher than that of smear (61.0%) and culture (67.8%). Conclusion: GS obtained by aspiration under routine programme conditions is useful for detecting TB and drug-resistant TB in adult patients unable to expectorate. Xpert, with its rapid testing, high proportion of interpretable results and better sensitivity, can substantially improve the diagnosis of bacteriologically confirmed TB and rifampicin resistance.


Medicolegal aspects of the orthopaedic care for shoulder injuries.
The medicolegal aspects of orthopaedic care increasingly are becoming an important focus of physicians. Because of the rarity of publications on the subject, I will examine medical litigation in orthopaedics, specifically in regards to shoulder injuries. There are several reasons for recent increases in malpractice litigation. Increased orthopaedic specialization and advanced technologies have raised patient expectations while the media have informed patients of the potential financial rewards of litigation. I will discuss three cases of litigation regarding shoulder injuries including reasons for malpractice and what can be done to avoid it. In Case 1 I examine an implant failure of a rotator cuff repair. The failure was caused by a manufacturing error; therefore, the importance of being familiar with the equipment and the companies that a physician deals with is emphasized in this case. Case 2 is another failed rotator cuff repair; this litigation stemmed from poor patient selection and a lack of preoperative patient-physician communication. Finally, Case 3 involved retained hardware, a surgical mistake that often results in a substantial settlement because it is considered indefensible. These cases highlight the potential for malpractice and can be applied more broadly to all branches of orthopaedics. Most litigation, however, can be avoided with careful diagnostic procedures, greater experience with equipment, and better communication.


Population Pharmacokinetics to Model the Time-Varying Clearance of the PEGylated Asparaginase Oncaspar® in Children with Acute Lymphoblastic Leukemia.
The pharmacokinetics of the polyethylene glycol (PEG)-conjugated asparaginase Oncaspar® are characterized by an increase in elimination over time. The focus of our analysis is the better understanding of this time-dependency. In paediatric acute lymphoblastic leukemia therapy (AIEOP-BFM ALL 2009), two administrations of Oncaspar® (2500 U/m2 intravenously) in induction phase (14-day interval) and one single administration in reinduction were followed by weekly monitoring of asparaginase activity. Non-linear mixed-effects modeling techniques (NONMEM) were used. Samples indicating immunological inactivation were excluded to describe the pharmacokinetics under standard conditions. Models with time-constant or time-varying clearance (CL) as well as transit compartment models with an increase in CL over a chain of compartments were investigated. Models with time-constant elimination could not adequately describe 6107 asparaginase activities from 1342 patients. Implementing a time-varying CL improved the fit. Modeling an increase of CL over time after dose (Emax- and Weibull-functions) were superior to models with an increase of CL over time after the first administration. However, a transit compartment model came out to be the best structural model. The increase in elimination of PEGylated asparaginase appears to be driven by physicochemical processes that are drug-related. The observed hydrolytically in vitro instability of the drug leads to the hypothesis that this increase in CL might be due to an in vivo hydrolysis of the instable ester bond between PEG and the enzyme combined with an increased elimination of the partly de-PEGylated enzyme (Trial registered at www.clinicaltrials.gov , NCT0111744).


Wireless EEG System Achieving High Throughput and Reduced Energy Consumption Through Lossless and Near-Lossless Compression.
This work presents a wireless multichannel electroencephalogram (EEG) recording system featuring lossless and near-lossless compression of the digitized EEG signal. Two novel, low-complexity, efficient compression algorithms were developed and tested in a low-power platform. The algorithms were tested on six public EEG databases comparing favorably with the best compression rates reported up to date in the literature. In its lossless mode, the platform is capable of encoding and transmitting 59-channel EEG signals, sampled at 500 Hz and 16 bits per sample, at a current consumption of 337 A per channel; this comes with a guarantee that the decompressed signal is identical to the sampled one. The near-lossless mode allows for significant energy savings and/or higher throughputs in exchange for a small guaranteed maximum per-sample distortion in the recovered signal. Finally, we address the tradeoff between computation cost and transmission savings by evaluating three alternatives: sending raw data, or encoding with one of two compression algorithms that differ in complexity and compression performance. We observe that the higher the throughput (number of channels and sampling rate) the larger the benefits obtained from compression.


Pharmacologic Interventions to Prevent Delirium in Trauma Patients: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
To compare the relative efficacy of pharmacologic interventions in the prevention of delirium in ICU trauma patients. We searched Medical Literature Analysis and Retrieval System Online, Embase, and Cochrane Registry of Clinical Trials from database inception until June 7, 2022. We included randomized controlled trials comparing pharmacologic interventions in critically ill trauma patients. Two reviewers independently screened studies for eligibility, extracted data, and assessed risk of bias. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines for network analysis were followed. Random-effects models were fit using a Bayesian approach to network meta-analysis. Between-group comparisons were estimated using hazard ratios (HRs) for dichotomous outcomes and mean differences for continuous outcomes, each with 95% credible intervals. Treatment rankings were estimated for each outcome in the form of surface under the cumulative ranking curve values. A total 3,541 citations were screened; six randomized clinical trials (n = 382 patients) were included. Compared with combined propofol-dexmedetomidine, there may be no difference in delirium prevalence with dexmedetomidine (HR 1.44, 95% CI 0.39-6.94), propofol (HR 2.38, 95% CI 0.68-11.36), nor haloperidol (HR 3.38, 95% CI 0.65-21.79); compared with dexmedetomidine alone, there may be no effect with propofol (HR 1.66, 95% CI 0.79-3.69) nor haloperidol (HR 2.30, 95% CI 0.88-6.61). The results of this network meta-analysis suggest that there is no difference found between pharmacologic interventions on delirium occurrence, length of ICU stay, length of hospital stay, or mortality, in trauma ICU patients.


Novel ureteroscopic technique for treatment of prolonged caliceal leak after partial nephrectomy.
Caliceal leak after partial nephrectomy (PN) typically resolves with conservative management. However, persistent fistulae pose a formidable challenge that may require additional therapeutic actions. We describe a case of a patient with a solitary kidney who suffered a persistent urine leak following PN. A novel retrograde ureteroscopic approach was taken that utilized the combined techniques of caliceal fulguration and fibrin glue injection. Imaging demonstrated resolution of the caliceal fistula at 13 months postoperatively. Persistent urine leak after PN remains a burdensome complication that often requires creative steps to resolve. Our case presents a solution using a novel ureteroscopic technique.


Tenecteplase and return of spontaneous circulation after refractory cardiopulmonary arrest.
Even with the benefit of cardiopulmonary resuscitation, the prognosis of cardiac arrest remains poor. Multiple case series describe survival with the use of thrombolytic therapy for refractory cardiac arrest. Presumably thrombolysis treats that subset of cardiac arrest cases resulting from fulminant pulmonary embolism, or perhaps massive myocardial infarctions. Published reports to date have dealt exclusively with streptokinase, urokinase, reteplase, or recombinant tissue plasminogen activator. The authors report the first case of return of spontaneous circulation with the administration of tenecteplase. Tenecteplase is a recently developed reengineered isomer of tissue plasminogen activator that possesses many properties of the ideal cardiac arrest thrombolytic agent. It is bolus dosed, stable at room temperature before reconstitution, and is compatible with most other advanced cardiac life support medications. Because of clinical equivalency and its logistical advantages, tenecteplase should be evaluated as an alternative to other thrombolytics in future trials involving cardiac arrest.


Importance of margin status in outcome of breast-conserving surgery for carcinoma.
The importance of margin status in breast-conserving therapy (BCT) for breast cancer remains unclear. We reviewed our experience with BCT to determine the risk of local recurrence as a function of margin status. Stages I and II breast cancers treated with BCT between 1985 and 1990 were reviewed. Two hundred eleven patients were classified based on initial margin status: negative (more than 3 mm), close (3 mm or less), positive, or unknown. The incidence of reexcision and residual tumor is reported in each group. Patients with 36 months or more of follow-up (n = 183) were also stratified by final margin to examine rates of local recurrence and distant recurrence. Residual carcinoma was found in 0%, 24%, 44%, and 48% of the negative, close, positive, and unknown initial margin groups, respectively. The local recurrence rate was equivalent by Fisher exact test in patients with negative and close final margins (3%). The negative and close groups were not different by chi-squared analysis in terms of T stage, estrogen receptor status, and nodal status. Although one fourth of patients with close margins have residual tumor, recurrence rates are similar to those with negative margins. Reexcision of close margins is not necessary in patients who undergo BCT for carcinoma.


Selection for donor-specific cytotoxic T lymphocytes within the allografted human heart.
Lymphocytes were cultured from cardiac biopsies following heart transplantation using interleukin-2-conditioned medium. Using the technique of limiting dilution analysis the frequency of donor specific cytotoxic T lymphocytes was measured in cells cultured from biopsies and compared with that in peripheral blood lymphocytes taken at the same time as the biopsy. The graft cell population showed a considerably higher frequency of donor-specific CTL when compared with the PBL. CTL frequencies in the graft cells were always higher against the donor than against third-party cells. These data demonstrate that there was either selective sequestration or selective expansion of donor-reactive T cells in the heart following cardiac transplantation. These results emphasize the need to investigate more closely the events occurring in the heart, and may explain the lack of specificity and sensitivity in immune monitoring (IM) or cytoimmune monitoring (CIM) seen in many centers.


Carotid intima media thickness and high sensitivity C-reactive protein as markers of cardiovascular risk in a malaysian population.
Carotid intima media thickness (CIMT) being a cost effective and easily performed technique is useful in the detection of subclinical atherosclerosis and has been shown to be a prognosticator of cardiovascular events. The primary objective of this study was to obtain the distribution of CIMT measurements, highly sensitive C reactive protein (hs-CRP) and assessing health awareness and attitudes of the Malaysian population at cardiovascular disease (CVD) risk and not receiving lipid lowering agents. Secondarily the study sought to assess the significance of the relationship between these measurements against various patient characteristics. Measurements of CIMT are obtained by ultrasonography of 12 sites within the common carotid artery was recorded for 123 subjects from a single centre tertiary hospital of Malaysia who had two or more CVD risk factors but were not receiving lipid lowering therapy. CVD risk factors and lipid and glucose profiles were analyzed with respect to distribution of CIMT and high-sensitivity Creactive protein (hs-CRP) values. The mean-max CIMT was 0.916±0.129mm (minimum 0.630mm, maximum 1.28mm) and the mean-mean CIMT was 0.743±0.110mm (minimum 0.482mm, maximum 1.050mm) and mean hs-CRP was 0.191mg/dL (minimum 0.030mg/dL, maximum 5.440mg/dL). Multivariate analyses confirmed a significant association between increasing CIMT and increasing age, total and low density lipoprotein cholesterol while log-transformed hs-CRP levels showed significant association with increasing body mass index, waist circumference, high blood glucose and triglyceride levels. Our patients had good health awareness on CVD. Newly defined CIMT measurements and hs-CRP levels may be useful adjunctive tools to screen for atherosclerosis in the Malaysian population. It may help in refining risk stratification on top of traditional clinical assessment.


Sports participation of Dutch lower limb amputees.
To analyze sports participation of Dutch lower limb amputees and factors influencing sports participation. A cross-sectional survey was performed. Dutch lower limb amputees (N = 2039) were invited to participate in a postal survey addressing personal and amputation characteristics, physical limitations, sports participation, skin problems, and prosthesis use. Only data concerning personal and amputation characteristics together with the data concerning sports participation were used for this study. Of the 816 questionnaires received, 780 were suitable for statistical analysis. The mean age of the participants was 59.6 years (SD 14.8), 62% were men and 27% of the amputations was due to vascular diseases or diabetes. Only 15% of all respondents participate in sports at least 5 hours a month. Smoking (odds ratio: 0.55), an age older than 60 (odds ratio: 0.97 per year), and a vascular cause of amputation (odds ratio: 0.42) were negatively associated with sports participation. Less than 15% of the Dutch lower limb amputees participate in sports at least 5 hours per month. Older age, smoking and a vascular cause of amputation have a negative influence on the sports participation of these individuals.


Enhancing their likelihood for a positive future: focus groups reveal the voice of inner-city youth.
To learn directly from adolescents living in a challenging environment what they believe would most influence their likelihood of achieving a positive future. A teen-centered methodology used focus groups, nominal group technique sessions, and a survey to allow adolescents to develop, prioritize, and explain their own solutions. AmeriCorps workers guided in-school 8th-, 9th-, and 12th-graders in north Philadelphia through a 4-stage hierarchical process. This article reports the qualitative explanations offered by adolescents in Stage 4 explanatory focus groups. In these 10 groups, 91 youth added meaning and context to the ideas their fellow students generated and prioritized. Transcriptions were reviewed for consistent themes. Direct quotations representative of those themes are offered here. Students in all grades gave highest priority to solutions that would promote educational or job opportunities. Solutions that would ameliorate disruptive surroundings or reduce risk behaviors were generally rated lower. Focus group participants agreed that education, improved employment opportunities, connection with adults, and meaningful uses of their time were the keys to positive change. They also expressed how a risky environment impacted on their chances for success and offered strategies for reducing their risks. They discussed how positive forces might counter the draw of the streets. Although most adolescents remained optimistic, some viewed problems in their neighborhood as intractable. An individual's ability to draw from protective resources while avoiding the challenges inherent to a risky environment may determine his/her ability to succeed. Youth have clear ideas about how they can best be supported to succeed. Adults should consider and incorporate their wisdom as they plan strategies to develop productive young adults.


Interferon Kappa Is Important for Keratinocyte Host Defense against Herpes Simplex Virus-1.
Type I interferon kappa (IFNκ) is selectively expressed in human keratinocytes. Herpes simplex virus-1 (HSV-1) is a human pathogen that infects keratinocytes and causes lytic skin lesions. Whether IFNκ plays a role in keratinocyte host defense against HSV-1 has not been investigated. In this study, we found that IFNκ mRNA expression was induced by addition of recombinant IFNκ and poly (I:C); and its expression level was significantly greater than IFNa2, IFNb1, and IFNL1 in both undifferentiated and differentiated normal human epidermal keratinocytes (NHEKs) under resting and stimulation conditions. Although IFNe was expressed at a relatively higher level than other IFNs in resting undifferentiated NHEK, its expression level did not change after stimulation with recombinant IFNκ and poly (I:C). HSV-1 infection inhibited gene expression of IFNκ and IFNe in NHEK. Silencing IFNκ in NHEK led to significantly enhanced HSV-1 replication in both undifferentiated and differentiated NHEK compared to scrambled siRNA-transfected cells, while the addition of recombinant IFNκ significantly reduced HSV-1 replication in NHEK. In addition, we found that IFNκ did not regulate protein expression of NHEK differentiation markers. Our results demonstrate that IFNκ is the dominant type of IFNs in keratinocytes and it has an important function for keratinocytes to combat HSV-1 infection.


Developing an App by Exploiting Web-Based Mobile Technology to Inspect Controlled Substances in Patient Care Units.
We selected iOS in this study as the App operation system, Objective-C as the programming language, and Oracle as the database to develop an App to inspect controlled substances in patient care units. Using a web-enabled smartphone, pharmacist inspection can be performed on site and the inspection result can be directly recorded into HIS through the Internet, so human error of data translation can be minimized and the work efficiency and data processing can be improved. This system not only is fast and convenient compared to the conventional paperwork, but also provides data security and accuracy. In addition, there are several features to increase inspecting quality: (1) accuracy of drug appearance, (2) foolproof mechanism to avoid input errors or miss, (3) automatic data conversion without human judgments, (4) online alarm of expiry date, and (5) instant inspection result to show not meted items. This study has successfully turned paper-based medication inspection into inspection using a web-based mobile device.


When less may be more: calorie restriction and response to cancer therapy.
Calorie restriction (CR) extends lifespan and has been shown to reduce age-related diseases including cancer, diabetes, and cardiovascular and neurodegenerative diseases in experimental models. Recent translational studies have tested the potential of CR or CR mimetics as adjuvant therapies to enhance the efficacy of chemotherapy, radiation therapy, and novel immunotherapies. Chronic CR is challenging to employ in cancer patients, and therefore intermittent fasting, CR mimetic drugs, or alternative diets (such as a ketogenic diet), may be more suitable. Intermittent fasting has been shown to enhance treatment with both chemotherapy and radiation therapy. CR and fasting elicit different responses in normal and cancer cells, and reduce certain side effects of cytotoxic therapy. Findings from preclinical studies of CR mimetic drugs and other dietary interventions, such as the ketogenic diet, are promising for improving the efficacy of anticancer therapies and reducing the side effects of cytotoxic treatments. Current and future clinical studies will inform on which cancers, and at which stage of the cancer process, CR, fasting, or CR mimetic regimens will prove most effective.


ANXIETY LEVELS IN PATIENTS WITH PAROXY-SMAL SUPRAVENTRICULAR TACHYCARDIA IN RELATION WITH THE PATIENT DEMOGRAPHICS, TYPE OF SUPRAVENTRICULAR TACHYCARDIA AND THEIR PERSONALITY TYPE.
The aim of the study was to evaluate the incidence of different personality types and state and trait anxiety levels in patients with paroxysmal supraventricular tachycardia and their association with patients age, gender and the mechanism of the paroxysmal SVT. 62 patients with documented paroxysmal supraventricular tachycardia who underwent endocardial eletrophysiological study and catheter ablation of the paroxysmal SVT were included in the study. The patients were asked to fill out the Myers-Brigss Type Indicator and State-Trait Anxiety Inventory questionnaires and the results were analyzed and correlated with the arrhythmia mechanism determined during electrophysiological study and catheter ablation procedure, and the patients' demographics (age and gender). There was no significant difference in State (mean 41.53±13.51, p=0.893) or Trait (mean 44.70±12.62, p=0.315) anxiety scores according to gender although higher scores were found in females. Older patients (≥50 years old compared to <50 years old) had higher anxiety scores but with no statistical significance (p=0.344 for state anxiety and p=0.100 for trait anxiety). The patients with AVNRT had significantly higher Trait anxiety scores (mean 46.82±10.52) than the patients with AVRT or AT (mean 40.59±10.91) (p=0.032). State anxiety score was not significantly different between patients with different SVT types (p=0.706). Anxiety is an important factor to be considered in patients with paroxysmal supraventricular tachycardia. It doesn't seem to be associated with different personality types. Female and older patients tend to show higher anxiety levels. The atrioventricular Nodal Reentrant Tachycardia (AVNRT) is associated with significantly higher trait anxiety levels compared to other types of paroxysmal supraventricular tachycardia.


Silane coatings of metallic biomaterials for biomedical implants: A preliminary review.
In response to increased attention in literature, this work provides a qualitative review surrounding the application of silane-based coatings of metallic biomaterials for biomedical implants. Included herein is both a brief summary of existing knowledge and concepts regarding silane-based thin films, along with an analysis of recent peer-reviewed publications and advances towards their practical application for biomedical coatings. Specifically, the review identifies innovative silane-based coatings according to their molecular identity and film structure and analyses their impact on the biocorrosion resistance, protein adsorption, cell viability, and antimicrobial properties of the overall coated implant. It is shown that a range of common silanes clearly exhibit promising properties for biomedical implant coatings, but further work is needed, particularly on mechanisms of physiological interaction and characteristic effects of silane functional groups, before seeing clinical use. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2901-2918, 2018.


Direct evidence of atomic-scale structural fluctuations in catalyst nanoparticles.
Rational catalyst design requires an atomic scale mechanistic understanding of the chemical pathways involved in the catalytic process. A heterogeneous catalyst typically works by adsorbing reactants onto its surface, where the energies for specific bonds to dissociate and/or combine with other species (to form desired intermediate or final products) are lower. Here, using the catalytic growth of single-walled carbon nanotubes (SWCNTs) as a prototype reaction, we show that the chemical pathway may in-fact involve the entire catalyst particle, and can proceed via the fluctuations in the formation and decomposition of metastable phases in the particle interior. We record in situ and at atomic resolution, the dynamic phase transformations occurring in a Cobalt catalyst nanoparticle during SWCNT growth, using a state-of-the-art environmental transmission electron microscope (ETEM). The fluctuations in catalyst carbon content are quantified by the automated, atomic-scale structural analysis of the time-resolved ETEM images and correlated with the SWCNT growth rate. We find the fluctuations in the carbon concentration in the catalyst nanoparticle and the fluctuations in nanotube growth rates to be of complementary character. These findings are successfully explained by reactive molecular dynamics (RMD) simulations that track the spatial and temporal evolution of the distribution of carbon atoms within and on the surface of the catalyst particle. We anticipate that our approach combining real-time, atomic-resolution image analysis and molecular dynamics simulations will facilitate catalyst design, improving reaction efficiencies and selectivity towards the growth of desired structure.


Starving for a drink: Sexual objectification is associated with food-restricted alcohol consumption among college women, but not among men.
Interpersonal sexual objectification, or being treated as an object by others, is linked to poorer body image and, in turn, engagement in weight management behaviors that promote conformity to unrealistic appearance standards while simultaneously undermining health. Although these associations emerge consistently among women, the evidence has been less clear among men. The present study introduced a novel weight control behavior, food-restricted alcohol consumption (i.e., limiting food intake prior to alcohol consumption), and examined whether sexual objectification was associated with this phenomenon and whether this association differed among women and men. During the fall of 2012 and the spring of 2013, 410 undergraduates reported how often they felt objectified by others and restricted what they ate before drinking alcohol in the past month. Controlling for past drinking, sexual objectification was significantly and positively associated with food-restricted alcohol consumption for women; however, sexual objectification was unrelated to food-restricted alcohol consumption for men. The results suggest that sexual objectification might operate differently across the sexes and particularly be related to this specific health-risk behavior among women.


MCR Approach Revealing Protein, Water, and Lipid Depth Profile in Atopic Dermatitis Patients' Stratum Corneum via in Vivo Confocal Raman Spectroscopy.
Confocal Raman has been widely used for measuring the water concentration profile inside skin to calculate clinical end points, such as stratum corneum thickness. In this article, multivariate curve resolution was applied to resolve the pure components contained in high frequency (2500-4000 cm-1) in vivo confocal Raman data. Three components were identified by comparing with reference spectra of materials in skin. These three components are water, protein, and lipid. The score values associated with these three components were transformed to mass ratio by leveraging the response factors for protein and lipid in a calibration model utilizing the pure material spectra. The concentration profiles for protein and lipid as a function of depth across the stratum corneum are utilized as new clinical end points. Results from an in vivo study with individuals who experience atopic dermatitis symptoms successfully demonstrated a statistical difference between Raman spectra from nonlesion and lesion skin sites. Trends in the depth profiles of the skin components are consistent with previous literature reports.


H19 promotes the migration and invasion of colon cancer by sponging miR-138 to upregulate the expression of HMGA1.
Colon cancer is the most common digestive system malignancy, along with high mortality rate, familial transmissibility and hepatic metastasis. Our study investigated the role of long non-coding RNA H19 in colon cancer. We found that H19 was overexpressed in colon cancer tissues and cell lines, the interference of H19 by short hairpin RNA (shRNA) effectively decreased the migration and invasion of colon cancer cells (HT-29 and RKO). Besides, miR-138 was predicted a target of H19, and low expression of miR-138 was found in colon cancer tissues and cells. The silence of H19 strongly increased the expression of miR-138. The decreased level of miR-138 was elevated adding miR-138 mimic in RKO cells transfected with lncRNA-H19. Similarly, the upregulated level of miR-138 was downregulated adding miR-138 inhibitor in RKO cells transfected with H19 shRNA. The luciferase reporter confirmed the targeting reaction between H19 and miR-138. Moreover, the high-mobility group A (HMGA1) protein was predicted as a target of miR-138. HMGA1 was suppressed by H19 shRNA and could be up-regulated by miR-138 inhibitor. The migration and invasion ability of colon cancer was restrained by H19 shRNA and promoted by miR-138 inhibitor. Finally, the in vivo experiment revealed that H19 shRNA strongly reduced the tumor growth and tumor volume. H19 shRNA also inhibited metastasis via suppressing hepatic metastases and the expression of metastasis-related proteins. Taken together, our research indicated an H19-miR138-HMGA1 pathway in regulating the migration and invasion of colon cancer, providing new insight for treatment of colon cancer.


Sequential determination of nickel and cadmium in tobacco, molasses and refill solutions for e-cigarettes samples by molecular fluorescence.
In this work, a new procedure was developed for separation and preconcentration of nickel(II) and cadmium(II) in several and varied tobacco samples. Tobacco samples were selected considering the main products consumed by segments of the population, in particular the age (youth) and lifestyle of the consumer. To guarantee representative samples, a randomized strategy of sampling was used. In the first step, a chemofiltration on nylon membrane is carried out employing eosin (Eo) and carbon nanotubes dispersed in sodium dodecylsulfate (SDS) solution (phosphate buffer pH 7). In this condition, Ni(II) was selectively retained on the solid support. After that, the filtrate liquid with Cd(II) was re-conditioned with acetic acid /acetate buffer solution (pH 5) and followed by detection. A spectrofluorimetric determination of both metals was carried out, on the solid support and the filtered aqueous solution, for Ni(II) and Cd(II), respectively. The solid surface fluorescence (SSF) determination was performed at λem = 545nm (λex = 515nm) for Ni(II)-Eo complex and the fluorescence of Cd(II)-Eo was quantified in aqueous solution using λem = 565nm (λex = 540nm). The calibration graphs resulted linear in a range of 0.058-29.35μgL-1 for Ni(II) and 0.124-56.20μgL-1 for Cd(II), with detection limits of 0.019 and 0.041μgL-1 (S/N = 3). The developed methodology shows good sensitivity and adequate selectivity, and it was successfully applied to the determination of trace amounts of nickel and cadmium present in tobacco samples (refill solutions for e-cigarettes, snuff used in narguille (molasses) and traditional tobacco) with satisfactory results. The new methodology was validated by ICP-MS with adequate agreement. The proposed methodology represents a novel fluorescence application to Ni(II) and Cd(II) quantification with sensitivity and accuracy similar to atomic spectroscopies, introducing for the first time the quenching effect on SSF.


Safety evaluation of the food enzyme cellulase from the non-genetically modified Aspergillus niger strain 294.
The food enzyme cellulase (4-(1,3;1,4)-β-d-glucan-4-glucanohydrolase; EC 184.108.40.206) is produced with the non-genetically modified Aspergillus niger strain 294 by Kerry Ingredients & Flavours Ltd. The food enzyme is considered free from viable cells of the production organism. The enzyme is intended to be used in eight food manufacturing processes: baking processes, cereal-based processes, brewing processes, grain treatment for the production of starch and gluten fractions, fruit and vegetable processing for juice production, fruit and vegetable processing for products other than juices, distilled alcohol production and wine and wine vinegar production. Since residual amounts of total organic solids (TOS) are removed during distilled alcohol production and grain treatment for the production of starch and gluten fractions, dietary exposure was only calculated for the remaining six food manufacturing processes. It was estimated to be up to 5.706 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 794 mg TOS/kg bw per day, the highest dose tested. The calculated margin of exposure for each age group was 184 (infants), 146 (toddlers), 139 (children), 219 (adolescents), 305 (adults) and 441 (the elderly). A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and four matches were found. The Panel considered that, under the intended conditions of use (other than distilled alcohol production), the risk of allergic reactions by dietary exposure cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use for adolescents, adults and the elderly.


Growth in fishes.
Fishes exhibit a 'determinate' type of growth in short-lived species of warmer regions and an 'indeterminate' type in long-lived species of colder regions. Growth is measured in units of length and weight and is best represented as the specific growth rate. The relationship between weight and length provides an index of the state of well-being of a fish (condition factor 'K'). Growth could also be measured by using certain other criteria such as glycine uptake by scales, hepatosomatic index, RNA:DNA ratio and protein retention in the tissues. Nutrition, including the quality and quantity of food, plays a significant role in growth regulation. A number of environmental factors, such as temperature, oxygen concentration, salinity and photoperiod, influence the rate of growth. Recent data suggest that genotypes, hormones and physiological conditions of the individual are also equally important endogenous regulators of growth.


Mixed-Generation PAMAM G3-G0 Megamer as a Drug Delivery System for Nimesulide: Antitumor Activity of the Conjugate Against Human Squamous Carcinoma and Glioblastoma Cells.
Polyhydroxylated dendrimer was synthesized from poly(amidoamine) (PAMAM) dendrimer generation 3 by addition of glycidol (G3gl). G3gl megamer was further modified by binding PAMAM G0 dendrimers by activation of G3gl with p-nitrophenylchloroformate, followed by the addition of excess PAMAM G0 and purification using dialysis. The maximum G0 binding capacity of G3gl was 12 in the case when G0 was equipped with two covalently attached nimesulide equivalents. Nimesulide (N) was converted into N-(p-nitrophenyl) carbonate derivative and fully characterized using X-ray crystallography and spectral methods. Nimesulide was then attached to G0 via a urea bond to yield G02N. The mixed generation G3gl-G02N megamer was characterized using 1H NMR spectroscopy, and its molecular weight was estimated to be 22.4 kDa. The AFM image of G3gl-G02N deposited on mica demonstrated aggregation of nimesulide-covered megamer. The height of the deposited megamer was 8.5 nm. The megameric conjugate with nimesulide was tested in vitro on three human cell lines: squamous cell carcinoma (SCC-15) and glioblastoma (U-118 MG) overexpressing cyclooxygenase-2 (COX-2), and normal skin fibroblasts (BJ). The conjugate efficiently penetrated into all cells and was more cytotoxic against SCC-15 than against BJ. Moreover, the conjugate produced a strong and selective antiproliferative effect on both cancer cell lines (IC50 < 7.5 µM).


Neonatal sex steroids affect ventilatory responses to aspartic acid and NMDA receptor subunit 1 in rats.
We hypothesized that administration of estradiol benzoate to males and testosterone propionate to female neonatal rat pups alters sex-specific ventilatory responses to aspartic acid with correspondent changes in N-methyl-D-aspartate receptor subunit 1 (NR1) expression determined by Western blot in specific brain regions. One-day-old rat pups received estradiol benzoate, testosterone propionate, or vehicle and were studied at weanling and adulthood. Different groups had distinct patterns of changes in tidal volume and frequency of breathing after aspartic acid administration. NR1 expression in hypothalamus was altered by age, sex, and treatment. Medullary and pontine NR1 expression correlated with baseline ventilation and magnitude of the ventilatory response to aspartic acid in some groups. Thus 1) tidal volume and breathing frequency patterns in response to aspartic acid are gender, age, and treatment dependent; 2) sex, age, and exogenous steroid hormones affect NR1 expression primarily in the hypothalamus; and 3) there is correlation between NR1 expression in pons and medulla with ventilatory parameters.


Universal health coverage: breakthrough or great white elephant?
Will the Sustainable Development Goal 3 sub-goal "Achieve universal health coverage, including financial risk protection, access to quality essential health care services and…safe, effective, quality and affordable essential medicines and vaccines for all" be judged a breakthrough or a great white elephant in implementation, when we look back with the clear eyes of hindsight in 2030? What are the ways in which this agenda might play out in implementation and why might it do so? Drawing on a desk review, this Essay explores dominant ideas, ideology, institutions, and interests in relation to global versus Ghana national health priorities since the WHO constitution came into effect in 1948, to reflect on these questions.


Vitreous fluorophotometry in children with type I diabetes mellitus.
A clinical, biochemical and ocular study was carried out on 17 children with type I diabetes mellitus. Eight had no clinical or angiographic evidence of retinopathy (Stage 0), seven had stage 1, one had stage 2 background retinopathy (Malone's classification) and one had intraretinal microvascular abnormalities. The vitreous fluorescein concentration 3 to 5 mm in front of the macula in those without retinopathy varied from low to abnormally high, while the concentrations in those with retinopathy were above normal. There was no correlation between haemoglobin A1 estimations taken at the time of the study and the vitreous fluorophotometry readings. This variation in fluorophotometry values obtained in diabetics with stage 0 disease differs from the findings in previous reports and may be of prognostic value in determining those patients at risk of developing retinopathy, and may be an indication for improving diabetic control.