More than the eyes can see: The worrying scenario of canine leishmaniasis in the Brazilian side of the triple border.
A cross-sectional epidemiological study in the extreme-west of the state of Paraná was carried out to access the prevalence, distribution, and risk variables of canine Visceral Leishmaniases (cVL). This study was conducted in three areas, two cities of far west of Parana state: Foz do Iguaçu (FI) and Santa Terezinha de Itaipu (STI), and along two transects between these two municipalities. To sample the entire urban area, the cities (FI and STI) were divided into a grid of squares of 400 m2 (patch). Among the 526 patches, 123 in FI, 40 in the transects and 33 in STI were selected according to the 'worst scenario' criterion. In the transect areas, in each 0.86 km five dogs from houses were surveyed to leishmaniasis. In each patch, blood of five dogs from houses (and from neighborhood when necessary) in the areas that seemed to be the most appropriate for the proliferation of vector were surveyed. The infection of the dogs by cVL were assessed using two serological tests were used (cELISA and TR-DPP®), and, for those seropositive for both methods, the PCR method were used. Moreover, dogs presenting clinical signs or cutaneous lesions were sampled to PCR. The identification of Leishmania species was confirmed using PCR-RFLP followed by DNA sequencing. Micro, meso and macro scale environmental variables were also surveyed and statistically analyzed. The prevalence rate Leishmania infantum was 23.8% in FI, 4.7% in STI and 9.1% in the transects areas. Among the extrinsic variables analysed, the number of vectors and the presence of infected dogs in neighbouring were positively correlated with the occurrence of infected dogs. Dog size was positively correlated with cVL infection, while the quality of the dog's nutrition affected cVL negatively. As for cutaneous leishmaniasis (CL), the first registry of dogs infected with L. braziliensis in the region shows that there is potential for transmission in peri-urban areas, since environmental conditions allow the proliferation of vectors capable of transmitting this species of parasite. cVL is widely spread in FI, with high prevalence. This supports the hypothesis that the parasite has been present in the region for longer than previously believed, despite the fact that the presence of leishmaniais in the region has only been recognized recently. It is important to control the population of dogs infected with L. infantum (parasite and non-antibodies) to prevent the spread of the disease to other dogs and also to people in the region.


Combination of idarubicin and cyclophosphamide administered orally in untreated postmenopausal breast cancer patients. A phase II study.
On the basis of results obtained with oral idarubicin administration in breast cancer, which have shown an established antitumor activity in approximately 28% of cases, this compound was combined with cyclophosphamide (also given orally) in postmenopausal patients with an unknown or negative steroid receptor status. The study comprised 45 untreated patients out of which 44 were evaluable for response and toxicity. The mean age was 62.5 years (range 51-75). The majority of patients had soft tissue (24) and visceral organ (17) metastases. Idarubicin was administered in one oral daily dose of 45 mg/m2 on day 1; the oral cyclophosphamide dose was 200 mg/m2 daily on days 3, 4, 5 and 6. An objective response to treatment was observed in 41% of patients (18/44, 95% confidence interval 28-56%). Complete remission (lung) was observed in 2 patients (5%), while 16 patients achieved a partial response. Eleven patients showed no change, while 15 patients progressed. A particularly good response was obtained in soft tissue metastases (54%, 13/24) while in visceral organs a response was achieved in 31% of patients (5/16). The remissions lasted 2-14 months (median 7 months), and median survival was 14+ months. Toxicity was mild and the treatment well tolerated. Grade I/II leukopenia was observed in 24% of patients (median WBC nadir 3,100); there were no signs of cardiotoxicity. Grade I and II alopecia was observed in 75% of patients: nausea/vomiting were present in 73% of cases. The results of this study indicate that oral administration of idarubicin and cyclophosphamide produces a valuable antitumorigenic effect in postmenopausal breast cancer patients, particularly in soft tissue metastases. Further randomized studies will be needed to evaluate this treatment approach.


Return to School After Traumatic Brain Injury: Description of Implementation Settings.
Children who experience traumatic brain injury (TBI) of any severity may need accommodations when they return to school-the setting that manages academic achievement and learning. However, variations exist in current return to school (RTS) programs that address a child's transition to school following TBI. This article describes some of these return to school (RTS) programs and how they vary by setting. This article provides insights from a modified evaluability assessment that examined RTS programs and their readiness for rigorous evaluation. A secondary analysis was conducted to better describe the types and location of programs examined. Differences exist in program structure, access, and how care for children is monitored over time. RTS programs that serve children following TBI are located in healthcare settings, schools, and state agencies and vary in models of care due to their location and organizational structure. Children who experience TBI benefit from a healthcare assessment and follow-up upon RTS that includes parental involvement. Models of care for this process vary based on program location and organizational structure. Further research and program evaluation are needed to better understand effectiveness and how to optimally monitor and care for children returning to school after a concussion or TBI.


Irritant contact dermatitis and chrome-passivated metal.
An outbreak of hand dermatitis is reported amongst employees working on a new assembly line of an electronics factory. 24 out of 41 employees had signs of irritant contact dermatitis. The fingertips and the dorsal parts of the hands were especially affected. Mechanical factors in combination with zinc-chromium compounds from galvanised steel seemed to be responsible for the dermatitis and the dry skin. The use of an emollient solved the problem.


A new alkaloid from Portulaca oleracea L. and its antiacetylcholinesterase activity.
A new alkaloid, (10E, 12E)-9-ureidooctadeca-10, 12-dienoic acid, named oleraurea (1) and 10 known compounds, p-hydroxybenzaldehyde (2), p-hydroxybenzoic acid (3), p-hydroxyacetophenone (4), benzamide (5), (E)-p-coumaramide (6), (E)-ferulamide (7), soyalkaloid A (8), β-carboline-3-carboxylic acid (9), 2, 3, 4, 9-tetrahydro-1H-pyrido [3, 4-b] indole-3-carboxylic acid (10), (1S, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-β-carboline-3-carboxylic acid (11) were obtained from Portulaca oleracea L., in which, compounds 4, 5, 8-11 were isolated from the plant for the first time. The structure of the compound 1 was identified using spectroscopic methods including 1D and 2D NMR, HR-ESI-TOF-MS. The compounds 1, 5-11 presented anticholinesterase activities, but the P. oleracea extract (POE) presented very low anticholinesterase activity.


SARS-CoV-2-Associated Obliterative Arteritis Causing Massive Testicular Infarction.
A 26-year-old man with symptomatic SARS-CoV-2 infection developed a sudden-onset acute testicular pain. The echo-doppler images showed massive testicular infarction, so orchiectomy was performed. On gross examination, the surgical specimen showed complete testicular necrosis and diffuse thickening of the testicular coverings. Under the microscope, a severe obliterative arteritis was evidenced. SARS-CoV-2 spike antibody was detected by immunohistochemistry in the arterial endothelium. Electron microscopy displayed intracytoplasmic spiky viral particles in endothelial cells. The patient was treated with corticoids and was asymptomatic at last contact.


Cataract surgery outcomes in bangladeshi children.
To measure visual acuity (VA) outcomes, complication rates, and the social impact of cataract surgery in a cohort who underwent surgery as children in Bangladesh. Case series. A total of 471 of 850 children from 6 Bangladeshi districts who had been identified as cataract blind using key informants (KIs) between 2004 and 2009 during the Bangladesh Childhood Cataract Campaign (BCCC) together with all those children not included in the BCCC database but in the Child Sight Foundation (CSF) database who had been identified as cataract blind. The subjects and families were contacted again by KIs and transported to local examination centers, where parents and subjects were administered a questionnaire and subjects underwent full ocular examination. Where operative data were available (15%), they were analyzed in conjunction with questionnaire and examination findings. Statistical analysis was performed using SPSS Statistics (IBM, Armonk, NY). Presenting and best-corrected visual acuities (BCVAs), cause(s) of poor outcome, postoperative refraction, and school attendance. A total of 407 of the participants had undergone bilateral surgery as children, with a mean follow-up of 8.8 years. The mean age at examination was 16 years (range, 5-28 years; standard deviation [SD], 4.6 years); 63% of those examined were male; 22% had a binocular presenting VA of >20/60; and 53% were severely visually impaired or blind (VA <20/200). After refraction, 33% had VA >20/60 in their better eye and 33% had VA <20/200. Factors that predicted poor VA in multivariate logistic regression analysis were nystagmus (P < 0.001), longer delay in presentation (P < 0.001), and magnitude of absolute spherical equivalent refractive error (P<0.001). Some 50% had nystagmus, and 69% of those currently aged ≤16 years were attending school. Better acuity was associated with school attendance (P < 0.001), whereas gender was not. Approximately one third of all participants had a BCVA of ≥20/60 in their better eye. Amblyopia and nystagmus limited visual outcome, indicating the need for earlier detection and treatment. This is the first study to show the link between pediatric cataract outcome and access to education, a millennium development goal.


Genetic effects of fresh cigarette smoke in Saccharomyces cerevisiae.
Ability of fresh cigarette smoke from University of Kentucky reference cigarette 2R1 to induce gene conversion, reverse mutation and mitotic crossing-over in strain D7 of Saccharomyces cerevisiae was examined. A closed cell suspension-recycle system using 2 peristaltic pumps interconnected to a single-port reverse-phase smoking machine was developed to provide complete exposure of cells to smoke within 0.2--10 sec of its generation. The exposed cells showed a dose-dependent increase in the frequency of all the 3 genetic endpoints examined. Cell age was an important factor with younger cells being more sensitive than older. Filtration studies showed that the gas phase possessed as much as 25% of the total whole-smoke activity. Activated charcoal reduced the activity of smoke in direct proportion to its amount in the filter. Acetate filter did not appreciably alter the activity. A comparison of whole smoke from various cigarettes showed that: (1) the nicotine content of a cigarette does not affect the genetic activity of smoke; (2) burley and flue-cured tobaccos have differential activity in gene conversion and reverse mutation systems; and (3) the genetic effects of whole smoke are not peculiar to tobacco pyrolysis because similar effects are produced by smokes from lettuce and other non-tobacco cigarettes. It is concluded that the yeast D7 system can be used effectively for the quantitative evaluation of genetic effects of smoke from different cigarettes, and both whole cigarette smoke and its gas phase possess mutagenic as well as recombinogenic activity that can be modified by the use of filters.


Lipomatous hypertrophy of the interatrial septum: an overview.
Lipomatous hypertrophy of the interatrial septum is a rare, but increasingly recognized, anomalous developmental or neoplastic lesion of the heart. This entity was first described in 1964 at autopsy and is identified before death based on its distinctive characteristics on echocardiography, computed tomography, and magnetic resonance imaging. Although it is often asymptomatic, the mass has been associated with supraventricular arrhythmias and sudden death. In rare patients who experience intractable symptoms, surgical excision of the lesion may provide relief. Therefore, lipomatous hypertrophy of the interatrial septum is of interest to the pathologist when a cardiac mass is received for evaluation or at autopsy when a patient has experienced sudden death from an unknown cause.


Characterization of nickel-doped biphasic calcium phosphate/graphene nanoplatelet composites for biomedical application.
The effect of the addition of an ionic dopant to calcium phosphates for biomedical applications requires specific research due to the essential roles played in such processes. In the present study, the mechanical and biological properties of Ni-doped hydroxyapatite (HA) and Ni-doped HA mixed with graphene nanoplatelets (GNPs) were evaluated. Ni (3wt.% and 6wt.%)-doped HA was synthesized using a continuous precipitation method and calcined at 900°C for 1h. The GNP (0.5-2wt.%)-reinforced 6% Ni-doped HA (Ni6) composite was prepared using rotary ball milling for 15h. The sintering process was performed using hot isostatic pressing at processing conditions of 1150°C and 160MPa with a 1-h holding time. The results indicated that the phase compositions and structural features of the products were noticeably affected by the Ni and GNPs. The mechanical properties of Ni6 and 1.5Ni6 were increased by 55% and 75% in hardness, 59% and 163% in fracture toughness and 120% and 85% in elastic modulus compared with monolithic HA, respectively. The in-vitro biological behavior was investigated using h-FOB osteoblast cells in 1, 3 and 5days of culture. Based on the osteoblast results, the cytotoxicity of the products was indeed affected by the Ni doping. In addition, the effect of GNPs on the growth and proliferation of osteoblast cells was investigated in Ni6 composites containing different ratios of GNPs, where 1.5wt.% was the optimum value.


An effective way to biosynthesize α-glucosyl eugenol with a high yield by Xanthomonas maltophilia.
Eugenol is known for its analgesic, local anesthetic, anti-inflammatory, antibacterial, and hair growing effects, the application of which, however, is limited by its low solubility, liability of sublimating, and its pungent smell. Compared to eugenol, its glycosylated derivate [eugenol α-glucoside (α-EG)] has more advantages in application. The biosynthesis of α-EG by Xanthomonas maltophilia Hugh (Xanthomonadaceae) BT-112 and the optimum conditions for α-EG production are investigated here. The α-EG was obtained by fermentation using Xanthomonas maltophilia BT-112 and purified by macroporous absorption resin. The identity of α-EG is confirmed by high performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). The maximum yield of α-EG reached 10.62 g/L broth when the suspension of Xanthomonas maltophilia strain was incubated at 30°C with 70 mM eugenol and 1.0 M maltose. Bio-fermentation was applied in this work to get α-EG with a high mole conversion, which is a potentially efficient and highly promising approach to modify phenolic compounds into glucosides.


Enterochromaffin cells in the rat gastrointestinal tract. Aspects of factors influencing quantification.
A quantitative study was made of the enterochromaffin (EC) cells, visualized with the Masson (slightly modified) and Falck-Hillarp techniques, in the rat gastrointestinal tract. Different factors influencing the quantification were analysed and the magnitude of methodological errors was estimated. The two histochemical techniques visualized the EC cells in different ways, influencing the quantification results. This means that a comparison of the quantitative results obtained by these techniques can only be made after correction by some factors. The frequency of EC cells is given as the number of cells both per mm3 mucosa (cellular density) and per segment of mucosa with a base of 1 mm2. The latter information takes into account both cellular density and mucosal thickness. The highest frequency of EC cells was found in the pyloric gland area of the stomach. On the border with the duodenum there was a marked decrease in this frequency and in the whole intestine the frequency was low, with only minor fluctuations of the mean values. The frequency was increased in the caecum, followed by a gradual decrease in the large intestine. The quantitative variation of the EC cells at the same gastrointestinal level was considerable, and was greater between animals than between serial sections within the same animal. The difference in EC cell frequency that was required to give significance was calculated. For quantitative studies the Masson method has some minor advantages over the Falck-Hillarp technique, as routine formalin-fixed deparaffinized sections can be used and no counterstaining is needed for the areal estimation.


Sonography, a complementary examination to alpha-fetoprotein testing for fetal neural tube defects.
Neural tube defects (NTDs) are among the most common congenital anomalies in the United States, with an estimated prevalence of 16 per 10,000 births. The measurement of amniotic fluid alpha-fetoprotein (AF-AFP) concentration has been used to detect NTDs since the early 1970s. When the AF-AFP concentration is elevated, ultrasonography is commonly used to confirm the presence of a NTD. In this study, patient charts, amniocentesis records, and ultrasound reports from a three-year period were reviewed. The 97 fetuses identified as being at high risk for NTDs were divided into four groups: those with high AF-AFP concentrations (Groups 1 and 2, with from 3 to 5 standard deviations (SD) above the mean and with more than 5 SD above the mean, respectively): those referred from other institutions because of suspicious sonographic results (Group 3); and those at risk because of a previous sibling with a NTD (Group 4). Ultrasonography was 100 per cent sensitive and 100 per cent specific in diagnosing NTDs. Thus, in pregnancies with an elevated AF-AFP concentration, ultrasonography can reliably identify normal fetuses as well as differentiate between those with NTDs and those with other congenital anomalies. Also, since AF-AFP concentrations decline after 20 weeks' gestation, ultrasonography may be a better test than a repeat amniocentesis in equivocal cases of AF-AFP elevation.


Stimulation of megakaryocytopoiesis in mice by human recombinant interleukin-6.
The in vivo effects of purified human recombinant interleukin-6 (IL-6) on murine megakaryocytopoiesis were examined. IL-6 was administered subcutaneously to Swiss Webster mice, followed by evaluation of bone marrow megakaryocyte ploidy, size and frequency, and median platelet volume 24, 48, and 72 hours after the initiation of IL-6 administration. In addition, bone marrow megakaryocyte morphology was examined using electron microscopy at 72 hours. IL-6 (10,000 U per subcutaneous injection) was administered three times during the first 24 hours, three times during the second 24 hours, and twice during the last 24-hour period. IL-6 bioactivity (10 U/ng) was determined using the IL-6-dependent murine hybridoma cell line B9. Megakaryocyte ploidy distribution, measured by two-color flow cytometry, demonstrated a shift in the modal ploidy class from 16N to 32N and a significant increase in the relative frequency of 64N megakaryocytes 48 and 72 hours (but not 24 hours) after initiation of IL-6 administration (cumulative doses of 60,000 and 80,000 U at 48 and 72 hours, respectively). In addition, ploidy levels were increased in animals that received a cumulative IL-6 dose of only 40,000 U (evaluated after 72 hours). The size of recognizable bone marrow megakaryocytes, determined by the cross-sectional areas of plastic embedded bone marrow megakaryocytes, was increased at the 48-hour (60,000 U IL-6) and 72-hour (80,000 U IL-6) time points. Megakaryocyte frequency, measured by flow cytometry, was unaffected at all time points and doses of IL-6. Median platelet volume, measured by electrical impedance, was not consistently altered by administration of IL-6. Electron microscopic examination of bone marrow megakaryocytes showed an increase in the proportion of megakaryocytes with a wide, peripheral, organelle-deficient zone from 20% +/- 9% (SD) in control animals to 50% +/- 7% (SD) (P less than .02) in animals that received IL-6. No changes were observed in the distribution of the demarcation membranes. IL-6 is a potent stimulator of murine megakaryocytopoiesis, in vivo, and appears to act early in megakaryocyte differentiation.


Dose density in adjuvant chemotherapy for breast cancer.
Dose-dense chemotherapy increases the dose intensity of the regimen by delivering standard-dose chemotherapy with shorter intervals between the cycles. This article discusses the rationale for dose-dense therapy and reviews the results with dose-dense adjuvant regimens in recent clinical trials in breast cancer. The papers for this review covered evidence of a dose-response relation in cancer chemotherapy; the rationale for dose-intense (and specifically dose-dense) therapy; and clinical experience with dose-dense regimens in adjuvant chemotherapy for breast cancer, with particular attention to outcomes and toxicity. Evidence supports maintaining the dose intensity of adjuvant chemotherapy within the conventional dose range. Disease-free and overall survival with combination cyclophosphamide, methotrexate, and fluorouracil are significantly improved when patients receive within 85% of the planned dose. Moderate and high dose cyclophosphamide, doxorubicin, and fluorouracil within the standard range results in greater disease-free and overall survival than the low dose regimen. The sequential addition of paclitaxel after concurrent doxorubicin and cyclophosphamide also significantly improves survival. Disease-free and overall survival with dose-dense sequential or concurrent doxorubicin, cyclophosphamide, and paclitaxel with filgrastim (rhG-CSF; NEUPOGEN) support are significantly greater than with conventional schedules (q21d). The delivered dose intensity of adjuvant chemotherapy within the standard dose range is an important predictor of the clinical outcome. Prospective trials of high-dose chemotherapy have shown no improvement over standard regimens, and toxicity was greater. Dose-dense adjuvant chemotherapy improves the clinical outcomes with doxorubicin-containing regimens. Filgrastim support enables the delivery of dose-dense chemotherapy and reduces the risk of neutropenia and its complications.


Lymphoma-associated hemophagocytic syndrome in six dogs.
Hemophagocytic syndrome (HPS) is a clinicopathological entity characterized by histiocytic proliferation, with marked hemophagocytosis in the reticuloendothelial organs. HPS caused by lymphoma is termed lymphoma-associated hemophagocytic syndrome (LAHS), and there are few reports on canine and feline LAHS. The objective of this study was to examine the clinical, diagnostic, and clinicopathologic features of LAHS in six dogs. The diagnostic criteria of LAHS consisted of lymphoma, bicytopenia or pancytopenia in the blood, and increased hemophagocytosis in the reticuloendothelial organs. In one dog, an ocular form of lymphoma was recognized. A splenic form was recognized in two dogs, and a hepatosplenic form was recognized in three dogs. Immunophenotyping revealed T-cell origin in five dogs and B-cell origin in one dog by polymerase chain reaction for antigen receptor rearrangement analysis. Nonspecific esterase stain was performed to differentiate between neoplastic lymphocytes and hemophagocytes. All five dogs with T-cell lymphoma were diagnosed with large granular lymphocyte (LGL) lymphoma. In three cases, palliative therapy with glucocorticoids was conducted, while the other three cases received chemotherapy as well. The survival times for the three dogs with glucocorticoids only were 6, 6, and 10 days and were 30, 54, and 68 days for the three treated with anticancer therapy. The median survival time for the dogs was 20 days. This report indicates that canine LAHS is likely to be caused by LGL lymphoma, and it has an aggressive behavior and poor general prognosis, as seen in humans.


Long-term neuronal damage and recovery after a single dose of MDMA: expression and distribution of serotonin transporter in the rat brain.
"Ecstasy", 3,4-methylenedioxymethamphetamine (MDMA), an amphetamine analogue is one of the most widely used recreational drugs. In spite of the fact that neurotoxic effects of MDMA has been found in several species from rodents to non-human primates, and results increasingly point to damage also in human MDMA users, data about the sensitivity of different brain areas and the recovery after neuronal damage are scarce. Serotonin transporter (5-HTT) mRNA in the raphe nuclei also has not been examined. Humans with genetic predisposition for the slow metabolism of MDMA, the so-called "poor metabolizers" of debrisoquin are at higher risk. Five- 9% of the Caucasian population is considered to carry this phenotype. These studies were carried out in Dark Agouti rats, a special strain that show decreased microsomal CYP2D1 isoenzyme activity, and thus may serve as a model of vulnerable human users. These works were designed to characterize MDMA-induced damage and recovery of the serotonergic system including sleep and morphological changes within 180 days. In our experiments we investigated the 5-HTT mRNA expression in the brainstem and medullary raphe nuclei, 5-HTT immunoreactive (IR) fibre densities in several brain areas, and 16 functional measures of sleep in response to a single dose of +/- MDMA (15mg\kg). Furthermore, behavioural experiments were performed 21 days after MDMA treatment. We found similar changes in 5-HTT mRNA expression in the examined raphe nuclei, namely transient increases 7 days after MDMA treatment followed by transient decreases at 21 days. Significant (20-40%), widespread reductions in 5-HTT-IR fibre density were detected in most brain areas at 7 and 21 days after MDMA administration. All cortical, but only some brainstem areas were damaged. Parallel to the neuronal damage we observed significant reductions in rapid eye movement (REM) sleep latency, increased fragmentation of sleep and increases in delta power spectra in non-REM sleep. At 180 days almost all functional changes in sleep were normalized together with 5-HTT mRNA expression in the examined raphe nuclei and the recovery of 5-HTT-IR fibre density in most brain areas. Our results also suggest that the acute MDMA administration abolished aggressive behaviour but MDMA pretreatment and the consequent depletion of serotonergic terminals did not affect aggression. Our findings concerning the changes detected in 5-HTT mRNA expression and fibre density indicate lasting impairment of the serotonergic system and suggest that a single use of MDMA may be associated with long-lasting cognitive, learning, memory and mood deficits and sleep disturbances particularly when a constellation of genetic vulnerability and certain environmental factors are present. Our data provide further evidence for the connection between altered serotonergic functions and sleep disturbance.


Mesoscale structure-function relationships in mitochondrial transcriptional condensates.
In live cells, phase separation is thought to organize macromolecules into membraneless structures known as biomolecular condensates. Here, we reconstituted transcription in condensates from purified mitochondrial components using optimized in vitro reaction conditions to probe the structure-function relationships of biomolecular condensates. We find that the core components of the mt-transcription machinery form multiphasic, viscoelastic condensates in vitro. Strikingly, the rates of condensate-mediated transcription are substantially lower than in solution. The condensate-mediated decrease in transcriptional rates is associated with the formation of vesicle-like structures that are driven by the production and accumulation of RNA during transcription. The generation of RNA alters the global phase behavior and organization of transcription components within condensates. Coarse-grained simulations of mesoscale structures at equilibrium show that the components stably assemble into multiphasic condensates and that the vesicles formed in vitro are the result of dynamical arrest. Overall, our findings illustrate the complex phase behavior of transcribing, multicomponent condensates, and they highlight the intimate, bidirectional interplay of structure and function in transcriptional condensates.


The Clinical Evaluation of Alcohol Intoxication Is Inaccurate in Trauma Patients.
Discharging patients from emergency centers based on the clinical features of intoxication alone may be dangerous, as these may poorly correlate with ethanol measurements. We determined the feasibility of utilizing a hand-held breath alcohol analyzer to aid in the disposition of intoxicated trauma patients by comparing serial breathalyzer (Intoximeter, Alco-Sensor FST, St. Louis, Missouri, USA] data with clinical assessments in determining the readiness of trauma patients for discharge. A total of 20 legally intoxicated (LI) patients (blood alcohol concentration (BAC) >80 mg/dL) brought to our trauma center were prospectively investigated. Serial breath samples were obtained using a breathalyzer as a surrogate measure of repeated BAC. A clinical exam (nystagmus, one-leg balance, heel-toe walk) was performed prior to each breath sampling. The enrollees were 85% male, age 30±10 (range 19-51), with a body mass index (BMI) of 29±7. The average initial body alcohol level (BAL) was 245±61 (range 162-370) mg/dL. Based on breath samples, the alcohol elimination rates varied from 21.5 mg/dL/hr to 45.7 mg/dL/hr (mean 28.5 mg/dL/hr). There were no significant differences in alcohol elimination rates by gender, age, or BMI. The clinical exam also varied widely among patients; only seven of 16 (44%) LI patients demonstrated horizontal nystagmus (suggesting sobriety when actually LI) and the majority of the LI patients (66%) were able to complete the balance tasks (suggesting sobriety). Intoxicated trauma patients have an unreliable clinical sobriety exam and a wide range of alcohol elimination rates. The portable alcohol breath analyzer represents a potential option to easily and inexpensively establish legal sobriety in this population.


A new job for ancient extracellular matrix proteins: Hemicentins stabilize cleavage furrows.
Interactions between extracellular matrix (ECM) proteins and transmembrane receptors mediate changes in cell shape during cell migration, adhesion, differentiation and polarization. Cytokinesis is the final step in cell division as cells employ a contractile ring composed of actin and myosin to partition one cell into two. During the partition process, an invagination in nascent membrane forms a new extracellular space called the cleavage furrow. Despite the dramatic changes in cell shape during cytokinesis, existing models include no role for the ECM. In a recent paper, we show that hemicentins assemble in the cleavage furrow of C. elegans germ cells and mouse embryo blastomeres. Hemicentin depletion results in membrane destabilization, cleavage furrow retraction and cytokinesis failure. The data suggest that hemicentins and other ECM proteins stabilize the cleavage furrow during cytokinesis of multiple cell types.


Costs and risks of weekend anesthesia staffing at 6 independently managed surgical suites.
We previously developed a statistical method that managers can use to assure that nurse anesthetists are on call on weekends for as few hours as possible while providing a specified level of care for operating room (OR) patients. The statistically derived staffing solutions are optimal, meaning that the total number of staffed hours is guaranteed to be as low as possible to achieve the specified risk of being unable to care for patients as promptly as they had in the recent past. We used the statistical method to review nurse anesthetist weekend staffing at 6 surgical suites that were part of a healthcare system with a cost-conscious management team. Four of the suites had already made staffing changes resulting in a greater than 6% risk of being understaffed. One suite had adequate current staffing but slightly exceeded the minimum total staffing hours. One suite had more anesthetist coverage than was needed, resulting in excess staffing costs greater than $200,000 per year. We conclude that the principal value of the statistical method may be in helping healthcare system administrators and anesthetists quantify the impact of contemplated reductions in staffing on their risk of understaffing and prologing patients' wait for OR care.


Interleukin-1 genetic association with periodontitis in clinical practice.
Periodontitis is a bacterial disease modified by multiple risk factors. The pro-inflammatory cytokine interleukin- (IL-1) is a key regulator of the host responses to microbial infection and a major modulator of extracellular matrix catabolism and bone resorption. It has been reported that variations in the IL-1 gene cluster on chromosome 2 are associated with increased susceptibility to severe adult periodontitis. The present study evaluated the association between a composite IL-1 genotype, including allele 2 at each of two loci (IL-1A +4845 plus IL- B +3954), and a broad spectrum of periodontally healthy to diseased patients in a population that is typically encountered in a dental practice setting. Ninety patients, non-smokers or former smokers with less than 10 pack-year (pk/yr) history, were recruited from a private dental practice. The major outcome variable was bone loss determined by computerized linear measurements of radiographs. Genotypes were analyzed from finger-stick blood samples using previously reported methods. Multivariate logistic regression models demonstrated that patient age, former smoking history, and the IL-1 genotype were significantly associated with severity of adult periodontitis. For non-smokers or former light smokers (<5 pk/yr), IL-1 genotype positives were at increased odds ratio of having moderate to severe periodontal disease of 3.75 (95% CI: 1.04-13.50) to 5.27 (95% CI: 1.23-22.70), depending on ethnicity, compared to IL-1 genotype negatives. Former moderate smokers (>5 pk/yr and <10 pk/yr) who were IL-1 genotype negative were at increased odds ratio of having moderate to severe periodontal disease of 7.43 (95% CI: 1.20-46.20) compared to non-smokers or former light smokers who were IL-1 genotype negative. In addition, past smoking history was also a significant effect modifier as demonstrated by the statistically significant interaction between past smoking history status and IL-1 genotype status. This study demonstrates that the composite IL-1 genotype is significantly associated with the severity of adult periodontitis. It also confirmed that both IL-1 genotyping and smoking history provide objective risk factors for periodontal disease in a private practice environment.


Improving Fast Pyrolysis Bio-Oil Yield and Quality by Alkali Removal from Feedstock.
Alkali removal from forest residues, eucalyptus residues, and wheat straw was studied by water and dilute nitric acid leaching. Leaching parameters were optimized for each feedstock in laboratory-scale experiments. After the optimization of leaching on the laboratory scale, nitric acid-leached and untreated feedstocks were pyrolyzed in a bench-scale bubbling fluidized bed unit. In the case of eucalyptus residues and wheat straw, nitric acid leaching was found to increase the organic liquid yield compared to untreated feedstock. In addition, the sugar content of the fast pyrolysis bio-oils was increased, and the alkali content reduced. On the other hand, the pyrolysis experiments with acid-leached forest residues were unsuccessful due to the bed agglomeration. These problems are expected to be a result of the lack of catalytically active elements in biomass which enhance especially the cracking reactions of lignin. Finally, the results were demonstrated in the pilot-scale unit where nitric acid-leached oat straw was pyrolyzed with high organic liquid yield.


One allogeneic cytolytic T lymphocyte clone distinguishes three different HLA-B27 subtypes: identification of amino acid residues influencing the specificity and avidity of recognition.
The HLA-B27 antigen may be divided into at least three subgroups, designated HLA-B27.1, -B27.2, and -B27.3, by specific cytolytic T lymphocytes. In an attempt to explore the functional relevance of HLA polymorphism, an alloimmune cytolytic T cell clone T3+, T8+, T4- has been characterized, which displays a distinct reactivity pattern with each one of the three HLA-B27 subtypes. This cell kills both B27.1- and B27.2- but not B27.3-positive targets. Its lytic efficiency is greater with B27.1 than with B27.2 cells. The clone does not recognize either B7-positive targets or most B27-negative cells. But HLA-B40-bearing cells are lysed, albeit with significantly less efficiency than any B27-positive targets. The differences in killing ability for B27.1, B27.2, and B40 are also evident in cold-target inhibition studies, indicating that a) B27.1 cells can efficiently inhibit lysis of B27.2 and B40 targets, b) B27.2 cells inhibit the lysis of B40 but not of B27.1 targets, and c) B40 cells do not inhibit B27.1 or B27.2 target lysis. In addition, anti-T3 and anti-T8 antibodies are much more effective in inhibiting the lysis of B27.2 targets than that of B27.1-positive cells, suggesting that the observed differences in killing efficiency of the various targets are due to the fact that the tightness of the effector-target interaction is affected by the structural changes between the different HLA antigens. A correlation of the reactivity pattern of this T cell clone with the known amino acid sequences of the HLA-B27, HLA-B40, and HLA-B7 antigens suggests that the clone recognizes a conformational determinant contributed to by residues within the segments 149-156 and 67-83. Those in the former segment appear to be an essential portion of this determinant, whereas polymorphism in the region 67-83 has a modulating effect on the reactivity of the effector but does not abrogate recognition.


Adenosine as a neuroprotectant: therapeutic perspectives.
The potential for exploiting the neuroprotective properties of the purine nucleoside, adenosine, in a variety of CNS disorders, including: ischemic and traumatic injuries, neurodegenerative disorders, epilepsy and pain, has aroused considerable interest in both academic and pharmaceutical circles. A variety of approaches have been employed, ranging from the development of new selective agonists and antagonists for adenosine receptors, to compounds which can either potentiate extracellular levels of endogenously released adenosine or enhance its actions at receptors. Although many of these approaches were successful in animal studies, clinical trials have been delayed by the need to develop more potent and selective agents. With the recent promising advances in this area, future prospects for the development of new neurotherapeutic agents now appear promising.


Genetic variations of the Hemagglutinin gene of Pandemic Influenza A (H1N1) viruses in Assam, India during 2016.
Since its emergence in 2009, Influenza A/H1N1pdm09 virus has evolved continuously. Marked genetic variations have occurred in the HA1 domain of the hemagglutinin gene causing the emergence of new variants. The present study genetically characterized the hemagglutinin (HA) gene of Influenza A/H1N1pdm09 strains from Assam circulating in 2016 that caused a mild outbreak without any reported mortality. Sequence analysis of the HA gene of 20 positive Assam/H1N1pdm09 strains revealed 3 mutations (K180Q, S202T, S220T) at the antigenic sites along with several other reported mutations which are in close proximity to the antigenic sites and therefore might affect the viral antigenicity. Phylogenetically, the Assam/H1N1pdm09 strains clustered into genogroup 6B. These genetic variations highlight the importance of continuous surveillance and characterization of Influenza A/H1N1pdm09 virus activity to track the genetic makeup and diversification that may affect the behavior of the virus.


Contamination of animal feedingstuffs with nicarbazin: investigations in a feed mill.
Some mechanisms of nicarbazin contamination were investigated in a feed mill. Three sequential 3-tonne batches of nicarbazin-free feed were produced directly after a batch of nicarbazin-containing feed (125 mg kg(-1)). Sampling of the nicarbazin-free feed took place at two points before pelleting and at one point post-pelleting. The study was repeated on two further occasions, i.e. three separate nicarbazin-containing feeds and 27 tonnes of 'flushing' feeds were manufactured and sampled in total. Pre-pelleting, the highest nicarbazin concentrations (3.4+/- 0.26 mg kg(-1)) were observed in the first tonne milled after the nicarbazin containing ration. Thereafter, concentrations steadily declined in successive batches. Post-pelleting samples contained much higher concentrations of the drug. After 8 tonnes had passed through, the concentrations (7.2+/- 1.29 mg kg(-1)) were between 10 and 20 times greater than the corresponding concentrations detected post-mixing. These concentrations are sufficient to cause violative residues in eggs and broiler liver. The practice of returning post-press sieved material to the pre-press bins was identified as the cause of the problem. Re-routing of sieved material along with better segregation of nicarbazin-containing and nicarbazin-free feedingstuffs markedly reduced the incidence of feed contamination with this compound.


A prospective 5-year multicenter study of the Cresco implantology concept.
The purpose of this study was to investigate the clinical and radiographic outcome of a prospective 5-year longitudinal multicenter test of a simplified implantology concept comprising an abutment-free implant system (Cresco) and a new method for fabrication of passively fitting superstructures, the Cresco Ti Precision method. The tests were carried out at three different centers. Sixty partially or completely edentulous patients were restored by fixed implant-supported superstructures fabricated according to the Cresco Ti Precision method. In all, 215 Cresco implants were placed for the support of the superstructures. For various reasons, eight patients (13%) could not be followed through the 5 years. The radiographic measurements were recorded from radiographs exposed perpendicular to the implants. The initial implant failure rate (during the healing phase) was 2%, and the survival rate after loading was 98%. The mean peri-implant bone loss was 0.29 mm (SD 0.57). Of the measured sites, 71% showed a crestal bone loss of less than 0.5 mm. Very few mechanical complications were observed. This was attributed to the passively fitting superstructures. The results from the present multicenter test demonstrated that the abutment-free Cresco implantology concept is a reliable alternative method for implant-supported fixed prosthetic rehabilitation of edentulous and partially edentulous jaws.


Serum cytokine profiles and their correlations with disease activity in Takayasu's arteritis.
To investigate serum profiles of inflammatory cytokines in patients with Takayasu's arteritis (TA) and to determine their correlations with disease activity of TA. Forty-nine patients with TA and 12 age- and sex-matched controls were studied. Blood samples were obtained and were divided into active and stable disease groups. Paired blood samples were available in 19 patients at the active stage before treatment and at the remitted stage after treatment. Serum tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-6, IL-12 and IL-18 levels were determined by enzyme-linked immunosorbent assay. Serum TNF-alpha, IL-6 and IL-18 levels of patients with TA were significantly higher than those of controls (P<0.05), but IFN-gamma and IL-12 levels were not. Serum IL-6 and IL-18 levels were significantly higher in the active disease group than in the stable disease group (P<0.05), but the levels of TNF-alpha were not different between the groups. In the 19 patients with paired samples, serum IL-18 levels at the remitted stage after treatment were significantly decreased compared with the active stage before treatment (P<0.001). The changes in IL-18 levels between active and remitted stages correlated well with changes in erythrocyte sedimentation rate (P<0.001). Serum IL-18 and IL-6 levels were elevated in patients with TA, especially in those with active disease. Serum IL-18 levels correlated well with disease activity of TA. These results suggest that IL-6 and IL-18 might contribute to the pathogenesis of TA and that IL-18 could be a useful marker for monitoring disease activity of TA.


Human antral follicles <6 mm: a comparison between in vivo maturation and in vitro maturation in non-hCG primed cycles using cumulus cell gene expression.
Within the context of an oocyte in vitro maturation (IVM) program for reproductive treatment, oocyte cumulus complexes (COCs) derived from follicles <6 mm in patients with PCOS were matured in vitro. Key transcripts related to meiotic maturation (FSHR, LHCGR, EGFR, PGR) and oocyte competence (AREG, ADAMTS, HAS2, PTGS2) were quantified in cumulus cells (CCs) before and after maturation. Control CC samples were collected from PCOS and normo-ovulatory patients who had undergone conventional gonadotrophin stimulation for IVF/ICSI. Additional control samples from a non-stimulated condition were obtained ex vivo from patients undergoing ovariectomy for fertility preservation. Expression data from CCs from follicles with a diameter of <6 mm before (IVM-CCs) and after in vitro maturation (IVM-CCs) were obtained after pooling CCs into four groups in relation to the percentage of matured (MII) oocytes obtained after 40 h of IVM (0; 40-60; 61-80; 100% MII) and values were compared with in vivo matured controls (IVO-CCs). Genes encoding key receptors mediating meiotic resumption are expressed in human antral follicles of <6 mm before and after IVM. The expression levels of FSHR, EGFR and PGR in CCs were significantly down-regulated in the IVO-CCs groups and in the 100% MII IVM group compared with the BM groups; all the receptors studied in the 100% MII IVM group reached an expression profile similar to that of IVO-CCs. However, after maturation in a conventional IVF/ICSI cycle, IVO-CCs from large follicles contained significantly increased levels of ADAMTS1, AREG, HAS2 and PTGS2 compared with IVM-CCs and IVM-CCs; the expression patterns for these genes in all IVM-CCs were unchanged compared with IVM-CCs. In conclusion, genes encoding receptors involved in oocyte meiotic resumption appeared to be expressed in CCs of small human antral follicles. Expression levels of genes-encoding factors reflecting oocyte competence were significantly altered in IVM-CCs compared with in vivo matured oocytes from large follicles. Observed differences might be explained by the different stimulation protocols, doses of gonadotrophin or by the intrinsic differences between in vivo and in vitro maturation.


A Case of Clear Cell Hidradenoma Found During Abdominal Cyst Excision.
Clear cell hidradenoma (CCH), a rare yet benign finding, is a tumor that originates from sweat glands. It mainly presents as a slow-growing cystic nodule on the scalp or trunk. We report a case of a 60-year-old man who presented with an abdominal subcutaneous mass. This mass was excised and pathology confirmed the presence of CCH, with cytology negative for malignant cells. Although benign, CCHs cannot be confirmed as such until excision and pathologic analysis, which is the standard treatment of choice.


Capillary gel electrophoresis for precise protein quantitation.
CGE, also known as SDS-CGE, is being established in the pharmaceutical industry replacing SDS-PAGE. In most cases, the method is applied for the identity and purity control of proteins, for example monoclonal antibodies. In order to quantify these components with sufficient precision using the same quality control method, a RSD for the quantitative analysis under 2% is required. A reliable and highly precise CGE method could be obtained after thorough optimization. It was crucial to increase the sample concentration and the injection volume in order to achieve sufficiently high S/N ratios (>70). The application of hydrodynamic injection is beneficial for the precision of the method compared to the traditionally used electrokinetic one. Linearity was demonstrated and LOD and LOQ were estimated. Both injection modes were compared in long series runs (n = 48). Furthermore, the use of an internal standard was investigated. Thus, the RSD% of the migration time was reduced from 0.9 to 0.2% and the RSD% of peak areas was greatly improved. However, the normalization to the total area further reduced the influence of the injection error. RSD% for the peak area ratios of typically between 1 and 2% was provided.


A students' survey of cultural competence as a basis for identifying gaps in the medical curriculum.
Assessing the cultural competence of medical students that have completed the curriculum provides indications on the effectiveness of cultural competence training in that curriculum. However, existing measures for cultural competence mostly rely on self-perceived cultural competence. This paper describes the outcomes of an assessment of knowledge, reflection ability and self-reported culturally competent consultation behaviour, the relation between these assessments and self-perceived cultural competence, and the applicability of the results in the light of developing a cultural competence educational programme. 392 medical students, Youth Health Care (YHC) Physician Residents and their Physician Supervisors were invited to complete a web-based questionnaire that assessed three domains of cultural competence: 1) general knowledge of ethnic minority care provision and interpretation services; 2) reflection ability; and 3) culturally competent consultation behaviour. Additionally, respondents graded their overall self-perceived cultural competence on a 1-10 scale. 86 medical students, 56 YHC Residents and 35 YHC Supervisors completed the questionnaire (overall response rate 41%; n= 177). On average, respondents scored low on general knowledge (mean 46% of maximum score) and knowledge of interpretation services (mean 55%) and much higher on reflection ability (80%). The respondents' reports of their consultation behaviour reflected moderately adequate behaviour in exploring patients' perspectives (mean 64%) and in interaction with low health literate patients (mean 60%) while the score on exploring patients' social contexts was on average low (46%). YHC respondents scored higher than medical students on knowledge of interpretation services, exploring patients' perspectives and exploring social contexts. The associations between self-perceived cultural competence and assessed knowledge, reflection ability and consultation behaviour were weak. Assessing the cultural competence of medical students and physicians identified gaps in knowledge and culturally competent behaviour. Such data can be used to guide improvement efforts to the diversity content of educational curricula. Based on this study, improvements should focus on increasing knowledge and improving diversity-sensitive consultation behaviour and less on reflection skills. The weak association between overall self-perceived cultural competence and assessed knowledge, reflection ability and consultation behaviour supports the hypothesis that measures of sell-perceived competence are insufficient to assess actual cultural competence.


Objective measures of sleep disturbances in children with Potocki-Lupski syndrome.
Potocki-Lupski syndrome (PTLS; MIM 610883) is a neurodevelopmental disorder caused by a microduplication, a 3.7 Mb copy number variant, mapping within chromosome 17p11.2, encompassing the dosage-sensitive RAI1 gene. Whereas RAI1 triplosensitivity causes PTLS, haploinsufficiency of RAI1 due to 17p11.2 microdeletion causes the clinically distinct Smith-Magenis syndrome (SMS; MIM 182290). Most individuals with SMS have an inversion of the melatonin cycle. Subjects with PTLS have mild sleep disturbances such as sleep apnea with no melatonin abnormalities described. Sleep patterns and potential disturbances in subjects with PTLS have not been objectively characterized. We delineated sleep characteristics in 23 subjects with PTLS who underwent a polysomnogram at Texas Children's Hospital. Eleven of these subjects (58%) completed the Child's Sleep Habits Questionnaire (CSHQ). Urinary melatonin was measured in one patient and published previously. While the circadian rhythm of melatonin in PTLS appears not to be disrupted, we identified significant differences in sleep efficiency, percentage of rapid eye movement sleep, oxygen nadir, obstructive apnea hypopnea index, and periodic limb movements between prepubertal subjects with PTLS and previously published normative data. Data from the CSHQ indicate that 64% (7/11) of parents do not identify a sleep disturbance in their children. Our data indicate that younger individuals, <10 years, with PTLS have statistically significant abnormalities in five components of sleep despite lack of recognition of substantial sleep disturbances by parents. Our data support the contention that patients with PTLS should undergo clinical evaluations for sleep disordered breathing and periodic limb movement disorder, both of which are treatable conditions.


A potential role for islet-1 in post-natal angiogenesis and vasculogenesis.
The LIM-homeobox transcription factor islet-1 (Isl1) marks a cell population which gives rise to myocardial, pacemaker, endothelial and smooth muscle cells, which are derived from the secondary heart field during heart embryogenesis. Isl1+ precursors have the potential of self-renewal and differentiation into endothelial, cardiomyocyte and smooth muscle lineages. The primary objective of this study was to determine whether retroviral gene delivery of Isl1 to endothelial cells and mesenchymal stem cells (MSCs) could promote angiogenic and vasculogenic properties. To this end, endothelial cells and rat MSCs were retrovirally transduced to express Isl1. Isl1 expression in endothelial cells resulted in enhanced proliferation and adhesion to fibronectin. In addition, increased IL-1b and VEGF secretion was evident in Isl1 transduced endothelial cells, concomitant with increased migratory and tube formation properties of the endothelial cells. Isl1 expression in MSCs promoted their vasculogenic properties and resulted in enhanced in vitro tube formation. Finally, Isl1 expressing endothelial cells induced enhanced in vivo vascularisation in C57BL/6J mice. These data suggest, for the first time, that Isl1 promotes postnatal angiogenesis and vasculogenesis by improving the angiogenic properties of endothelial cells and MSCs.


Recombinant activated factor VII for postoperative hemorrhage following repair of acute type A aortic dissection.
Perioperative hemorrhage in the repair of acute type A aortic dissection increases morbidity, mortality, and costs of treatment. Recombinant activated factor VII (rFVIIa) mitigates intractable blood loss in surgery. By enhancing thrombin generation on activated platelet surfaces and activating thrombin-activatable fibrinolysis inhibitor and factor XIII, rFVIIa promotes platelet aggregation and fibrin plug formation at the site of endothelial injury. We report outcomes for type A aortic dissection patients treated postoperatively with rFVIIa for life-threatening hemorrhage. Patients' charts were reviewed to gather demographic, procedural, and laboratory data as well as information regarding clinical outcomes and blood product use. Nine patients with acute type A aortic dissection received rFVIIa in the perioperative period. In the 6 hour period after rFVIIa treatment, transfusion of blood products was reduced. The international normalized ratio decreased after treatment (1.6 versus 0.9, P < .01). One patient experienced perioperative stroke. In patients with acute type A aortic dissections who have life-threatening bleeding, early administration of rFVIIa may safely normalize coagulation variables, decrease transfusion requirements, and enhance hemostasis.


MicroRNA-based therapeutic approaches in the cardiovascular system.
MicroRNAs (miRNAs) are endogenous small ribonucleotides that participate in the orchestration of the genome by regulating target messenger RNA translation. MiRNAs control physiological processes and misexpression of miRNAs is pathogenically involved in many diseases including cardiovascular diseases. Normalization of miRNA expression and thus downstream target networks may have enormous therapeutic chances but also risks. We here highlight and discuss recent advances in the development and use of miRNA therapeutics to target miRNAs in vivo that may translate into novel therapeutic strategies for cardiovascular diseases in the future.


Cocaine increases phosphorylation of MeCP2 in the rat striatum in vivo: a differential role of NMDA receptors.
Methyl CpG-binding protein-2 (MeCP2) is a transcriptional regulator that binds to methylated DNA at CpG sites and functions to silence DNA transcription. MeCP2 is subject to the phosphorylation modification at serine 421 (S421), which releases MeCP2 from DNA and thus facilitates gene expression. As a transcriptional repressor densely expressed in limbic reward circuits of adult mammalian brains, MeCP2 is recently emerging as a critical epigenetic factor in experience-dependent neural plasticity and psychostimulant addiction. In this study, we investigated the regulation of MeCP2 phosphorylation in the rat striatum by the psychostimulant cocaine in vivo. We found that acute systemic injection of cocaine increased MeCP2 phosphorylation at S421 in the rat striatum, including both the caudate putamen and the nucleus accumbens, while cocaine did not affect MeCP2 phosphorylation in the medial prefrontal cortex. The cocaine-stimulated MeCP2 phosphorylation in the nucleus accumbens was a rapid and transient event, as it was evident at 20 min and returned to normal levels 3h after drug injection. The cocaine effect in the caudate putamen was however relatively delayed. Reliable induction of MeCP2 phosphorylation in this region was detected at 60 min. Pretreatment with an N-methyl-d-aspartate (NMDA) glutamate receptor antagonist significantly reduced the cocaine-stimulated MeCP2 phosphorylation in the caudate putamen, although not in the nucleus accumbens. Our data support that MeCP2 is a sensitive target of psychostimulants. Its phosphorylation status is regulated by psychostimulant exposure. NMDA receptors play a region-specific role in linking cocaine to MeCP2 phosphorylation in striatal neurons in vivo.


Effect of Quinoline on the Phospholipid Profile of Curvularia lunata and Its Microbial Detoxification.
Quinoline is an N-heterocyclic compound commonly found in wastewater, especially that derived from coal processing, chemical, and pharmaceutical industries. In the present study, the microscopic fungus Curvularia lunata IM 4417, which is known to degrade various xenobiotics, was used. The aim of the research was to study the elimination of quinoline and its influence on fungal phospholipids, which are considered to be excellent indicators of environmental monitoring. Quinoline biodegradation products and phospholipid contents were analyzed using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. C. lunata IM 4417 degraded quinoline, which led to the formation of conjugates of glucose with hydroxylated derivatives of the compound. Toxicity tests (Artoxkit M and Microtox assay) indicated that the elimination of lower concentrations of quinoline was efficient and led to a reduction in sample toxicity. The presence of quinoline also significantly affected the profile of fatty acids and phospholipids. The addition of quinoline to a culture of C. lunata IM 4417 caused an increase in the content of phosphatidylcholine (PC) and a decrease in the amount of phosphatidylethanolamine (PE), two major structural lipids. Additionally, decreases in the contents of phosphatidylinositol (PI) and phosphatidylserine (PS), which are responsible for tolerance to toxic substances, cell viability, and signal transduction, were noted. Thus, it can be concluded that the presence of quinoline modifies the membrane composition, and this change may be an important indicator of the presence of N-heterocyclic compounds or other toxins in the environment.


Two Penicillium camembertii mutants affected in the production of cyclopiazonic acid.
Penicillium camembertii was mutated and screened for cyclopiazonic acid-negative mutants. With a simple and rapid mini-extraction method for detection of cyclopiazonic acid production, we were able to isolate two strains which were affected in the production of this metabolite. One strain had completely lost the ability to synthesize detectable amounts of this secondary metabolite, whereas the other mutant produced 50 to 100 times less cyclopiazonic acid than the wild type. Also, the former strain had a changed morphology compared with the wild type. This morphological alteration appears to be coupled to the inability to produce cyclopiazonic acid because morphological revertants were able to synthesize cyclopiazonic acid to a level comparable to the wild type. The second mutant accumulated a new metabolite which was detectable by two-dimensional thin-layer chromatography. This new metabolite, however, appears not to be a direct precursor of cyclopiazonic acid.


An ethnographic study of nursing home culture to define organizational realities of culture change.
The current system of delivery of nursing home care is costly both in dollars and in human terms. Culture change may provide solutions to both issues. Culture change has a different meaning for different organizations depending on where they are in the continuum of change. Detailed observation of staff members "in action" in three long-term care facilities over a period of several months was supplemented by formal and informal interviews of organization members to gain an understanding of the culture of the nursing home organization. Four three-hour observations in each of three facilities, representing privately-held and not-for-profit organizations in urban, suburban, and rural locations yielded insights into the routine, recruitment, training, teamwork, activities, leadership, role-modeling, mentoring, staff and resident satisfaction, weekend staffing and activities, bureaucratic structure, and sharing of best practices. Discussion of each of these issues may provide a starting point for all those facilities that are contemplating significant culture change. If the objective is to have facilities truly embrace a new set of values, then the change begins with the owners and administrators of nursing homes who need to focus on building new relationships with all the stakeholders. In-depth interviews of organization members and six chief executive officers in long-term care in the Western New York area culminated the study with the development of a fifty-question survey for decision makers.


The effect of quercetin on the pharmacokinetics of verapamil and its major metabolite, norverapamil, in rabbits.
We have investigated the effect of quercetin on the pharmacokinetics of verapamil and its major metabolite, norverapamil, in rabbits. Pharmacokinetic parameters of verapamil and norverapamil were determined after the oral administration of verapamil (10 mg kg(-1)) to rabbits in the presence and absence of quercetin (5.0 and 15 mg kg(-1)). While co-administration of quercetin concurrently was not effective to enhance the oral exposure of verapamil, pretreatment of quercetin 30 min before verapamil administration significantly altered the pharmacokinetics of verapamil. Compared with the control group (given verapamil alone), the C(max) and AUC of verapamil increased approximately twofold in the rabbits pretreated with 15 mg kg(-1) quercetin. There was no significant change in T(max) and terminal plasma half-life (t(1/2)) of verapamil in the presence of quercetin. Consequently, absolute and relative bioavailability values of verapamil in the rabbits pretreated with quercetin were significantly higher (P < 0.05) than those from the control group. Metabolite-parent AUC ratio in the rabbits pretreated with quercetin decreased by twofold compared with the control group, implying that pretreatment of quercetin could be effective to inhibit the CYP3A4-mediated metabolism of verapamil. In conclusion, pretreatment of quercetin significantly enhanced the oral exposure of verapamil. This suggested that concomitant use of quercetin or a quercetin-containing dietary supplement with verapamil requires close monitoring for potential drug interaction.


Particle-Breaking Hartree-Fock Theory for Open Molecular Systems.
In this work we present the particle-breaking Hartree-Fock (PBHF) model which is a mean-field approach to open molecular systems. The interaction of a system with the environment is parametrized through a particle-breaking term in the molecular Hamiltonian. The PBHF wave function is constructed through an exponential unitary transformation of a Slater determinant with a given number of electrons. We consider only the closed-shell formalism. The parametrization results in a linear combination of Slater determinants with different numbers of electrons, i.e., the PBHF wave function is not an eigenfunction of the number operator. As a result, the density matrix may have fractional occupations which are, because of the unitary parametrization, always between 0.0 and 2.0. The occupations are optimized simultaneously with the orbitals, using the trust-region optimization procedure. In the limit of a particle-conserving Hamiltonian, the PBHF optimization will converge to a standard Hartree-Fock wave function. We show that the average number of electrons may be decreased or increased depending on whether the particle-breaking term affects occupied or virtual orbitals.


Copying actions and copying outcomes: social learning through the second year.
The present work documents how the logic of a model's demonstration and the communicative cues that the model provides interact with age to influence how children engage in social learning. Children at ages 12, 18, and 24 months (n=204) watched a model open a series of boxes. Twelve-month-old subjects only copied the specific actions of the model when they were given a logical reason to do so--otherwise, they focused on reproducing the outcome of the demonstrated actions. Eighteen-month-old subjects focused on copying the outcome when the model was aloof. When the model acted socially, the subjects were as likely to focus on copying actions as outcomes, irrespective of the apparent logic of the model's behavior. Finally, 24-month-old subjects predominantly focused on copying the model's specific actions. However, they were less likely to produce the modeled outcome when the model acted non-socially.


A multiepitope vaccine candidate against infectious bursal disease virus using immunoinformatics-based reverse vaccinology approach.
Infectious bursal disease virus is the causative agent of infectious bursal disease (Gumboro disease), a highly contagious immunosuppressive disease of chicken with a substantial economic impact on small- and large-scale poultry industries worldwide. Currently, live attenuated vaccines are widely used to control the disease in chickens despite their issues with safety (immunosuppression and bursal atrophy) and efficiency (breaking through the maternally-derived antibody titer). To overcome the drawbacks, the current study has, for the first time, attempted to construct a computational model of a multiepitope based vaccine candidate against infectious bursal disease virus, which has the potential to overcome the safety and protection issues found in the existing live-attenuated vaccines. The current study used a reverse vaccinology based immunoinformatics approach to construct the vaccine candidate using major and minor capsid proteins of the virus, VP2 and VP3, respectively. The vaccine construct was composed of four CD8+ epitopes, seven CD4+ T-cell epitopes, 11 B-cell epitopes and a Cholera Toxin B adjuvant, connected using appropriate flexible peptide linkers. The vaccine construct was evaluated as antigenic with VaxiJen Score of 0.6781, immunogenic with IEDB score of 2.89887 and non-allergenic. The 55.64 kDa construct was further evaluated for its physicochemical characteristics, which revealed that it was stable with an instability index of 16.24, basic with theoretical pI of 9.24, thermostable with aliphatic index of 86.72 and hydrophilic with GRAVY score of -0.256. The docking and molecular dynamics simulation studies of the vaccine construct with Toll-like receptor-3 revealed fair structural interaction (binding affinity of -295.94 kcal/mol) and complex stability. Further, the predicted induction of antibodies and cytokines by the vaccine construct indicated the possible elicitation of the host's immune response against the virus. The work is a significant attempt to develop next-generation vaccines against the infectious bursal disease virus though further experimental studies are required to assess the efficacy and protectivity of the proposed vaccine candidate in vivo.


Effects of selective neonatal temporal lobe lesions on socioemotional behavior in infant rhesus monkeys (Macaca mulatta).
Normal infant monkeys and infant monkeys with neonatal damage to either the medial temporal lobe or the inferior temporal visual area were assessed in dyadic social interactions at 2 and 6 months of age. Unlike the normal infant monkeys, which developed strong affiliative bonds and little or no behavioral disturbances, the lesioned monkeys (each of which was observed with an unoperated control) exhibited socioemotional abnormalities and aberrant behaviors. The socioemotional changes predominated at 6 months of age and were particularly severe in monkeys with medial temporal lesions. In both the pattern and time course, the socioemotional deficits produced by the neonatal medial temporal lesions bear a striking resemblance to the behavioral syndrome in children with autism. Further analysis of these lesion-induced abnormalities in nonhuman primates may therefore provide insight into this debilitating human developmental disorder.


A pilot study on peritraumatic dissociation and coping styles as risk factors for posttraumatic stress, anxiety and depression in parents after their child's unexpected admission to a Pediatric Intensive Care Unit.
To study the prevalence of posttraumatic stress disorder (PTSD), anxiety and depression in parents three months after pediatric intensive care treatment of their child and examine if peritraumatic dissocation and coping styles are related to these mental health problems. This is a prospective cohort study and included parents of children unexpectedly admitted to the Pediatric Intensive Care Unit (PICU) from January 2006 to March 2007. At three months follow-up parents completed PTSD (n = 115), anxiety and depression (n = 128) questionnaires. Immediately after discharge, parents completed peritraumatic dissocation and coping questionnaires. Linear regression models with generalized estimating equations examined risk factors for mental health problems. Over 10% of the parents were likely to meet criteria for PTSD and almost one quarter for subclinical PTSD. Respectively 15% to 23% of the parents reported clinically significant levels of depression and anxiety. Peritraumatic dissocation was most strongly associated with PTSD, anxiety as well as depression. Avoidance coping was primarily associated with PTSD. A significant number of parents have mental health problems three months after unexpected PICU treatment of their child. Improving detection and raise awareness of mental health problems is important to minimize the negative effect of these problems on parents' well-being.


From Left Ventricular Dysfunction to Heart Failure in the Elderly Patient.
The pathophysiology of the syndrome of congestive heart failure (CHF) is different in elderly patients compared to middle-aged subjects. When the syndrome of CHF predominantly results from left ventricular (LV) systolic dysfunction, peripheral mechanisms in elderly patients are less apt to compensate for the decline in LV performance due to deconditioning of the skeletal muscles, decreased vasodilatory response to exercise, and reduced capacity to excrete sodium. These all develop with age. LV diastolic dysfunction, i.e., LV filling impairment, appears to be a more frequent cause of CHF in elderly patients than in middle-aged subjects. Hypertrophy of the cardiac myocyte is associated with a prolongation of the calcium transient which, in turn, results from a decreased concentration of the enzyme responsible for reuptake of calcium in the sarcoplasmic reticulum. Cardiac myocyte hypertrophy results from a steady loss of myocytes and a progressive rise in arterial impedance which are both observed with aging. Notwithstanding subendocardial myocardial ischemia which is frequently associated with LV wall hypertrophy, prolongation of the calcium transient leads to impaired LV wall relaxation and the syndrome of LV diastolic dysfunction. The goals of therapy are also different in elderly patients compared to middle-aged patients. In elderly patients, one is less concerned about restoring a near normal exercise capacity, and aims at preventing acute episodes of decompensation which frequently accompany excessive sodium intake. Therefore, strict adherence to diet and careful titration of the dosages of medication to renal function are important considerations when treating CHF in elderly patients. In particular, cardiac glycosides, which should be avoided with CHF due to LV diastolic dysfunction, should be carefully titrated to creatinine clearance and body weight when treating elderly patients with LV systolic dysfunction in sinus rhythm. Similarly, the dosages of most angiotensin-converting enzyme inhibitors should be reduced in elderly patients.


Cantilever sensor for nanomechanical detection of specific protein conformations.
A fast, label-free, and multiplexed method based on piezoresistive cantilevers is reported for the detection of specific protein conformations at the nanoscale level. The ligand-binding domain of the human oestrogen receptor (ERalpha-LBD) is used as the experimental model system, and ERalpha-LBD with or without oestradiol (E2) is detected using the conformation-specific peptides alpha/betaI (Ser-Ser-Asn-His-Gln-Ser-Ser-Arg-Leu-Ile-Glu-Leu-Leu-Ser-Arg, which recognizes E2-bound ER) and alpha/betaII (Ser-Ala-Pro-Arg-Ala-Thr-Ile-Ser-His-Tyr-Leu-Met-Gly-Gly, which recognizes E2-free ER). Target-specific signals are obtained in situ at protein concentrations of 2.5-20 nM. The in-build electrical readout of the piezoresistive cantilevers provides a convenient alternative to the conventional optical detection, and the presented method offers the possibility of detecting protein conformational changes using miniaturized microarrays.


Multicontrast sequences with continuous table motion: a novel acquisition technique for extended field of view imaging.
A novel acquisition technique called multicontrast imaging is presented that provides multiple datasets of different image contrasts covering an extended field of view within one measurement procedure. The technique uses a continuously moving table and is based on the repetitive acquisition of axial volume sections while the patient moves through the scanner once. To compensate for the table motion during the measurement, adaptive slice shifting is applied. Multicontrast imaging is designed to combine the comfort of a moving table examination with the high time efficiency of a multitask protocol and can be used for generating differences in both contrast and spatial parameters of the acquired data. The technique and its properties are demonstrated on healthy human volunteers.


Acute psychosis and type 2 diabetes mellitus:should screening guidelines be revised?
Although psychosis increases the risk for developing type 2 diabetes, the temporal relationship between the onset of psychosis and the onset of diabetes has not been studied. We present 6 cases of acute psychosis, which led to the new diagnosis of type 2 diabetes during inpatient psychiatric admission within days to weeks of the psychotic episode. The implications of these findings and the efficacy of current diabetes screening guidelines are discussed.


Anti-hepato-cytotoxic serum treatment results in acute liver failure.
Only few conditions in medicine are more dramatic or more devastating than acute liver failure, severe liver-cell dysfunction strikes previously well people suddenly, and many of them die. Acute liver failure (ALF) is broad term that refers to both fulminant hepatic failure (FHF) and sub-fulminant hepatic failure (or late-onset hepatic failure). FHF may result from a variety of hepatic disease processes. Viral hepatitis and hepatotoxic drugs are the most common factors inducing severe illness with the loss of hepatic function. Elevated serum concentrations of bacterial endotoxin, tumor necrosis factor-a, and interleukin-1 and interleukin-6 have been found in FHF, but the specific roles of these inflammatory factors are unclear. Numerous causes of FHF exist, but viral hepatitis and acetaminophen overdoses are the most common. The cause remains unknown in as many as 15% of patients. The aim of the study was the evaluation of the clinical course and complications of acute liver failure in experiment, We created an experimental model using hepatotoxic substance (CCL4), which causes centrilobular lesions in liver parenchyma. Nowadays, total or subtotal liver transplantation supposed to be an effective method. The restrictions of this method includes: 1. Donor organ deficit, 2. Post-operative complications, 3. Lifetime immunosuppression, 4. Expensiveness of the method. Our method proposes treatment by anti-hepato-cytotoxic serum, which induces stimulation of hepatocyte regeneration. It consists of vasoactive mediators (nitric oxide, carbon monoxide), activated complement cascade components, immunomodulators, regenerative hepatocytes, membrano-protectors and hepato-stimulator medications.


[Carcinoma of the urachus--report of 4 cases].
Four cases of urachal carcinoma are presented. The first case was a 36-year-old man who was admitted with the chief complaint of macrohematuria with mucinous debris. Cystoscopic examination revealed a single tumor at the dome of the bladder. Partial cystectomy and postoperative radiation therapy were performed. Histological findings showed a well differentiated adenocarcinoma. He has been well for twelve years postoperatively. The second case was a 52-year-old man who was admitted with the chief complaint of macrohematuria with mucinous debris. Cystoscopic examination revealed a single tumor at the dome of the bladder. Partial cystectomy and postoperative radiochemotherapy were performed. Histological findings showed a moderately differentiated adenocarcinoma. He died of a recurrent tumor 30 months after operation. The third case was 70-year-old man who was admitted with the chief complaint of macrohematuria with mucinous debris. Cystoscopic examination revealed multiple tumors at the dome of the bladder, internal urethral orifice and right lateral wall. Total cystectomy, ureterocutaneostomy and postoperative chemotherapy were performed. Histological findings showed a poorly differentiated adenocarcinoma. He died of a recurrent tumor 30 months after operation. The fourth case was a 68-year-old woman who was admitted with the chief complaint of macrohematuria with mucinous debris. Cystoscopic examination revealed a single tumor at the dome of the bladder. CT scan demonstrated a mass with calcification extending from the bladder dome superiorly. Partial cystectomy and postoperative chemotherapy were performed. Histological findings showed a well differentiated adenocarcinoma. She has been well for three months postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)


A novel fluorescent assay for T-synthase activity.
Loss of T-synthase (uridine diphosphate galactose:N-acetylgalactosaminyl-α1-Ser/Thr β3galactosyltransferase), a key enzyme required for the formation of mucin-type core 1 O-glycans, is observed in several human diseases, including cancer, Tn syndrome and IgA nephropathy, but current methods to assay the enzyme use radioactive substrates and complicated isolation of the product. Here we report the development of a novel fluorescent assay to measure its activity in a variety of tumor cell lines. Deficiencies in T-synthase activity correlate with mutations in the gene encoding the molecular chaperone Cosmc that is required for folding the T-synthase. This new high-throughput assay allows for facile screening of tumor specimens and other biological material for T-synthase activity and could be used diagnostically.


JS‑K induces G2/M phase cell cycle arrest and apoptosis in A549 and H460 cells via the p53/p21WAF1/CIP1 and p27KIP1 pathways.
Lung cancer is one of the most common malignancies worldwide, with high mortality and morbidity rates. O2‑(2,4‑dinitrophenyl)‑1‑[(4‑ethoxycarbonyl)piperazin‑1‑yl]diazen‑1‑ium‑1,2‑diolate (JS‑K) is a potent anticancer agent that acts against a subset of human non‑small cell lung cancer (NSCLC) cell lines; however, the underlying mechanisms of JS‑K in NSCLC remain unclear. The present study aimed to evaluate the anticancer effect of JS‑K and investigate its underlying mechanisms in A549 and H460 cells. In the present study, A549 and H460 cells were treated with JS‑K, and then evaluated by cell viability assay, flow cytometry and western blot analysis. JS‑K markedly induced cell cycle arrest at the G2/M phase in a concentration and time‑dependent manner in both cell lines. This was associated with increased expression levels of p53, and the cell cycle inhibitors p21WAF1/CIP1 and p27KIP1, which, in turn, inhibited the expression of Cdc2, cyclin B1 and cyclin‑dependent kinase 2. In addition, JS‑K‑induced inhibition of proliferation was revealed to be partially modulated by the upregulation of p53 and p21WAF1, the ratio of Bax/Bcl‑2, and the activation of both the intrinsic and extrinsic apoptotic pathways in A549 and H460 cells. These results demonstrated that JS‑K could trigger cell cycle arrest at the G2/M phase and apoptosis in A549 and H460 cells, which was likely mediated via the p53/p21WAF1/CIP1 and p27KIP1 pathways. Overall, the results indicated that JS‑K may be used as an anticancer agent for the treatment of NSCLC.


Risk factor analysis of postoperative acute respiratory distress syndrome after type A aortic dissection repair surgery.
To investigate the incidence, outcomes, and risk factors of postoperative acute respiratory distress syndrome (ARDS) in patients undergoing surgical repair for acute type A aortic dissection.This retrospective study involved 270 patients who underwent surgical repair for acute type A aortic dissection between January 2009 and December 2015. Data on clinical characteristics and outcomes were collected. Patients who immediately died after surgery and with preoperative myocardial dysfunction were excluded. The included patients were divided into the ARDS (ARDS patients who met the Berlin definition) and non-ARDS groups. Primary outcome was postoperative ARDS, according to the 2012 Berlin definition for ARDS and was reviewed by 2 qualified physicians with expertise in critical care and cardiac surgery. Outcomes of interest were the incidence and severity of risk factors for ARDS in this population, and perioperative outcomes and survival rates were compared with patients with or without ARDS.A total of 233 adult patients were enrolled into this study; of these, 37 patients (15.9%) had ARDS. Three, 20, and 14 patients had mild, moderate, and severe ARDS, respectively, according to the Berlin definition, with no significant difference in age, sex, and underlying disease. The ARDS group had lower mean oxygenation index (OI) than the non-ARDS group in the first 3 days post-surgery and demonstrated an improvement in lung function after the fourth day. Postoperative complication risks were higher in the ARDS group than in the non-ARDS group. However, no significant difference was observed in in-hospital mortality between the 2 groups (10.8% vs 5.6%, P = .268). Additionally, there was also no significant difference in the 3-year mortality rate between the 2 groups (P of log-rank test = .274). Postoperative hemoglobin level (odds ratio [OR]: 0.78; 95% confidence interval [CI]: 0.62-0.99) and perioperative blood transfusion volume (OR: 1.07; 95% CI: 1.03-1.12) were associated with ARDS risk.Postoperative ARDS after type A aortic dissection repair surgery was associated with risks of postoperative complications but not with risk of in-hospital mortality or 3-year mortality. A higher perioperative blood transfusion volume and a lower postoperative hemoglobin level may be risk factors for ARDS.


[Value of prokinetics in enteral nutrition intolerance].
Malnutrition is associated with an increase in morbidity and mortality and therefore a raise in hospitalization's costs. Nevertheless, an early nutritional support can reverse this trend. Gastrointestinal dysfunctions (gastroparesis, abdominal distension, high gastric residues) in patient on enteral nutrition, may appear and very likely generate an increasing risk of regurgitations, pulmonary aspiration and infection. These symptoms represent the main factors limiting dosage in administering enteral nutrition. Prokinectics agents (metoclopramid, cisaprid and erythromycin) which improve gastric motility are often used in order to maintain enteral nutrition and to cover the energetic needs of patients. This revenue shows some way of using prokinectics in case of enteral nutrition intolerance and propose a step-by-step guideline on how to start and increase progressively enteral nutrition.


Surface Charge-Reversible Tubular Micromotors for Extraction of Nucleic Acids in Microsystems.
Extraction of nucleic acids in microsystems is of significance for biomedical applications, but the current extraction methods generally require sophisticated microchannels and external equipment, hindering their practical applications. In this work, we have demonstrated a simple, versatile and efficient approach to extract nucleic acids in microsystems by developing cationic branched polyethyleneimine (PEI)-functionalized tubular micromotors. The as-developed tubular micromotors are fabricated by a two-step process combining the template-assisted electrodeposition and carbodiimide chemistry, and contain an inner catalytic Pt layer, a middle magnetic Ni layer and an outer cationic PEI layer. They exhibit autonomous bubble-propelled motion in aqueous hydrogen peroxide solutions, which can be guided by an external magnetic field, and the surface charges can be reversibly modulated by changing the pH value of the solution. Consequently, the as-developed tubular micromotors can selectively absorb nucleic acids from acidic solutions and desorb them into alkaline solutions, leading to the extraction of nucleic acids with high efficiency without external stirring. Furthermore, they can be operated in a microchannel chip without the aid of a pumping system. Our results indicate that this PEI-functionalized tubular micromotor platform provides a novel, simple and versatile microsystem nucleic acid extraction technology, holding considerable promise for important practical applications.


Quantum-Chemical Insights into the Phosphorescence Efficiencies of Blue-Emitting Platinum Complexes with Phenylene-Bridged Pincer Ligands.
Blue phosphorescent platinum complexes with phenylene-bridged pincer ligands, [Pt(dmib)Cl] [1; dmib = m-bis(methylimidazolyl)benzene], [Pt(mizb)Cl] [2; mizb = bis( N-methylimidazolium)benzene], and [Pt(dpzb)Cl] [3; dpzb = m-bis(3,5-dimethylpyrazolyl)benzene], have been investigated theoretically to rationalize the marked differences of their phosphorescence efficiencies. On the basis of density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations, the geometrical and electronic structures, absorption and emission properties, and radiative and nonradiative processes are analyzed in detail. The emission from the emissive lowest triplet state (T1) originates from a mixture of metal-to-ligand charge-transfer (3MLCT) and intraligand charge-transfer (3ILCT) states. The calculated radiative decay rate constants of T1 of the complexes are comparable and in the same order of magnitude with the experimental measurements. Therefore, the potential energy profiles for the deactivation processes from T1 via temperature-independent and -dependent pathways are explored to reveal the effect of nonradiative decay on phosphorescence. The calculated results indicate that the very weak emission of 3 could be ascribed to the deactivation process via the metal-centered (3MC) state, which can be readily accessible via a spontaneous process from the T1 state. This work provides more in-depth insight into the nature of the emissive excited state, shielding light on a better understanding of the excited-state behavior of phosphorescent platinum complexes.


[Effects of aging on drug receptor mechanisms in smooth muscles].
The effects of aging on some drug receptor mechanisms were studied in isolated smooth muscles. Potencies of alpha- and beta-adrenoceptor agonists increased from the young stage to the adult stage and decreased slowly thereafter to the old stage. The affinities of the adrenergic drugs on their receptors did not alter with aging. Excellent relationships between the potencies or efficacies of the agonists and the amounts of receptors or receptor reserve were found, suggesting that changes in the adrenoceptor mechanisms with aging were due to changes in the amount of receptors. However, it was also found that the decrease in the potency of beta-adrenoceptor agonists in preparations from the older animals was due to the change in post beta-adrenoceptor processes in responsiveness. However, the serotonin, acetylcholine (ACh) and tachykinin (NK2) receptor mechanisms did not alter with aging. Enzyme activities altered with aging. For example, activities of acetylcholinesterase and choline acetyltransferase decreased with aging. The potencies of nicotine, which accelerates ACh release, and exogenously applied ACh were modified by the change in enzyme activities with aging. Similar observations were obtained in the tachykinin (NK2) receptor mechanism. Effects of aging on physiological functions seem to be complementary. In iris dilator muscles, the potency of norepinephrine (NE), which altered with aging, was proportional in the receptor reserve. No age-related change was observed in the activity of sympathetic nerves, which innervate the iris dilator muscles. On the other hand, in iris sphincter muscles innervated by parasympathetic nerves, the ACh (muscarine) receptor mechanisms did not alter, but the activity in cholinergic nerves changed with aging.


Preparation for cesarean delivery: a multicomponent analysis of treatment outcome.
We evaluated the effects of sensory information about cesarean delivery on prenatal maternal anxiety and on recovery subsequent to delivery by cesarean section. The 42 participants were recruited from a population of obstetric patients. Patients were assigned to either treatment or control groups and identified as sensitizers or repressors. Treatment groups viewed a slide/tape program presenting procedures involved in cesarean delivery. Control groups viewed a program presenting neutral information. Prepared patients classified as sensitizers showed less physiologic arousal during surgery and enhanced postsurgical recovery. Physiologic and self-report measures of anxiety indicated that the intervention itself was not a stressful event. The relations among arousal, subjective anxiety, coping styles, and treatment outcome are discussed and recommendations are made for further investigation.


Identification of tool marks of a sickle on a telephone cable.
Linkage of a cutting tool (a sickle) with a telephone cable of 100 pairs of copper wires is reported in a case of theft of a telephone cable. Telephone cables contain numerous insulated copper wires of small diameter inside an outer covering and are stolen for the relatively precious copper. The cutting pattern of the cable can only point to the type of the tool but because of the large number of copper wires, it is practically difficult to make a definite linkage with the tool used to cut the cable by comparing the tool marks. The present work reports the successful attempt of the authors in establishing a definite linkage of a stolen telephone cable with a sickle recovered from the suspects. Spot microchemical test was performed for detection of copper on the blade of the sickle, and then tool mark comparison was performed to link the tool marks on the metal strip inside the outer covering of the cable to the blade of the sickle.


Timing of blastocyst expansion affects spatial messenger RNA expression patterns of genes in bovine blastocysts produced in vitro.
Blastocyst formation and expansion are dependent on the differentiation and function of a proper transport of nutrients through the trophectoderm (TE) enclosing the inner cell mass (ICM). Coincident with compaction and cavitation, glucose becomes the preferred energy substrate of the early embryo. These hallmarks in early development require well-orchestrated gene expression patterns specifically with regard to timing and localization. The present study investigated the relative abundance (RA) of gene transcripts in the two lineages of in vitro-produced expanded bovine blastocysts in relation to timing of development, i.e., blastocyst expansion and localization of specific mRNAs. Expanded blastocysts from either Day 7 or Day 8 or isolated ICMs derived thereof were analyzed with the aid of a semiquantitative reverse transcriptase-polymerase chain reaction assay for gene transcripts, which are thought to play a pivotal role in blastocyst expansion, i.e., Na/K-ATPase alpha1 subunit (Na/K), E-cadherin (E-cad), zonula occludens protein-1 (ZO-1), desmocollin II (Dc II), plakophilin (Plako), trophoblastic function (interferon tau [IFtau]), and glucose transport (glucose transporter-1, -3, -4 [Glut-1, -3, -4]). Total cell number, ICM cell number, or ICM/total cells ratio were similar in Day 7 and Day 8 expanded blastocysts. Significant differences were determined in the RA for Na/K, E-cad, Dc II, Plako, and ZO-1 transcripts between TE cells of expanded blastocysts derived from either Day 7 or Day 8. The RA of Dc II, Glut-1, and Glut-4 was significantly decreased in the ICM compared with the TE at Day 7. Similarly, the RA of Na/K, Dc II, Glut-1, and Glut-4 at Day 8 of development was significantly decreased in the ICM compared with the TE. Interestingly, no differences were observed when comparing ICMs originating from blastocysts expanded at either Day 7 or Day 8. Plako and IFtau transcripts were not detected in isolated ICMs, indicating that expression of these mRNAs is restricted to the TE. In contrast, similar expression patterns within the ICM and TE were determined for Na/K, E-cad, ZO-1, and Glut-3 mRNA. Dc II, Glut-1, and Glut-4 were more abundant in the TE than in ICM. Results show that expression of developmentally important genes is related to the two cell lineages in the early embryo and emphasize the critical role of a well controlled spatial gene expression pattern for regular preimplantation development.


Epstein-Barr Virus miRNA BART2-5p Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing RND3.
Nasopharyngeal carcinoma is an Epstein-Barr virus (EBV)-related malignancy. Recently, we found that the EBV-encoded miRNA BART2-5p was increased in the serum of patients with preclinical nasopharyngeal carcinoma and that the copy number positively correlated with disease progression. In this study, we established its role in nasopharyngeal carcinoma progression and explored underlying mechanisms and clinical significance. BART2-5p was an independent unfavorable prognostic factor for progression-free survival and its circulating abundance positively associated with distant metastasis. Ectopic expression of BART2-5p promoted migration and invasion of EBV-negative nasopharyngeal carcinoma cells, whereas genetic downregulation of BART2-5p in EBV-positive nasopharyngeal carcinoma cells decreased aggressiveness. Mechanistically, BART2-5p targeted RND3, a negative regulator of Rho signaling. Downregulation of RND3 phenocopied the effect of BART2-5p and reconstitution of RND3 rescued the phenotype. By suppressing RND3, BART2-5p activated Rho signaling to enhance cell motility. These findings suggest a novel role for EBV miRNA BART2-5p in promoting nasopharyngeal carcinoma metastasis and its potential value as a prognostic indicator or therapeutic target. SIGNIFICANCE: This study shows that EBV-encoded BART2-5p miRNA suppresses expression of the RND3 Rho family GTPase, consequently promoting ROCK signaling, cell motility, and metastatic behavior of NPC cells.