The effects of high pressure treatment on the structural and digestive properties of myoglobin.
The effects of high pressure treatment (100-400 MPa for 20 min) on the structural and digestive properties of myoglobin were investigated by UV-vis absorption spectroscopy, intrinsic and synchronous fluorescence spectroscopy and molecular dynamics simulation. High pressure treatment induced the exposure of aromatic residues and changed the interaction between heme and globin, which in turn increased the gastrointestinal digestibility of myoglobin. Molecular dynamics simulation indicated that the hydrophobic interaction and hydrogen bonds of the myoglobin-pepsin complex were weakened after high pressure treatment, but the dipolar interaction was strengthened. The findings revealed the mechanisms on high pressure-induced increase in digestibility of myoglobin.


Food, physiology and drug delivery.
Gastrointestinal physiology is dynamic and complex at the best of times, and a multitude of known variables can affect the overall bioavailability of drugs delivered via the oral route. Yet while the influences of food and beverage intake as just two of these variables on oral drug delivery have been extensively documented in the wider literature, specific information on their effects remains sporadic, and is not so much contextually reviewed. Food co-ingestion with oral dosage forms can mediate several changes to drug bioavailability, yet the precise mechanisms underlying this have yet to be fully elucidated. Likewise, the often detrimental effects of alcohol (ethanol) on dosage form performance have been widely observed experimentally, but knowledge of which has only moderately impacted on clinical practice. Here, we attempt to piece together the available subject matter relating to the influences of both solid and liquid foodstuffs on the gastrointestinal milieu and the implications for oral drug delivery, with particular emphasis on the behaviour of modified-release dosage forms, formulation robustness and drug absorption. Providing better insight into these influences, and exemplifying cases where formulations have been developed or modified to circumvent their associated problems, can help to appropriately direct the design of future in vitro digestive modelling systems as well as oral dosage forms resilient to these effects. Moreover, this will help to better our understanding of the impact of food and alcohol intake on normal gut behaviour and function.


Steroid alkaloid glycosides from Solanum robustum.
Solamargine, solasonine, N-hydroxyrobustine and a new glycoalkaloid, N-hydroxysolamargine, has been isolated from the leaves of Solanum robustum, the structure of which has been elucidated as (25R)-3beta-{O-alpha-L-rhamnopyranosyl-(1-->2)-O-[alpha-L- rhamnopyranosyl- (1-->4)]-beta-D-glucopyranosyloxy}-22alphaN- spirosol-5-en-N-ol.


Mechanically durable anti-bacteria non-fluorinated superhydrophobic sponge for highly efficient and fast microplastic and oil removal.
Microplastics (MPs) pollution evolves into a global environmental problem to be solved urgently. Although many studies are exploring ways to remove MPs from water environment, most of them are lack of selectivity and low efficiency. Herein, considering the fascinating absorption selectivity of superwetting materials, a robust magnetic-responsive superhydrophobic and superoleophilic sponge was firstly used to quickly eliminate MPs from water with very high efficiency. The functional sponge was fabricated by a non-fluorinated coating technique that consisted of polydimethylsiloxane (PDMS) grafted Fe3O4 particle, PDMS grafted halloysite nanotubes, and PDMS binder. The coated sponge achieved excellent mechanically durable and chemically stable superhydrophobicity that resisted a series of severe treatments. It was unquestionable to show very fast oil absorption. What's more, it especially showed very high adsorption capacity (24.3-48.2 mg/g) and could quickly adsorb almost 100% MPs (polypropylene, polyvinyl chloride, and polyethylene) from aqueous suspensions. Moreover, the removal rates remained almost 100% for these MPs after 50 cycles. Besides, the coated sponge had excellent salt tolerance and antibacterial activity to Escherichia coli (E. coli) (99.91%) and Staphylococcus aureus (S. aureus) (90.46%). The adsorption mechanism of the coating was discussed from the perspectives of molecular structure, electronic effect, steric hindrance, and size-scale effect. The absorption driving force mainly derived from the intra-particle diffusion under capillary attraction, whilst slight electrostatic interaction, hydrogen bond interaction, and σ-p (or p-p) conjugation between PDMS and MPs. This functional sponge was destined to be a new strategy in the removal of MPs and other solid pollutants, especially in the high-salinity and rich-microorganism water environment.


Systemic fat embolism and the patent foramen ovale--a prospective autopsy study.
A fat embolism is a known and common complication of blunt force injuries, especially pelvic and long bones fractures. The aim of this study was to determine the importance of a patent foramen ovale (PFO) in developing systemic fat embolism (SFE) and eventually fat embolism syndrome (FES) in patients suffering from orthopaedic blunt injuries and consequent lung fat embolism. The sample was divided: 32 subjects with a sealed foramen ovale (SFO), and 20 subjects with a PFO. In our sample, there was no difference in either the incidence of renal fat embolism in subjects with PFO compared to those with SFO (Fisher's exact test 0.228, p=0.154) or in the grade of renal fat embolism (Pearson Chi-square 2.728, p=0.435). However, there was a statistically significant correlation between the grade of lung fat embolism and the number of fractured bones for the whole sample (Spearman's rho 0.271, p=0.052), but no correlation between the grade of lung fat embolism and the ISS or NISS (Pearson correlation 0.048, p=0.736, and 0.108, p=0.445, respectively). In our study, the presence of fat emboli in the kidney, i.e. SFE, could effectively be predicted by the grade of lung fat embolism (the moderate and slight grades of lung fat embolism were better predictors than the massive one: logistic regression - Wald. Coeff.=11.446, p=0.003, Wald. Coeff.=10.553, p=0.001, and Wald. Coeff.=4.128, p=0.042), and less effectively by presence of PFO (Wald. Coeff.=2.850, p=0.091). This study pointed out that lung and SFE are not pure biomechanical events, so the role of a PFO is not crucial in developing a lung fat embolism into a systemic embolism: the fat embolism is more of a biochemical and pathophsyiological event, than a biomechanical one. The appearance of a patent foramen ovale associated with a systemic fat embolism should be less emphasised: maybe arteriovenous shunts and anastomosis between the functional and nutritive, i.e. systemic circulation of lungs play a more important role in developing a SFE than a PFO.


Variations in endogenous phosphodiesterase activator content of rat aorta.
The variations with age and blood pressure in the cyclic nucleotide phosphodiesterase activator content of rat aorta were studied. Activator content increased with age and was less in mineralocorticoid-hypertensive than in control rats. These variations were more pronounced in the particulate than in the soluble fraction of aorta. The data do not demonstrate any relationship between the activator level and blood pressure, but they suggest that the activator may modulate cyclic nucleotide metabolism in rat aorta.


Antithrombotic prophylaxis in multiparous women with preeclampsia or intrauterine growth retardation in an antecedent pregnancy.
To determine whether prophylactic low dose aspirin (LDA) alone or in combination with low-molecular-weight-heparin (LMWH) reduces the recurrence of adverse pregnancy outcome (APO). In this retrospective cohort study, 84 consecutive multiparous patients with a previous history of severe preeclampsia (sPE) and intrauterine growth restriction (IUGR) (<10%ile) were assigned to receive no treatment, LDA alone, or LDA and LMWH. Odds ratios were calculated from logistic regression models. Combined LDA and LMWH significantly reduced the risk of developing IUGR in the index pregnancy (OR = 0.16, 95% CI: 0.03-0.98). Among women with antecedent sPE (n=52), combined treatment reduced APO in the index pregnancy (OR = 0.08, CI: 0.01-0.96), IUGR (OR = 0.02, CI: <0.01-0.46), and IUGR with sPE (OR = 0.08, CI: 0.01-0.96). Combined treatment with LDA and LMWH is strongly protective against the development of APO in a cohort of women with antecedent APO.


Development of a machine learning algorithm to predict intubation among hospitalized patients with COVID-19.
The purpose of this study is to develop a machine learning algorithm to predict future intubation among patients diagnosed or suspected with COVID-19. This is a retrospective cohort study of patients diagnosed or under investigation for COVID-19. A machine learning algorithm was trained to predict future presence of intubation based on prior vitals, laboratory, and demographic data. Model performance was compared to ROX index, a validated prognostic tool for prediction of mechanical ventilation. 4087 patients admitted to five hospitals between February 2020 and April 2020 were included. 11.03% of patients were intubated. The machine learning model outperformed the ROX-index, demonstrating an area under the receiver characteristic curve (AUC) of 0.84 and 0.64, and area under the precision-recall curve (AUPRC) of 0.30 and 0.13, respectively. In the Kaplan-Meier analysis, patients alerted by the model were more likely to require intubation during their admission (p < 0.0001). In patients diagnosed or under investigation for COVID-19, machine learning can be used to predict future risk of intubation based on clinical data which are routinely collected and available in clinical setting. Such an approach may facilitate identification of high-risk patients to assist in clinical care.


A further study on the number of silver stained granules of active nucleolus organizer regions in mitotic Yoshida and Zajdela rat experimental tumor cells.
Yoshida ascitic sarcoma and Zajdela ascitic hepatoma were investigated in Norway rats to provide more information on active nucleolus organizer regions (NORs) represented by silver stained granules (SSGs). Diploid Yoshida sarcoma cells were characterized by the presence of 6 (3 doublets) of SSGs in the metaphase and 3 + 3 SSGs in future daughter nuclei in the anaphase or telophase. In contrast Zajdela hepatoma cells (frequently hypoploid) possessed 6 SSGs less frequently in the metaphase and the number of anaphasic or telophasic cells with 3 SSGs in future daughter nuclei was also reduced. The number of SSGs in future nuclei of anaphasic or telophasic Yoshida sarcoma cells was usually the same, i.e. such anaphases or telophases were symetric. In Zajdela hepatoma cells the number of symetric anaphases and telophases was substantially reduced in favor of asymetric anaphases or telophases which contained different number of SSGs in future nuclei.


Relationship between metabolism and radioprotective activity of 2-phenylthiazolidine and its m-bromo derivative.
Molecular biotransformation of 2-phenylthiazolidine (1) and its m-bromo derivative (2) in the mouse is followed by autoradiographic studies and assessed by analysis of urinary metabolites. Cysteamine (4) is one of the metabolites of compounds 1 and 2. Radioprotective activity and efficacy over a period of time of 1, 2, and 4 correlate closely with distribution and metabolism.


Asymmetric supercapacitor of functionalised electrospun carbon fibers/poly(3,4-ethylenedioxythiophene)/manganese oxide//activated carbon with superior electrochemical performance.
Asymmetric supercapacitors (ASC) have shown a great potential candidate for high-performance supercapacitor due to their wide operating potential which can remarkably enhance the capacitive behaviour. In present work, a novel positive electrode derived from functionalised carbon nanofibers/poly(3,4-ethylenedioxythiophene)/manganese oxide (f-CNFs/PEDOT/MnO2) was prepared using a multi-step route and activated carbon (AC) was fabricated as a negative electrode for ASC. A uniform distribution of PEDOT and MnO2 on f-CNFs as well as porous granular of AC are well-observed in FESEM. The assembled f-CNFs/PEDOT/MnO2//AC with an operating potential of 1.6 V can achieve a maximum specific capacitance of 537 F/g at a scan rate of 5 mV/s and good cycling stability (81.06% after cycling 8000 times). Furthermore, the as-prepared ASC exhibited reasonably high specific energy of 49.4 Wh/kg and low charge transfer resistance (Rct) of 2.27 Ω, thus, confirming f-CNFs/PEDOT/MnO2//AC as a promising electrode material for the future energy storage system.


Single tottering mutations responsible for the neuropathic phenotype of the P-type calcium channel.
Recent genetic and molecular biological analyses have revealed many forms of inherited channelopathies. Homozygous ataxic mice, tottering (tg) and leaner (tgla) mice, have mutations in the P/Q-type Ca2+ channel alpha1A subunit gene. Although their clinical phenotypes, histological changes, and locations of gene mutations are known, it remains unclear what phenotypes the mutant Ca2+ channels manifest, or whether the altered channel properties are the primary consequence of the mutations. To address these questions, we have characterized the electrophysiological properties of Ca2+ channels in cerebellar Purkinje cells, where the P-type is the dominant Ca2+ channel, dissociated from the normal, tg, and tgla mice, and compared them with the properties of the wild-type and mutant alpha1A channels recombinantly expressed with the alpha2 and beta subunits in baby hamster kidney cells. The most striking feature of Ca2+ channel currents of mutant Purkinje cells was a marked reduction in current density, being reduced to approximately 60 and approximately 40% of control in tg and tgla mice, respectively, without changes of cell size. The Ca2+ channel currents in the tg Purkinje cells showed a relative increase in non-inactivating component in voltage-dependent inactivation. Besides the same change, those of the tgla mice showed a more distinct change in voltage dependence of activation and inactivation, being shifted in the depolarizing direction by approximately 10 mV, with a broader voltage dependence of inactivation. In the recombinant expression system, the tg channel with a missense mutation (P601L) and one form of the two possible tgla aberrant splicing products, tgla (short) channel, showed a significant reduction in current density, while the other form of the tgla channels, tgla (long), had a current density comparable to the normal control. On the other hand, the shift in voltage dependence of activation and inactivation was observed only for the tgla (long) channel. Comparison of properties of the native and recombinant mutant channels suggests that single tottering mutations are directly responsible for the neuropathic phenotypes of reduction in current density and deviations in gating behavior, which lead to neuronal death and cerebellar atrophy.


Predictors for the Development of Hypoxia or Prolonged Acute Symptoms among Non-Hospitalized Mild-to-Moderate Patients with Coronavirus Disease 2019.
The coronavirus disease 2019 (COVID-19) pandemic remains a global public health concern. The clinical course and risk of developing severe illness among patients with COVID-19 who are at low-risk of severe COVID-19 remain uncertain. This retrospective cohort study from an isolation facility for low-risk COVID-19 patients in Japan evaluated the potential risks for severe disease with hypoxia (SpO2 ≤ 93%) or experiencing prolonged isolation period longer than 14 days with persistent acute symptoms. The study was performed before the spread of the alpha variant in the country and before the start of a nationwide mass vaccination campaign against COVID-19. Among the 929 participants with reliable outcome data regarding the development of hypoxia, 63 (6.8%) developed severe disease with hypoxia during their stays at the facility. Higher age [adjusted odds ratio (aOR), 1.08; 95% confidence interval (CI), 1.06-1.10] and male sex (aOR, 4.70; 95% CI, 2.39-9.22) were associated with this outcome. As for the experience of prolonged isolation period, higher age (aOR, 1.02; 95% CI, 1.01-1.04), atopic diseases (aOR, 1.69, 95% CI, 1.09-2.64), presence of cough at onset (aOR, 1.64; 95% CI, 1.09-2.48), and prescription of oral antibiotics before positive test results for COVID-19 (aOR, 2.37; 95% CI, 1.33-4.22) were associated with this outcome. In summary, 5-10% of low-risk COVID-19 patients later develop hypoxia. Older age and male sex were associated with both the development of hypoxia and prolonged acute symptoms. The unnecessary prescription of antibiotics before COVID-19 diagnosis may prolong COVID-19 symptoms.


Cryogenic Refrigerant Burns: A Rare Occupational Hazard.
Cryogenic burns induced by coolant gases used in refrigerators and air conditioners are rarely encountered, despite the wide use of these gases. To date, only a few cases have been reported in the literature. This study examined the occupational circumstances leading to such injuries, relevant injury sites, types of chemicals involved, and treatment measures. This study was conducted in a tertiary burn center in India between March 2015 and March 2019. The demographic details, chemicals involved, and burn regions and characteristics were analyzed. There were 15 burn cases all involving injury to the hand. All injuries were managed initially with dressings and nonoperative management. One patient required anti-edema therapy with limb elevation and fingertip debridement, while another patient required skin grafting. All patients had satisfactory hand function after treatment. Cryogenic burn injuries caused by refrigerants are rare, and their etiology varies considerably. Exposure time is the primary factor that determines burn depth and severity; hence, reducing exposure time is important in first aid. Our findings suggest that after exposure, the patient should be treated in a specialized burn center. Adequate knowledge regarding the pathophysiology of these types of burn injuries and their management is necessary; otherwise, misjudgments in the treatment plan can lead to adverse consequences.


Measurement of enthalpy and volume changes in photoinitiated reactions on the ms timescale with a novel pressure cell.
Time-resolved photoacoustics is an excellent method with which to measure enthalpy and volume changes of photochemical and photobiological reactions. However, it fails at times longer than approximately 10 micros. The design principles of a pressure or volume cell covering the time range of 20 micros to several seconds is presented. The sensitivity of the cell has been verified and its application to the photocycle of bacteriorhodopsin is presented. Because of the similar cell structure and data analysis it is now possible to determine enthalpy and volume changes in photo-initiated reactions over the timescale of nanoseconds to seconds with the same solution.


Radiation resistance of clinical Acinetobacter spp.: a need for concern?
As part of an epidemiological investigation of hospital infections caused by Acinetobacter spp. the radiation resistance of 15 clinical isolates and four reference strains was assessed. The radiation resistance (in D-6 values, viz. the dose necessary for reducing the initial number of colony forming units by a factor of 10(6)) was, in general, higher in the isolates of A. radioresistens than in the isolates of the A. calcoaceticus-A. baumannii complex and of A. lwoffi. However, the least resistant isolates of A. radioresistens had a D-6 value equal to or lower than the most resistant isolates of the other groups. The lowest D-6 values found were for two of the reference strains. The highest D-6 value was 35 kGy. Three isolates of A. johnsonii could not survive long enough in a dried preparation to make an assessment of the D-6 values possible. The radiation resistance of the 15 clinical isolates in the present study was higher than the resistance found in a study of similar isolates in 1970.


Clinical potential of inhibitors of survival pathways and activators of apoptotic pathways in treatment of cervical cancer: changing the apoptotic balance.
Cervical cancer is the most common gynaecological malignant disorder worldwide. The best possible treatment of locally advanced cervical cancer is a combination of radiation and cisplatin-based chemotherapy. However, 5-year overall survival is still only 52%. To improve treatment results, research should focus on the discovery of innovative drug strategies. Drugs directed at inducing tumour-cell apoptosis are regarded as important treatment modalities. Here, we present an overview of the molecular options that can change the apoptotic balance in cervical cancer, through increasing death-receptor-mediated apoptosis, the use of proteasome inhibitors, short interfering RNAs, or non-steroidal anti-inflammatory drugs (NSAIDs). Furthermore, the potential of attacking prosurvival signalling through the epidermal-growth-factor receptor and insulin-like-growth-factor receptor to support the apoptotic process is discussed. Additional research is needed to elucidate the clinical potential of these compounds in the treatment of cervical cancer.


Increased serum lactate dehydrogenase isoenzyme 1 and macro creatine kinase type 2 in a patient with lung cancer.
A 72-yr-old man, having a lung tumor with metastatic spread to liver and bone, was hospitalized with a lactate dehydrogenase (LD; EC 126.96.36.199) activity and a creatine kinase (CK; EC 188.8.131.52) activity in serum of 30 and 2 times the upper reference limit (URL), respectively. The LD isoenzyme-1/LD activity ratio was 62% (2 times URL). This ratio was maintained throughout hospitalization, during which LD activity increased up to 90 times URL. Macro CK type 2 activity represented almost all of the CK activity, which increased up to 4 times URL during hospitalization. The patient died the 29th day after admission. The enzyme abnormalities were thought to stem from tumor tissue.


Association Between State Hepatitis A Vaccination Requirements and Hepatitis A Vaccination Rates.
Using National Immunization Survey Child and Teen (2008-2017), we associated state vaccination requirements with hepatitis A (Hep A) vaccination rates in children and adolescents. States with school entry or both childcare and school entry requirements were associated with 35%-40% higher Hep A vaccination rates, compared with states without such requirements.


Endocrine, inflammatory and immune responses and individual differences in acute hypobaric hypoxia in lowlanders.
When lowlanders are exposed to environments inducing hypobaric hypoxia (HH) such as high mountains, hemodynamic changes occur to maintain oxygen levels in the body. However, changes to other physiological functions under such conditions have yet to be clarified. This study investigated changes in endocrine, inflammatory and immune parameters and individual differences during acute HH exposure using a climatic chamber (75 min of exposure to conditions mimicking 3500 m) in healthy lowlanders. Aldosterone and cortisol were significantly decreased and interleukin (IL)-6, IL-8 and white blood cell (WBC) counts were significantly increased after HH. Lower peripheral oxygen saturation (SpO2) was associated with higher IL-6 and WBC counts, and higher IL-8 was associated with higher cortisol. These findings suggest that endocrine, inflammatory and immune responses are evoked even with a short 75-min exposure to HH and individuals with lower SpO2 seemed to show more pronounced responses. Our results provide basic data for understanding the physiological responses and interactions of homeostatic systems during acute HH.


This civic honour is just the boost our humble nursing spirits need.
For the nurses of Belfast, May 25 marked a special occasion as Belfast City Council conferred the Freedom of the City award to the RCN and Belfast nurses.


Peripheral myxoma of the infratemporal region: An unusual case report.
Odontogenic myxoma (OM) is a rare locally invasive benign neoplasm, almost exclusively occurring in the jawbones, comprising 3-6% of all the odontogenic tumors. The mandible is more commonly involved than the maxilla. Intraoral soft tissue myxoma is an extremely rare lesion and only few reports are available in the literature. We present probably the first of its kind in literature a soft tissue OM occurring in an unusual location: the infratemporal fossa.


Plasma lipid lowering activity of acipimox in patients with type II and type IV hyperlipoproteinemia. Results of a multicenter trial.
A multicenter study was carried out in 130 out-patients to assess the plasma lipid lowering activity of acipimox in type IIa, IIb and IV hyperlipoproteinemia. The study consisted of two periods, an 8-week randomized, double-blind comparison of active drug versus placebo and a 16-week open follow-up with acipimox (400 mg and 250 mg t.i.d., respectively, in type II and IV patients). During the double-blind phase acipimox, compared to placebo, showed a highly significant triglyceride lowering effect in type IV patients (-43% vs. +4%, P less than 0.01), while reducing plasma cholesterol significantly in type II patients (-7% vs. -3%, P less than 0.05). Further reductions in plasma lipids were obtained in both types of hyperlipoproteinemia after the 16-week follow-up. In type II patients, total cholesterol fell by 9% in the former acipimox group and 17% in the former placebo group, whereas a 34% reduction in triglycerides was found in type IV patients previously treated with placebo. Treatment had to be discontinued in 4 patients during the double-blind phase and in 5 patients during follow-up, because of adverse events such as skin reactions and gastric disturbances. Statistical analysis of hematological and biochemical variables expressing safety did not show any significant change during treatment.


Climate change and livestock herders wellbeing in Pakistan: Does nexus of risk perception, adaptation and their drivers matter?
Rural people, particularly in developing nations, rely on livestock as a key source of income. In Pakistan, rural people depend profoundly on buffalo, cows, sheep, and goats to earn their livelihood. The systems of agricultural production are at risk because of the negative effects of climate change. It badly affects production and quality of milk and meat, animal health, productivity, breeding, feed, and rangelands of livestock production. Climate change risks assessment and adaptation are required to minimize losses from these effects, which are not just technical but also socioeconomically significant. Hence, based on data collected from 1080 livestock herders using a multistage sampling technique in Punjab, Pakistan this study aims to assess perceived impact of climate change on livestock production and to assess coping strategies. In addition, determinants of adaptation strategies and their effects on livestock production was also estimated. Binary Logistic Regression was used to identify the drivers of adaptation strategies. In addition, Multi Group Analysis (MGA) in Partial Least Squares Path Modelling (PLS-PM) was applied to compare adapter and non-adapter of climate change adaptation strategies. Findings indicated that there are spread of various diseases to livestock due to adverse effects of climatic variability. There was reduction in the availability of the livestock's feed. Moreover, competition of water and land resources of livestock was also increasing. Low production efficiency resulted in decline of milk yield and meat production. Likewise, mortality of livestock, increased in still births, reduction in reproductive performance, decline in animal fertility, longevity, and general fitness, decreased birthing rates, rises in age at foremost calving in beef cattle was also prevailing. There were different adaptation policies used by farmers to handle with climate change and these were influenced by several demographic, socioeconomic, and agronomic aspects. Findings indicated that nexus of risk perception, adaptation plans and their determinants are beneficial to reduce the consequences of climatic variability and it improve the wellbeing of the herders. Risk management system may be created to protect livestock against losses caused by extreme weather events by providing awareness regarding influence of climate change on livestock. Easy and cheaper credit should be provided to the farmers to manage with the vulnerabilities of climate change.


Molecular ordering in self-organized dye particles: polarized evanescent-field studies.
Self-organized rhodamine 6G particles prepared by wetting/dewetting process of an ethanol solution on a hydrophilic glass surface did show fluorescence without quenching. Polarized evanescent-field excitation showed that the molecule's transition moment within dye particles was oriented unidirectionally and parallel to the substrate surface. The deduced dye orientation showed correlation between adjacent particles, which implies a simultaneous aggregate growth from a common crystal seed grown in a possible 'arm' region connecting the adjacent droplets just before these droplets were disconnected upon solvent evaporation. The dye orientation of most particles pointed about 45 degrees off the dewetting direction. By contrast, the particles of another pi-conjugated NK1420 dye, J-aggregates of which grow easily from an oversaturated solution, showed dye orientation along the dewetting direction preferably, still indicating the effect of self-organization, however based on a different mechanism.


Glycerin prevents the 'heat-death' of Ehrlich ascites tumor cells.
When heated to 45 degrees C for 20 min Ehrlich ascites tumor and NK-lymphoma cells are irreversibly damaged, so that they lose transplantability. The presence of 7-8% glycerol during heat treatment protects EAT cells completely and NK-lymphoma cells partly against this injury.


Enhanced 2,3-butanediol production by Klebsiella pneumoniae SDM.
Enhanced 2,3-butanediol (BD) production was carried out by Klebsiella pneumoniae SDM. The nutritional requirements for BD production by K. pneumoniae SDM were optimized statistically in shake flask fermentations. Corn steep liquor powder and (NH(4))(2)HPO(4) were identified as the most significant factors by the two-level Plackett-Burman design. Steepest ascent experiments were applied to approach the optimal region of the two factors and a central composite design was employed to determine their optimal levels. The optimal medium was used to perform fed-batch fermentations with K. pneumoniae SDM. BD production was then studied in a 5-l bioreactor applying different fed-batch strategies, including pulse fed batch, constant feed rate fed batch, constant residual glucose concentration fed batch, and exponential fed batch. The maximum BD concentration of 150 g/l at 38 h with a diol productivity of 4.21 g/l h was obtained by the constant residual glucose concentration feeding strategy. To the best of our knowledge, these results were new records on BD fermentation.


The influence of histamine and PGE2-induced hyperaemia and oedema on respiratory metabolism in normal human forearm skin.
Transcutaneous measurements of pO2 and pCO2 were made on the forearm skin after intradermal injection of histamine, PGE2, and saline. The mediators, used at concentrations which induce intense hyperaemia, did not modify the steady state tcpO2/pCO2 levels measured with a sensor head temperature of 44 degrees C when breathing air or hyperbaric (2ATA) oxygen. It was deduced that gas transport is unaffected by mediator-induced conditions in the skin. The rates of fall of tcpO2 and of rise of tcpCO2 after arresting the forearm circulation by cuff occlusion of the arm were significantly less at the histamine site than at the PGE2 and saline sites. The values over the PGE2 and saline injection sites were less than those over undisturbed skin. The dynamic tests of respiratory gas exchange indicate that the skin metabolic rate is reduced at all injection sites and the greatest effect was seen with histamine. Measurement of dermal thickness after saline injection has shown that the excess interstitial fluid persists at the time of maximal hyperaemia: this is further accentuated at the histamine site through active oedema formation. Accumulation of excess interstitial fluid (persistence of aqueous injection or oedema generated by the action of mediator) separates the tissue cells. The reduction in the number of cells per unit volume is sufficient to explain the observed reduction in oxygen consumption per unit volume of skin. It is concluded that the increased diffusional distances in mediator-induced oedema are unimportant for the respiration of otherwise normal tissues, but that oedema by reducing oxygen flux may contribute appreciably to the hypoxia of inflamed tissue infiltrated with metabolically active cells.


Changes in preschool children's OHRQoL after treatment of dental caries: responsiveness of the B-ECOHIS.
Oral health-related quality of life (OHRQoL) measures should be tested for responsiveness to change if they are to be used as outcomes in randomized clinical trials. To assess the responsiveness of the Brazilian ECOHIS (B-ECOHIS) to dental treatment of dental caries. One hundred parents of 3- to 5-year-old children completed the B-ECOHIS prior to their children's treatment and 7-14 days after completion of treatment. The post-treatment questionnaire also included a global transition judgment that assessed parent's perceptions of change in their children's oral health following treatment. Change scores, longitudinal construct validity, standardized effect sizes (ES) and standardized response mean (SRM) were calculated. Improvements in children's oral health after treatment were reflected in mean pre- and post-treatment B-ECOHIS scores. They declined considerably significantly from 17.4 to 1.6 (P < 0.0001), as did the individual domain scores (P < 0.0001). There were significant differences in the pre- and post-treatment scores of children who reported little improvement (P < 0.0001) as well as in those who reported large improvements (P < 0.0001). The ES and SRM based on change scores mean for total scores and for categories of global transitions judgments were large. Dental treatment resulted in significant improvement of the preschool children's OHRQoL. The B-ECOHIS is responsive.


[Imaging in the diagnosis and the staging of gallbladder tumors].
Most of gallbladder tumors are benign. Adenoma, cholesterol polyps, or adenomyomatosis are most frequently typical on ultrasonographic images. All symptomatic lesions must be considered as indications for surgery. It may be difficult to identify precancerous or malignant lesion. Polyps over 1cm are indication for preventive cholecystectomy. In case of suspicious polyp or suspicious wall thickening, endoscopic ultrasonography can be helpful to evaluate local tumoral spread and eliminate differential diagnosis. Unfortunately, diagnosis of gallbladder cancer is often late, when surgical resection can't be curative. Computed tomography and magnetic resonance imaging examinations are then useful for local and metastatic staging.


Pathways of cell signaling in hyperoxia.
Administration of high concentrations of oxygen (hyperoxia) is a mainstay of supportive treatment for patients suffering from severe respiratory failure. However, hyperoxia, by generating excess systemic reactive oxygen species (ROS), can exacerbate organ failure by causing cellular injury. Therefore, a better understanding of the signal transduction pathways in hyperoxia may provide the basis for effective therapeutic interventions. The major biological effects of hyperoxia include cell death, induction of stress responses, inflammation, and modulation of cell growth. Major signaling pathways that appear to be involved include the mitogen-activated protein kinases (MAPKs), AP-1, and NF-kappa B, which converge, ultimately, to the expression of a range of stress response genes, cytokines, and growth factors.


Mathematical modeling of cell migration.
Mathematical modeling has become increasingly important in many areas of biology during the past two decades, and the area of cell migration and motility has seen significant contributions from a wide range of modeling approaches. In this chapter, we cover examples from the broad range of work in this area, emphasizing the models' biological significance and the relationships between them. We focus on three specific areas: cell protrusion, cell adhesion, and retraction/whole-cell models. At the end of this chapter, we provide our perspective on issues that future models and experiments should consider in order to advance the boundaries of this field.


Anterolateral thigh butterfly free flap for reconstruction of laryngopharyngeal defect: surgical considerations.
Reconstruction of a pharyngoesophageal defect remains a challenging problem, especially with involvement of the neck skin. This study aimed to demonstrate the surgical technique of utilising a butterfly modification of the anterolateral thigh flap. Reconstruction of the pharyngoesophageal defect was accomplished using the butterfly modification of the anterolateral thigh free flap. The flap was tubed on the leg while still being attached to the pedicle, to minimise the ischaemia time. Butterfly anterolateral thigh free flap allows for multi-layer closure of the neopharynx and can be utilised for reconstruction of pharyngoesophageal and neck skin defects.


No apparent difference in the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the sympathetic system in NMRI and C57 BL/6 mice.
The parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to possess marked species as well as strain differences in toxicity on central catecholaminergic systems. In the present study the effects on the peripheral sympathetic nervous system following treatment with MPTP, as well as its metabolite 1-methyl-4-phenylpyridine (MPP+) and the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) were studied in mice of the NMRI and C57 BL/6 strains, two strains that possess marked difference in MPTP toxicity on central catecholaminergic neurons. No strain differences in the depletions of noradrenaline (NA) in iris and heart auricula and of NA and dopamine (DA) in superior cervical ganglion or in the reduction of the in vitro [3H]NA uptake in iris or heart auricula were found following MPTP treatment (2 X 40 mg/kg s.c., 2 and 7 days). Treatment with the NA uptake blocker desipramine (DMI) did not affect the MPTP-induced NA depletion in either strain. Following treatment with MPP+ (30 mg/kg i.v., 7 days) no differences in the two strains were seen on the reduction of NA levels in iris and heart auricula or decrease in [3H]NA uptake. In addition, no differences were found on NA levels in iris and heart auricula after 6-OHDA treatment (15 mg/kg i.v., 7 days). The data indicate that in the NMRI and C57 BL/6 mice peripheral NA neurons do not possess any notable strain difference in the vulnerability to MPTP or in the mechanism of action of MPTP.


Effects of diet-induced obesity on motivation and pain behavior in an operant assay.
Obesity has been associated with multiple chronic pain disorders, including migraine. We hypothesized that diet-induced obesity would be associated with a reduced threshold for thermal nociception in the trigeminal system. In this study, we sought to examine the effect of diet-induced obesity on facial pain behavior. Mice of two different strains were fed high-fat or regular diet (RD) and tested using a well-established operant facial pain assay. We found that the effects of diet on behavior in this assay were strain and reward dependent. Obesity-prone C57BL/6J mice fed a high-fat diet (HFD) display lower number of licks of a caloric, palatable reward (33% sweetened condensed milk or 30% sucrose) than control mice. This occurred at all temperatures, in both sexes, and was evident even before the onset of obesity. This diminished reward-seeking behavior was not observed in obesity-resistant SKH1-E (SK) mice. These findings suggest that diet and strain interact to modulate reward-seeking behavior. Furthermore, we observed a difference between diet groups in operant behavior with caloric, palatable rewards, but not with a non-caloric neutral reward (water). Importantly, we found no effect of diet-induced obesity on acute thermal nociception in the absence of inflammation or injury. This indicates that thermal sensation in the face is not affected by obesity-associated peripheral neuropathy as it occurs when studying pain behaviors in the rodent hindpaw. Future studies using this model may reveal whether obesity facilitates the development of chronic pain after injury or inflammation.


Antiretroviral therapy with protease inhibitors in human immunodeficiency virus type 1- and human herpesvirus 8-coinfected patients.
Human herpesvirus 8 (HHV-8) is believed to play a role in the pathogenesis of Kaposi's sarcoma (KS) and possibly in other proliferative disorders often associated with human immunodeficiency virus type 1 (HIV-1) infection. Recent case reports have indicated resolution of KS and clearance of HHV-8 DNA from peripheral blood mononuclear cells (PBMC) in HIV-1-infected subjects following highly effective antiretroviral therapy, including HIV-1 protease inhibitors (PI), suggesting a possible activity for these compounds on HHV-8 replication. In the present study, the time course of PBMC HHV-8 DNA levels, plasma HIV-1 RNA load, and CD4+ T-cell counts were followed up in six coinfected subjects (four with and two without KS) under antiretroviral therapy with PI. A specific anti-HHV-8 role for PI was not consistently found, since fluctuation of HHV-8 viral load over time appeared to be independent of treatment. Nevertheless, our data support the hypothesis that KS patients may significantly benefit from PI therapy as an indirect consequence of partial restoration of immune functions following effective anti-HIV-1 combination therapy.


Surface charge of Plasmodium falciparum merozoites as revealed by atomic force microscopy with surface potential spectroscopy.
Electric charges on the surface of Plasmodium falciparum merozoites and erythrocytes were investigated by atomic force microscopy with surface potential spectroscopy. The apical end of merozoites was positively charged, while the entire erythrocyte surface was negatively charged. Transmission electron microscopy also demonstrated that negatively charged nanogold particles attached to the apical end of merozoites, and cationized ferritin particles attached to the entire surface of the erythrocyte. This indicates that the surface charge at the apical end of the merozoite may play an important role in invasion of the erythrocyte.


Nomifensine: A review of its pharmacological properties and therapeutic efficacy in depressive illness.
Nomifensine is a tetrahydoisoquinoline antidepressant which is chemically unrelated to the tricyclic or tetracyclic antidepressants, the monoamine oxidase inhibitors or the recently introduced agents. Nomifensine resembles the tricyclic antidepressants in many of its pharmacological effects in animal models of depressive illness, but differs from them in that it strongly inhibits the re-uptake of dopamine as well as noradrenaline and is a relatively weak inhibitor of serotonin uptake. It has an overall efficacy comparable with that of imipramine and amitriptyline in depressive illness, but at dosages which have achieved a similar overall clinical improvement, nomifensine causes little or no sedation, fewer and milder anticholinergic side effects, and also appears less likely than these drugs to cause serious cardiotoxicity on overdosage. Nomifensine may aggravate the psychopathology of patients with schizo-affective disorders and intensification of the psychosis may require neuroleptic therapy. Nomifensine also has antianxiety activity, but its role in treating anxiety associated with primary depression has still to be clarified. Nomifensine appears to be well tolerated by the elderly.


Variations in quality of Home Care between sites across Europe, as measured by Home Care Quality Indicators.
The increase in the proportion of elderly people and a consequent increase in the demand for care have caused healthcare systems to become overloaded. This paper describes the use of Home Care Quality Indicators (HCQIs), derived from the Minimum Data Set for Home Care, for monitoring quality of care. Research questions were, "Do HCQI scores vary between home care organizations in different countries?" and "Are one or more country-specific sites consistently scoring better on most or all HCQIs"? a cross-sectional observational study of 65+ randomly selected clients of home care organizations in urban areas in 11 European countries who had been receiving home care for at least two weeks. Data were collected with the MDS-HC. The scoring of 16 prevalent quality indicators for home care, adjusted for population differences, was calculated with baseline data. Population size at baseline was 4,007 clients. Among home care clients in Europe, "rehabilitation potential in Activities of Daily Living and no therapies" (average 75.9%) and "inadequate pain control" were the most common quality problems. The prevalence between populations studied in various countries varied substantially. No country-specific site consistently scored worst or best. HCQIs derived from the MDS-HC detect variance in quality scores between home care in the 11 partner countries. The highest prevalence of unwanted outcomes were most often found in the Czech Republic, Italy and Germany. Although further research is necessary, we believe that HCQIs may be of great value for quality improvement in home care.


Trends in proportions of hospitals and operators not meeting minimum percutaneous coronary intervention volume standards in Taiwan, 2001-2013.
To examine trends in proportions of hospitals and operators not meeting the minimum percutaneous coronary intervention (PCI) volume standards in Taiwan during 2001-2013. The 2013 Clinical Competence Statement recommends that operators perform a minimum of ≥50 PCIs annually (averaged over a 2-year period) in hospitals conducting ≥200 PCIs annually. Taiwan National Health Insurance claims data from 2001 to 2013 are used to determine the annual numbers of PCIs performed by each hospital and operator. The percentage of hospitals conducting annual PCI volumes of <200 decreased from 57% (26/46) in 2001 to 39% (29/74) in 2007 and 33% (33/91) in 2013; the percentage of operators conducting PCI volumes <50 annually remained relatively constant at 60% (146/243) in 2001, 60% (270/452) in 2007, and 58% (354/611) in 2013; and the percentage of operators conducting low volumes (<50) in low-volume hospitals (<200) decreased from 24% (57/243) in 2001 to 15% (66/452) in 2007 and 12% (76/611) in 2013. Approximately one-third of hospitals and three-fifths of operators in Taiwan failed to meet minimum PCI volume standards. Further research examining patient outcomes from PCIs performed by low-volume hospitals and operators is recommended.


Monoclonal antibody in the identification of Haemophilus somnus.
Electrophoretic comparisons of outer membrane proteins of Haemophilus somnus isolates revealed 2 major protein bands (46 and 14 kilodaltons [kD]) common to all isolates tested. A monoclonal antibody raised against H. somnus reacted to the 46-kD band. Coagglutination tests were performed using a monoclonal antibody coagglutination assay. The monoclonal reagent was produced by incubating Cowan strain Staphylococcus aureus suspension, used as a source of crude protein A, with mouse ascitic fluid monoclonal antibody or goat anti-H. somnus hyperimmune serum. Bacteria to be tested were suspended at a concentration of 4.5 x 10(9) cells/ml. The coagglutination test was performed by the addition of 50 microliters of the monoclonal reagent to 50 microliters of the bacterial suspension on a glass plate and manual rotation for 2-3 minutes. The coagglutination assay using Cowan strain Staphylococcus aureus protein A, coupled with the monoclonal antibody, agglutinated 10 different H. somnus isolates. The antibody reagent did not coagglutinate with Actinobacillus suis, A. equuli, Pasteurella haemolytica, P. multocida, or P. pneumotropica under similar test conditions.


Development of highly potent inhibitors of the Ras-targeting human acyl protein thioesterases based on substrate similarity design.
A matter of common sense: a common recognition motif consisting of a negatively charged group five to six bonds away (red) from the (thio)ester functionality (green) and a positively charged tail group ten to twelve bonds away (blue) was identified in two native acyl protein thioesterase 1 (APT1) substrates. This similarity led to the design of potent inhibitors of the Ras-depalmitoylating enzyme APT1.


Cytotoxic and antibacterial substances against multi-drug resistant pathogens from marine sponge symbiont: Citrinin, a secondary metabolite of Penicillium sp.
To Isolate, purify, characterize, and evaluate the bioactive compounds from the sponge-derived fungus Penicillium sp. FF001 and to elucidate its structure. The fungal strain FF001 with an interesting bioactivity profile was isolated from a marine Fijian sponge Melophlus sp. Based on conidiophores aggregation, conidia development and mycelia morphological characteristics, the isolate FF001 was classically identified as a Penicillium sp. The bioactive compound was identified using various spectral analysis of UV, high resolution electrospray ionization mass spectra, 1H and 13C NMR spectral data. Further minimum inhibitory concentrations (MICs) assay and brine shrimp cytotoxicity assay were also carried out to evaluate the biological properties of the purified compound. Bioassay guided fractionation of the EtOAc extract of a static culture of this Penicillium sp. by different chromatographic methods led the isolation of an antibacterial, anticryptococcal and cytotoxic active compound, which was identified as citrinin (1). Further, citrinin (1) is reported for its potent antibacterial activity against methicillin-resistant Staphylococcus aureus (S. aureus), rifampicin-resistant S. aureus, wild type S. aureus and vancomycin-resistant Enterococcus faecium showed MICs of 3.90, 0.97, 1.95 and 7.81 µg/mL, respectively. Further citrinin (1) displayed significant activity against the pathogenic yeast Cryptococcus neoformans (MIC 3.90 µg/mL), and exhibited cytotoxicity against brine shrimp larvae LD50 of 96 µg/mL. Citrinin (1) is reported from sponge associated Penicillium sp. from this study and for its strong antibacterial activity against multi-drug resistant human pathogens including cytotoxicity against brine shrimp larvae, which indicated that sponge associated Penicillium spp. are promising sources of natural bioactive metabolites.


Potential ultrasonic anatomical markers of obstructive sleep apnoea-hypopnoea syndrome.
To investigate the potential value of ultrasonography in evaluating the pathophysiology of obstructive sleep apnoea-hypopnoea syndrome (OSAHS) by assessing the correlation of critical ultrasonic anatomical characteristics of the oropharynx with the severity of OSAHS. One hundred and seventy-one patients with suspected OSAHS underwent oropharyngeal sonographic examination and overnight polysomnography. Ultrasonic measurement was compared with the apnoea-hypopnoea index (AHI) and other parameters. An ordinal logistic regression model was used to identify potential ultrasonic anatomical markers for OSAHS. The AHI was significantly correlated with lingual height (r=0.40, p<0.01), maximal width of the tongue (r=0.35, p<0.01), and distance from the symphysis of the mandible to the hyoid bone (M-HB) (r=0.24, p<0.01). A positive relationship between Friedman tongue position (FTP) grades and lingual height (r=0.24, p<0.01), between FTP grades and maximal width of the tongue (r=0.23, p<0.01), and between FTP grades and width of tongue base (TB; r=0.17, p<0.05) was found. Multivariate models adjusted for sex, age, and body mass index (BMI) revealed that lingual height (95% confidence interval [CI]: 1.04-1.24; p=0.004) is independently associated with a higher risk for the severity of OSAHS. Ultrasonography may be a potential imaging method for providing additional useful information about the correlation between ultrasound findings and the severity of OSAHS. Lingual height could be considered an ultrasonic anatomical marker for determining the severity of OSAHS patients independent of age, sex, and BMI.


Renal Insufficiency in Patients with Cirrhosis.
Renal failure is one of the most prevalent complications in patients with cirrhosis and is of the utmost prognostic relevance. Acute kidney injury (AKI) in cirrhosis results from a spectrum of etiologies, of which hepatorenal syndrome (HRS) carries the worst prognosis. Correct differentiation of the etiology of AKI in cirrhosis is imperative, as treatment defers substantially. This review summarizes the current diagnostic criteria, pathophysiology, diagnosis, and therapeutic concepts for AKI and HRS-AKI in cirrhosis.


The imminent role of microRNAs in salivary adenoid cystic carcinoma.
Unfortunately, despite the severe problem associated with salivary adenoid cystic carcinoma (SACC), it has not been studied in detail yet. Therefore, the time has come to understand the oncogenic cause of SACC and find the correct molecular markers for diagnosis, prognosis, and therapeutic target to tame this disease. Recently, we and others have suggested that non-coding RNAs, specifically microRNAs and long non-coding RNAs, can be ideal biomarkers for cancer(s) diagnosis and progression. Herein, we have shown that various miRNAs, like miR-155, miR‑103a‑3p, miR-21, and miR-130a increase the oncogenesis process, whereas some miRNAs such as miR-140-5p, miR-150, miR-375, miR-181a, miR-98, miR-125a-5p, miR-582-5p, miR-144-3p, miR-320a, miR-187 and miR-101-3p, miR-143-3p inhibit the salivary adenoid cystic carcinoma progression. Furthermore, we have found that miRNAs also target many vital genes and pathways like mitogen-activated protein kinases-snail family transcriptional repressor 2 (MAPK-Snai2), p38/JNK/ERK, forkhead box C1 protein (FOXC1), mammalian target of rapamycin (mTOR), integrin subunit beta 3 (ITGB3), epidermal growth factor receptor (EGFR)/NF-κB, programmed cell death protein 4 (PDCD4), signal transducer and activator of transcription 3 (STAT3), neuroblastoma RAS (N-RAS), phosphatidylinositol-3-kinase (PI3K)/Akt, MEK/ERK, ubiquitin-like modifier activating enzyme 2 (UBA2), tumor protein D52 (TPD52) which play a crucial role in the regulation of salivary adenoid cystic carcinoma. Therefore, we believe that knowledge from this manuscript will help us find the pathogenesis process in salivary adenoid cystic carcinoma and could also give us better biomarkers of diagnosis and prognosis of the disease.


A thalamocortical pathway for fast rerouting of tactile information to occipital cortex in congenital blindness.
In congenitally blind individuals, the occipital cortex responds to various nonvisual inputs. Some animal studies raise the possibility that a subcortical pathway allows fast re-routing of tactile information to the occipital cortex, but this has not been shown in humans. Here we show using magnetoencephalography (MEG) that tactile stimulation produces occipital cortex activations, starting as early as 35 ms in congenitally blind individuals, but not in blindfolded sighted controls. Given our measured thalamic response latencies of 20 ms and a mean estimated lateral geniculate nucleus to primary visual cortex transfer time of 15 ms, we claim that this early occipital response is mediated by a direct thalamo-cortical pathway. We also observed stronger directed connectivity in the alpha band range from posterior thalamus to occipital cortex in congenitally blind participants. Our results strongly suggest the contribution of a fast thalamo-cortical pathway in the cross-modal activation of the occipital cortex in congenitally blind humans.


Autoimmune pulmonary alveolar proteinosis with a history of vaping and vitamin E-positive bronchoalveolar lavage.
Pulmonary alveolar proteinosis (PAP) can be due to primary autoimmune and secondary causes, including e-cigarette, or vaping, product use-associated lung injury. We present a 33-year-old male presenting with PAP and a history of vaping. Serum anti-granulocyte-macrophage colony-stimulating factor antibodies were present. Vitamin E (VE), but not VE acetate, was detected in bronchoalveolar lavage. This is the first report of potential association between vaping and autoimmune PAP.


Development of competency model for family physicians against the background of 'internet plus healthcare' in China: a mixed methods study.
Identification of the service competences of family physicians is central to ensuring high-quality primary care and improving patient outcomes. However, little is known about how to assess the family physicians' service competences in primary care settings. It is necessary to develop and validate a general model of core competences of the family physician under the stage of construction of family doctor system and implementation of 'Internet Plus Healthcare' service model in China. The literature review, behavioural event interviews, expert consultation and questionnaire survey were performed. The scale's 35 questions were measured by response rate, highest score, lowest score, and average score for each. Delphi method was used to assess content validity, Cronbach's α to estimate reliability, and factor analysis to test structural validity. Respondents were randomly divided into two groups; data for one group were used for exploratory factor analysis (EFA) to explore possible model structure. Confirmatory factor analysis (CFA) was then performed. Effective response rate was 93.56%. Cronbach's α coefficient of the scale was 0.977. Factor analysis showed KMO of 0.988. Bartlett's test showed χ2 of 22 917.515 (df = 630), p < .001. Overall authority grade of expert consultation was 0.80, and Kendall's coefficient of concordance W was 0.194. By EFA, the five-factor model was retained after thorough consideration, and four items with factor loading less than 0.4 were proposed to obtain a five-dimension, 32-item scale. CFA was performed on the new structure, showing high goodness-of-fit test (NFI = 0.98, TLI = 0.91, SRMSR = 0.05, RMSEA = 0.04). Overall Cronbach's α coefficients of the scale and each sub-item were greater than 0.9. The scale has good reliability, validity, and credibility and can therefore serve as an effective tool for assessment of Chinese family physicians' service competences.


Antepartum fetal heart rate variability and intervillous placental blood flow in association with smoking.
Intervillous placental blood flow and indices of fetal heart rate variability were measured from seven healthy pregnant women in the last trimester of pregnancy, once before and twice after smoking one cigarette. A blood flow reduction was observed in seven, a rise in five, and no change in two measurements. When intervillous placental blood flow decreased both indices of variability decreased (p less than 0.001), and when it increased the short-term component of fetal heart rate variability increased more significantly (p less than 0.001) than did the long-term component (p less than 0.01).


Predictors for the development of neurological immune-related adverse events of immune checkpoint inhibitors and impact on mortality.
Little is known about risk factors for developing neurological immunological adverse events (neuro-irAEs) from immune checkpoint inhibitors (ICIs). We report the incidence, predictors for development, impact on mortality of neuro-irAEs, and impact of ICIs on pre-existing neurological conditions in a large clinical cohort. Patients who received ICIs between January 2011 and December 2018 were identified from a tertiary cancer center registry. Descriptive statistics were used to summarize patient, cancer, and treatment data. Odds ratios from univariable and multivariable logistic regression models were calculated to identify potential predictors for developing a neuro-irAE. Impact of neuro-irAEs on overall survival was estimated by Kaplan-Meier and Cox proportional hazard models. Overall frequency of neurological irAEs was 2.3%. Peripheral nervous system complications were most frequent (53.6%). Melanoma, younger age, prior chemotherapy, prior resection, CTLA-4 ICIs exposure, and combination PD-1 and CTLA-4 ICIs exposure had significantly higher odds for developing a neuro-irAE (p < 0.05) in univariate but not multivariate models. Those with a neuro-irAE were less likely to die at 3 years compared to those without a neuro-irAE (69% vs. 55%, p = 0.004) in univariate but not multivariate model. Flare of pre-existing neurological condition after exposure to ICIs was present (15.4%, 2 of 13 patients) but manageable. One patient was rechallenged with ICIs without recurrent flare. Neuro-irAEs are not associated with increase in overall mortality. Potential predictors for the development of neuro-irAEs are younger age, melanoma, prior chemotherapy and resection, CTLA-4, or combination ICIs exposure.


Intracorneal ring segment implantation for the management of keratoconus: safety and efficacy.
To assess the safety and efficacy of intracorneal ring segment (Intacs, Addition Technology, Inc.) implantation in the management of keratoconus. Department of Ophthalmology and Ophthalmic Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran. This prospective case series comprised 30 keratoconic eyes (22 patients) with a clear central cornea that had Intacs implantation. All patients were contact-lens intolerant. The main outcome measures were uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), refraction, keratometry, and pachymetry. Patients were examined before Intacs implantation as well as 1 week and 1, 3, and 6 months postoperatively. The mean age of the 5 women and 17 men was 25.9 years +/- 5.29 (SD). The mean UCVA improved from 0.60 +/- 0.311 logMAR preoperatively to 0.29 +/- 0.20 logMAR 6 months postoperatively (P<.001) and the mean BSCVA, from 0.25 +/- 0.16 logMAR to 0.13 +/- 0.14 logMAR, respectively (P<.001). The mean spherical equivalent improved from -6.93 +/- 3.52 diopters (D) preoperatively to -3.23 +/- 2.81 D at 6 months and the mean refractive cylinder, from -4.65 +/- 1.85 D to -3.90 +/- 1.70 D, respectively. The mean keratometry decreased from 49.84 +/- 3.58 D preoperatively to 47.90 +/- 3.58 D postoperatively (P<.001). Three eyes had ring exposure, and 1 eye had bacterial keratitis and ring exposure. Intacs implantation appeared to be effective in improving UCVA and BSCVA in patients with mild to moderate keratoconus and contact-lens intolerance.


Poly(phenylene) and m-Terphenyl as Powerful Protecting Groups for the Preparation of Stable Organic Hydroxides.
Four benzimidazolium hydroxide compounds, in which the C2-position is attached to a phenyl group possessing hydrogen, bromine, methyl groups, or phenyl groups at the ortho positions, are prepared and investigated for stability in a quantitative alkaline stability test. The differences between the stability of the various protecting groups in caustic solutions are rationalized on the basis of their crystal structures and DFT calculations. The highest stability was observed for the m-terphenyl-protected benzimidazolium, showing a half-life in 3 M NaOD/CD3OD/D2O at 80 °C of 3240 h. A high-molecular-weight polymer analogue of this model compound is prepared that exhibits excellent mechanical properties, high ionic conductivity and ion-exchange capacity, as well as remarkable hydroxide stability in alkaline solutions: only 5% degradation after 168 h in 2 M KOH at 80 °C. This is the most stable hydroxide-conducting benzimidazolium polymer to date.


IL-6, TNF-α, IL-10, and nutritional status in pediatric patients with biliary atresia.
The objective of the present study is to evaluate whether IL-6, TNF-α, IL-10 are associated with nutritional status in patients with cirrhosis secondary to biliary atresia and compare to healthy controls. The parameters used for nutritional assessment were the standard deviation scores of height-for-age and of triceps skinfold thickness-for-age. The severity of cirrhosis was evaluated using the Child-Pugh score and PELD/MELD. Serum cytokines were measured using Cytometric Bead Array flow cytometry. IL-6, TNF-α, and IL-10 were significantly higher in the cirrhosis group when compared with the control group (2.4 vs. 0.24 (p<0.001), 0.21 vs. 0.14 (p=0.007), and 0.65 vs. 0.36 (p=0.004), respectively. IL-6 and IL-10 were positively correlated with disease severity (0.450 [p=0.001] and 0.410; [p=0.002], respectively). TNF-α did not show a significant correlation with disease severity (0.100; p=0.478). Regarding nutritional evaluation, IL-6 was negatively correlated with the standard deviation score of height-for-age (-0.493; p<0.001) and of triceps skinfold thickness-for-age (-0.503; p<0.001), respectively. IL-10 exhibited a negative correlation with the standard deviation score of height-for-age (-0.476; p<0.001) and the standard deviation score of triceps skinfold thickness-for-age (-0.388; p=0.004). TNF-α did not show any significance in both anthropometric parameters (-0.083 (p=0.555) and -0.161 (p=0.253). The authors suggest that, in patients with cirrhosis secondary to biliary atresia, IL-6 could be used as a possible supporting biomarker of deficient nutritional status and elevated IL-10 levels could be used as a possible early-stage supporting biomarker of deteriorating nutritional status.


Increasing the role of belief information in moral judgments by stimulating the right temporoparietal junction.
Morality plays a vital role in our social life. A vast body of research has suggested that moral judgments rely on cognitive processes mediated by the right temporoparietal junction (rTPJ), an area thought to be involved in belief attribution. Here we assessed the role of the rTPJ in moral judgments directly by means of transcranial direct current stimulation (tDCS)--a non-invasive brain stimulation technique that, by applying a weak current to the scalp, allows modulating cortical excitability of the area being stimulated. Participants were randomly and equally assigned to receive anodal stimulation (to increase cortical excitability), cathodal stimulation (to decrease cortical excitability), or sham (placebo) stimulation over the rTPJ before completing a moral judgment task. Participants read stories in which protagonists produced either a negative or a neutral outcome based on either a negative or a neutral belief that they were causing harm or no harm, respectively. Results revealed a selective group difference when judging the moral permissibility of accidental harms (belief neutral, outcome negative), but not intentional harms (belief negative, outcome negative), attempted harms (belief negative, outcome neutral), or neutral acts (belief neutral, outcome neutral). Specifically, participants who received anodal stimulation assigned less blame to accidental harms compared to participants who received cathodal or sham stimulation. These results are consistent with previous findings showing that the degree of rTPJ activation reflects reliance on the agent's innocent intention. Crucially, our findings provide direct evidence supporting the critical role of the rTPJ in mediating belief attribution for moral judgment.


[Cp*Rh(bpy)(H2O)]2+ as a coenzyme substitute in enzymatic oxidations catalyzed by Baeyer-Villiger monooxygenases.
[Cp*Rh(bpy)(H2O)]2+ was applied as a flavin regenerating reagent in BVMO catalyzed oxidations of organic sulfides to chiral sulfoxides.


[Bilateral pheochromocytoma of the adrenal glands and a solitary neurofibroma of the dorsal mucosa of the tongue associated with a solid medullary carcinoma of the thyroid gland in Hashimoto's lymphocytic thyroiditis].
A female aged 22 died 13 hours after having given birth to a live mature fetus. On autopsy, bilateral phoechromyocytomas, a mucosal neurofibroma of the tongue and a solid medulary carcinoma of the thyroid with amyloid associated with Hashimoto's lymphocytic thyroiditis were detected. After parturition, there occurred bleeding into the left-side pheochromocytoma followed by a release of phenyl alkylamines into the circulation. This resulted in fatal peripheral circulatory failure.


Metabolic syndrome in Japanese patients with obstructive sleep apnea syndrome.
We investigated the prevalence of metabolic syndrome in patients with obstructive sleep apnea syndrome (OSAS) referred to a tertiary university-based medical center. A cross-sectional study of patients with a definite diagnosis of OSAS was performed using new diagnostic criteria for metabolic syndrome that were designed for the Japanese population. Clinical features and comorbidities related to metabolic syndrome were compared between 819 patients with OSAS (719 men and 100 women) and 89 control subjects without OSAS. Metabolic syndrome was significantly more common in the patients with OSAS than in the controls (49.5% vs. 22.0% for men, p < 0.01; 32.0% vs. 6.7% for women, p < 0.01). Men with OSAS (apnea-hypopnea index [AHI] > or =5/h) had a higher risk of metabolic syndrome compared with controls (odds ratio [OR]: 3.47; 95% confidence interval [CI]: 1.84-6.53). There was a significantly increased risk of metabolic syndrome in men with moderate OSAS (AHI: 15-29.9/h) (OR: 2.83; 95% CI: 1.42-5.66) and men with severe OSAS (AHI > or =30/h) (OR: 5.09; 95% CI: 2.67-9.71). Women with OSAS (AHI> or =5/h) also had an increased risk of metabolic syndrome (OR: 6.59; 95% CI: 1.47-29.38), and the risk was significantly higher in women with severe OSAS (AHI > or =30/h) (OR 14.00; 95% CI: 2.93-66.82). Risk factors for metabolic syndrome differed by gender: in men, age, body mass index (BMI), and OSAS (AHI > or =15/h) were significantly associated with metabolic syndrome, whereas, in women, BMI was the only risk factor for metabolic syndrome. The increase of metabolic syndrome in Japanese OSAS patients suggests that this patient population is burdened with multiple risk factors for cardiovascular disease.


Non-epithelial uterine tumours induced in CBA mice by 1,2-dimethylhydrazine.
In CBA mice treated with weekly subcutaneous injections of 1,2-dimethylhydrazine an unusually high incidence of uterine sarcomas was observed in two successive experiments. The tumours are easily transplantable. The description of their histological structure is presented and their histogenesis is discussed.


Effect of oestrogen replacement therapy on development of experimental arteriosclerosis: a study in transplanted and balloon-injured rabbit aortas.
The mechanism underlying possible protection of oestrogen replacement therapy against cardiovascular disease appears to go beyond beneficial changes in plasma lipoproteins. A direct action of oestrogen on the metabolism of lipoproteins after entering the arterial wall may occur. The present study evaluated whether oestrogen replacement therapy affects the development of experimental arteriosclerosis in immunologically injured (experiment A + B) and balloon-injured (experiment B) aortas in ovariectomized rabbits maintained at a human level of plasma cholesterol; both models involve severe damage to the endothelium with resulting rapid accumulation of lipoproteins in the arterial intima and therefore appear suitable for studying factors directly affecting subendothelial lipoprotein metabolism. In experiment A, dietary cholesterol required to maintain a human level of plasma cholesterol was significantly higher for the oestrogen group than for the placebo group. Similarly, cholesterol accumulation in the aortic grafts was borderline higher for the oestrogen than the placebo group, whilst intimal hyperplasia was without difference between the groups. Due to a modified schedule of cholesterol feeding in experiment B, oestrogen and placebo groups received the same amount of dietary cholesterol, and cholesterol accumulation and intimal hyperplasia were similar in immunologically injured and balloon-injured parts of the aorta in both groups. These results suggest that in the female rabbit maintained at a human level of plasma cholesterol, oestrogen replacement therapy has no direct action on the development of experimental arteriosclerosis when induced by immunological or mechanical injury to the endothelium.


Therapy-relevant discrepancies between diagnoses of institutional pathologists and experienced hematopathologists in the diagnosis of malignant lymphoma.
We have studied therapy-relevant discrepancies in the diagnoses of institutional pathologists and a panel of 4 experienced hematopathologists in 375 cases from patients with malignant lymphoma. Two hundred and fifty four cases (68%) were contributed by non-panel pathologists and 121 (32%) by individual panel pathologists. Overall, in 24% (91/375) of the cases, therapy-relevant discrepancies were present between institutional pathologists and panel diagnoses. Thirty-four percent (87/254) therapy-relevant discrepancies were present in cases contributed by non-panel pathologists, whereas in only 3% (4/121) discrepancies were found in cases forwarded by individual panel pathologists. The percentages erroneously diagnosed Hodgkin's disease by non-panel pathologists and individual panel pathologists were 8 and 0% respectively and faulty diagnosed Non-Hodgkin lymphomas 5 and 0%, whereas the number of consultation cases, in which the referring pathologist was not certain of his diagnosis, appeared to be 24 and 3% for non-panel and panel pathologists respectively. In addition, in 14% of panel confirmed NHL contributed by non-panel pathologists, therapy-relevant discrepancies in the degree of malignancy grading according to the Working Formulation were present, whereas no discrepancies in malignancy grading were noted between individual panel members and panel diagnoses. Apart from extensive hematopathological experience, a reason for the higher diagnostic accuracy of the panel pathologists could well be the frequency in which the diagnoses were supplemented by immunophenotyping: in 22% of the cases from non-panel pathologists and 63% of the cases from panel pathologists immunophenotyping on frozen sections was carried out.(ABSTRACT TRUNCATED AT 250 WORDS)


Prediction of large-for-gestational-age neonates: screening by maternal factors and biomarkers in the three trimesters of pregnancy.
To develop a model based on maternal characteristics and medical history (maternal factors) for the prediction of delivery of large-for-gestational-age (LGA) neonates, and to examine the potential value of first-, second- and third-trimester fetal biometry and biomarkers in improving such a model. This was a screening study in 76 300, 54 999, 25 727 and 6181 singleton pregnancies at 11-13, 19-24, 30-34 and 35-37 weeks' gestation, respectively. The a-priori risk for LGA with birth weight > 95(th) percentile (LGA > 95(th) ) was calculated using multivariable logistic regression analysis to determine which of the maternal factors had a significant contribution. Regression analysis was then used to determine whether screening by a combination of maternal factors, fetal biometry and various biophysical and biochemical markers had significant contribution in predicting delivery of LGA neonates. The likelihood of LGA > 95(th) increased with increasing maternal weight and height and was lower in women of Afro-Caribbean and South Asian racial origins, in cigarette smokers and in nulliparous women. The risk was higher in women with pre-existing diabetes mellitus Type I and lower in those with chronic hypertension. In parous women, the risk increased with birth-weight Z-score in previous pregnancy and prior history of gestational diabetes and decreased with interpregnancy interval. Screening by maternal factors at 11-13 weeks predicted 32%, 44% and 60% of LGA > 95(th) at false-positive rates (FPRs) of 5%, 10% and 20%, respectively. With the addition of fetal biometry, the detection rates improved to 37%, 51% and 68% at 19-24 weeks, 50%, 65% and 81% at 30-34 weeks and 60%, 73% and 85% at 35-37 weeks at FPRs of 5%, 10% and 20%, respectively. The addition of biomarkers did not improve the detection rates achieved when screening by a combination of maternal factors and fetal biometry. Combined screening by maternal factors and fetal biometry can predict a high proportion of pregnancies that will deliver LGA neonates. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.


Correction to: Best MRI sequences for identifying axillary lymph node markers in patients with metastatic breast cancer: an inter-reader observational study.
An amendment to this paper has been published and can be accessed via the original article.


Application of conjugation using phiC31 att/int system for Actinoplanes teichomyceticus, a producer of teicoplanin.
Actinoplanes teichomyceticus produces teicoplanin, which is a glycopeptide antibiotic for Gram-positive pathogenic bacteria and methicillin-resistant Staphylococcus aureus (MRSA). For a molecular genetic study of A. teichomyceticus, an effective transformation method using the conjugal transfer of DNA from E. coli to spores of A. teichomyceticus was established for the first time, based on the bacteriophage varphiC31 att/int system, in the genus of Actinoplanes. The high frequency of transconjugation was obtained on MS medium containing 40 mM MgCl(2), using 1.25 x 10(8) E. coli donor cells and 10(5) spores without a heat treatment. In addition, by cloning and sequencing the attB site A. teichomyceticus was shown to contain a single attB site within an ORF coding for a pirin homolog. Also, its attB site sequence showed high homology to that of Streptomyces lividans, unlike the case of Kitasatospora setae despite being a non-Streptomyces actinomycete, which seems to be closely related to the high transconjugation frequency of A. teichomyceticus.


Chiral bisoxazoline ligands designed to stabilize bimetallic complexes.
Chiral bisoxazoline ligands containing naphthyridine, pyridazine, pyrazole, and phenol bridging units were prepared and shown to form bimetallic complexes with various metal salts. X-ray crystal structures of bis-nickel naphthyridine-bridged, bis-zinc pyridazine-bridged, and bis-nickel as well as bis-palladium pyrazole-bridged complexes were obtained.


Break of reciprocity principle due to localized nonlinearities in concrete.
The effects of localized nonlinearities on the reciprocity principle in the context of ultrasounds and nonlinear elasticity are discussed in this paper. Experiments will be presented to prove that a localized crack in a concrete beam causes a break of reciprocity in the ultrasonic response to a mechanical excitation. The link between non-reciprocity and asymmetry in the nonlinear response will be demonstrated and discussed as a tool for NonDestructive Evaluation.


Endocrine analytes in multiple-marker screening.
Prenatal serum screening is based on the observation that secretory products of the placenta and fetus are altered in maternal serum of pregnancies affected with certain birth defects. Most of these products are hormones that have been previously characterized, although the pathophysiologic basis of the altered maternal serum levels of these products that occurs in association with fetal chromosome for the most part is unknown. Prenatal serum screening is in a period of transition, with the relatively recent advance of second trimester triple-marker screening (AFP, uE3, hCG) and now the improved performance of the four-marker test that adds inhibin. A. Proposed first trimester screening and other new second trimester serum markers may dramatically change prenatal screening practices as we enter the next century.


Structural and antioxidant analysis of Tartary buckwheat (Fagopyrum tartaricum Gaertn.) 13S globulin.
The main component of buckwheat seed storage proteins is 13S globulin. In this study, Tartary buckwheat 13S globulin was separated and its structural features were investigated using Edman sequencing and matrix-assisted laser desorption / ionization time of flight mass spectrometry (MALDI-TOF-MS). The protective effect of its enzymatic hydrolysates against oxidative stress induced by H2 O2 was also evaluated to elucidate the antioxidant mechanism. Results showed that the isolated Tartary buckwheat 13S globulin contained one acidic and one basic subunit, which were linked by a disulfide bond. Six Tartary buckwheat active peptides were obtained from the enzymatic hydrolysates of Tartary buckwheat 13S globulin acidic subunit with a molecular weight of 38 kDa, namely Pep-1, Pep-2, Pep-3, Pep-4, Pep-5, and Pep-6. Pre-treatment of cells with Tartary buckwheat active peptides maintained the redox state balance of HepG2 cells and protected the activity of antioxidant enzymes in HepG2 cells. The Tartary buckwheat active peptides improved oxidative stress in HepG2 cells via the PPAR-α/HO-1 pathway. These results provide an insight into the antioxidant mechanism of Tartary buckwheat 13S globulin and suggest that Tartary buckwheat active peptides can be used as a functional ingredient in the food industry. © 2019 Society of Chemical Industry.


Haemonchus contortus: molecular cloning, sequencing, and expression analysis of the gene coding for the small subunit of ribonucleotide reductase.
Gastro-intestinal (GI) parasites are of great agricultural importance, annually costing the livestock industry vast amounts in resources to control parasitism. One such GI parasite, Haemonchus contortus, is principally pathogenic to sheep; with the parasite's blood-feeding behaviour causing effects ranging from mild anaemia to mortality in young animals. Current means of control, which are dependent on repeated treatment with anthelmintic chemicals, have led to increasing drug resistance. Together with the growing concern over residual chemicals in the environment and food chain, this has led to attempts to better understand the biology of the parasite with the aim to develop alternate or supplementary means of control, including the development of molecular vaccines. As a first step towards the understanding of the synthesis of deoxyribonucleotides in H. contortus, and its potential application to therapeutic control of this economically important parasite, we report the cloning, sequencing, and mRNA expression analysis of the ribonucleotide reductase R2 gene.


Endoscopic-assisted intraoral approach for mandibular condyle fracture management: A systematic review and meta-analysis.
Surgical innovation led to an endoscopic-assisted intraoral approach for managing condyle fractures. The purpose of this systematic review is to purview the role of the endoscope and determine the range of information, summarizing the evidence for the benefit of surgeons on an endoscopic-assisted intraoral approach. A literature search was conducted in PubMed, Google Scholar, Semantic Scholar, and Cochrane Library databases for studies mentioning the endoscopic intraoral approach for managing mandibular condylar fractures. Outcomes include the role of the endoscope, challenges, adjunct armamentarium, duration, and complications associated with the transoral and transbuccal approach for screw fixation. The meta-analysis was conducted with prevalence estimates and standardized means using STATA. Thirty-nine studies were included. A 30° angulated, 4-mm-thick endoscope was the most commonly used endoscope. Two mini plates were most commonly used for fixation. Facial nerve weakness was higher in the transbuccal approach (1.24%) than in the transoral approach (0.8%). Pooled analysis (6 studies) showed that the duration of the surgical procedure was less in the transoral approach compared with the transbuccal approach for screw fixation. The bailout was 1.49%. The endoscopic-assisted intraoral approach is reliable for condylar fracture management. The transoral and transbuccal approaches can be used for screw fixation with comparable outcomes.


Evaluation of 1,3-pentadiene for mutagenicity by the Salmonella/mammalian microsome assay.
1,3-Pentadiene, a food contaminant produced by some molds when they metabolize sorbic acid, was tested for mutagenicity, using variations of the Salmonella/mammalian microsome assay. The chemical was incorporated into the test system (with and without S9 mix) by 3 methods: (a) the standard plate incorporation assay, (b) a liquid preincubation procedure and (c) exposure of test bacteria in the soft agar overlay to gaseous 1,3-pentadiene. The chemical was extremely toxic to the test bacteria with amounts as low as 2.0 microgram/plate causing cell death. However, none of the nonlethal concentrations tested by any of the methods was mutagenic to Salmonella typhimurium strains TA97, TA98, TA100, TA1535, TA1537 or TA1538.


Fabrication and Electrochemical Behavior Investigation of a Polypyrrole/4-Hydroxy-6-methyl-2-mercaptopyrimidine Comodified Gold Electrode.
A polypyrrole (PPy)/4-hydroxy-6-methyl-2-mercaptopyrimidine (HMMP) comodified gold electrode was prepared and characterized in the form of PPy/HMMP/Au. The polymerization mechanisms of pyrrole on a bare Au electrode, a dodecanethiol-modified gold electrode, and a HMMP/Au electrode are compared and discussed. With ascorbic acid as a probe, various factors affecting the electrochemical characteristics of the PPy/HMMP/Au electrode are investigated. The catalytic activity for the electrochemical oxidation of l-ascorbic acid was studied in 0.1 mol. L-1 NaCl and 1.0 x 10(-3) mol. L-1 HCl. Both the kinetics of oxidation and the reproducibility of the electrochemical response are enhanced at the comodified electrode compared to that of an unmodified metal electrode or the PPy/Au electrode in determination of ascorbic acid. Copyright 1999 Academic Press.


Update on newer approaches to prevent or treat COVID-19 infection: What we all need the most right now!!
COVID-19 convalescent plasma (CCP) therapy involves the use of circulating antibodies administration from recovered COVID 19 patients as a practical strategy to provide immediate passive immunity in susceptible recipients in need. Global concern over the potential for "second" or "third" waves of infection to occur before effective vaccines or drug therapies are available has many looking at other biological sources for large-scale production of neutralizing SARS-CoV-2 antibodies. This report summarizes some of the novel strategies for developing alternative safe sources of therapeutic autologous antibodies from COVID -19 infected patients, and provides some original thoughts on how to rapidly implement a safe passive immunity in those COVID-19 patients who are most in need of intervention. COVID-19 antibodies can be isolated or delivered using a number of other techniques including: plasmapheresis, plasma cryoprecipitate reduced (cryosupernatant), antibody hyperconcentrates and advanced cell-based delivery systems. While these proposed technological options may, in some cases, be theoretical, the growing concern over the rapid spread of the SARS-CoV-2 virus has prompted many to pursue innovative and creative solutions to reduce the mortality and morbidity resulting from the current global pandemic. A comparative analysis of various strategies currently in use deserved exploring and this highlighted separately as the essential part of this concise theme.


Long Noncoding RNA ASLNC07322 Functions in VEGF-C Expression Regulated by Smad4 during Colon Cancer Metastasis.
Deletion and mutation of the Smad4 gene are favorable events for the progression of colon cancer, which is related to the negative regulation of vascular endothelial growth factor C (VEGF-C). However, the regulatory mechanism between Smad4 and VEGF-C remains unclear. We reported first that Smad4 can increase the transcription of miR-128-3p, a microRNA targeting VEGF-C mRNA, resulting in a negative correlation between Smad4 and VEGF-C. Moreover, we found that Smad4 combined with Smad3 can positively regulate VEGF-C during colon cancer metastasis through binding to VEGF-C gene promoter. Further, results revealed a mechanism that long noncoding RNA (lncRNA) ASLNC07322 increased specifically in metastatic colon cancer and decreased miR-128-3p as a sponge, leading to a subsequent elevation of VEGF-C. In a word, there are two pathways in the progression of colon cancer, including Smad4/miR-128-3p/VEGF-C and Smad4/VEGF-C pathways in non-metastatic and metastatic colon cancer, respectively. ASLNC07322 crucially controlled this negative and positive regulatory transformation between them. Additionally, ASLNC07322 knockdown combined with Smad4 overexpression could efficiently inhibit lymphatic endothelial cells (LECs) proliferation and tube formation in vitro, as well as tumor growth and lymphangiogenesis in vivo. These data explained the underlying mechanism of Smad4 contribution on VEGF-C expression during metastasis where ASLNC07322 functions vitally as a switch in colon cancer.


On the active transport of organic acids (fluorescein) in the choroid plexus of the rabbit.
The kinetics of active transport of an organic acid (fluorescein) through the membranes of the choroid plexus from the lateral ventricules of the brain of rabbit was studied both morphologically and functionally. It was shown that fluorescein is actively translocated through the apical and basal membrane of the epithelium and is accumulated in blood capillaries at a concentration exceeding one order of magnitude that in the incubation medium. The kinetic curves displaying saturation and the demonstration of inhibition by other acids shows that a specific carrier is involved in the transfer across the membrane. The active transport of fluorescein at 20 degrees C was found to be sodium independent. Total exclusion of sodium from the incubation medium does not change the Michaelis constant (Km) and maximal velocity (V). The active transport depends on the operation of (Na+ + K+)-ATPase as energy source but obviously no specific complexes with the participation of sodium are involved.


Polysialylated neural cell adhesion molecule in childhood ganglioneuroma and neuroblastoma of different histological grade and clinical stage.
Neuroblastoma cells express the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), which normally becomes restricted to a few neural regions after embryogenesis. The aim of the present study was to evaluate PSA-NCAM as a marker in childhood neuroblastoma. We studied the expression of PSA-NCAM on tumor specimens and in sera of 27 children, altogether, with ganglioneuroma and neuroblastoma of different histological grades and clinical stages. For both methods, immunohistochemistry on 5-microm frozen sections and immunoluminescence serum assay, the polysialic-acid-specific monoclonal antibody 735 was used. PSA-NCAM expression was highest in patients with undifferentiated neuroblastoma and advanced stages of disease, whereas children with differentiated tumor types and low clinical stages had distinctly reduced or no reactivity in immunohistochemistry and, simultaneously, normal serum levels. PSA-NCAM expression correlated with other prognostic and diagnostic markers, such as MYCN gene amplification, and serum concentrations decreased during successful treatment. We conclude that PSA-NCAM, both immunohistochemically and in the serum, is a promising candidate for another useful diagnostic and prognostic tumor marker in childhood neuroblastoma.


Bisphosphonates induce apoptosis in CLL cells independently of MDR phenotype.
The anti-tumoral activity of bisphosphonates (BPs) has been reported in leukemia. In this study, we attempted to evaluate the apoptotic effects of the BPs pamidronate (PAM) and zoledronic acid (ZOL) in chronic lymphocytic leukemia (CLL) samples, and to correlate it with clinical parameters and multidrug resistance (MDR) phenotype (P-glycoprotein and multidrug resistance-related protein expression and/or their functional activity). Both BPs were able to induce apoptosis significantly. No correlation was observed between BP-induced apoptosis and clinical parameters or MDR phenotype. Our data suggest that concurrent or sequential administration of BPs with conventional chemotherapeutic drugs may have significant therapeutic potential for CLL patients.


CircCNTNAP3-TP53-positive feedback loop suppresses malignant progression of esophageal squamous cell carcinoma.
Mutation or downregulation of p53 (encoded by TP53) accelerates tumorigenesis and malignant progression in esophageal squamous cell carcinoma (ESCC). However, it is still unknown whether circular RNAs (circRNAs), a novel class of endogenous noncoding RNAs, participate in the regulation of this progress. In this study, we explored the expression profiles of circRNAs in three paired samples of ESCC and identified cCNTNAP3, which is a circRNA that originates from the CNTNAP3 gene transcript and is highly expressed in normal human esophageal tissue. However, we found that the cCNTNAP3 expression level was significantly downregulated in ESCC tissues. In vitro and in vivo studies revealed that cCNTNAP3 inhibited proliferation and increased apoptosis in p53 wild-type ESCC cells, but not in mutant cells. Mechanistically, we found that cCNTNAP3 promotes the expression of p53 by sponging miR-513a-5p. Rescue assay confirmed that the suppressive function of cCNTNAP3 was dependent on miR-513a-5p. We also observed that p53/RBM25 participated in the formation of cCNTNAP3, which implied the existence of a positive feedback loop between cCNTNAP3 and p53. Furthermore, the downregulation of cCNTNAP3 was significantly correlated with later T stage and thus can serve as an independent risk factor for the overall survival of patients with p53 wild-type ESCC. In conclusion, the cCNTNAP3-TP53 positive feedback loop may provide a potential target for the management of ESCC, which also reveals the important role of circRNAs in the regulation of p53.


Stimulation of monovalent cation fluxes by electron donors in the human red cell membrane.
When human red cells are incubated at 37 degrees C with the artificial electron donor system ascorbate + phenazine methosulphate the fluxes of Rb+ (K+) through the cell membrane are increased. The effect of this donor system is much stronger in energy-depleted than in normal cells. The same effects are produced by HS-glutathione, NADH or NADPH loaded into resealed ghosts, but these electron donors were ineffective when added to the incubation medium. The Rb+ (K+) fluxes induced by electron donors resemble closely those induced by an increase of intracellular Ca2+ (Gardos effect). The electron donors require the presence of intracellular Ca2+ to be effective, but at levels that do not stimulate by themselves the fluxes of K+. Flavoenzyme inhibitors (atebrin and chlorpromazine), oligomycin and quinine prevented the effects of both electron donors and Ca2+ alone; antimycin, upcouplers and ethacrynic acid inhibited them partially; ouabain, furosemide, and rotenone had no effect. The results could be explained if the effect of electron donors is to bring about a change in the redox state of some membrane component(s) that makes intracellular Ca2+ more effective to elicit rapid K+ movements. Plasma membrane oxidoreductase activities could be engaged in this change.


History of cerebrovascular disease but not dementia increases the risk for secondary vascular events during SARS-CoV-2 infection with presumed Omicron variant: a retrospective observational study.
This study aimed to investigate if pre-existing neurological conditions, such as dementia and a history of cerebrovascular disease, increase the risk of severe outcomes including death, intensive care unit (ICU) admission and vascular events in patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 2022, when Omicron was the predominant variant. A retrospective analysis was conducted of all patients with SARS-CoV-2 infection, confirmed by polymerase chain reaction test, admitted to the University Medical Center Hamburg-Eppendorf from 20 December 2021 until 15 August 2022. In all, 1249 patients were included in the study. In-hospital mortality was 3.8% and the ICU admission rate was 9.9%. Ninety-three patients with chronic cerebrovascular disease and 36 patients with pre-existing all-cause dementia were identified and propensity score matching by age, sex, comorbidities, vaccination status and dexamethasone treatment was performed in a 1:4 ratio with patients without the respective precondition using nearest neighbor matching. Analysis revealed that neither pre-existing cerebrovascular disease nor all-cause dementia increased mortality or the risk for ICU admission. All-cause dementia in the medical history also had no effect on vascular complications under investigation. In contrast, an increased odds ratio for both pulmonary artery embolism and secondary cerebrovascular events was observed in patients with pre-existing chronic cerebrovascular disease and myocardial infarction in the medical history. These findings suggest that patients with pre-existing cerebrovascular disease and myocardial infarction in their medical history may be particularly susceptible to vascular complications following SARS-CoV-2 infection with presumed Omicron variant.