Functional single-walled carbon nanotubes 'CAR' for targeting dopamine delivery into the brain of parkinsonian mice.
Current treatments for Parkinson's disease (PD) are limited, partly due to the difficulties posed by the blood brain barrier (BBB) when delivering drugs to the brain. Herein, we explore the feasibility and efficacy of functional single-walled carbon nanotubes 'CAR' (SWCNT-PEGs-Lf) which carry and target-deliver dopamine (DA) to the brain in PD mice for treatment. SWCNTs can penetrate the cell-membrane remarkably, with the characteristics including high drug-loading and pH-dependent therapeutic unloading capacities. It has been reported that polyethylene glycol (PEG)-coated SWCNTs could increase the circulation time and thus prolong the concentration gradient of SWCNTs to the brain. Besides, an obvious lactoferrin-nanoparticle (Lf-NP) accumulation in the striatum, wherein the pharmacological target site of PD has been reported, a dual modification of PEG and Lf onto SWCNTs was applied and thus a specific 'CAR' to carry DA. The results from in vitro studies demonstrate that with 20 mol L-1 DA loaded onto SWCNT-polyethylene glycol (PEGs) in addition to 100 μmol L-1 6-hydroxydopamine (6-OHDA), the activity of PC12 cells increases significantly (p < 0.05), and that the lactate dehydrogenase (LDH) levels and reactive oxygen species (ROS) content also significantly decrease (p < 0.01). Furthermore, the levels of oxidative stress, tumor necrosis factor (TNF)-α and interleukin (IL)-1β are all reduced significantly in PD mice and the CAR-25 mg kg-1 DA group in comparison with that in 6-OHDA-lesioned mice with saline and 6-OHDA-lesioned mice, as well as the Tyrosine hydroxylase-immunoreactive (TH-ir) density increased (p < 0.01). The toxicity of CAR was in vitro and in vivo investigated, showing that the safe dose of SWCNT-PEG exposure to PC12 cells was 6.25 μg μl-1 or lower with a higher metabolic activity in comparison with that in the control group and the safe dose of CAR in the mice experiments was 3.25 mg kg-1 or less, given by intraperitoneal injection with a lower level of oxidative stress and inflammatory responses in comparison with that in the control group. This study suggests that 25 mg kg-1 DA loaded onto 3.25 mg kg-1 CAR can alleviate the oxidative stress and inflammatory responses in parkinsonian mice and increase the TH-ir density in the striatum.


Personal carbon monoxide exposure levels: contribution of local sources to exposures and microenvironment concentrations in Milan.
In the framework of the EXPOLIS study in Milan, Italy, 48-h carbon monoxide (CO) exposures of 50 office workers were monitored over a 1-year period. In this work, the exposures were assessed for different averaging times and were compared with simultaneous ambient fixed-site concentrations. The effect of gas cooking and smoking and different methods of commuting on the microenvironment and exposure levels of CO were investigated. During the sampling the subjects completed a time-microenvironment-activity diary differentiating 11 microenvironments and three exposure influencing activities: gas cooking, smoking and commuting. After sampling, all exposure and time allocation data were stored in a relational database that is used in data analyses. Ambient 48-h and maximum 8-h distributions were similar compared to the respective personal exposures. The maximum 1-h personal exposures were much higher than the maximum 8-h exposures. The maximum 1-h exposures were as well higher than the corresponding ambient distribution. These findings indicate that high short-term exposures were not reflected in ambient monitoring data nor by long-term exposures. When gas cooking or smoking was present, the indoor levels at "home-" and in "other indoor" microenvironments were higher than without their presence. Compared with ambient data, the latter source was the most affective to increase the indoor levels. Exposure during commuting was higher than in all other microenvironments; the highest daily exposure contribution was found during "car/taxi" driving. Most of the CO exposure is acquired in indoor microenvironments. For the indoor microenvironments, ambient CO was the weakest predictor for "home indoor" concentrations, where the subjects spent most of their time, and the strongest for "other indoor" concentrations, where the smallest fraction of the time was spent. Of the main indoor sources, gas cooking, on average, significantly raised the indoor exposure concentrations for 45 min and tobacco smoking for 30 min. The highest exposure levels were experienced in street commuting. Personal exposures were well predicted, but 1-h maximum personal exposures were poorly predicted, by respective ambient air quality data. By the use of time-activity diaries, ETS exposure at the workplaces were probably misclassified due to differences in awareness to tobacco smoke between smokers and nonsmokers.


Age dependence of laryngeal chemoreflex in puppies.
Previously collected data have indicated that the laryngeal chemoreflex (LCR) response is exaggerated during a critical period of postnatal development in several experimental animals. These animals had fewer anatomic and physiological similarities to humans than do puppies. This investigation of the LCR in 14 anesthetized puppies was undertaken to determine age-related differences in the response to stimulation of the supraglottic laryngeal mucosa by saline solution, distilled water, cow's milk, and acid at pH 1.0. The dogs were divided into 3 age groups: group 1 consisted of 4 dogs that were 2 weeks old, and in groups 2 and 3 there were 5 puppies each, of 4 and 6 weeks of age, respectively. The LCR response (laryngospasm, apnea, respiratory depression, and bradycardia) was found in the puppies only after stimulation of the laryngeal mucosa with acid at pH 1.0, and it was more easily achieved in the 4- and 6-week age groups than in the 2-week group. These findings suggest that the LCR is an age-dependent response that appears in dogs only after 2 weeks of age. The important implication of this finding is that postnatal neural maturation may influence the laryngeal reflex in humans to some extent.


Practice patterns for spasticity management with phenol neurolysis.
To present practice patterns for phenol neurolysis procedures conducted for spasticity management. A retrospective review of 185 persons with spasticity who underwent phenol neurolysis procedures (n = 293) at an academic rehabilitation hospital and clinic. Patient demographics, concomitant spasticity treatments, and procedure relevant information were collected. The cohort included 71.9% males and 61.6% inpatient procedures. Neurological diagnoses included stroke (41.0%), traumatic brain injury (28.6%) and spinal cord injury (24.3%). Musculoskeletal diagnoses included spastic hemiplegia or paresis (51.3%), tetraplegia (38.4) and paraplegia (9.2%). At the time of phenol neurolysis, most patients (77.5%) received concomitant pharmacological treatments for spasticity. Injection guidance modalities included electrical stimulation and ultrasound (69.3%) or ultrasound only (27.3%). A mean of 3.48 ml of phenol were injected per nerve and 10.95 ml of phenol were used per procedure. Most commonly injected nerves included the obturator nerve (35.8%) and sciatic branches to the hamstrings and adductor magnus (27.0%). Post-phenol neurolysis assessment was recorded in 54.9% of encounters, in which 84.5% reported subjective benefit. Post-procedure adverse events included pain (4.0%), swelling and inflammation (2.7%), dysaesthesia (0.7%) and hypotension (0.7%). Phenol neurolysis is currently used to reduce spasticity for various functional goals, including preventing contractures and improving gait. Depending on the pattern of spasticity displayed, numerous peripheral nerves in the upper and lower extremities can be targeted for treatment with phenol neurolysis. Further research into its role in spasticity management, including studies exploring its cost-effectiveness and pharmacological and side-effects compared with other treatment options are needed.


[Quantitative detection of SARS-CoV RNA in excreta and oropharyngeal washing fluid from convalescence patients with severe acute respiratory syndrome].
To detect the severe acute respiratory syndrome coronavirus (SARS-CoV) RNA in excreta and oropharyngeal washing fluid (OWF) from the convalescence SARS patients, and to determine whether convalescence patients carry the SARS-CoV, and whether having infectivity. Totally 531 samples (including urine, stool, and OWF) were collected from 177 convalescence patients with positive SARS antibody which were confirmed by ELISA method. Real-time quantitative PCR was performed to detect the RNA of the SARS-CoV, and results were analyzed by SPSS analysis software. There were 49 (27.7%) cases of SARS-CoV RNA detection positive in 177 patients, including 31 (17.5%) cases with one sample positive, 14 (7.9%) cases with two samples positive, and 4 (2.3%) cases with three samples positive. The positive rates of urine, stool, and OWF were 14.7% (26/177), 11.9% (21/177), and 13.6% (24/177), respectively. The quantity of SARS-CoV RNA in samples was 100-47 000 copies/ml. No significant difference was found among urine, stool, and OWF on the difference grade quantity of SARS-CoV RNA quantity. About 10% convalescence SARS patients might still carry the SARS-CoV in hospitalization. The detection of SARS-CoV RNA by real-time quantitative PCR may become a laboratory examination warranty for convalescence SARS patients to discharge hospital and relieve separation.


Expected adverse events in a mass smallpox vaccination campaign.
Recent anthrax attacks in the United States have raised concern about the nation's vulnerability to a smallpox attack. Many strategies have been suggested to minimize the impact of such an attack, ranging from quarantine and vaccination of case contacts to resumption of routine vaccination. Before the latter strategy is adopted, an understanding of the likely consequences of mass vaccination is essential. Number of adverse events resulting from two vaccination campaigns: vaccinating persons 1 to 29 years of age and vaccinating those 1 to 65 years of age. Number of adverse events = incidence rate of adverse events x number vaccinated. We assumed 75% vaccine uptake in the target group (i.e., we estimated that about 25% of potential vaccine recipients would be excluded because they are, or have close contact with, individuals who have eczema or are immunocompromised). Historical data on the incidence of adverse events from smallpox vaccination were identified by a literature search. Number vaccinated was drawn from the January 2000 U.S. Census estimate. Fever (<1 case per 5 vaccine recipients) and rash (<1 case per 100 vaccine recipients) would be the most common adverse events. Serious adverse events, including encephalitis (<3 cases per million) and death (<2 cases per million), although rare, would be more common than with other currently recommended vaccines. After excluding high-risk individuals and their contacts, we estimate that a vaccination strategy directed at people aged 1 to 29 years would result in approximately 1600 serious adverse events and 190 deaths. Vaccinating people aged 1 to 65 years would result in approximately 4600 serious adverse events and 285 deaths. While advances in health care over the past three decades could mitigate vaccine complications, the increased number of unimmunized high-risk individuals (e.g., those with eczema or immune suppression) could increase complication rates. The decision to resume smallpox vaccination depends on weighing the likelihood of a smallpox attack and its anticipated mortality against expected harm from a mass immunization program. Smallpox vaccine has a higher complication rate than any other vaccine currently being used. Careful prevaccination exclusion of high-risk individuals and their close contacts would be essential to minimize complications of a mass vaccination campaign, although such exclusions necessarily mean that some proportion of the population will remain susceptible to smallpox.


Sequence and regulatory responses of a ribosomal protein gene from the fission yeast Schizosaccharomyces pombe.
We have determined the nucleotide sequence and mapped the 5' and 3' termini of a ribosomal protein gene. The gene is transcribed into a RNA molecule of about 770 nt and appears to initiate at multiple sites, as judged by SI nuclease analysis. Gene dosage experiments with a plasmid born gene leads to a proportional increase of the messenger RNA, but not to an overproduction of the protein, suggesting a posttranscriptional control mechanism. However, the heat shock response of this gene indicates that there is also a potential for transcriptional control. Comparison of the 5' flanking region of this gene with the ribosomal protein gene S 6 from Schizosaccharomyces pombe and with ribosomal protein genes from Saccharomyces cerevisiae revealed homologous sequences, which may be involved in the regulation of ribosomal protein genes.


Unraveling the reactions that unravel cellulose.
For over 90 years, researchers have postulated mechanisms for the cleavage of cellulose's glycosidic bonds and resulting formation of levoglucosan without reaching consensus. These reactions are key primary reactions in thermal processes for the production of carbon-neutral, renewable transportation fuels. Previous literature reports have proposed a variety of mainly heterolytic and homolytic mechanisms, but there has been insufficient evidence to settle the debate. Using density functional theory (DFT) methods and implicit solvent, we compared the likelihood of forming either radical or ionic intermediates. We discovered a concerted reaction mechanism that is more favorable than previously proposed mechanisms and is in better alignment with experimental findings. This new understanding of the mechanism of cellulose thermal decomposition opens the door to accurate process modeling and educated catalyst design, which are vital steps toward producing more cost-efficient renewable energy.


Evaluation of 90 day repeated dose oral toxicity and reproductive/developmental toxicity of 3'-hydroxypterostilbene in experimental animals.
3'-Hydroxypterostilbene (3'-HPT) is one of the active constituents of Sphaerophysa salsula and Pterocarpus marsupium. Despite many proposed therapeutic applications, the safety profile of 3'-HPT has not been established. The present work investigated 90 day repeated oral dose and reproductive (developmental) toxicity of 3'-HPT as a test substance in rats as per OECD guidelines. 90 day toxicity was conducted in sixty Sprague Dawley rats of each sex (120 rats), grouped into six dosage groups of 0 (control), 0 (control recovery), 20 (low dose), 80 (mid dose), 200 (high dose) and 200 (high dose recovery) mg/kg bwt/day (body weight/day) respectively. For the reproductive toxicity study forty Wistar rats of each sex (80 rats) divided into four dosage groups received 0 (vehicle control), 20 (low dose), 100 (mid dose) and 200 (high dose) mg/kg bwt/day of 3'-HPT respectively for a period of two weeks while pre-mating, mating, on the day before sacrifice, in females during pregnancy and four days of lactation period. Results showed no significant differences in body weight, food intake, absolute organ weight, haematology, with no adverse effects (toxicity) on biochemical values nor any abnormal clinical signs or behavioural changes were observed in any of the control/treatment groups, including reproductive and developmental parameters, gross and histopathological changes. In conclusion, the results suggested a No-Observed-Adverse-Effect-Level (NOAEL) of 200 mg/kg bwt/day in rats after oral administration, implying 3'-HPT did not exhibit any toxicity under the study conditions employed.


RNA-Seq analysis of differential gene expression in electroporated chick embryonic spinal cord.
In ovo electroporation of the chick neural tube is a fast and inexpensive method for identification of gene function during neural development. Genome wide analysis of differentially expressed transcripts after such an experimental manipulation has the potential to uncover an almost complete picture of the downstream effects caused by the transfected construct. This work describes a simple method for comparing transcriptomes from samples of transfected embryonic spinal cords comprising all steps between electroporation and identification of differentially expressed transcripts. The first stage consists of guidelines for electroporation and instructions for dissection of transfected spinal cord halves from HH23 embryos in ribonuclease-free environment and extraction of high-quality RNA samples suitable for transcriptome sequencing. The next stage is that of bioinformatic analysis with general guidelines for filtering and comparison of RNA-Seq datasets in the Galaxy public server, which eliminates the need of a local computational structure for small to medium scale experiments. The representative results show that the dissection methods generate high quality RNA samples and that the transcriptomes obtained from two control samples are essentially the same, an important requirement for detection of differential expression genes in experimental samples. Furthermore, one example is provided where experimental overexpression of a DNA construct can be visually verified after comparison with control samples. The application of this method may be a powerful tool to facilitate new discoveries on the function of neural factors involved in spinal cord early development.


Chemical characterization and source identification of polycyclic aromatic hydrocarbons in aerosols originating from different sources.
To obtain the characteristic factors or signatures of particulate polycyclic aromatic hydrocarbons (PAHs) to help identify the sources of particulate PAHs in the atmosphere, different carbonaceous aerosols were generated by burning different fossil fuels and biomass under different conditions in the laboratory, and the chemical characteristics of 14 PAHs were studied in detail. The results showed that (1) carbonaceous aerosols derived from domestic burning of coal, diesel fuel, and gasoline have much higher concentrations of PAHs than those derived from domestic burning of biomass; (2) carbonaceous aerosols derived from domestic burning of diesel fuel/gasoline have similar PAH components as those derived from high-temperature combustion of diesel fuel/gasoline, although the former have much higher concentrations of PAHs than the latter, suggesting that the burning temperature obviously affects the emitting amount of particulate PAHs, but only slightly influences the PAHs components; and (3) the ratios of benzo[b]fluoranthene/acenaphthylene, benzo[b]fluoranthene/fluorene, dibenzo[a,h]anthracene/acenaphthylene, dibenzo[a,h]anthracene/fluorine, and benzo[b]fluoranthene/benzo[k]fluoranthene in carbonaceous aerosols are sensitively dependent on their sources, indicating that these ratios are suitable for use as characteristic factors or signatures of particulate PAHs in the atmosphere.


Parity, age at first birth, and risk of death from chronic renal failure: a cohort study of parous women in Taiwan.
This study was undertaken to examine whether there is an association between parity and age at first birth and risk of death from chronic renal failure (CRF). Prospective cohort study. The study cohort consisted of 1 292 462 women who had a first and singleton childbirth between January 1, 1978 and December 31, 1987. We tracked each woman from the time of their first childbirth to December 31, 2009, and their vital status was ascertained by linking records with the computerized mortality database. Parity and age at first birth. Death of chronic renal failure (CRF). There were 225 CRF deaths during 34 980 246 person-years of follow-up. The mortality rate of CRF was 0.64 cases per 100 000 person-years. Adjusted hazard ratios (HRs) were 1.75 (95% CI= 1.30-2.36) for women who gave birth between 26 and 30 years, 2.52 (95% CI=1.57-4.04) for women who gave birth after 30 years, respectively, when compared with women who gave birth younger than 25 years. Adjusted HRs were 0.47 (95% CI= 0.33-0.66) for women who had two children, and 0.40 (95% CI=0.28-0.58) for women with three or more births, respectively, when compared with women who had given birth to only one child. There was a significant decreasing trend in the HRs of CRF death with increasing parity. This study provides evidence that reproductive factors (parity and early age at first birth) may confer a protective effect on the risk of CRF death.


Comparison of intranasal and transcutaneous immunization for induction of protective immunity against Chlamydia muridarum respiratory tract infection.
Chlamydia pneumoniae causes a range of respiratory infections including bronchitis, pharyngitis and pneumonia. Infection has also been implicated in exacerbation/initiation of asthma and chronic obstructive pulmonary disease (COPD) and may play a role in atherosclerosis and Alzheimer's disease. We have used a mouse model of Chlamydia respiratory infection to determine the effectiveness of intranasal (IN) and transcutaneous immunization (TCI) to prevent Chlamydia lung infection. Female BALB/c mice were immunized with chlamydial major outer membrane protein (MOMP) mixed with cholera toxin and CpG oligodeoxynucleotide adjuvants by either the IN or TCI routes. Serum and bronchoalveolar lavage (BAL) were collected for antibody analysis. Mononuclear cells from lung-draining lymph nodes were stimulated in vitro with MOMP and cytokine mRNA production determined by real time PCR. Animals were challenged with live Chlamydia and weighed daily following challenge. At day 10 (the peak of infection) animals were sacrificed and the numbers of recoverable Chlamydia in lungs determined by real time PCR. MOMP-specific antibody-secreting cells in lung tissues were also determined at day 10 post-infection. Both IN and TCI protected animals against weight loss compared to non-immunized controls with both immunized groups gaining weight by day 10-post challenge while controls had lost 6% of body weight. Both immunization protocols induced MOMP-specific IgG in serum and BAL while only IN immunization induced MOMP-specific IgA in BAL. Both immunization routes resulted in high numbers of MOMP-specific antibody-secreting cells in lung tissues (IN>TCI). Following in vitro re-stimulation of lung-draining lymph node cells with MOMP; IFNgamma mRNA increased 20-fold in cells from IN immunized animals (compared to non-immunized controls) while IFNgamma levels increased 6- to 7-fold in TCI animals. Ten days post challenge non-immunized animals had >7,000 IFU in their lungs, IN immunized animals <50 IFU and TCI immunized animals <1,500 IFU. Thus, both intranasal and transcutaneous immunization protected mice against respiratory challenge with Chlamydia. The best protection was obtained following IN immunization and correlated with IFNgamma production by mononuclear cells in lung-draining LN and MOMP-specific IgA in BAL.


[Pay attention to digestive tract reconstruction after curative resection of gastric cancer].
Several reconstruction techniques are available after gastrectomy. Roux-en-Y reconstruction following distal gastrectomy is the reference in terms of long-term functional and endoscopic outcomes. It is the preferred reconstruction for benign lesions and early gastric cancer. In patients with advanced gastric cancer, BillrothII (reconstruction is an acceptable alternative. After total gastrectomy, Roux-en-Y reconstruction is the simplest solution, with satisfactory functional outcome. Addition of a jejunal reservoir seems to improve long-term outcome after total gastrectomy and could be of benefit to patients with good prognosis. After distal or total gastrectomy, hand-sewn anastomoses should be preferred because of lower costs. Mechanical sutures can facilitate transhiatal esophagojejunostomy. After proximal gastrectomy, esophago-gastric anastomosis is the basic reconstruction method. Gastric remnant is made into gastric tube in the operation. The effect of pyloroplasty remains controversial, and further study is needed to improve the quality of life after operation.


Size-dependent binding energies of methane to small gold clusters.
The reactions of small gold cluster cations Au(x)(+) (x=2-6) with CH(4) were studied by joint gas-phase kinetics and first-principles density functional theory calculations. The experimentally obtained temperature-dependent low pressure rate constants were analyzed by employing the Lindemann energy transfer model for association reactions in conjunction with statistical RRKM theory. In this way cluster-size-dependent binding energies of methane to the gold cluster cations were determined from the experimental data for two different transition-state models. The experimental binding energies obtained by employing a "loose" transition-state model are in good agreement with the theoretical values at the optimal adsorption geometries, while a "tight" transition-state model clearly gives a lower limit for the binding energies. Additionally, Kohn-Sham molecular orbitals of Au(x)-CH(4)(+) are presented to gain detailed insight into the cluster-methane bonding mechanism.


Leg length discrepancy treatment with subtrochanteric shortening osteotomy and blade plate fixation.
Subtrochanteric femoral shortening osteotomy is a method of surgical treatment of lower limb discrepancy (LLD). It is less commonly used due to numerous limitations and the resulting decrease in height, which is an undesirable effect for most patients. The aim of this study was to analyze the results and complications of treatment of leg length discrepancy (LLD) by femoral shortening osteotomy fixed with a blade plate and screws. The study group comprised 18 patients treated by subtrochanteric shortening osteotomy fixed with a blade or straight plate and screws. The age of patients at the time of the operation ranged from 12 years and two months to 24 years and 3 months (mean 17 years and 8 months). Before the operation, the mean LLD amounted to 4.1cm (from 2,5 to 7,0). The size of the same-time resection of the femur at the level of the subtrochanteric osteotomy ranged from 2.5 cm to 5.0 cm (mean 3.7). The follow-up period ranged from 6 months to 15 years and 9 months (mean 3 years and 6 months). The analysis of the results was based on the following criteria. A good result was defined as obtaining an equal length of both legs or achieving the intended amount of shortening. A fair result was defined as a post-operative LLD from 0.5 cm to 1 cm. A poor result comprised patients with post-operative LLD greater than 1 cm or with complications that leave a lasting impact or complications requiring revision surgery. A good result was obtained in 15 patients and a fair one in 3 patients. Complications appeared in 5 (28%) patients. The most common complication was delayed bone healing. Full weight -bearing of the operated limb was allowed between 12 and 32 weeks post-surgery (mean 19 weeks). The final LLD ranged from 0 cm to 3 cm (mean 0.6 cm). Equal limb length was obtained in 13 (72%) patients. 1. Subtrochanteric femoral shortening osteotomy fixed with a plate and screws, taking into consideration the limitation of possible correction to 5-6 cm, is an effective method of treatment of lower limb discrepancy with a relatively low complication rate. 2. The most common complications of subtrochanteric shortening osteotomy are disorders of bone union. 3. The use of lag screws for stabilisation of the osteotomy with an angle plate may reduce the risk of complications.


Exploring cultivable Bacteria from the prokaryotic community associated with the carnivorous sponge Asbestopluma hypogea.
Combining culture-dependent and independent approaches, we investigated for the first time the cultivable fraction of the prokaryotic community associated with the carnivorous sponge Asbestopluma hypogea. The heterotrophic prokaryotes isolated from this tiny sponge were compared between specimens freshly collected from cave and maintained in aquarium. Overall, 67 isolates obtained in pure culture were phylogenetically affiliated to the bacterial phyla Proteobacteria, Bacteroidetes, Actinobacteria, and Firmicutes. This cultivable diversity was lower than the prokaryotic diversity obtained by previous pyrosequencing study and comparable to that of another Mediterranean demosponge, the filter-feeding Phorbas tenacior. Furthermore, using fluorescence in situ hybridization, we visualized bacterial and archaeal cells, confirming the presence of both prokaryotes in A. hypogea tissue. Approximately 16% of the bacterial isolates tested positive for chitinolytic activity, suggesting potential microbial involvement in the digestion processes of crustacean prey by this carnivorous sponge. Additionally, 6% and 16% of bacterial isolates revealed antimicrobial and antioxidant activities, respectively. One Streptomyces sp. S1CA strain was identified as a promising candidate for the production of antimicrobial and antioxidant secondary metabolites as well as chitinolytic enzymes. Implications in the context of the sponge biology and prey-feeding strategy are discussed.


Sensitization of naive beagles by intradermal injection of an ascaris antigen: induction of a model of skin allergy.
Ascaris suum-hypersensitive beagles represent a unique model of skin allergy. Despite its suitability, the need to test numerous dogs prior to the selection of natural positive responders causes many complications. We hypothesized that the model could be induced in adult beagles by primary sensitization. Ten dogs were included in an intradermal sensitization program using ascaris antigen and were thereafter tested for cutaneous reaction. After 2 weeks, 60% developed a positive reaction that lasted for months. We therefore present a straightforward method to establish the Ascaris canine model of allergy that will extend its availability for research in cutaneous allergy immunomodulation.


Effects of Food on the Pharmacokinetics of Omega-3-Carboxylic Acids in Healthy Japanese Male Subjects: A Phase I, Randomized, Open-label, Three-period, Crossover Trial.
Omega-3-carboxylic acids (OM3-CA) contain omega-3 free fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as carboxylic acids. Food intake is known to affect the bioavailability of ethyl ester fatty acid formulations. We conducted a phase I study to investigate the effects of the timing of OM3-CA administration relative to food intake on the pharmacokinetics of EPA and DHA. In this randomized, open-label, three-period crossover study, Japanese healthy male subjects were administered 4×1 g OM3-CA capsules with continued fasting, before a meal, or after a meal. All subjects fasted for ≥10 h prior to drug/meal administration. The primary objective was to examine the effect of meal timing on the pharmacokinetics of EPA and DHA after OM3-CA administration. The secondary objectives were to examine the safety and tolerability of OM3-CA. A total of 42 Japanese subjects was enrolled in the study. The baseline-adjusted maximum concentration and area under the concentration-time curve from 0 to 72 h for EPA, DHA, and EPA +DHA were lower in the fasting and before meal conditions than in the after meal condition. The maximum total EPA, total DHA, and total EPA+DHA concentrations were reached later when administered in fasting conditions than in fed conditions, indicating slower absorption in fasting conditions. Diarrhea was reported by five, six, and no subjects in the fasting, before meal, and after meal conditions, respectively. The timing of OM3-CA administration relative to food intake influences the systemic bioavailability of EPA and DHA in healthy Japanese male subjects. NCT02372344.


A community-based delivery system of intermittent preventive treatment of malaria in pregnancy and its effect on use of essential maternity care at health units in Uganda.
Community delivery of intermittent preventive treatment of malaria in pregnancy (IPTp) is one potential option that could mitigate malaria in pregnancy. However, there is concern that this approach may lead to complacency among women with low access to essential care at health units. A non-randomised community trial assessed a new delivery system of IPTp through traditional birth attendants, drug shop vendors, community reproductive health workers and adolescent peer mobilisers (the intervention) compared with IPTp at health units (control). The study enrolled a total of 2081 pregnant women with the new approaches. Data on care-seeking practices before and after the intervention were collected. The majority of women with the new approaches accessed IPTp in the second trimester and adhered to two doses of sulfadoxine/pyrimethamine (SP) (1404/2081; 67.5%). Antenatal care (four recommended visits) increased from 3.4% (27/805) to 56.8% (558/983) (P<0.001). The proportion of women delivering at health units increased from 34.3% (276/805) to 41.5% (434/1045) (P=0.02), whilst the proportion of women seeking care for malaria at health units increased from 16.7% (128/767) to 36.0% (146/405) (P<0.001). Similarly, use of insecticide-treated nets increased from 7.7% (160/2081) to 22.4% (236/1055) (P<0.001). In conclusion, the community-based system was effective in delivering IPTp, whilst women still accessed and benefited from essential care at health units.


The value of nursing care in the paradigm of chronicity and dependency. New roles and redesigns.
The future of Healthcare Systems not only faces financial troubles, but also--perhaps worse, the need to redesign its service offers. It is necessary to work for all the knowledge available to be placed at the service of patients and society, generating much more efficient services and opening to a redesign where nurses lead in new services supported on the strategy of effective care. Additionally, it is hoped that patients assume a responsibility and nurses another: that of accompanying patients during their disease process to become for them a support in their self-care efforts. The new role that must be assumed by community nurses is that of becoming the coaches of chronic patients and of their caregivers so they can reach a situation of equilibrium, between their desires and what they must do, to, thus, assume their responsibility in the self-provision of Basic Care.


Preservation versus resection of Denonvilliers' fascia in total mesorectal excision for male rectal cancer: follow-up analysis of the randomized PUF-01 trial.
Traditional total mesorectal excision (TME) for rectal cancer requires partial resection of Denonvilliers' fascia (DVF), which leads to injury of pelvic autonomic nerve and postoperative urogenital dysfunction. It is still unclear whether entire preservation of DVF has better urogenital function and comparable oncological outcomes. We conducted a randomized clinical trial to investigate the superiority of DVF preservation over resection (NCT02435758). A total of 262 eligible male patients were randomized to Laparoscopic TME with DVF preservation (L-DVF-P group) or resection procedures (L-DVF-R group), 242 of which completed the study, including 122 cases of L-DVF-P and 120 cases of L-DVF-R. The initial analysis of the primary outcomes of urogenital function has previously been reported. Here, the updated analysis and secondary outcomes including 3-year survival (OS), 3-year disease-free survival (DFS), and recurrence rate between the two groups are reported for the modified intention-to-treat analysis, revealing no significant difference. In conclusion, L-DVF-P reveals better postoperative urogenital function and comparable oncological outcomes for male rectal cancer patients.


Evaluation of renal parenchyma in children by DMSA scintigraphy, X-ray computed tomography and intravenous urography.
The demonstration of diminished or scarred renal parenchyma in children is often the decisive factor in determining the future management of children with urinary tract malformations. Renal scintigraphy using technetium 99m-labelled dimercaptosuccinic acid (DMSA), computed tomography (CT) and intravenous urography (IU) were used to evaluate the renal parenchyma prior to ureter re-implantation in a series of 13 children. Their ages ranged from 5 months to 3 years 8 months. The indication for operation was ureteric reflux in 8 children and distal ureteric stenosis in 5. CT was performed on a Toshiba TCT-80 scanner. Renal scintigraphy was performed 3 hours after intravenous injection of DMSA. Compared with IU, DMSA imaging gave more information about the renal parenchyma in 6 children, gave equal information in 6 and less in 1. Compared with CT, DMSA imaging gave more information in 2 children, was equally informative in 8 and less so in 3. Accordingly, DMSA imaging was judged to be more sensitive than IU and as sensitive as CT. DMSA imaging can be used both for the initial evaluation and for follow-up assessment of renal parenchymal damage.


Effect of traditional Greek Mediterranean meals on platelet aggregation in normal subjects and in patients with type 2 diabetes mellitus.
Patients with type 2 diabetes mellitus have increased risk of cardiovascular disease. Epidemiological studies have shown a correlation between diet and incidence of coronary heart disease. The aim of the study is to determine the effect of a traditional Greek Mediterranean diet on platelet aggregation induced by ADP, arachidonic acid (AA), and especially platelet-activating factor (PAF) on patients with type 2 diabetes mellitus as well as on healthy volunteers. The patients were randomized into two subgroups, A and B. The lipid extracts from traditional Greek Mediterranean-type meals were tested in in vivo for their ability to reduce PAF- or thrombin-induced platelet aggregation. The meals with the most potent anti-aggregating activity were chosen for the diet of both subgroup A and healthy subjects and consumed for a period of 28 days, whereas subgroup B kept to their regular diet that was followed before entering the study. Platelet-rich plasma was isolated before and after the diet, and the ability of platelets to aggregate under the aggregating factors was tested. One-month consumption of diet resulted in a significant reduction in PAF- and ADP-induced aggregation of platelets in both groups of healthy volunteers (PAF and ADP, P < .05) and subgroup A (PAF, P < .001; ADP, P < .05), whereas the AA-induced aggregation was not affected. No effect was observed in subgroup B, which followed the standard diet. Thus the consumption of a traditional Greek Mediterranean diet even for a short period can reduce platelet activity in patients suffering from type 2 diabetes mellitus and in healthy subjects.


Cardiovascular studies of phenylpropanolamine.
Phenylpropanolamine is found in a number of over-the-counter preparations commonly used for appetite control or as a cold remedy. Even though widely used, some questions still exist as to its effect on the cardiovascular system of man. Both anesthetized and unanesthetized adult beagle dogs were used in this study. In the unanesthetized conditioned dog, blood pressure and heart rate were measured using an inflatable tail cuff. In the first group, consisting of 12 dogs, phenylpropanolamine was given (0.0, 3.1, 6.25 and 12.5 mg/kg) via a stomach tube and the animals were followed for 300 minutes. Each dose of phenylpropanolamine was given to 4 groups made up of 3 dogs each. It produced dose-dependent increases in blood pressure and decreases of heart rate. Maximum changes were noted at 30 to 60 minutes, lasting for 3 to 5 hours. A second group of 9 unanesthetized dogs was given repeated oral doses of phenylpropanolamine (3 groups of 3 animals each). Doses of 3 mg/kg and 6 mg/kg, given orally, produced approximately the same increase in blood pressure and decrease of heart rate as previously observed. At 6 hours, these same doses of phenylpropanolamine produced little or no change in either parameter. At 24 hours after the first dose, however, the dogs responded in much the same manner as with the first administration of phenylpropanolamine. Control dogs given water did not exhibit any degree of tachyphylaxis. Dogs anesthetized with Na pentobarbital were given oral and intravenous doses of phenylpropanolamine (0.0-25 mg/kg). The overall response was like that observed in the unanesthetized preparation with the important exception that low doses (0.1-3 mg/kg) produced significant increases in both heart rate and blood pressure, while higher doses (6-25 mg/kg) resulted in a lesser overall effect. Six anesthetized animals were used to study the effects of phenylpropanolamine and norepinephrine on the cardiovascular function. Both the increase in blood pressure and left ventricular force of contraction, produced by the first dose of phenylpropanolamine, were markedly reduced or absent with the second administration of the drug. In addition, the classic blood pressure response to norepinephrine was likewise increased by prior administration of phenylpropanolamine.(ABSTRACT TRUNCATED AT 400 WORDS)


Early debridement in pit viper bites.
From my observations of snakebite over the last 22 years and the studies I have done, several things are important: (1) Pit viper envenomation is a surgical emergency as is any disease in which gangrene of human tissue occurs. (2) Severe pit viper envenomation causes complex problems similar to those seen in Gram-negative septicemia, and they require complex methods of treatment. (3) Early surgical inspection of the snakebite wound is as essential as early appendectomy in appendicitis. Its results are as gratifying. (4) Present knowledge of anesthesia, coagulation problems, infections and antibiotics, blood gas changes, electrolytes and fluid therapy, and other advances in the surgical field allow the physician to treat severe pit viper envenomation by scientific means rather than by hocus-pocus. (5) Crippling from pit viper envenomation is caused by too little treatment, too much first aid, or both.


Replacing CAR-T cell resistance with persistence by changing a single residue.
Sustained persistence of chimeric antigen receptor T (CAR-T) cells is a key characteristic associated with long-term remission in patients with hematologic malignancies. Attempts to uncover mechanisms that enhance persistence and thus functionality will have a substantial impact in broadening application of CAR-T cell therapy, especially for solid tumors. In this issue of the JCI, Guedan et al. describe a promising strategy to limit T cell exhaustion and improve persistence by changing a single amino acid in the costimulatory domain of CD28. The authors demonstrated that this single amino acid substitution in CD28-based mesothelin CAR-T cells results in improved persistence and functionality in a xenograft model of pancreatic cancer. Furthermore, reciprocal alteration of the same residue in inducible costimulator-containing (ICOS-containing) CAR-T cells resulted in limited antitumor activity and persistence. These findings suggest that simple alterations in the costimulatory domain may enhance CAR-T cell persistence, warranting future evaluation in other CD28-costimulatory CARs in an effort to improve durable antitumor effects.


Opioid peptides and central control of blood pressure.
The role of endogenous opioids in central modulation of baroreceptor reflex function has been assessed in rabbits and in man using stable enkephalin analogues and synthetic opiates with a range of mu, delta and kappa opiate receptor agonist specificity. In addition the effects of naloxone, a mu opiate receptor antagonist, have been studied. In rabbits descarboxy-leu-enkephalin (RX783016) given by intracisternal injection reduced baroreflex sensitivity as assessed by heart rate responses to phenylephrine, sodium nitroprusside and controlled haemorrhage. These effects were prevented by intravenous naloxone. Naloxone alone increased the slope of the heart period: mean arterial pressure relationship and thus increased baroreflex sensitivity. In conscious man essentially similar results were found following intravenous dosing with a stable met-enkephalin analogue (DAMME, FK33824) or naloxone with decreases and increases respectively in the sensitivity of baroreflex responses to sodium nitroprusside. In rabbits and man arterial baroreceptor reflexes mediating heart rate responses can be pharmacologically modified by exogenous opiates and may be under some tonic endogenous opiate peptide influences.


Error-correcting codes on scale-free networks.
We investigate the potential of scale-free networks as error-correcting codes. We find that irregular low-density parity-check codes with the highest performance known to date have degree distributions well fitted by a power-law function p (k) approximately k(-gamma) with gamma close to 2, which suggests that codes built on scale-free networks with appropriate power exponents can be good error-correcting codes, with a performance possibly approaching the Shannon limit. We demonstrate for an erasure channel that codes with a power-law degree distribution of the form p (k) = C (k+alpha)(-gamma), with k> or =2 and suitable selection of the parameters alpha and gamma, indeed have very good error-correction capabilities.


A Preligamentous Variant of the Thenar Motor Branch of the Median Nerve.
We report a rare variant of the thenar motor branch (TMB) of the median nerve. A preligamentous TMB was discovered during revision carpal tunnel release in a 49-year-old man. The prevalence and characteristics of TMB variations are discussed. The literature describing iatrogenic injury to the TMB variants, surgical treatment, and preoperative screening tools is reviewed. Recognition of anatomic variants of the TMB is essential considering notable consequences of iatrogenic injury.


SARS-CoV-2 escape from a highly neutralizing COVID-19 convalescent plasma.
To investigate the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the immune population, we coincupi bated the authentic virus with a highly neutralizing plasma from a COVID-19 convalescent patient. The plasma fully neutralized the virus for seven passages, but, after 45 d, the deletion of F140 in the spike N-terminal domain (NTD) N3 loop led to partial breakthrough. At day 73, an E484K substitution in the receptor-binding domain (RBD) occurred, followed, at day 80, by an insertion in the NTD N5 loop containing a new glycan sequon, which generated a variant completely resistant to plasma neutralization. Computational modeling predicts that the deletion and insertion in loops N3 and N5 prevent binding of neutralizing antibodies. The recent emergence in the United Kingdom, South Africa, Brazil, and Japan of natural variants with similar changes suggests that SARS-CoV-2 has the potential to escape an effective immune response and that vaccines and antibodies able to control emerging variants should be developed.


[Medical history impressions of Karl Marx 1983].
Excerpts of his London era first published on the occasion of the Karl Marx testimonials of 1983 gave rise to extend the memory of the fundamental achievements of Karl Marx to medico-historical aspects. In this case Karl Marx paid special attention to the working and living conditions of the working class and an analysis of his adequate statements and records shows multifarious details which give a research basis also for the history of medicine. Marx and Engels had friendly contacts with several physicians who shared the opinions of the two classics: their way of life is shown in the most important points.


Antenatal iron-folic acid supplementation reduces risk of low birthweight in Pakistan: secondary analysis of Demographic and Health Survey 2006-2007.
The aim of the current study was to examine the impact of antenatal iron-folic acid (IFA) supplementation on perceived birth size and birthweight in Pakistan over a 5-year period from 2002 to 2006. The data source was the Pakistan Demographic and Health Survey (PDHS) 2006-2007. Information from 5692 most recent live-born infants within 5 years prior to the survey was examined. The primary outcomes were maternal perception of birth size and birthweight, and the main exposure was any use of antenatal IFA supplements. Birthweight was reported for only 10% of the live births in the PDHS 2006-2007. Multivariate logistic regression analysis was adjusted for the cluster sampling design and for 13 potential confounders. The risk of having smaller than average birth size newborn was significantly reduced by 18% (adjusted odds ratio 0.82, 95% confidence interval 0.71, 0.96) for mothers who used any IFA supplements compared with those who did not. A similar (18%), but non-significant reduction in the risk of low birthweight, was found with the maternal use of IFA supplements. The risk of having smaller than average birth size babies was significantly reduced by 19% in those women who started IFA in the first trimester of pregnancy. About 11% of babies with smaller than average birth size were attributed to non-use of antenatal IFA supplements. Antenatal IFA supplementation significantly reduces the risk of a newborn of smaller than average birth size in Pakistan. Universal coverage of supplementation would improve birth size.


Verification of patient-specific dose distributions in proton therapy using a commercial two-dimensional ion chamber array.
The purpose of this study was to determine whether a two-dimensional (2D) ion chamber array detector quickly and accurately measures patient-specific dose distributions in treatment with passively scattered and spot scanning proton beams. The 2D ion chamber array detector MatriXX was used to measure the dose distributions in plastic water phantom from passively scattered and spot scanning proton beam fields planned for patient treatment. Planar dose distributions were measured using MatriXX, and the distributions were compared to those calculated using a treatment-planning system. The dose distributions generated by the treatment-planning system and a film dosimetry system were similarly compared. For passively scattered proton beams, the gamma index for the dose-distribution comparison for treatment fields for three patients with prostate cancer and for one patient with lung cancer was less than 1.0 for 99% and 100% of pixels for a 3% dose tolerance and 3 mm distance-to-dose agreement, respectively. For spot scanning beams, the mean (+/- standard deviation) percentages of pixels with gamma indices meeting the passing criteria were 97.1% +/- 1.4% and 98.8% +/- 1.4% for MatriXX and film dosimetry, respectively, for 20 fields used to treat patients with prostate cancer. Unlike film dosimetry, MatriXX provides not only 2D dose-distribution information but also absolute dosimetry in fractions of minutes with acceptable accuracy. The results of this study indicate that MatriXX can be used to verify patient-field specific dose distributions in proton therapy.


Transcriptome analysis of neonatal larvae after hyperthermia-induced seizures in the contractile silkworm, Bombyx mori.
The ability to respond quickly and efficiently to transient extreme environmental conditions is an important property of all biota. However, the physiological basis of thermotolerance in different species is still unclear. Here, we found that the cot mutant showed a seizure phenotype including contraction of the body, rolling, vomiting gut juice and a momentary cessation of movement, and the heartbeat rhythm of the dorsal vessel significantly increases after hyperthermia. To comprehensively understand this process at the molecular level, the transcriptomic profile of cot mutant, which is a behavior mutant that exhibits a seizure phenotype, was investigated after hyperthermia (42°C) that was induced for 5 min. By digital gene expression profiling, we determined the gene expression profile of three strains (cot/cot ok/ok, +/+ ok/ok and +/+ +/+) under hyperthermia (42°C) and normal (25°C) conditions. A Venn diagram showed that the most common differentially expressed genes (DEGs, FDR<0.01 and log2 Ratio≥1) were up-regulated and annotated with the heat shock proteins (HSPs) in 3 strains after treatment with hyperthermia, suggesting that HSPs rapidly increased in response to high temperature; 110 unique DEGs, could be identified in the cot mutant after inducing hyperthermia when compared to the control strains. Of these 110 unique DEGs, 98.18% (108 genes) were up-regulated and 1.82% (two genes) were down-regulated in the cot mutant. KEGG pathways analysis of these unique DEGs suggested that the top three KEGG pathways were "Biotin metabolism," "Fatty acid biosynthesis" and "Purine metabolism," implying that diverse metabolic processes are active in cot mutant induced-hyperthermia. Unique DEGs of interest were mainly involved in the ubiquitin system, nicotinic acetylcholine receptor genes, cardiac excitation-contraction coupling or the Notch signaling pathway. Insights into hyperthermia-induced alterations in gene expression and related pathways could yield hints for understanding the relationship between behaviors and environmental stimuli (hyperthermia) in insects.


Arginine GlcNAcylation and Activity Regulation of PhoP by a Type III Secretion System Effector in Salmonella.
Salmonella type III secretion system (T3SS) effector SseK3 is a glycosyltransferase delivered directly into the host cells to modify host protein substrates, thus manipulating host cellular signal transduction. Here, we identify and characterize the Arg-GlcNAcylation activity of SseK3 inside bacterial cells. Combining Arg-GlcNAc protein immunoprecipitation and mass spectrometry, we found that 60 bacterial proteins were GlcNAcylated during Salmonella infection, especially the two-component signal transduction system regulatory protein PhoP. Moreover, the Arg-GlcNAcylation of PhoP by SseK3 was detected in vivo and in vitro, and four arginine residues, Arg65, Arg66, Arg118, and Arg215 were identified as the GlcNAcylation sites. Site-directed mutagenesis showed that the PhoP R215A change significantly reduced the DNA-binding ability and arginine to alanine change at all four sites (PhoP 4RA) completely eliminated the DNA-binding ability, suggesting that Arg215 is essential for the DNA-binding activity of PhoP and GlcNAcylation of PhoP affects this activity. Additionally, GlcNAcylation of PhoP negatively regulated the activity of PhoP and decreased the expression of its downstream genes. Overall, our work provides an example of the intra-bacterial activities of the T3SS effectors and increases our understanding of endogenous Arg-GlcNAcylation.


Real-time MR-thermometry and dosimetry for interventional guidance on abdominal organs.
The use of proton resonance frequency shift-based magnetic resonance (MR) thermometry for interventional guidance on abdominal organs is hampered by the constant displacement of the target due to the respiratory cycle and the associated thermometry artifacts. Ideally, a suitable MR thermometry method should for this role achieve a subsecond temporal resolution while maintaining a precision comparable to those achieved on static organs while not introducing significant processing latencies. Here, a computationally effective processing pipeline for two-dimensional image registration coupled with a multibaseline phase correction is proposed in conjunction with high-frame-rate MRI as a possible solution. The proposed MR thermometry method was evaluated for 5 min at a frame rate of 10 images/sec in the liver and the kidney of 11 healthy volunteers and achieved a precision of less than 2 degrees C in 70% of the pixels while delivering temperature and thermal dose maps on the fly. The ability to perform MR thermometry and dosimetry in vivo during a real intervention was demonstrated on a porcine kidney during a high-intensity focused ultrasound heating experiment.


Is electrodiathermy coagulation (EDC) of cervical ectropion effective in the prevention of cervical carcinoma?
The Authors report their experience on the treatment of cervical ectropion by electrodiathermy coagulation (EDC). The effectiveness of this therapeutic approach in the prevention of cervical carcinoma is examined. Finally, it seems that this treatment can be a preventive measure of the precancerous lesions of the cervix, while it results unjustified the EDC treatment of cervical ectropion and TRZ .


Suppressive effect of administration of recombinant human thioredoxin on cutaneous inflammation caused by UV.
Thioredoxin (TRX) is small ubiquitous protein, which regulates cellular redox status and scavenges reactive oxygen species (ROS). TRX has been shown to exert suppressive effect on skin inflammation where oxidative stress is involved in its pathogenesis. We investigated the effect of TRX on UVB response. Ear swelling after UVB irradiation was significantly reduced in TRX-transgenic mouse compared with wild-type mouse. Furthermore, we have demonstrated that intraperitoneal administration of recombinant human thioredoxin (rhTRX) also reduced acute skin inflammatory reaction, such as skin erythema and edema. Histologically, inflammatory cells including neutrophils and lymphocytes were significantly reduced and average size of the caliber of blood vessels were also reduced in rhTRX-injected mice. The number of apoptotic keratinocytes, were significantly reduced in rhTRX-injected mice. Immunohistochemical intensity of 8-hydroxy-2'-deoxyguanosine was strikingly reduced in rhTRX-injected mouse. Western blotting showed that administration of rhTRX inhibited phosphorylation of p38 mitogen-activated protein kinases and c-Jun NH 2-terminal kinase, which play important roles in inflammatory and apoptotic signaling. These findings indicated that rhTRX attenuated inflammatory and apoptotic responses by UVB. Possible mechanisms for this might be via redox regulation of stress signaling and reduction of reactive oxygen species. We discussed the future use of TRX for sedative use of skin inflammation.


Rearrangement of neuronal responses in the trigeminal system of the rat following peripheral nerve section.
The infraorbital nerve was cut in either neonatal (on day 0) or adult (day 60) rats and the peripheral regeneration prevented. After 60 days either anatomical or electrophysiological techniques were used to study the peripheral nerve, trigeminal nucleus and somatosensory cortex. In neonatally sectioned animals the number of myelinated fibres surviving, at 60 days, in the peripheral nerve proximal to the lesion was 11% compared with 100% survival after adult nerve section. This reduction in surviving nerve fibres in neonatally lesioned animals was associated with a significant reduction in cross-sectional area of all trigeminal nuclei (principalis, oralis, interpolaris and caudalis) of 18-29%. No significant change in area was present in animals sectioned as adults. Neonatally lesioned animals also showed a reduction of approximately 20% in the number of cells visible in cross-sections of all trigeminal nuclei. Animals sectioned as neonates showed marked plasticity at all nuclei in the trigeminal complex as well as in the cortex. Deafferented cells responded to new peripheral receptive fields so that the somatotopic organization of these cells was modified. Such cells are referred to throughout as 'reactivated' cells. However, in animals sectioned as adults no evidence of plasticity could be detected in the trigeminal nuclei. Only very limited reactivation was apparent in the cortex, so that the majority of deafferented cells remained unresponsive at both sites. A detailed comparison was made of twenty-three reactivated cells and twenty-five normal cells from nucleus principalis of animals with nerve section on day 0. The reactivated cells commonly showed larger, more complex receptive fields, longer latencies and lower following frequencies, although stimulus thresholds were similar. Thus reactivated cells showed more convergence and poorer synaptic security than normal cells. However, stimulation of the contralateral thalamus produced similar responses from both groups of cells, suggesting that not all inputs to reactivated cells were modified. The time course of the reactivation of cells in nucleus caudalis from animals lesioned on day 0 was followed over 30 days. No acute effect, for up to 24 h, was detected. However, somatotopic reorganization had started by day 7, proceeded rapidly between days 7 and 14, and was completed by day 21.


Nuclear Magnetic Resonance Structure of the Human Polyoma JC Virus Agnoprotein.
Agnoprotein is an important regulatory protein of the human polyoma JC virus (JCV) and plays critical roles during the viral replication cycle. It forms highly stable dimers and oligomers through its Leu/Ile/Phe-rich domain, which is important for the stability and function of the protein. We recently resolved the partial 3D structure of this protein by NMR using a synthetic peptide encompassing amino acids Thr17 to Gln52, where the Leu/Ile/Phe- rich region was found to adopt a major alpha-helix conformation spanning amino acids 23-39. Here, we report the resolution of the 3D structure of full-length JCV agnoprotein by NMR, which not only confirmed the existence of the previously reported major α-helix domain at the same position but also revealed the presence of an additional minor α-helix region spanning amino acid residues Leu6 to lys13. The remaining regions of the protein adopt an intrinsically unstructured conformation. J. Cell. Biochem. 118: 3268-3280, 2017. © 2017 Wiley Periodicals, Inc.


Analysis of the ion channel complement of the rat oligodendrocyte progenitor in a commonly studied in vitro preparation.
We have analysed the ion channel complement of the oligodendrocyte-type 2 astrocyte (O-2A) glial cell progenitor obtained from the commonly studied neonatal rat mixed brain preparation. Ionic currents, in O-2A progenitors identified on both morphological and immunological grounds, were recorded using the whole-cell variant of the patch-clamp technique. The cells had an average resting membrane potential close to -50 mV and fired single action potentials in response to suprathreshold current injections. Using voltage-clamp methods we were able to identify and characterize a voltage-activated TTX-sensitive Na+ current, two classes of voltage-activated outward K+ currents, an inactivating inwardly rectifying K+ current, a voltage-activated Cl- current and at least three classes of Ca2+ current.


Supramolecular assemblies of trinuclear triangular copper(II) secondary building units through hydrogen bonds. Generation of different metal-organic frameworks, valuable catalysts for peroxidative oxidation of alkanes.
Formation of the trinuclear triangular copper derivative [Cu3(mu3-OH)(mu-pz)3(EtCOO)2(H2O)] x H2O, 1b (Hpz = pyrazole), has been simply achieved by addition of Hpz to a water solution of Cu(EtCOO)2 x H2O and leaving the resulting solution to crystallize at ca. 12 degrees C. When the reaction and crystallization were carried out at a slightly higher temperature (18-22 degrees C), the compound [Cu3(mu3-OH)(mu-pz)3(EtCOO)2(H2O)], 1c, formed. Single-crystal X-ray molecular structure determinations show that both compounds have analogous trinuclear triangular structures, but very different supramolecular assemblies, due mainly, but not only, to the crystallization molecule of H2O in 1b. In particular, contrarily to the previously reported, strictly related, [Cu3(mu3-OH)(mu-pz)3(EtCOO)2(EtOH)], 1a, the propionate ions in 1b and 1c do not bridge different triangular units, whereas they are involved in intra- and intermolecular H-bonds, generating complex supramolecular 2-D MOFs. Compounds 1a and 1c act as remarkably active and selective catalysts or catalyst precursors for liquid biphasic (MeCN/H2O) peroxidative oxidation of cyclohexane and cyclopentane to the corresponding alcohols and ketones.


Evaluating the Effectiveness of End-Tidal Carbon Dioxide Monitoring During Burn Wound Care in the Nonintubated Patient Population.
Daily burn wound care for nonintubated patients involves administration of intravenous analgesic and sedation agents. Vital signs and oxygen saturation monitoring alone can result in late signs of oversedation and ineffective breathing. End-tidal carbon dioxide (EtCo2) monitoring provides immediate feedback of effective breathing during procedural sedation. The purpose of this study was to describe the nurse's sedation and analgesic therapy management of nonintubated patients during burn wound care when EtCo2 was used. This IRB approved study involved observing 22 burn nurses and 4 burn technicians during burn wound care of nonintubated patients. This descriptive, observational study compared adverse breathing/airway events, pain measurements, and sedation effectiveness, before and after introducing EtCo2 monitoring. Patients observed in this study were similar in age, type and size of burn, and use of recreational substances. Nurses and technicians also had similar burn experience. No statistically significant findings were found in this study; however, nurses in practice longer were found to apply oxygen sooner, which prevented decreased oxygen saturation events. When EtCo2 was used, less analgesia and sedation were required to maintain patient comfort. Time required for burn wound care was reduced by 22%, and 30% less overall analgesic and sedation agent dosages were administered after the introduction of EtCo2 monitoring. EtCo2 was found to enhance nurses' assessment of patients' response to intravenous analgesia and sedation effectiveness during burn wound care for nonintubated patients. Nurses with greater experience used oxygen sooner in the procedure, and patients had fewer decreases in SpO2.


[Dysphonia in childhood].
Dysphonia can be found more often in childhood than in grown-up people. Disturbances of vocal purity occur at least at certain age levels in 23% of all children. Since dysphonia is the most important laryngeal symptom, it should be clarified exactly despite the difficulties of examination in children, in order to exclude tumours, which in most cases will be papillomas. For this purpose we developed a schema which includes not only subjective but also measuring and objective methods. The examples of congenital-inherited, congenital-acquired, non-congenital-inherited and non-congenital-acquired vocal disturbances show that there is a broad spectrum between the evaluation of the first cry, the right evaluation of numerous symptoms, the right evaluation of mutative dysphonias and the assessment of rhinophonias . In cases where it is not possible to clarify sufficiently well the causes of pathological vocal disorders by means of less complicated methods, it is advisable to employ the explained specific examination methods with objective documentation. The oto-rhino-laryngologist consulted by the parents of a child carries considerable responsibility also for the child's subsequent professional career if he is called upon to treat the patient's childhood dysphonia.


Case report: Treatment-resistant schizophrenia with auto-aggressive compulsive behavior-Successful management with cariprazine.
The present case report describes a patient with treatment-resistant schizophrenia and auto-aggressive compulsive behavior who was effectively treated with a third-generation antipsychotic medication, cariprazine. The diagnosis was made 12 years ago, and the patient has been hospitalized 14 times and undergone various antipsychotic treatments. Despite receiving both inpatient and outpatient care, the patient's response to treatment has been only partial, and he has been classified as a treatment-resistant case. Therefore, the patient was switched to cariprazine, which led to significant improvements in both positive and negative symptoms, as well as the complete reduction of auto-aggressive compulsive behavior. These improvements contributed to the patient's overall social functioning and the achievement of remission, while also avoiding polypharmacy and eliminating the metabolic side effects associated with previous treatments.


Highly Stable Organic Small Molecular Nanoparticles as an Advanced and Biocompatible Phototheranostic Agent of Tumor in Living Mice.
Near-infrared (NIR)-absorbing organic small molecules hold great promise as the phototheranostic agents for clinical translation by virtue of their intrinsic advantages such as well-defined chemical structure, high purity, and good reproducibility. However, most of the currently available ones face the challenges in varying degrees in terms of photothermal instability, and photobleaching/reactive oxygen nitrogen species (RONS) inresistance, which indeed impair their practical applications in precise diagnosis and treatment of diseases. Herein, we developed highly stable and biocompatible organic nanoparticles (ONPs) for effective phototheranostic application by design and synthesis of an organic small molecule (namely TPA-T-TQ) with intensive absorption in the NIR window. The TPA-T-TQ ONPs with no noticeable in vivo toxicity possess better capacities in photothermal conversion and photoacoustic imaging (PAI), as well as show far higher stabilities including thermal/photothermal stabilities, and photobleaching/RONS resistances, when compared with the clinically popularly used indocyanine green. Thanks to the combined merits, the ONPs can serve as an efficient probe for in vivo PAI in a high-contrast manner, which also significantly causes the stoppage of tumor growth in living mice through PAI-guided photothermal therapy. This study thus provides an insight into the development of advanced NIR-absorbing small molecules for practical phototheranostic applications.


Concentrate supplementation of a diet based on medium-quality grass silage for 4 weeks prepartum: Effects on cow performance, health, metabolic status, and immune function.
Because negative energy balance (EB) contributes to transition-period immune dysfunction in dairy cows, dietary management strategies should aim to minimize negative EB during this time. Prepartum diets that oversupply energy may exacerbate negative EB in early lactation, with detrimental effects on immune function. However, with lower body condition score (BCS) cows, it has been shown that offering concentrates in addition to a grass silage-based diet when confined during an 8-wk dry period resulted in increased neutrophil function in early lactation. The aim of this study was to examine if similar benefits occur when concentrate feeding was restricted to a 4-wk period prepartum. Twenty-six multiparous and 22 primiparous Holstein-Friesian cows were offered ad libitum access to medium-quality grass silage until 28 d before their predicted calving dates (actual mean of 32 d prepartum; standard deviation = 6.4). At this time multiparous cows had a mean BCS of 2.9 (standard deviation = 0.12) and primiparous cows a mean BCS of 3.0 (standard deviation = 0.14) on a 1 to 5 scale. Cows were then allocated in a balanced manner to 1 of 2 treatments (13 multiparous cows and 11 primiparous cows on each treatment): silage only (SO) or silage plus concentrates (S+C) until calving. Cows on SO were offered the same grass silage ad libitum. Cows on S+C were offered an ad libitum mixed ration of the same grass silage and additional concentrates in a 60:40 dry matter (DM) ratio, which provided a mean concentrate DM intake (DMI) of 4.5 kg/cow per d. After calving, all cows were offered a common mixed ration (grass silage and concentrates, 40:60 DM ratio) for 70 d postpartum. Offering concentrates in addition to grass silage during the 4 wk prepartum increased prepartum DMI (12.0 versus 10.1 kg/cow per d), EB (+40.0 versus +10.6 MJ/cow per d), and body weight (BW; 640 versus 628 kg), and tended to increase BCS (3.02 versus 2.97). However, postpartum DMI, milk yield, milk composition, BW change, BCS change, serum nonesterified fatty acid, and β-hydroxybutryrate concentrations, health, and corpus luteum measures were unaffected by treatment. The in vitro assays of neutrophil phagocytosis, neutrophil oxidative burst, and interferon gamma production, conducted on blood samples obtained at d 14 prepartum and d 3, 7, 14, and 21 postpartum, were unaffected by treatment. Primiparous cows had higher phagocytic fluorescence intensity at d 14 prepartum and d 3 and 7 postpartum; a higher percentage of neutrophils undergoing oxidative burst at d 3, 7, and 21 postpartum; and a higher oxidative burst fluorescence intensity at d 14 prepartum and d 7, 14, and 21 postpartum compared with multiparous cows. This suggests that neutrophil function of primiparous cows was less sensitive to the changes occurring during the transition period than that of multiparous cows. In conclusion, offering concentrates during the 4-wk period prepartum had no effect on postpartum DMI, milk yield, body tissue mobilization, EB, measures of neutrophil or lymphocyte function, health, or corpus luteum activity.


Prenatal physical activity and diet composition affect the expression of nutrient transporters and mTOR signaling molecules in the human placenta.
Adequate nutrient delivery to the fetus is essential for optimal growth. Differences in prenatal physical activity level and diet quality influence maternal energy balance and these factors may alter placental nutrient transport. We investigated the associations between meeting physical activity guidelines and the quality of maternal diet on the expression of genes involved in fatty acid, amino acid and glucose transport, and mammalian target of rapamycin (mTOR) and insulin signaling in the placenta from 16 term pregnancies. Physical activity was directly measured with accelerometry, diet composition was assessed with 24 h dietary recalls, and gene expression was measured with custom polymerase chain reaction (PCR) arrays. Women who met physical activity guidelines had lower gene expression of fatty acid transport protein 4 (FATP4), insulin-like growth factor 1 (IGF1), and the beta non-catalytic subunit of AMP-activated protein kinase (AMPK), and a higher expression of SNAT2. There was a strong positive correlation observed between total sugar intake and glucose transporter 1 (GLUT1) (r = 0.897, p = 0.000, n = 12), and inverse correlations between total sugar and mTOR and IGF1 expression. Percentage of total calories from protein was inversely related to insulin-like growth factor 1 receptor (IGF1R) (r = -0.605, p = 0.028, n = 13). Variations in maternal physical activity and diet composition altered the expression of genes involved in fatty acid, amino acid and glucose transport and mTOR signaling. Future research on placental nutrient transport should include direct measures of maternal PA and dietary habits to help eliminate confounding factors.


New aspects in thrombosis research: possible role of mast cells as profibrinolytic and antithrombotic cells.
Venous thromboembolism represents a significant cause of morbidity worldwide. The factors that underly thrombophilia are manifold. The concept of Virchow defines the well known triad of stasis, humoral factors, and pathologies of the vascular wall. In the current article, an additional factor, the "accumulation of repair cells" is discussed. This novel concept highlights the mast cell that accumulates around thrombosed vessels and provides a number of important repair molecules including heparin, profibrinolytic tPA, and fibrinogenolytic beta-tryptase. Thus, mast cell recruitment and activation may result in local thrombolysis and prevention of coagulation. In line with this concept, mast cell-deficient mice are more susceptible to lethal thrombogenic stimuli compared to normal mice. The factors (cytokines) that trigger mast cell accumulation and release of repair molecules have also been identified - the most important one appears to be stem cell factor (SCF). All in all. our novel concept suggests that the patho-physiology of thrombosis may involve a "physiologic" cell that provides the same repair molecules that are used for treatment of thrombotic disorders by the physician. Whether an altered availability of components of this cellular repair system can predispose for thrombophilia remains to be determined.


Charge Transfer States in Dilute Donor-Acceptor Blend Organic Heterojunctions.
We study the charge transfer (CT) states in small-molecule blend heterojunctions comprising the nonpolar donor, tetraphenyldibenzoperiflanthene (DBP), and the acceptor, C70, using electroluminescence and steady-state and time-resolved photoluminescence spectroscopy along with density functional theory calculations. We find that the CT exciton energy blue shifts as the C70 concentration in the blend is either decreased or increased away from 50 vol %. At 20 K, the increase in CT state lifetime is correlated with the increasing diameter of C70 nanocrystallites in the blends. A quantum confinement model is used to quantitatively describe the dependence of both CT energy and lifetime on the C70 or DBP domain size. Two discrete CT emission peaks are observed for blends whose C70 concentration is >65%, at which point C70 nanocrystallites with diameters >4 nm appear in high-resolution transmission electron micrographs. The presence of two CT states is attributed to coexistence of crystalline C70 and amorphous phases in the blends. Furthermore, analysis of CT dissociation efficiency versus photon energy suggests that the >90% dissociation efficiency of delocalized CT2 states from the crystalline phase significantly contributes to surprisingly efficient photogeneration in highly dilute (>80% C70) DBP/C70 heterojunctions.


Design and synthesis of novel 5-substituted acyclic pyrimidine nucleosides as potent and selective inhibitors of hepatitis B virus.
A novel class of 5-substituted acyclic pyrimidine nucleosides, 1-[(2-hydroxyethoxy)methyl]-5-(1-azidovinyl)uracil (9a), 1-[(2-hydroxy-1-(hydroxymethyl)ethoxy)methyl]-5-(1-azidovinyl)uracil (9b), and 1-[4-hydroxy-3-(hydroxymethyl)-1-butyl]-5-(1-azidovinyl)uracil (9c), were synthesized by regiospecific addition of bromine azide to the 5-vinyl substituent of the respective 5-vinyluracils (2a-c) followed by treatment of the obtained 5-(1-azido-2-bromoethyl) compounds (3a-c) with t-BuOK, to affect the base-catalyzed elimination of HBr. Thermal decomposition of 9b and 9c at 110 degrees C in dioxane yielded corresponding 5-[2-(1-azirinyl)]uracil analogues (10b,c). The 5-(1-azidovinyl)uracil derivatives 9a-c were found to exhibit potent and selective in vitro anti-HBV activity against duck hepatitis B virus (DHBV) infected primary duck hepatocytes at low concentrations (EC(50) = 0.01-0.1 microg/mL range). The most active anti-DHBV agent (9c), possessing a [4-hydroxy-3-(hydroxymethyl)-1-butyl] substituent at N-1, exhibited an activity (EC(50) of 0.01-0.05 microg/mL) comparable to that of reference compound (-)-beta-L-2',3'-dideoxy-3'-thiacytidine (3-TC) (EC(50) = 0.01-0.05 microg/mL). In contrast, related 5-[2-(1-azirinyl)]uracil analogues (10b,c) were devoid of anti-DHBV activity, indicating that an acyclic side chain at C-5 position of the pyrimidine ring is essential for anti-HBV activity. The pyrimidine nucleosides (9a-c, 10b,c) exhibited no cytotoxic activity against a panel of 60 human cancer cell lines. All of the compounds investigated did not show any detectable toxicity to several stationary and proliferating host cell lines or to mitogen stimulated proliferating human T lymphocytes, up to the highest concentration tested.


Scaphoid Bone Nonunions: Clinical and Functional Outcomes of Collagen/PGA Scaffolds and Cell-Based Therapy.
In this study, the procedure for treating the nonunion complication of scaphoid fractures using collagen/poly glycolic acid (CPGA) scaffolds with bone marrow mesenchymal stem cell (BM-MSC) therapy was adopted and compared with the commonly employed autologous bone tissue graft. With conducting a two-armed clinical trial, 10 patients with scaphoid nonunions were enrolled in this investigation. Patients were randomly assigned to two groups treated with (1) CPGA + cell therapy and (2) autologous iliac crest bone graft standard therapy. Treatment outcomes were evaluated three months after surgery, measuring the grip and pinch strengths and wrist range of motion, with two questionnaires: Patient-Rated Wrist Evaluation (PRWE) and Quick form of Disabilities of the Arm, Shoulder, and Hand (QDASH). We have also assessed the union rate using clinical and radiologic healing criteria one and three months post-operatively. Restorative effects of CPGA + cell therapy were similar to those of the autologous bone graft standard therapy, except for the grip strength (P = 0.048) and QDASH score (P = 0.044) changes, which were higher in the CPGA + cell therapy group. Three months following the surgery, radiographic images and computed tomography (CT) scans also demonstrated that the scaphoid union rate in the test group was comparable to that of scaphoids treated with the standard autograft method. Our findings demonstrate that the CPGA + cell therapy is a potential alternative for bone grafting in the treatment of bone nonunions.


Apoptotic changes in the cortex and hippocampus following minimal brain trauma in mice.
Interpretation of the cellular and molecular pathogenic basis of post-minimal traumatic brain injury is a significant clinical and scientific problem, especially due to the high prevalence of motor vehicle--and other accidents. Pathogenetic brain mechanisms following traumatic impact are usually investigated by using models of severe or moderate trauma. Apoptotic neuronal degeneration after notable brain trauma is a well-known phenomenon, but the source of its activation is not clear, especially after mild, subclinical brain trauma. In the present study, we used a closed head weight-drop model to induce minimal brain injury in mice. Pellets of 5, 10, 15, 20, 25 and 30 g were dropped on the right side of mice's head kept under light ether anesthesia. No abnormal behavioral or neurophysiological changes were seen following the head trauma. Morphological assessment was done 72 h after the traumatic impact using TUNEL assay and silver staining. We found gradual increase of TUNEL-positive and silver-impregnated cells number in different cortical and hippocampal regions of both injured and contralateral hemispheres. The threshold of traumatic impact that caused a significant activation was 10-15 g pellets (evident by silver staining), and 15-20 g for apoptosis. The most sensitive zones for trauma were anterior cingulate cortex and CA3 area of hippocampus. No bilateral hemispheric differences were found. Our results demonstrate that even closed head minimal traumatic brain injury can cause diffused neuronal damage and apoptosis. This results correlate well with cognitive and behavioral deficits described for mice suffering similar mTBI and can also explain the wide variety of mental disturbances described for post-concussion syndrome in patients who suffered mild head injury.


Gender-dependent negative correlation of peripheral E2 estradiol levels with ventricular diastolic functions.
The aim of this study to investigate the correlation of the peripheral concentrations of one representative estrogen, E2 estradiol, with various indicators reflecting different aspects of cardiac structures and functions. A total of 84 typical patients with hypertrophic cardiomyopathy (HCM) and 77 healthy subjects were enrolled. Venous blood samples were taken to test E2 estradiol contents. Echocardiographic imaging was performed to record various indices of cardiac structures and functions. Concentrations of peripheral E2 estradiol were decreased in female HCM patients, compared to female normal controls; after medical treatment, peripheral E2 estradiol levels were elevated, nearly to normal levels. Peripheral E2 estradiol concentrations were negatively correlated with LAV (r2=0.5078, P<0.001), LAVI (r2=0.4257, P<0.001), E/A ratio (r2=0.4328, P=0.006) and E/Ea ratio (r2=0.4393, P<0.001) in female controls and patients. Concentrations of peripheral E2 estradiol were negatively correlated with ventricular diastolic functions and this correlation was gender-dependent. Our study could provide clues to explore the molecular mechanisms of HCM, and clinic evidence for the diagnosis and prognostic management of HCM patients, as well as medical intervening for HCM.


Melanoma growth and lymph node metastasis is independent of host CD169 expression.
Metastasis to the lymph node is a frequent and early event in tumour dissemination. Tumour soluble factors, including extracellular vesicles, condition host organs for metastatic tumour spread, thereby facilitating tumour cell migration and survival. In the peripheral lymphatics, extracellular vesicles are captured via their sialic acids by lymph node macrophages expressing the CD169 (sialoadhesin) molecule, thereby suppressing the immune response. We hypothesised that the CD169 molecule could modulate primary tumour growth and invasion into the regional lymph node by altering the immune response to tumour extracellular vesicles, or by directly interacting with invading tumour cells. No significant difference was noted in primary tumour growth between wild-type and CD169-/- mice, and protection against tumour challenge with tumour extracellular vesicle immunisation was similar between the strains. Subcutaneous implantation of B16 (F1 or F10) into the ventral-carpal aspect of forelimb resulted in melanoma infiltration into the axillary and brachial lymph nodes. CD169-/- mice displayed a lower level of metastatic lymph node lesions, however this failed to reach statistical significance. Although CD169 participates in the immune response to tumour antigen and appears to be a positive prognostic marker for human cancers, its role in modulating melanoma growth and metastasis is less clear.


Growth and characterization of self-assembled InAs/InP quantum dot structures.
InAs quantum dots (QDs) are grown on InP or lattice matched GaInAsP buffers using horizontal flow metal-organic chemical vapor deposition (MOCVD) at a pressure of 180 mbar. A range of techniques, such as photoluminescence (PL), atomic force microscopy, and plan-view transmission electron microscopy is used to characterize the QD and other semiconductor layers. The effects of different growth parameters, such as V/III ratio and growth time, and the effects of buffer layers, interlayers, and cap layers are investigated and the optimized growth conditions are discussed. In the case of the QDs grown on InP buffers, the As/P exchange reaction is found to be prominent. A very thin (0.6 nm) GaAs interlayer grown between the buffer and the QD layers consumes segregated indium and minimizes the As/P exchange reaction. As a result, the QD PL emission energy increases, the PL intensity improves, and the PL linewidth decreases. The experimental results show that by changing the thickness of a GaAs interlayer (0.3-0.6 nm), the emission wavelength/energy of the QDs grown on a lattice matched GaInAsP buffer can be tuned over a wide range covering 1550 nm. However, further increase in the thickness of the GaAs interlayer results in the agglomeration of the QDs and the deterioration of the QD optical properties. Detailed microscopy studies show that capped QDs have higher density and are smaller in size on average compared to uncapped QDs, which undergo coalescence during cooling of the sample after growth. Overall, the QDs grown for shorter time with a smaller V/III ratio (approximately 8) show improved PL intensity and narrower PL linewidth.


Antioxidative and Anti-Melanogenic Activities of Bamboo Stems (Phyllostachys nigra variety henosis) via PKA/CREB-Mediated MITF Downregulation in B16F10 Melanoma Cells.
Phyllostachys nigra var. henosis, a domestic bamboo species, has been attracting much attention; its bioactive compounds (especially in the leaf) show antioxidant, anti-inflammatory, and anti-obesity activities. Little information is available on the antioxidative and anti-melanogenetic activities of the bioactive compounds in bamboo stems. The anti-melanogenic and antioxidative activities of the EtOAc fraction (PN3) of a P. nigra stem extract were investigated in a cell-free system and in B16F10 melanoma cells. PN3 consisted of a mixture of flavonoids, such as catechin, chlorogenic acid, caffeic acid, and p-coumaric acid. The antioxidant activity (2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS)), and hydroxyl radical scavenging) was evaluated, as well as the inhibition of reactive oxygen species (ROS) produced by the Fenton reaction. PN3 showed in vitro tyrosinase inhibition activity with the half maximal inbihitory concentration (IC50) values of 240 μg/mL, and in vivo cytotoxic concentration ranges > 100 μg/mL. The protein expression levels and mRNA transcription levels of TYR, TRP-1, and MITF were decreased in a dose-dependent manner by the treatment with PN3. PN3 interfered with the phosphorylation of intracellular protein kinase A (PKA)/cAMP response element-binding protein (CREB), demonstrating potent anti-melanogenic effects. PN3 could inhibit PKA/CREB and the subsequent degradation of microphthalmia-associated transcription factor (MITF), resulting in the suppression of melanogenic enzymes and melanin production, probably because of the presence of flavonoid compounds. These properties make it a candidate as an additive to whitening cosmetics.


Regulation of glucose metabolism in man.
Insulin is the dominant glucoregulatory factor; by suppressing endogenous glucose production and stimulating glucose utilization, it lowers the plasma glucose concentration. Normally, feedback-regulated changes in insulin secretion play a key role in maintaining plasma glucose levels within a rather narrow range (approximately 4.0-7.0 mmol l-1) despite marked changes in glucose influx (e.g. following a meal, compared to fasting), efflux (e.g. during exercise), or both. Severe insulin deficiency causes insulin-dependent diabetes mellitus (IDDM), and substantial insulin excess causes hypoglycaemia. However, the regulation of systemic glucose balance normally involves a highly co-ordinated interplay between the glucose-lowering effects of insulin and the glucose-elevating actions of an array of glucose counterregulatory hormones, primarily glucagon (and epinephrine under some conditions). Thus there are redundant glucoregulatory factors, and a hierarchy exists among the latter. Although insulin stands at the top of that hierarchy, glucoregulation is not achieved by insulin alone. This is emphasized by the glycaemic chaos of IDDM, with wide swings from hyperglycaemia to hypoglycaemia. The latter is not exclusively the result of the intermittent hyperinsulinaemia inherent in imperfect insulin replacement therapy. Deficient glucagon and epinephrine secretory responses occur, and are now known to increase the risk of iatrogenic hypoglycaemia. However, insulin is generally the dominant glucoregulatory hormone under physiological conditions. The glucose counterregulatory hormones approach parity with insulin only when plasma glucose concentrations are lowered to levels that threaten brain function.


Photocytotoxic lanthanum(III) and gadolinium(III) complexes of phenanthroline bases showing light-induced DNA cleavage activity.
Lanthanide complexes of formulation [La(B)(2)(NO(3))(3)] (1-3) and [Gd(B)(2)(NO(3))(3)] (4-6), where B is a N,N-donor phenanthroline base, namely, 1,10-phenanthroline (phen in 1, 4), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq in 2, 5) and dipyrido[3,2-a:2',3'-c]phenazine (dppz in 3, 6), have been prepared, characterized from physicochemical data, and their photoinduced DNA and protein cleavage activity studied. The photocytotoxicity of the dppz complexes 3 and 6 has been studied using HeLa cancer cells. The complexes exhibit ligand centered bands in the UV region. The dppz complexes show the lowest energy band at 380 nm in N,N-dimethylformamide (DMF). The La(III) complexes are diamagnetic. The Gd(III) complexes (4-6) have magnetic moments that correspond to seven unpaired electrons. The complexes are 1:1 electrolytic in aqueous DMF. The dpq and dppz complexes in DMF show ligand-based reductions. The complexes display moderate binding propensity to calf thymus DNA giving binding constant values in the range of 5.7 x 10(4)-5.8 x 10(5) M(-1) with a relative order: 3, 6 (dppz) > 2, 5 (dpq) > 1, 4 (phen). The binding data suggest DNA surface and/or groove binding nature of the complexes. The complexes do not show any hydrolytic cleavage of plasmid supercoiled pUC19 DNA. The dpq and dppz complexes efficiently cleave SC DNA to its nicked circular form on exposure to UV-A light of 365 nm at nanomolar complex concentration. Mechanistic studies reveal the involvement of singlet oxygen ((1)O(2)) and hydroxyl radical (HO*) as the cleavage active species. The complexes show binding propensity to bovine serum albumin (BSA) protein giving K(BSA) values of approximately 10(5) M(-1). The dppz complexes 3 and 6 show BSA protein cleavage activity in UV-A light of 365 nm. The dppz complexes 3 and 6 exhibit significant photocytotoxicity in HeLa cells giving respective IC(50) values of 341 nM and 573 nM in UV-A light of 365 nm for an exposure time of 15 min (IC(50) > 100 microM in dark for both the complexes). Control experiments show significant dark and phototoxicity of the dppz base alone (IC(50) = 413 nM in light with 4 h incubation in dark and 11.6 microM in dark with 24 h incubation). A significant decrease in the dark toxicity of the dppz base is observed on binding to the lanthanide ions while retaining similar phototoxicity.


Adaptation of ACMG-ClinGen Technical Standards for Copy Number Variant Interpretation Concordance.
This study aimed to evaluate inter-laboratory classification concordance for copy number variants (CNVs) with a semiquantitative point-based scoring metric recommended by the American College of Medical Genetics and Genomics (ACMG) and Clinical Genome Resources (ClinGen). A total of 234 CNVs distributed by the National Center of Clinical Laboratories (NCCLs), and 72 CNVs submitted by different laboratories, were distributed to nine clinical laboratories performing routine clinical CNV testing in China and independently classified across laboratories. The overall inter-laboratory complete classification concordance rate of the 234 distributed CNVs increased from 18% (41/234) to 76% (177/234) using the scoring metric compared to the laboratory's previous method. The overall inter-laboratory complete classification concordance rate of the 72 submitted CNVs was 65% (47/72) using the scoring metrics. The 82 variants that initially did not reach complete concordance classification and 1 additional CNV deletion were reviewed; 34 reached complete agreement, and the overall post-review complete concordance rate was 85% (260/306). Additionally, the overall percentage of classification discordance possibly impacting medical management [i.e., pathogenic (P) or likely pathogenic (LP) vs. variant of uncertain significance (VUS)] was 11% (35/306). The causes of initial and final discordance in the classification were identified. The ACMG-ClinGen framework has promoted consistency in interpreting the clinical significance of CNVs. Continuous training among laboratories, further criteria and additional clarification of the standards, sharing classifications and supporting evidence through public database, and ongoing work for dosage sensitive genes/regions curation will be beneficial for harmonization of CNVs classification.


The Role of Circulating Regulatory T Cell Levels on Subclinical Atherosclerosis and Cardiovascular Risk Factors in Women with Systemic Lupus Erythematosus.
The increase in cardiovascular disease (CVD) in patients with systemic lupus erythematosus (SLE) is not fully explained by traditional CVD risk factors. Regulatory T cells (Treg cells) are considered atheroprotective. We investigated the relationship between the absolute number of different phenotypes of Treg cells and abnormal carotid intima-media thickness (IMT) in women with SLE. Sixty-six women with SLE with no history of CV disease were included. Carotid IMT was quantified by ultrasound. Abnormal carotid IMT was defined as ≥0.8 mm and two groups were compared according to this definition. Flow cytometry was used to analyze Foxp3 and Helios expression in peripheral blood CD4 T cells. A significantly higher level of absolute CD4+CD25+FoxP3high T cells was present in patients with abnormal carotid IMT compared with those without (1.795 ± 4.182 cells/μl vs. 0.274 ± 0.784 cells/μl; p = 0.003). However, no correlations were found between any Treg cell phenotypes and carotid IMT. Only the absolute number of CD4+CD45RA+FoxP3low T cells was significantly decreased in SLE patients with low HDL cholesterol compared with those with normal HDL cholesterol (0.609 ± 2.362 cells/μl vs. 1.802 ± 4.647 cells/μl; p = 0.009 and 15.358 ± 11.608 cells/μl vs. 28.274 ± 34.139; p = 0.012, respectively). In conclusion, in SLE women, diminished levels of Treg cells based on flow cytometry were not a good indicator of abnormal carotid IMT.


Building sustainable multi-functional prospective electronic clinical data systems.
A better alignment in the goals of the biomedical research enterprise and the health care delivery system can help fill the large gaps in our knowledge of the impact of clinical interventions on patient outcomes in the real world. There are several initiatives underway to align the research priorities of patients, providers, researchers, and policy makers. These include Agency for Healthcare Research and Quality (AHRQ)-supported projects to build flexible prospective clinical electronic data infrastructure that meet the needs of these diverse users. AHRQ has previously supported the creation of 2 distributed research networks as a new approach to conduct comparative effectiveness research (CER) while protecting a patient's confidential information and the proprietary needs of a clinical organization. It has applied its experience in building these networks in directing the American Recovery and Reinvestment Act funds for CER to support new clinical electronic infrastructure projects that can be used for several purposes including CER, quality improvement, clinical decision support, and disease surveillance. In addition, AHRQ has funded a new Electronic Data Methods forum to advance the methods in clinical informatics, research analytics, and governance by actively engaging investigators from the American Recovery and Reinvestment Act-funded projects and external stakeholders.