Parallel changes in behaviour and hippocampal monoamine metabolism in rats after administration of ACTH-analogues.
Application of footshock during the acquisition trial of a one-trial passive avoidance test is associated with a rise in the concentration of serotonin in the hippocampi of rats 24 hr after termination of the acquisition trial. Rats subjected to amnesic treatment with carbon dioxide (CO2) immediately after footshock do not show this rise in the hippocampal concentration of serotonin. The ACTH-analogues, ACTH 4-10 and ACTH 4-10 (7D-Phe), alleviate CO2-induced amnesia for the passive avoidance response when administered 1 hr before retrieval test 24 hr after acquisition. These peptides do not have anti-amnesic activity when given before acquistion. Another ACTH-analogue, ACTH 11-24 does not affect amnesia, given before either the acquisition or the retrieval test. The anti-amnesic effect of ACTH 4-10 AND ACTH 4-10 (7D-Phe), was correlated with a rise in the hippocampal serotonin concentration similar to that observed in non-amnesic animals. Pre-acquisition treatment with ACTH 4-10 or administration of ACTH 11-24 did not affect hippocampal serotonin concentrations. Changes in the hippocampal concentrations of noradrenaline, dopamine, tryptophan and tyrosine were not related to the behavioural activity of any of the peptides. It is suggested that alterations in hippocampal serotonin metabolism 24 hr after acquisition of a passive avoidance response are associated with the retrieveability of the passive avoidance response.


Mechanisms and Pathways for Coordinated Control of Fine Particulate Matter and Ozone.
Fine particulate matter (PM2.5) and ground-level ozone (O3) pose a significant risk to human health. The World Health Organization (WHO) has recently revised healthy thresholds for both pollutants. The formation and evolution of PM2.5 and O3 are however governed by complex physical and multiphase chemical processes, and therefore, it is extremely challenging to mitigate both pollutants simultaneously. Here, we review mechanisms and discuss the science-informed pathways for effective and simultaneous mitigation of PM2.5 and O3. Global warming has led to a general increase in biogenic emissions, which can enhance the formation of O3 and secondary organic aerosols. Reductions in anthropogenic emissions during the COVID-19 lockdown reduced PM2.5; however, O3 was enhanced in several polluted regions. This was attributed to more intense sunlight due to low aerosol loading and non-linear response of O3 to NO x . Such contrasting physical and chemical interactions hinder the formulation of a clear roadmap for clean air over such regions. Atmospheric chemistry including the role of biogenic emissions, aerosol-radiation interactions, boundary layer, and regional-scale transport are the key aspects that need to be carefully considered in the formulation of mitigation pathways. Therefore, a thorough understanding of the chemical effects of the emission reductions, changes in photolytic rates and boundary layer due to perturbation of solar radiation, and the effect of meteorological/seasonal changes are needed on a regional basis. Statistical emulators and machine learning approaches can aid the cumbersome process of multi-sector multi-species source attribution.


IL12B polymorphisms are linked but not associated with Plasmodium falciparum parasitemia: a familial study in Burkina Faso.
Chromosome 5q31-q33 has been linked to Plasmodium falciparum parasitemia in several independent studies. This chromosomal region contains numerous immunoregulatory genes. Among these, IL12B that encodes the p40 subunit of interleukin-12 (IL-12) appeared to be a promising functional candidate gene, and IL12Bpro, a promoter polymorphism, was associated with mortality from severe malaria in children. In this study, we characterized genetic variation in IL12B in 215 individuals belonging to 34 families and evaluated linkage and association of parasitemia with IL12B polymorphisms and haplotypes. We searched for IL12B polymorphisms in the coding regions and the corresponding intron-exon borders. We also examined IL12Bpro and IL12B 3'untranslated region (UTR) polymorphisms, which are thought to influence the production of IL-12. We showed a high level of conservation of IL12B-coding regions and identified five polymorphisms in introns and the two polymorphisms in the promoter and the 3'UTR regions. Although IL12B polymorphisms were linked to parasitemia, there was association of parasitemia with neither polymorphisms nor haplotypes. We cannot exclude that an unknown IL12B cis-regulatory element polymorphism affects both IL-12 production and parasitemia. However, our results suggest that genetic variation in IL12B does not explain differences in parasitemia in individuals living in an endemic area.


MicroRNA-148a-3p suppresses cell proliferation and migration of esophageal carcinoma by targeting CEP55.
This study evaluated microRNA-148a-3p in esophageal carcinoma cells. The prediction of bioinformatics analysis revealed that microRNA-148a-3p may target CEP55. qRT-PCR and western blot showed that CEP55 level in esophageal carcinoma cells and tissue was dramatically higher than that of normal cells and tissue, while microRNA-148a-3p was the opposite. Forced expression of microRNA-148a-3p restrained cell malignant behaviors of esophageal carcinoma, and repression of microRNA-148a-3p resulted in the converse results in terms of cell function. Dual-luciferase assay confirmed that microRNA-148a-3p targeted CEP55. CEP55 attenuated the suppressive effect of microRNA-148a-3p on proliferation and migration of esophageal carcinoma cells, demonstrating that microRNA-148a-3p regulated function of esophageal carcinoma cells via decreasing CEP55 level. Microscopy observation indicated that cell morphology was also affected by the microRNA-148a-3p/CEP55 axis. Furthermore, western blot analysis revealed that the PI3K/AKT signaling pathway could be suppressed by activating the microRNA-148a-3p/CEP55 axis. Finally, in vivo experiments confirmed the effects of microRNA-148a-3p on tumorigenesis. Thus, microRNA-148a-3p could act as a repressor in esophageal carcinoma via binding to CEP55.


A possible critical point for nematic order on the basis of Landau free energy having dual instabilities for nano-segregated smectic liquid crystals.
Landau expansion of free energy assuming dual instabilities for the nano-segregated SmA phase is analyzed. In addition to known phase sequences (on cooling, disordered isotropic liquid → nematic phase → smectic phase, and disordered isotropic liquid → smectic phase), a new sequence (disordered isotropic liquid → density wave with subsidiary nematic order → smectic phase) and the existence of a critical point are demonstrated in the case where the instability for density wave formation occurs at a higher temperature.


Role of pulse shape in cell membrane electropermeabilization.
The role of the amplitude, number, and duration of unipolar rectangular electric pulses in cell membrane electropermeabilization in vitro has been the subject of several studies. With respect to unipolar rectangular pulses, an improved efficiency has been reported for several modifications of the pulse shape: separate bipolar pulses, continuous bipolar waveforms, and sine-modulated pulses. In this paper, we present the results of a systematic study of the role of pulse shape in permeabilization, cell death, and molecular uptake. We have first compared the efficiency of 1-ms unipolar pulses with rise- and falltimes ranging from 2 to 100 micros, observing no statistically significant difference. We then compared the efficiency of triangular, sine, and rectangular bipolar pulses, and finally the efficiency of sine-modulated unipolar pulses with different percentages of modulation. We show that the results of these experiments can be explained on the basis of the time during which the pulse amplitude exceeds a certain critical value.


CA15-3: its relationship to clinical stage and progression to metastatic disease in breast cancer.
There is increasing interest in the potential role of monoclonal antibodies as tumour markers in the early detection of metastatic disease. CA15-3 is a circulating antigen which is relatively specific for breast tissue and defined by two monoclonal antibodies. It is elevated in the serum of patients with breast cancer but its relationship to clinical stage and tumour progression has not been well defined. CA15-3 levels have been measured in a consecutive series of 97 patients with breast cancer at the time of diagnosis and at 3-monthly intervals thereafter. All patients have been evaluated and followed by using routine biochemical and radiological parameters to detect occult metastatic disease. There was no difference between a control group of patients who presented with benign disease (n = 18: means(s.d.) 18.0(5.1) units/ml): and those who presented with stage I disease (n = 37: 18.4(5.3) units/ml) or stage II disease (n =21: 18.0(4.0) units/ml). Patients with stage III disease (n = 23: 32.0(10.4) units/ml) had significantly elevated levels of CA15-3 compared with those in stage I (P less than 0.001). All patients with documented metastatic disease at presentation or at follow-up had markedly elevated CA15-3 levels (n = 10: 155.8(50.2) units/ml). CA15-3 is a reliable tumour marker in patients with advanced disease.


[Multilocular Paget's disease--a case report (author's transl)].
The simultaneous occurrence of Paget's disease in five different regions in a 76-year old woman is reported. Only one lesion exhibited the typical clinical appearance of this condition, whereas the others were diagnosed histologically. After radical surgical treatment of all lesions the patient has remained free from recurrence for more than three years.


Synthesis, Characterization and Cytotoxicity of Novel Multifunctional Fe₃O₄@SiO₂@GdVO₄:Dy3+ Core-Shell Nanocomposite as a Drug Carrier.
In this study, multifunctional Fe₃O₄@SiO₂@GdVO₄:Dy3+ nanocomposites were successfully synthesized via a two-step method. Their structure, luminescence and magnetic properties were characterized by X-ray diffraction (XRD), scanning electronic microscope (SEM), transmission electron microscopy (TEM), photoluminescence (PL) spectra and vibrating sample magnetometer (VSM). The results indicated that the as-prepared multifunctional composites displayed a well-defined core-shell structure. The composites show spherical morphology with a size distribution of around 360 nm. Additionally, the composites exhibit high saturation magnetization (20.40 emu/g) and excellent luminescence properties. The inner Fe₃O₄ cores and the outer GdVO₄:Dy3+ layers endow the composites with good responsive magnetic properties and strong fluorescent properties, which endow the nanoparticles with great potential applications in drug delivery, magnetic resonance imaging, and marking and separating of cells in vitro.


Optimization of the liquid chromatography enantioseparation of chiral acidic compounds using cellulose tris(3-chloro-4-methylphenylcarbamate) as chiral selector and polar organic mobile phases.
The LC enantioseparation of chiral acidic and zwitterionic drugs selected as model compounds was optimized using chlorine containing cellulose based chiral stationary phases and polar organic mobile phases. The main solvent of the mobile phase was acetonitrile, the temperature was settled at 25°C and a stationary phase with cellulose tris(3-chloro-4-methylphenylcarbamate) as chiral selector (3-Cl-4-Me-PC) was selected. In the screening step, the nature and concentration of both acidic and basic additives were found to have a significant effect on retention, selectivity and resolution. Acetic acid (AcA) was selected as acidic additive for the optimization step since it could lead to the enantioseparation of more acidic compounds than trifluoroacetic acid (TFA) and formic acid (FA), while among the three basic additives tested, diethylamine (DEA) most often gave better results with respect to enantioresolution and selectivity than butylamine (BuA) and triethylamine (TEA). The optimization was performed using a central composite face-centered design with two factors, namely the concentration of acetic acid (0.1-0.3%) and the concentration of DEA (0.01-0.1%) in the mobile phase. On the basis of the results obtained in the screening and optimization steps, a strategy for the rapid development of methods for the enantioseparation of acidic or neutral compounds was proposed.


In utero cardiac fetal surgery: laser atrial septotomy in the treatment of hypoplastic left heart syndrome with intact atrial septum.
The purpose of this study was to report a novel technique, laser atrial septotomy, for the in utero treatment of hypoplastic left heart syndrome with intact atrial septum. In utero atrial septotomy by Neodymium-YAG laser photofulguration in a fetus with hypoplastic left heart syndrome (HLHS) and intact atrial septum was performed at 30 4/7 weeks of gestation. Percutaneous fetal cardiocentesis was performed to guide a contact (Neodymium-YAG) laser fiber into the right atrium with the objective of creating an interatrial communication by photofulguration of the septal tissue. New onset of blood flow from the left to the right atrium was confirmed by color Doppler imaging during the procedure. The neoatrial septal defect remained patent until delivery. A 3400-g neonate was born by spontaneous vaginal delivery at 37 weeks of gestation. A first stage Norwood procedure was performed on the first day of life and surgical correction of an obstructed right pulmonary vein at 3 months. Although pulmonary vascular resistance was normal at cardiac catheterization at 2 months of age, the infant died at 5 months of age from multiple organ failure. An autopsy was declined. In utero laser atrial septotomy is feasible. Further experience is necessary to determine the risks and benefits of this technique for the treatment of fetuses hypoplastic left heart syndrome with intact atrial septum.


Surgical correction of complete bifid scrotum using subcutaneous pedicle flaps; a report of two cases.
A method of surgical correction for the separation and severe transposition of the scrotum associated with perineal hypospadias is reported. Although this is a rare congenital anomaly, we have treated two cases in the past 7 years. A technique has been devised by which the scrotum is divided into two subcutaneous pedicle flaps, enabling complete correction of the transposed penis and scrotum.


Effect of anti-ER antibodies within the ER lumen of living cells.
We describe the production and partial characterization of 12 monoclonal antibodies raised against a preparation of endoplasmic reticulum membranes obtained from Xenopus laevis liver. Four of the antibodies cross-react with liver melanocytes; two of the antibodies recognize extracellular antigens, whilst the remaining six recognize antigens present in hepatocytes. The concentrations of these latter antigens increase markedly in livers stimulated by estrogen. Western blotting analysis revealed that the six anti-hepatocyte monoclonal antibodies recognize at least five different antigens whose molecular weights are 14K, 18K, 19K, 43K, and 125K. The possible functional involvement of the various antigens in the secretory pathway was investigated using Xenopus oocytes as a surrogate secretory system. The mRNAs coding for the monoclonal antibodies were injected into oocytes and the resulting immunoglobulin chains were translated and assembled into active anti-ER antibodies inside the lumen of the ER. The effect on secretion was then observed. Our data indicate that the binding of antibodies to most antigens of the endoplasmic reticulum membrane may result in a blockage of secretion.


Gochnatia polymorpha ssp. floccosa: bioprospecting of an anti-inflammatory phytotherapy for use during pregnancy.
Gochnatia polymorpha ssp. floccosa is used in folk medicine to treat inflammation and infections. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly consumed medications during pregnancy in women with inflammatory diseases. However, the relationship between the use of NSAIDs and the risk of miscarriage and birth defects and/or benefits is not fully understood. Thus, an investigation regarding the use of Gochnatia polymorpha during gestation is of relevance for developing safe anti-inflammatory drugs for use during pregnancy. The pregnant females were randomly divided into 5 groups. Control group received a hydroalcoholic solution (1.2%), via gavage, for at least 15 days prior to mating and throughout the gestational period. The pre-treatment group received Gochnatia polymorpha ethanol extract (GPEE), via gavage, at a dose of 100mg/kg body weight (b.w.) for at least 15 days prior to mating and up to the appearance of the vaginal plug. The organogenesis group received GPEE at a dose of 100mg/kg (b.w.), via gavage, on the 5-15th gestacional day. The pregnancy group received GPEE at a dose of 100mg/kg (b.w.), via gavage, throughout the gestational period (from the 1st to the 18th day of pregnancy). The pre+pregnancy group received GPEE at a dose of 100mg/kg (b.w.), via gavage, for at least 15 days prior to mating and throughout the entire gestational period. The clinical signals of maternal toxicity and teratogenesis were evaluated. Additional assays to evaluate chronic inflammation, antigenotoxicity and immunomodolatory activity were performed. The results indicated that GPEE does not interfere with reproductive performance or embryo-fetal development but does correlate with reduced weight and fetal length. The extract was not teratogenic or mutagenic or an immunomodulator. However, GPEE did exhibit effective anti-inflammatory activity. Based on this study, it can be inferred that GPEE is an important, safe anti-inflammatory agent for use during pregnancy according to the experimental design we utilized, which opens up possibilities for the bioprospecting of a new anti-inflammatory phytotherapy for use during pregnancy.


Interventional treatment of infantile hepatic hemangioendothelioma.
Hemangioendothelioma is the most frequent liver tumor in infancy. Untreated symptomatic patients with heart failure have a high mortality rate. Symptomatic forms may request nonoperative treatment, because surgery is burdened with high risks in patients with heart failure. The authors report their experience with interventional coil occlusion of infantile hepatic hemangioendothelioma (IHE). Four patients (age range, 2 to 146 days; mean, 53 days) suffering from IHE associated with heart failure were treated by endovascular coil occlusion of arterial feeders. Catheter intervention was performed via an arterial (n = 2) or venous (n = 2) approach. Signs of heart failure resolved within 2 to 8 days after occlusion in 3 patients. Tumor regression could be observed sonographically within 4 weeks postinterventionally. In 3 children, tumor size was reduced from a mean of 544 mL (65 to 1,350) to a mean of 4 mL (2 to 6); Mean systolic peak velocity in the hepatic artery was decreased from 170 cm/s (140 to 200) before occlusion to 45 cm/s (36 to 70) during follow-up. In the fourth patient, endovascular intervention could not control a rapidly progressing hemangioendotheliomatosis, and finally a liver transplantation had to be performed. Interventional occlusion of feeding arteries in symptomatic IHE is a safe and effective alternative to early open surgery. The efficacy of endovascular intervention in multifocal tumors seems questionable.


Enhancement and inhibition of benzo[a]pyrene-induced SOS function in E. coli by synthetic antioxidants.
8 antioxidants were tested in the SOS chromotest for induction of SOS function and for modulation of benzo[a]pyrene-induced SOS function. None of the antioxidants leads to increased beta-galactosidase activity by itself. Butylated hydroxytoluene at concentrations between 10(-5) M and 3 X 10(-4) M enhances benzo[a]pyrene-induced SOS function at benzo[a]pyrene concentrations between 10(-6) M and 3 X 10(-5) M. Butylated hydroxyanisole, ethoxyquin, propyl gallate and octyl gallate also slightly enhance benzo[a]pyrene-induced SOS function at concentrations up to 3 X 10(-4) M though to a lesser degree than butylated hydroxytoluene. Dodecyl gallate, vitamin C and alpha-tocopherol do not increase benzo[a]pyrene action. In concentrations exceeding 3 X 10(-4) M all synthetic antioxidants tested but not vitamin C and alpha-tocopherol decrease beta-galactosidase activity both in the absence and, more extensively, in the presence of benzo[a]pyrene. Preliminary data suggest that the apparent suppression of benzo[a]pyrene-induced SOS function is not due to an effect on the formation of benzo[a]pyrene metabolites by the metabolizing system used.


Gender differences and determinants of prevalence, awareness, treatment and control of hypertension among adults in China and Sweden.
Failure to promote early detection and better management of hypertension will contribute to the increasing burden of cardiovascular diseases. This study aims to assess the gender differences in the prevalence, awareness, treatment and control of hypertension, together with its associated factors, in China and Sweden. We used data from two cross-sectional studies: the Västerbotten Intervention Program in northern Sweden (n = 25,511) and the Shanghai survey in eastern China (n = 25,356). We employed multivariable logistic regression to examine the socio-demographics, lifestyle behaviours, and biological factors associated with the prevalence, awareness, treatment and control of hypertension. Men had a higher prevalence of hypertension (43% in Sweden, 39% in China) than their female counterparts (29 and 36%, respectively). In Sweden, men were less aware of, less treated for, and had less control over their hypertension than women. Chinese men were more aware of, had similar levels of treatment for, and had less control over their hypertension compared to women. Awareness and control of hypertension was lower in China compared to Sweden. Only 33 and 38% of hypertensive Chinese men and women who were treated reached the treatment goals, compared with a respective 48 and 59% in Sweden. Old age, impaired glucose tolerance or diabetes, a family history of hypertension or cardiovascular diseases, low physical activity and overweight or obesity were found to increase the odds of hypertension and its diagnosis. This study shows the age and gender differences in the prevalence, awareness, treatment and control of hypertension among adults in China and Sweden. Multisectoral intervention should be developed to address the increasing burden of sedentary lifestyle, overweight and obesity and diabetes, all of which are linked to the prevention and control of hypertension. Development and implementation of the gender- and context-specific intervention for the prevention and control of hypertension facilitates understanding with regard to the implementation barriers and facilitators.


Biomechanical evaluation of three adjunctive methods of orthopedic tension band-wire fixation to augment simulated patella tendon repairs in dogs.
To evaluate the effects of three adjunctive methods of tension band wire fixation (TBWF) on the biomechanical properties, gap formation, and failure mode in simulated canine patella tendon rupture (RPT). Randomized, ex vivo. Paired hindlimbs from 32 dog cadavers. Patellar tendons (PTs) and associated bone-muscle-tendon units were harvested. Each PT was transected then sutured using a core locking loop and simple continuous epitendinous pattern. Each hindlimb was randomly assigned to one of three groups (n = 18 hindlimbs/group) using 18 gauge 316 L wire, anchored to the tibial crest distally, to perform transpatellar, suprapatellar, or combined tension band-wire (TBW) augmentation. Ten hindlimbs were utilized as control specimens. Yield, peak, and failure loads, stiffness, loads to 1 and 3 mm gap formation, and failure mode were evaluated. Combined transpatellar and suprapatellar TBW augmentation was superior to transpatellar or suprapatellar groups alone. Yield (p = .0008), peak (p = .004), and failure loads (p = .005) were greater for the combined group than for the transpatellar (p = .048) and suprapatellar groups (p = .01) respectively. There was no difference regarding the occurrence of 1 or 3 mm gap formation (1 mm, p = .05; 3 mm, p = .06); however, loads required to cause gap formation were greater in the combined group (p = .036). Mode of failure differed between techniques used for PT augmentation (p < .001). Combined transpatellar and suprapatellar adjunctive TBW augmentation for simulated PT repairs was biomechanically superior to either transpatellar or suprapatellar TBWF alone. Combined suprapatellar and transpatellar TBWF may offer a viable surgical option for increased repair-site strength and greater loads to gap formation. Further studies investigating alternative techniques and materials for RPT repair augmentation are warranted.


Vascular anomalies. A primer for pediatricians.
The future is bright for children with vascular anomalies. Children with vascular anomalies no longer have to languish in the interface between various medical specialties. Vascular anomalies centers are available for consultation. Not only are specialists focusing on the conditions, but basic science has brought us to the horizon of new insights into etiology and thus the possibility for new treatment. For children with vascular tumors, newer antiangiogenic agents are already in clinical trials. For children with vascular malformations, research in molecular genetics has begun to uncover the genes responsible for normal fetal vasculogenesis and angiogenesis. Molecular studies of familial vascular malformative syndromes are just beginning to pinpoint causative mutations. Next, animal models of vascular abnormalities will be engineered to elucidate pathogenesis, and these studies, in turn, should lead to development of novel therapies.


The activity of pramipexole in the mouse forced swim test is mediated by D2 rather than D3 receptors.
Recent studies have reported antidepressant-like activities of the dopamine D2/D3 agonist pramipexole in the chronic mild stress model and in the forced swim test, suggesting that D3 receptor agonists may represent a new class of antidepressant drugs. However, the relative contribution of D2 or D3 receptors to the activity of pramipexole in these models is unclear. The aim of the current studies was to explore the role of dopamine D2 and D3 receptors in the activity of pramipexole in the mouse forced swim test. The effect of pramipexole (0.1-3.2 mg/kg) in the mouse forced swim test was examined both in conjunction with D2 and D3 receptor antagonists (haloperidol (0.1-1 mg/kg) and LU-201640 (A-437203, 5.6-17.8 mg/kg), as well as in D3 receptor knockout mice obtained on two different background strains (C57BL/6J and B6129SF2/J). Locomotor activity was also assessed following pramipexole administration. RESULTS. Pramipexole produced dose-dependent reductions in immobility in the forced swim test at doses that did not produce generalized increases in locomotor activity. LU-201640, the D3 selective antagonist, failed to block the antidepressant-like effects of pramipexole. In contrast, the efficacy of pramipexole in the forced swim test was completely blocked by the D2 antagonist, haloperidol. No baseline differences were observed between knockout and wild-type mice from either background strain in locomotor activity or in the forced swim test. Furthermore, in both background strains, pramipexole showed similar efficacy in the forced swim test for both wild-type and knockout mice. Taken together, these studies suggest that the D2 receptor rather than the D3 receptor is important for the antidepressant-like activity observed for pramipexole in the mouse forced swim test.


Factors associated with an extended length of stay in the pediatric burn patient.
The Center for Medicaid and Medicare Services predicts the length of stay for pediatric burn patients based on several variables. However, many patients exceed their anticipated length. This study looks to identify aspects of patient presentation, wound characteristics, treatment, and discharge that are associated with a longer-than-predicted length of stay to identify strategies to safely reduce it. We conducted a retrospective chart review of 535 pediatric burn patients admitted to our academic hospital from January 2018 to December 2020. 405 patients met inclusion criteria. Data were collected and analyzed. Average patient age was 3.36 years. 72.3% were treated for scald burns. Average length of stay was 13.5 days. 20.5% (n = 83) of patients exceeded their predicted length of stay. In comparing patients who exceeded their predicted length of stay to those who did not, the former had significant differences in burn causes, percent total body surface area burned (12.80% vs 4.24% [P = .000]), and body areas involved. Patients who exceeded length of stay had a higher incidence of endotracheal intubation (15.7% vs 1.3%), surgical intervention (85.5% vs 29.2%), need for tube-feeding (48.2% vs 4.3%), and intensive care unit admissions (22.9% vs 2.2% [P = .00 all]). They also averaged more operations, autografting (31.3% vs 1.6% [P = .00]), total operating room time (250 vs 31 minutes [P = .00]), and time to the first operation (2.32 vs 1.64 days [P = .00]). Tube-feeding averaged 9.52 vs 0.72 days (P = .00) extending patient stay after wound stability (43.9% vs 4.3% [P = .00]). These patients also required more discharge planning, with higher rates of Child Protective Services involvement (39.8% vs 10.9% [P = .00]), services consulted (1.06 vs 0.24 [P = .00]), and discharges to inpatient rehabilitation (8.6% vs 0.6% [P = .00]). 89.6% of all patients followed up in clinic. Twenty percent of pediatric burn patients had a longer length of stay than predicted by the Center for Medicaid and Medicare Services. Many factors were strongly associated with a longer-than-predicted length of stay. Identifying these early on might help reduce length of stay and meet the targets of the Center for Medicaid and Medicare Services.


Radioimmunodetection of human small cell lung carcinoma xenografts in the nude rat using 111in-labelled monoclonal antibody MOC-31.
The applicability of mouse monoclonal antibody MOC-31 for in vivo radioimmunodetection of human small cell lung cancer (SCLC) was investigated in a nude rat xenograft model. MOC-31 is reactive with a 38 kD pancarcinoma membrane antigen. [111In]DTPA-MOC-31 showed good in vivo immunolocalisation to xenografted SCLC cells, whereas antigen-related uptake was low in normal rat tissues and in a control antigen-negative, human-derived tumour. Non-antigen-related uptake in the liver could be blocked by pretreatment with irrelevant antibody. It is concluded that MOC-31 can be used for radioimmunodetection of SCLC in vivo and may be suitable as a targeting device in patients.


Synthesis of a series of sulfinic acid analogs of GABA and evaluation of their GABAB receptor affinities.
A series of gamma-aminobutyric acid (GABA) 1 analogs was prepared in which the carboxylic acid group of GABA was replaced with a sulfinic acid group and their affinity for the GABAB receptor investigated.


Favorable survival even with high disease-specific complication rates in lymphangioleiomyomatosis after lung transplantation-long-term follow-up of a Japanese center.
Lung transplantation (LT) is a reliable therapeutic option for end-stage pulmonary lymphangioleiomyomatosis (LAM). Long-term outcome of LAM recipients after LT remains unknown. The aim of this study was to describe the outcomes of LT for LAM with a long-term follow-up, comparing those for other diseases in the same period. We retrospectively reviewed consecutive 145 LT recipients between 1998 and 2015 at Okayama University Hospital with minimum 3-year follow-up. Twelve LAM recipients including nine sporadic-LAM and three tuberous sclerosis complex -LAM were identified. Nine of 12 underwent bilateral LT including four living-donor lobar LT. There was no significant difference in overall survival between the two groups. (P = 0.15). Chronic lung allograft dysfunction free survival rate in LAM compared with other diseases tended to be better (P = 0.058). However, the rate of requiring hemodialysis was significantly higher in LAM recipients than in the recipients of other diseases (P = 0.047). Notably, 8 of 12 (67%) LAM patients encountered LAM-related complication including chylothorax and pneumothorax, seven (58%) had proliferative diseases consisting of renal angiomyolipoma and recurrent LAM. Nine patients required mTOR inhibitors for LAM-related problems, contributing to improved control of LAM-related problems. While all nine recipients of bilateral LT have still survived, two patients died of diseases in their native lungs and one required re-LT among three recipients of single LT. Although the rates of LAM-related complications were unexpectedly high in the long term, LT is a feasible therapeutic option for patients with advanced pulmonary LAM.


Clonal proliferation of lymphoid and myeloid progenitor cells in patients with hematological abnormalities.
Myeloid and lymphoid stem cell colony formation (GM-CFU) and L-CFU) was studied in patients with lymphoproliferative diseases, aplastic anemia and other hematological abnormalities. Most patients with acute lymphatic leukemia had low number of L-CFU with decreased or normal GM-CFU, while in Hodgkin's disease and chronic lymphatic leukemia L-CFU growth was very poor with only minor abnormalities of GM-CFU formation. Aplastic anemia was characterized by a decreased GM-CFU and normal L-CFU. Coculture studies suggested that a diminished colony formation may be linked to circulating lymphocytes that inhibit L-CFU as well as the reduction in number of precursor cells.


Trade-off between the spatial and the frequency resolutions in measuring the power spectrum of the Brillouin backscattered light in an optical fiber.
We theoretically analyze the relation between the pulse width of light launched into an optical fiber and the resultant power spectrum of spontaneous Brillouin backscattered light. Through this analysis, we determine numerically that the bandwidth of the Brillouin backscattered light becomes wider, and thus the measurement accuracy in determining the peak-power frequency degrades in approximately inverse proportion to the launched pulse width. Experimental results with various pulse widths are in good agreement with the derived theoretical results.


VEGF and GM-CSF levels in nodular thyroid diseases.
VEGF is a specific mitogen for endothelial cells. GM-CSF is a key player in the regulation of steady-state functions. The aim of this study was to evaluate VEGF and GM-CSF levels in thyroid nodules >1 cm, which are negative for malignancy with fine needle aspiration biopsy. Age, serum VEGF, GM-CSF, TSH, fT3, fT4, anti-TG, anti-TPO, thyroid size, and thyroid volume were compared between 41 female patients and 20 healthy female volunteers. This study was performed with 41 female patients who were euthyroid and whose nodules were benign. Twenty healthy female volunteers were enrolled as the control group. VEGF and GM-CSF were assayed by ELISA; TSH, fT3, and fT4 were detected by electrochemiluminescence method and anti-TPO and anti-TG were detected by competitive immunoassay method. Only thyroid volume and anti-TG levels were significantly different between the two groups (p < 0.007 and p < 0.026, respectively). Other parameters including VEGF and GM-CSF were not significantly different. VEGF has a weak positive correlation only with anti-TPO levels in the patient group (r = 0.325, p = 0.036). There was a weak positive correlation between anti-TPO and anti-TG (r = 0.388, p = 0.007). There was a positive correlation between nodule size and thyroid volume (r = 0.464, p = 0.015). GM-CSF was not correlated with any parameters. VEGF and GM-CSF were not found to be increased in euthyroid patients with benign nodules and they do not seem to play a role in development of simple nodular goiter.


Outcome of extremely low birth weight infants: what's new in the third millennium? Neuropsychological profiles at four years.
Extremely low birth weight (ELBW) infants, even those not presenting severe neuromotor sequelae, continue to be at risk of developing multiple, complex disorders involving the cognitive, emotional and behavioural domains. Follow-up protocols are able, in the short term, to identify subjects at risk of developing major sequelae, however they fail to identify all children at risk of developing disorders. To investigate the cognitive, neuropsychological and behavioural outcomes of a sample of ELBW children at the age of four years in order to identify characteristic profiles. Longitudinal study. 16 healthy ELBW children born in 2005 and followed up until the age of four. Performances on standardised tests evaluating intelligence, memory, cognitive visual functions, attention, and executive functions. General intelligence was within normal range. Cognitive profile showed mild or moderate deficits with different levels of involvement in many of the examined functions, in particular executive functions, attention and naming. There emerged a wide-ranging spectrum of weaknesses and deficits involving all the functions examined, which together give rise to a dysexecutive syndrome. Analysis of cognitive profiles showed that the sample could be divided into two subgroups of subjects that differ in the quality of their global cognitive and behavioural functioning. Our results confirm the need to continue follow up of ELBW children until school age, as this will allow early detection of at-risk children and the planning of timely preventive interventions.


The relative influence of arterial pressure versus intraoperative distention on lipid accumulation in primate vein bypass grafts.
Atherosclerotic degeneration has been well documented to be the limiting factor for long-term function of aortacoronary vein bypass grafts. Injury, including that induced by pressure distention in preparation for grafting, is thought to play a role in this degeneration. Injury can be minimized by limiting the distending pressure, but vein grafts are chronically subjected to arterial pressures that far exceed native venous pressure. We evaluated the relative influence of arterial pressure and of higher pressure of distention on cholesterol and apolipoprotein-B accumulation by grafts in our established animal model of graft atherogenesis. Grafts were interposed in the femoral arteries of eight normolipemic stump-tailed macaque monkeys. Before insertion, each vein was distended at 125 mm Hg (arterial pressure) for 1 minute with autologous blood, followed by distention of one half of the vein at 350 mm Hg for 1 additional minute. Grafts and ungrafted control vein were removed 3 months later. Cholesterol concentration in grafts distended at 125 mm Hg was 213% (p less than 0.01) and apolipoprotein-B concentration was 430% (p less than 0.001) of that in ungrafted control veins, whereas in grafts distended at 350 mm Hg cholesterol was 250% (p less than 0.01) and apolipoprotein-B was 925% (p less than 0.001) of the control concentrations. Although morphologic differences between the two groups of grafts were less profound than biochemical differences, foam cells were observed more frequently in grafts distended at 350 mm Hg than in those distended at 125 mm Hg. These data demonstrate that chronic exposure to arterial pressure has a significant effect on graft cholesterol that is proportionally greater than that caused by intraoperative distention at moderate pressure. Nevertheless, the detrimental effects of excessive distending pressures should not be ignored.


Clinical, epidemiological and treatment failure data among HIV-1 non-B-infected patients in the Spanish AIDS Research Network Cohort.
The prevalence of HIV-1 non-B variants is increasing in Spain, showing a higher number of transmitted drug resistance mutations (TDR) since 2002. This study presents the features of non-B-infected patients enrolled in the cohort of antiretroviral treatment (ART) naïve HIV-infected patients included in the Research Network on HIV/AIDS (CoRIS). The study includes a selected group of HIV-1 non-B-infected subjects from 670 subjects with pol sequences collected from 2004 to 2008 in the CoRIS cohort. Epidemiological-clinical-virological data were analyzed since cohort entry until October 2011, considering the presence or absence of treatment failure (TF). Eighty two non-B infected subjects with known HIV-1 variants were selected from 2004 to 2008 in the CoRIS cohort, being mainly female, immigrants, infected by recombinant viruses, and by heterosexual route. They had an intermediate TDR rate (9.4%), a high rate of TF (25.6%), of losses to follow-up (35%), of coinfections (32.9%), and baseline CD4+ counts ≥350cells/mm(3) (61.8%). Non-B subjects with TF showed higher rates of heterosexual infection (85.7% vs. 69.5%, p<0.05), tuberculosis (30.8% vs. 9.1%, p=0.10) and hepatitis C (23.8% vs. 13.9%, p=0.34) coinfections and lower rates of syphilis (0% vs. 21.9%, p<0.05), and had more frequently received first-line ART including protease inhibitors (PIs) than patients without TF (70% vs. 30%, p<0.05). Interestingly, infection with non-B variants reduced the risk of TDR to nucleoside reverse transcriptase inhibitors and increased the risk to PIs. HIV-1 non-B-infected patients in Spain had a particular epidemiological and clinical profile that should be considered during their clinical management.


Prediction of starch pasting properties in barley flour using ATR-MIR spectroscopy.
The objective of this study was to evaluate the feasibility of using attenuated total reflectance (ATR) mid infrared (MIR) spectroscopy to predict starch pasting properties in barley flour samples. A total of 180 barley flour samples sourced from the University of Adelaide germplasm collection, harvested over three seasons (2009, 2010 and 2011) were analysed using both ATR-MIR and the rapid visco analyser (RVA) techniques. Calibrations (n=100) were developed using partial least squares (PLS1) regression and full cross validation. The coefficient of determination (R(2)) and the standard error in cross validation (SECV) were 0.74 (SECV=875 RVU) for peak viscosity (PV), 0.63 (SECV=561 RVU) for trough (THR), 0.80 (SECV=173 RVU) for breakdown (BRK), 0.74 (SECV=126 RVU) for setback (STB), 0.77 (SECV=679 RVU) for final viscosity (FV), and 0.73 (SECV=0.57 s) for time to peak (TTP). The RPD values (SD/SEP) from the validation indicated that only BRK can be accurately predicted (RPD=4). We have demonstrated that ATR-MIR spectroscopy has the potential to significantly reduce analytical time and cost during the analysis of barley flour for starch pasting properties.


The long-term influence of decentralisation or preganglionic hypogastric nerve stimulation in vivo on the reinnervation of minced vas deferens in the guinea-pig.
Previous studies have shown that minced regenerating smooth muscle of the guinea-pig vas deferens becomes reinnervated by nerves growing in from the surrounding intact vas deferens. Using electron microscopy, we have examined the effect of altering activity in the preganglionic nerves, either by decentralisation, or by chronic stimulation of the hypogastric nerve, in vivo, on the reinnervation of regenerating smooth muscle cells. Chronic stimulation induced earlier reinnervation than that seen in unstimulated (sham-operated) or decentralised preparations; the number of nerve profiles present in four preparations stimulated for up to 7 days was approximately 10-20 times that seen in unstimulated or decentralised preparations. However, electron micrographs revealed that "empty" nerve terminals were a feature following stimulation for longer periods. Decentralised preparations showed little change of reinnervation, at least up to 7 weeks. Compensatory changes in the density of innervation were found in the unstimulated contralateral vas deferens.


The origins of multicellular organisms.
Multicellularity has evolved in several eukaryotic lineages leading to plants, fungi, and animals. Theoretically, in each case, this involved (1) cell-to-cell adhesion with an alignment-of-fitness among cells, (2) cell-to-cell communication, cooperation, and specialization with an export-of-fitness to a multicellular organism, and (3) in some cases, a transition from "simple" to "complex" multicellularity. When mapped onto a matrix of morphologies based on developmental and physical rules for plants, these three phases help to identify a "unicellular ⇒ colonial ⇒ filamentous (unbranched ⇒ branched) ⇒ pseudoparenchymatous ⇒ parenchymatous" morphological transformation series that is consistent with trends observed within each of the three major plant clades. In contrast, a more direct "unicellular ⇒ colonial or siphonous ⇒ parenchymatous" series is observed in fungal and animal lineages. In these contexts, we discuss the roles played by the cooptation, expansion, and subsequent diversification of ancestral genomic toolkits and patterning modules during the evolution of multicellularity. We conclude that the extent to which multicellularity is achieved using the same toolkits and modules (and thus the extent to which multicellularity is homologous among different organisms) differs among clades and even among some closely related lineages.


Bilateral intravesical ureterocele associated with unilateral partial duplication of the ureter and other anomalies: proposal of a new variant to the classification of ureterocles based on a perinatal autopsy, review of the literature and embryology.
The aims of this study were to demonstrate a case of bilateral intravesical ureterocele associated with megacystis and mega-ureters, unilateral partial duplication of the ureter and unilateral segmental renal dysplasia of the upper pole and an accessory spleen and to propose an addition of the new variant to the classification of ureteroceles. A perinatal necropsy was conducted on the 21-week fetus by employing the Rokitansky procedure with evisceration performed in blocks. The autopsy revealed the aforementioned abnormalities without cardiac or neural anomalies. The amniocentesis report was normal. Ureterocele is a saccular expansion of the distal ureter. It is most commonly observed in females and children and usually affects the upper moiety of a complete pyeloureteral duplication. Four types of ureteroceles are described: (A) ureterocele with single ureter (10%); (B) ureterocele with total duplication and intravesical development (10%); (C) ureterocele with total duplication and extravesical development (62%); and (D) ureterocele with ectopic ureter (3%). One case in a new born with bilateral intravesical ureterocele associated with hydrouretero-nephrosis and hyperechogenic spots in kidneys has been reported, but bilateral intravesical ureterocele with unilateral incomplete pyeloureteral duplication has never been described in the literature.


Ability of human SNAP-23 to generate high molecular weight SDS-resistant ternary SNARE complexes is influenced by C-terminal coil content.
Using in vitro protein complex formation assay, ability of SNAP-25 isoforms to generate SDS-resistant ternary SNARE complexes with Syntaxin-1 and VAMP-2 was investigated. Major SNAP-25 family proteins were found to generate heat-resistant ternary complexes with varying efficiency. Compared to human SNAP-25, its non-neuronal counterparts SNAP-23 and SNAP-29 formed lower amounts of ternary complexes. Changing Pro182 in human SNAP-23 to Arg182 (SNAP-23 P182R) improved its ability to bind partners and form complexes. In silico analysis of C-terminal helical content in various SNAP-25 family members showed that except human SNAP-23, all others displayed secondary α-helical conformation. We also report that human SNAP-29 is resistant to the proteolytic action of botulinum neurotoxin A even when applied at large concentration.


Oriented growth and transdifferentiation of mesenchymal stem cells towards a Schwann cell fate on micropatterned substrates.
While Schwann cells (SCs) have a significant role in peripheral nerve regeneration, their use in treatments has been limited because of lack of a readily available source. To address this issue, this study focused on the effect of guidance cues by employing micropatterned polymeric films to influence the alignment, morphology and transdifferentiation of bone marrow-derived rat mesenchymal stem cells (MSCs) towards a Schwann cell-like fate. Two different types of polymers, biocompatible polystyrene (PS) and biodegradable poly(lactic acid) (PLA) were used to fabricate patterned films. Percentages of transdifferentiated MSCs (tMSCs) immunolabeled with SC markers (α-S100β and α-p75(NTR)) were found to be similar on patterned versus smooth PS and PLA substrates. However, patterning had a significant effect on the alignment and elongation of the tMSCs. More than 80% of the tMSCs were oriented in the direction of microgrooves (0°-20°), while cells on the smooth substrates were randomly oriented. The aspect ratio [AR, ratio of length (in direction of microgrooves) and breadth (in direction perpendicular to microgrooves)] of the tMSCs on patterned substrates had a value of approximately five, as compared to cells on smooth substrates where the AR was one. Understanding responses to these cues in vitro helps us in understanding the behavior and interaction of the cells with the 3D environment of the scaffolds, facilitating the application of these concepts to designing effective nerve guidance conduits for peripheral nerve regeneration.


Evaluation of histological classification in early gastric cancer (an analysis of 300 cases).
Using the Lauren approach of histological classification, 300 cases of early gastric cancer (EGC) were analysed with regard to their age distribution, to predisposing lesions, including gastritis, and survival rate. The average age of onset for EGC of the diffuse type is 56, ten years earlier than for the intestinal type. There was a significantly high percentage of EGC of the diffuse type without gastritis. On the other hand, gastritis in pernicious anaemia falls in the high-risk group. The survival rate in our cases is 98%, corrected for age. The results show that it is of utmost importance to differentiate between the histological types of gastric carcinoma; for there may be indeed a difference in pathogenesis and aetiology.


Identifying plastics with photoluminescence spectroscopy and machine learning.
A quantitative understanding of the worldwide plastics distribution is required not only to assess the extent and possible impact of plastic litter on the environment but also to identify possible counter measures. A systematic collection of data characterizing amount and composition of plastics has to be based on two crucial components: (i) An experimental approach that is simple enough to be accessible worldwide and sensible enough to capture the diversity of plastics; (ii) An analysis pipeline that is able to extract the relevant parameters from the vast amount of experimental data. In this study, we demonstrate that such an approach could be realized by a combination of photoluminescence spectroscopy and a machine learning-based theoretical analysis. We show that appropriate combinations of classifiers with dimensional reduction algorithms are able to identify specific material properties from the spectroscopic data. The best combination is based on an unsupervised learning technique making our approach robust to alternations of the input data.


Breakdown of psyllium hydrocolloid by strains of Bacterioides ovatus from the human intestinal tract.
Strains of Bacteroides ovatus from human feces produced extracellular enzymes which degraded psyllium hydrocolloid. Other species of saccharolytic bacteria which are found in high concentrations in human feces did not degrade psyllium.


National Institutes of Health stroke scale score at admission can predict functional outcomes in patients with ischemic stroke undergoing carotid endarterectomy.
The aim of present study was to evaluate the prognostic effect of the National Institutes of Health stroke scale (NIHSS) score for patients who had undergone acute carotid endarterectomy (CEA) and assess the clinical and morphologic factors that could predict for worse outcomes. The data from 183 consecutive patients who had undergone CEA after ischemic stroke were analyzed from January 2015 to January 2021. The patients were divided into two groups using the NIHSS score cutoff of 4. Functional dependence was assessed at hospital discharge and 90 days after discharge. Of the 183 patients, 102 (55.7%) had had a minor stroke (group A; NIHSS score of ≤4) and 81 (44.3%) had had a moderate to major stroke (group B; NIHSS score >4). Groups A and B showed significant differences in their intracranial anatomic features, including the presence of an incomplete circle of Willis (7.8% vs 17.3%; P = .05), cerebral ischemic lesion volume ≥4000 mm3 (5.9% vs 24.7%; P ≤ .001), and a high Alberta stroke program early computed tomography score of 8 to 10 (75.5% vs 44.4%; P ≤ .001). The overall rate of combined perioperative stroke, myocardial infarction, and death was 1.1%, with no strokes recorded during the interval to CEA. Patients in group A had a lower rate of functional dependence at discharge (4.9% vs 35.8%; P ≤ .001) and at 90 days after the index stroke event (2.5% vs 19.6%; P ≤ .001) compared with those in group B. Using multivariate binary logistic regression, an admission NIHSS score >4 was significantly associated with higher odds of functional dependence at discharge (odds ratio, 7.9; 95% confidence interval, 2.7-18.5; P ≤ .001) and at 90 days (odds ratio, 10.4; 95% confidence interval, 2.7-19.3; P = .002). An NIHSS score >4 at admission increased the risk of a higher modified Rankin scale score at both hospital discharge and 90 days after the index stroke event. Acute CEA was safe and feasible for patients with ischemic stroke, even if they had previously undergone intravenous thrombolysis.


EphB4-VAV1 signaling pathway is associated with imatinib resistance in chronic myeloid leukemia cells.
Imatinib (IM) resistant Chronic Myeloid Leukemia (CML) is an important issue to be addressed while treating CML patients. The present study analyzes the role of EphB4-VAV1 signaling in IM-resistant CML. EphB4 and VAV1 were overexpressed in IM-resistant CML patients and K562-R cell line (K562-R). Then, we established stable under-expressing EphB4 cell line K562-R-EphB4-sh. VAV1 was down-regulated in K562-R-EphB4-sh cells. K562-R-EphB4-sh cells gained re-sensitivity to IM and K562-R cells showed mild IM resistance. However, EphB4 was no changed when the VAV1 was down-regulated. EphB4 and VAV1 were overexpressed in IM-resistant CML, VAV1might be the downstream moleculars of EphB4. These results suggest a potential role of EphB4-VAV1 signaling as therapeutic target of IM-resistant CML.


Sp1 and c-Myc regulate transcription of BMI1 in nasopharyngeal carcinoma.
B-lymphoma mouse Moloney leukemia virus insertion region 1 (Bmi1), a member of the polycomb group, has elevated expression and is involved in the pathogenesis of various aggressive cancers, including nasopharyngeal carcinoma (NPC). To date, the mechanisms underlying the high expression of Bmi1 in NPC remain obscure. To gain new insights into the transcriptional regulation of BMI1, we cloned and characterized the promoter region of BMI1. Luciferase reporter assays demonstrated that the region from -783 to +375 showed significant promoter activity. With the use of a series of 5'-deletion and 3'-deletion promoter constructs in luciferase reporter assays, the +167/+232 and -536/-134 regions were found to be sufficient for full promoter activity. Transcriptional activity of the BMI1 promoter was dependent on the Sp1 binding site cluster (+181/+214) as well as the E-box elements (-181), and was abolished after mutation of the two cis-elements. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays demonstrated that Sp1 bound to the region from +181 to +214 within the BMI1 promoter. In addition, gain-of-function and loss-of-function analyses revealed that Sp1 augmented Bmi1 expression. Further investigations using immunohistochemistry and quantitative RT-PCR disclosed a significant positive correlation between the expression of Sp1 and Bmi1 in normal nasopharyngeal epithelial cells, NPC cells, and NPC tissue specimens. In addition, Myc, the known transcription factor for BMI1 in neuroblastomas, also activated the transcription of BMI1 through binding to the E-box element (-181) within its promoter, and showed a positive correlation with the mRNA level of BMI1 in NPC. In conclusion, these findings provide valuable mechanistic insights into the role of Sp1 and c-Myc in BMI1 transcription in NPC, and suggest that targeting of Sp1 or c-Myc may be a potential therapeutic strategy for NPC.


Air permeability of powder: a potential tool for Dry Powder Inhaler formulation development.
Dry Powder Inhalers have drawn great attention from pharmaceutical scientists in recent years in particular those consisting of low-dose micronized drug particles associated with larger carrier particles and called interactive mixtures. However, there is little understanding of the relation between bulk powder properties such as powder structure and its aerodynamic dispersion performance. The aim of this work was to develop a simple method to measure the air permeability of interactive mixtures used in Dry Powder Inhalers by using Blaine's apparatus--a compendial permeameter and to relate it to the aerodynamic behaviour. The study was done with fluticasone propionate and terbutaline sulphate as drug models that were blended with several lactoses having different particle size distribution thus containing different percentages of fine particle lactose. The quality of the blends was examined by analysing the drug content uniformity. Aerodynamic evaluation of fine particle fraction was obtained using a Twin Stage Impinger. A linear correlation between a bulk property--air permeability of packed powder bed--and the fine particle fraction of drug was observed for the tested drugs. The air permeability reflects the quantity of the free particle fraction in the interparticulate spaces of powder bed that leads to fine particle fraction during fluidization in air flow. A theoretical approach was developed in order to link the air permeability of powder bed and drag force acting on powders during aerosolization process. The permeability technique developed in this study provides a potential tool for screening Dry Powder Inhaler formulations at the development stage.


Clear cell adenocarcinoma arising from a giant cystic adenomyosis: a case report with immunohistochemical analysis of laminin-5 gamma2 chain and p53 overexpression.
We report a case of a clear cell adenocarcinoma arising from a giant cystic adenomyosis, with immunohistochemical analysis of p53 and laminin-5 gamma2 chain overexpression. Microscopically, not only clear cell adenocarcinoma showing myometrial invasion but also single-layered clear cell adenocarcinoma cells lining the cyst wall were observed. Transition from these single-layered tumor cells to papillary proliferative lesions of various degrees was recognized. Moreover, these tumor cells were continuous with minimal atypical cells. Although the tumor cells within the uterus showed a low positive cell ratio for p53, the metastatic foci showed a remarkable p53 overexpression. Laminin-5 gamma2 chain expression was low in papillary proliferation and high in myometrial invasion and metastatic foci. The single-layered tumor cells showing non-invasive proliferation also contained laminin-5 gamma2 chain-positive cells. When non-invasive tumor cells were considered to be at an early stage in tumor progression, some tumor cells had already acquired an invasive feature. p53 overexpression was not related to expression of the laminin-5 gamma2 chain.


Depression in Alzheimer's disease: heterogeneity and related issues.
Several studies have demonstrated that the great majority of Alzheimer's disease (AD) patients suffer "noncognitive" neuropsychiatric symptoms. Depression is one of the most frequent neuropsychiatric comorbidities of AD. Affecting up to 50% of AD patients, depression in AD is associated with serious negative consequences for patients and their caregivers. Yet available studies on the natural course, etiology, and treatment of depression in AD have been few and equivocal. Heterogeneity in research methodology and etiology of depression in AD might have contributed to inconsistent findings across studies. Recently, the National Institute of Mental Health (NIMH) convened the Depression of Alzheimer's Disease Workgroup, which proposed provisional diagnostic criteria for depression of Alzheimer's Disease (NIMH-dAD). These criteria may provide a framework for future studies to clarify the unresolved issues in nosology, etiology, and treatment of depression in AD. A longitudinal cohort study of depression in incident AD cases may provide further syndrome refinement that would facilitate investigation of the etiology and treatment of depression in AD.


Cannabis use correlates with schizotypal personality traits in healthy students.
The literature suggests that cannabis use and schizotypal traits both constitute risk factors for the later development of schizophrenia. However, their interrelationships remain to be evaluated. The present study examined the association between cannabis use and schizotypal traits in 232 healthy students who ranged in age from 18 to 25 years. All the students had completed the Schizotypal Personality Questionnaire and four of the Chapman Psychosis Proneness Scales: the Magical Ideation Scale; the Perceptual Aberration Scale; the Revised Physical Anhedonia Scale; and the Revised Social Anhedonia Scale. Subjects were divided into three groups according to cannabis use typology: those who had never used cannabis, those who were past or occasional users, and those who were regular users. Higher scores on the Schizotypal Personality Questionnaire and the Magical Ideation Scale characterized the regular and past or occasional users compared with those who had never used cannabis. The co-occurrence of cannabis use and schizotypal traits appeared to be independent of anxiety and depression dimensions. These data suggest that cannabis use and schizotypal traits have to be jointly considered in further longitudinal studies of schizophrenia risk factors.


Structural studies of lens fiber junction protein MP26 by cyanogen bromide cleavage.
The lens fiber-cell plasma membrane MP26 from chick, bovine, and human lenses yielded identical cyanogen bromide peptide maps, confirming the essential conservation of structure in the junction protein of vertebrate lens fiber cells. Immunoblot analyses of the cyanogen bromide peptide maps of human lens MP26 and of its age-dependent proteolytic product MP22 confirmed that MP22 is a derivative of MP26. The findings in this study are the first consistent with the positioning of the methionine residues in lens MP26 as predicted by its cDNA-derived sequence.


Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies.
Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. To understand how this glycan can be recognized, here we isolate two lineages of glycan276-dependent CD4bs antibodies. Antibody CH540-VRC40.01 (named for donor-lineage.clone) neutralizes 81% of a panel of 208 diverse strains, while antibody CH314-VRC33.01 neutralizes 45%. Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. By contrast, glycan276-independent CD4bs antibodies, such as VRC01, displace glycan276 upon binding. These results provide a foundation for understanding antibody recognition of glycan276 and suggest its presence may be crucial for priming immunogens seeking to initiate broad CD4bs recognition.


Adenosine and ADP prevent apoptosis in cultured rat cerebellar granule cells.
Cerebellar granule cells (CGCs) explanted in vitro undergo death via apoptosis when the concentration of potassium is shifted from 25 mM to 5 mM. We report that adenosine and ADP, which act as neurotransmitters and neuromodulators in the brain, exert in cultured cerebellar granule cells a specific and marked antiapoptotic action with half-maximal effect in the 10-100 microM range. The action of adenosine is partly inhibited by the A1AR antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and is mimicked by the A1AR agonist 2-chloro-N6-cyclopentyladenosine (CCPA), while ADP effect, that is completely blocked by the P2x, P2y receptors noncompetitive antagonist suramine, is restored in the presence of the selective P2x purinoceptors agonist beta, gamma-methylene-L-ATP. These findings demonstrate that adenosine and ADP markedly inhibit the program of cell death in cerebellar granule cells and suggest that such an action is mediated via interaction with, respectively, A1 and P2x receptors.


Role of the cerebellum in complex human behavior.
Thirty-three outpatient epileptics with normal CT scans (group 1) and 31 patients with cerebellar and brain stem (CBS) atrophy (group 2) were randomly included in this study. There were no significant statistical differences between the groups with regard to age, education, and number of grand mal and other seizures. Statistical analyses showed that group 2 had a longer history of epilepsy with a consequently longer duration of phenytoin (PHT) consumption. Neuropsychological assessment revealed lower performance by this group on the following measures: full I.Q. scale, verbal I.Q. scale, performance I.Q. scale, information, arithmetic, block design, object assembly, digit symbol, Stroop test forms I and II, the B-M dexterity test, and the simple visual and auditory reaction time. No significant differences were observed between the two groups for the remaining 5 subtests from the WAIS scale, for the immediate recall and the delayed recall subtests belonging to Wechsler memory scale as well as for visual and auditory movement time. Analysis of the composite scores of neuropsychological performance showed that the cerebellum interferes with the following complex behavioral functions: (i) visuo-spatial organization for a concrete task, a function related to the cerebello-parietal loops' (ii) planning and programming of daily activities, a function related to the cerebello-frontal loops; and (iii) the speed of information processing, a mainly subcortical function.


Reducing the risk of HIV in gay and bisexual men.
There is a continual increase in the incidence of HIV in the UK. This article looks at strategies that can be used by specialist health promotion nurses to meet the need for increased awareness among gay and bisexual men of the importance of maintaining safer sex in their relationships.


Potassium and melatonin-mediated regulation of fructose-1,6-bisphosphatase (FBPase) and sedoheptulose-1,7- bisphosphatase (SBPase) activity improve photosynthetic efficiency, carbon assimilation and modulate glyoxalase system accompanying tolerance to cadmium stress in tomato seedlings.
The mechanism of the combined action of potassium (K) and melatonin (Mel) in modulating tolerance to cadmium (Cd) stress in plants is not well understood. The present study reveals the synergistic role of K and Mel in enhancing physiological and biochemical mechanisms of Cd stress tolerance in tomato seedlings. The present findings reveal that seedlings subjected to Cd toxicity exhibited disturbed nutrients balance [nitrogen (N) and potassium (K)], chlorophyll (Chl) biosynthesis [reduced δ-aminolevulinic acid (δ-ALA) content and δ-aminolevulinic acid dehydratase (δ-ALAD) activity], pathway of carbon fixation [reduced fructose-1,6-bisphosphatase (FBPase) and sedoheptulose-1,7- bisphosphatase (SBPase) activity] and photosynthesis process in tomato seedlings. However, exogenous application of K and Mel alone as well as together improved physiological and biochemical mechanisms in tomato seedlings, but their combined application proved best by efficiently improving nutrient uptake, photosynthetic pigments biosynthesis (increased Chl a and b, and Total Chl), carbon flow in Calvin cycle, activity of Rubisco, carbonic anhydrase activity, and accumulation of total soluble carbohydrates content in seedlings under Cd toxicity. Furthermore, the combined treatment of K and Mel suppressed overproduction of reactive oxygen species (hydrogen peroxide and superoxide), Chl degradation [reduced chlorophyllase (Chlase) activity] and methylglyoxal content in Cd-stressed tomato seedlings by upregulating glyoxalase (increased glyoxalase I and glyoxalase II activity) and antioxidant systems (increased ascorbate-glutathione metabolism). Thus, the present study provides stronger evidence that the co-application of K and Mel exhibited synergistic roles in mitigating the toxic effect of Cd stress by increasing glyoxalase and antioxidant systems and also by improving photosynthetic efficiency in tomato seedlings.


Source apportionment of heavy metals in PM2.5 samples and effects of heavy metals on hypertension among schoolchildren in Tianjin.
The prevalence of hypertension in children has increased significantly in recent years in China. The aim of this study was to provide scientific support to control ambient heavy metals (HMs) pollution and prevent childhood hypertension. In this study, ambient HMs in PM2.5 were collected, and 1339 students from Tianjin were randomly selected. Positive matrix factorization (PMF) was used to identify and determine the sources of HMs pollution. The generalized linear model, Bayesian kernel machine regression (BKMR) and the quantile g-computation method were used to analyze the relationships between exposure to HMs and the risk of childhood hypertension. The results showed that HMs in PM2.5 mainly came from four sources: soil dust, coal combustion, incineration of municipal waste and the metallurgical industry. The positive relationships between As, Se and Pb exposures and childhood hypertension risk were found. Coal combustion and incineration of municipal waste were important sources of HMs in the occurrence of childhood hypertension. Based on these accomplishments, this study could provide guidelines for the government and individuals to alleviate the damaging effects of HMs in PM2.5. The government must implement policies to control prime sources of HMs pollution.


Genetic and phenotypic stability of poliovirus shed from infants who received novel type 2 or Sabin type 2 oral poliovirus vaccines in Panama: an analysis of two clinical trials.
Sabin strains used in oral poliovirus vaccines (OPV) can revert to virulence and, in rare instances, cause disease or generate vaccine-derived strains leading to outbreaks in areas of low immunisation coverage. A novel OPV2 (nOPV2) was designed to stabilise the viral genome against reversion and reduce recombination events that might lead to virulent strains. In this study, we evaluated the genetic and phenotypic stability of shed poliovirus following administration of one dose of monovalent OPV2 (mOPV2) or nOPV2 to infants aged 18-22 weeks. In two similarly designed clinical trials (NCT02521974 and NCT03554798) conducted in Panama, infants aged 18-22-weeks, after immunisation with three doses of bivalent OPV (types 1 and 3) and one dose of inactivated poliovirus vaccine, were administered one or two doses of mOPV2 or nOPV2. In this analysis of two clinical trials, faecally shed polioviruses following one dose of mOPV2 or nOPV2 were isolated from stools meeting predetermined criteria related to sample timing and viral presence and quantity and assessed for nucleotide polymorphisms using next-generation sequencing. A transgenic mouse neurovirulence test was adapted to assess the effect of the possible phenotypic reversion of shed mOPV2 and nOPV2 with a logistic regression model. Of the 91 eligible samples, 86 were able to be sequenced, with 72 evaluated in the transgenic mouse assay. Sabin-2 poliovirus reverts rapidly at nucleotide 481, the primary attenuation site in domain V of the 5' untranslated region of the genome. There was no evidence of neurovirulence-increasing polymorphisms in domain V of shed nOPV2. Reversion of shed Sabin-2 virus corresponded with unadjusted paralysis rates of 47·6% at the 4 log10 50% cell culture infectious dose (CCID50) and 76·7% at the 5 log10 CCID50 inoculum levels, with rates of 2·8% for 4 log10 CCID50 and 11·8% for 5 log10 CCID50 observed for shed nOPV2 samples. The estimated adjusted odds ratio at 4·5 log10 of 0·007 (95% CI 0·002-0·023; p<0·0001) indicates significantly reduced odds of mouse paralysis from virus obtained from nOPV2 recipients compared with mOPV2 recipients. The data indicate increased genetic stability of domain V of nOPV2 relative to mOPV2, with significantly lower neurovirulence of shed nOPV2 virus compared with shed mOPV2. While this vaccine is currently being deployed under an emergency use listing, the data on the genetic stability of nOPV2 will support further regulatory and policy decision-making regarding use of nOPV2 in outbreak responses. Bill & Melinda Gates Foundation.


Use of the ProSeal laryngeal mask airway for pressure-controlled ventilation with and without positive end-expiratory pressure in paediatric patients: a randomized, controlled study.
Tracheal intubation and positive end-expiratory pressure (PEEP) are frequently used in children to avoid airway closure and atelectasis during general anaesthesia. Also, the laryngeal mask airway (LMA(dagger)) is frequently used. However, one of the limitations with its use in children is that its low-pressure seal is often inadequate for positive pressure ventilation with PEEP. The ProSeal LMA (PLMA) has been shown to form a more effective seal than the Classic LMA. The ability to apply PEEP with the PLMA might improve gas exchange during positive pressure ventilation in children when the LMA is used. Twenty anaesthetized, non-paralysed children aged 55 (range 27-89) months, weighing 18 (sd 3) kg, were randomly allocated into two groups. Anaesthesia management and positive pressure ventilation were standardized. Size 2 and 2(1/2) PLMA were used. Artificial ventilation in Group I was with pressure controlled ventilation (PCV) and PEEP=5 cm H(2)O, in Group II with PCV without PEEP. A Fi(o(2)) = 1.0 was used for 20 min during induction of anaesthesia. Sixty minutes after induction of anaesthesia an arterial blood gas sample was taken under a Fi(o(2)) = 0.3. Groups were comparable with respect to demographic data. Pa(o(2)) in Group I [22.1 (1.6) kPa] was significantly (P=0.001) higher than in Group II [19.2 (1.7) kPa]. The PLMA can be used for PCV with PEEP in paediatric patients. Application of PEEP improves gas exchange.


Laparoscopic evacuation of a subcapsular renal hematoma causing symptomatic hypertension.
We report the case of a subcapsular hematoma following extracorporeal shockwave lithotripsy which presented as symptomatic hypertension. When medical therapy proved ineffective, laparoscopic decompression of the hematoma corrected the hypertension.


Spread of herpes simplex virus to the cerebrospinal fluid and the meninges in experimental mouse encephalitis.
The development of the inflammatory response within the brain, meninges and cerebrospinal fluid (CSF) compartment has been studied for the first time simultaneously in experimental herpes simplex virus (HSV) encephalitis after inoculation via the cornea. Two major viral pathways were found from the eye to the brain: one through the trigeminal nerve to the brain stem and one through the nasolacrimal duct to the olfactory system. Viral antigen was found to be present in the CNS before there were clinical signs or cellular infiltration of brain tissue. Subsequently, the virus spread to all parts of the trigeminal brain stem complex. This phenomenon was accompanied by severe inflammation of the meninges covering the trigeminal root near its entry into the brain stem. The meninges near the entry of the olfactory fila also contained antigen. However, HSV-1 did not spread along meningeal rami of the trigeminal nerve and, consequently, is--at least in this experimental model--not a route to reach the inferior frontal and temporal lobes. The development of CSF changes followed the histopathological development of meningitis and encephalitis closely. HSV-DNA could be detected in the CSF from day 4 post inoculation (p.i.) and HSV-1-specific immunofluorescence in CSF cells was convincingly present on day 5 p.i.; on the same days (4 and 5 p.i.) inflammatory cells were found in apposition to infected cells in the brain. We postulate that HSV is carried to the CSF by infected leukocytes rather than a direct spread to the CSF by simple extension of the encephalitic process to the meningeal surface.(ABSTRACT TRUNCATED AT 250 WORDS)


[Comparison of refraction with or without cycloplegia using Retinomax® or Plusoptix® devices].
To evaluate the refraction in children measured with Plusoptix® without cycloplegia vs. Retinomax® apparatus with cycloplegia. Measure of refraction with Plusoptix® in children>1year old referred for systematic vision screening, then measurement after cycloplegia with cyclopentolate by the Retinomax® device. Thirty-three children were included, i.e. 66eyes. Mean age was 40.7months (minimum 12; maximum 114). The Spearman correlation coefficient for the spherical equivalent was 0.52 (Plusoptix® vs. Retinomax® comparison; P<0.0001=moderate correlation). The Spearman correlation coefficient was 0.73 for astigmatism (Plusoptix® vs. Retinomax® comparison; P<0.0001=strong correlation). The Plusoptix® sensitivity for measurement of refraction was 57%, 43% and 43% respectively for spherical equivalent, sphere and astigmatism. The correlation of astigmatism values is strong, whereas the correlation of sphere values is moderate. Plusoptix® seems to be unable to measure the exact refraction, because there is too large a dispersion of refraction measurements with Plusoptix®, compared to the exact refraction measured with the Retinomax®. Moreover, the sensitivity of Plusoptix® is low. Cycloplegic refraction remains indispensable in children.


Characterization of C1q, C1s and C-1 Inh synthesized by stimulated human monocytes in vitro.
C1q, C1s and C1 Inh synthesized and secreted by human monocytes were characterized by SDS-PAGE. C1q is formed of three chains A (Mr approximately 35 000), B (Mr approximately 33 000) and C (Mr approximately 25 000) which are associated in two subunits A-B and C-C. It appears identical to C1q purified from plasma. C1s is secreted as a non-activated, monocatenar protein of Mr approximately 87 000 identical to proenzymic C1s from plasma. Secreted C1 Inh (Mr approximately 100 000) has a slightly higher Mr than purified plasmatic C1 Inh. Monensin treatment of the cells favours the intracytoplasmic accumulation of products at various glycosylation stages.


A dual optimization method for the material parameter identification of a biphasic poroviscoelastic hydrogel: Potential application to hypercompliant soft tissues.
A dual-indentation creep and stress relaxation methodology was developed and validated for the material characterization of very soft biological tissue within the framework of the biphasic poroviscoelastic (BPVE) constitutive model. Agarose hydrogel, a generic porous medium with mobile fluid, served as a mechanical tissue analogue for validation of the experimental procedure. Indentation creep and stress relaxation tests with a solid plane-ended cylindrical indenter were performed at identical sites on a gel sample with dimensions large enough with respect to indenter size in order to satisfy an infinite layer assumption. A finite element (FE) formulation coupled to a global optimization algorithm was utilized to simultaneously curve-fit the creep and stress relaxation data and extract the BPVE model parameters for the agarose gel. A numerical analysis with artificial data was conducted to validate the uniqueness of the computational procedure. The BPVE model was able to successfully cross-predict both creep and stress relaxation behavior for each pair of experiments with a single unique set of material parameters. Optimized elastic moduli were consistent with those reported in the literature for agarose gel. With the incorporation of appropriately-sized indenters to satisfy more stringent geometric constraints, this simple yet powerful indentation methodology can provide a straightforward means by which to obtain the BPVE model parameters of biological soft tissues that are difficult to manipulate (such as brain and adipose) while maintaining a realistic in situ loading environment.


Lack of association between ABCC2 gene variants and treatment response in epilepsy.
The aim of this study was to replicate a previously reported association between drug resistance in epilepsy patients and the 24C>T variant of the ABCC2 gene that codes for the drug efflux transporter MRP2. We genotyped 381 Caucasian epileptic patients (337 drug resistant and 44 drug responsive) and 247 healthy controls for the ABCC2 gene -24C>T polymorphism (rs717620) and two other nearby SNPs in linkage disequilibrium (1249G>A and 3972C>T). Genotype, allele and three-SNP-haplotype frequencies were compared between groups. Patients were further stratified into four groups according to their degree of drug resistance (as measured by seizure frequency under medication) to perform regression analysis against genotypes and haplotpyes. We detected no significant differences in the distribution of any of the tested alleles, genotypes or haplotypes between the investigated groups. Neither was there an association between genotypes or haplotypes and degree of drug resistance. This study was adequately powered to detect genotype relative risks of above two. Although adequately powered to detect the previously reported effect size and although our definition of drug resistance, following the International League Against Epilepsy guidelines, was slightly stricter than in the original study, we failed to confirm an association between the 24C>T variant in the ABCC2 gene and drug resistance in epilepsy.


Association between gingival parameters and Oral health-related quality of life in Caribbean adults: a population-based cross-sectional study.
Good oral health has been associated with better quality of life and general health. In the Caribbean, there have been no studies regarding the association between oral health conditions and the quality of life of the population. The main purpose of this study was to investigate the association between gingival parameters and oral health-related quality of life (OHRQoL) in Caribbean adults. A secondary aim of the study was to gain more information on factors that impact OHRQoL in this population. This cross-sectional, epidemiological, population-based study was conducted in community settings. After the participants with missing Oral Health Impact Profile (OHIP) data were excluded, the sample size was 1821 (weighted according to the age and gender distribution in each target population). OHIP-14 standardized questionnaires were used to collect information. In addition, a medical/oral health questionnaire including sociodemographics, general health, dental visits, oral hygiene habits and knowledge, the frequency of dental visits, prosthesis use/hygiene, and smoking was administered. A multivariate model included predictors that showed significant associations in the univariate models. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported; statistical significance was set at 0.05. In the multivariate analysis, current smokers (OR = 2.34, 95% CI: 1.74-3.14 vs. never smokers), those who visited the dentist only when problems arose (OR = 1.65, 95% CI: 1.13-2.40 vs. those visiting once a year), and participants with any chronic disease/condition (OR = 1.38, 95% CI: 1.06-1.78) had higher odds of being in the highest tertile for OHIP score (poorer health). The present multicenter study identified potential modifiable risk factors for poor OHRQoL among adults in three Caribbean cities.


Δ(9)Tetrahydrocannabinol impairs reversal learning but not extra-dimensional shifts in rhesus macaques.
Expansion of medical marijuana use in the US and the recently successful decriminalization of recreational marijuana in two States elevates interest in the specific cognitive effects of Δ(9)tetrahydrocannabinol (Δ(9)THC), the major psychoactive constituent of marijuana. Controlled laboratory studies in nonhuman primates provide mixed evidence for specific effects of Δ(9)THC in learning and memory tasks, with a suggestion that frontal-mediated tasks may be the most sensitive. In this study, adult male rhesus monkeys were trained on tasks which assess reversal learning, extradimensional attentional shift learning and spatial delayed-response. Subjects were challenged with 0.1-0.5mg/kg Δ(9)THC, i.m., in randomized order and evaluated on the behavioral measures. Peak plasma levels of Δ(9)THC were observed 30min after 0.2mg/kg (69±29ng/ml) and 60min after 0.5mg/kg (121±23ng/ml) was administered and behavioral effects on a bimanual motor task persisted for up to 2h after injection. An increase in errors-to-criterion (ETC) associated with reversal learning was further increased by Δ(9)THC in a dose-dependent manner. The increase in ETC associated with extradimensional shifts was not affected by Δ(9)THC. Spatial delayed-response performance was impaired by Δ(9)THC in a retention-interval-dependent manner. Overall the pattern of results suggests a more profound effect of Δ(9)THC on tasks mediated by orbitofrontal (reversal learning) versus dorsolateral (extradimensional shifts) prefrontal mechanisms.


Lumbar translaminar fenestration for insertion of intrathecal baclofen catheter: a novel technique.
Intrathecal baclofen has long been known to be an efficacious treatment of spasticity in children with cerebral palsy. Test bolus administration is often necessary to ensure patients will benefit from this treatment. The introduction of a intrathecal catheter for test bolus administration can prove challenging in a subset of this population, particularly those who have received surgery with postoperative spinal fusion masses. We outline a novel technique of inserting a spinal catheter for test bolus administration in a patient with a postoperative fusion mass whereby a fenestration is created through the lamina using an osteotomy needle.


Site-specific, covalent immobilization of an engineered enterokinase onto magnetic nanoparticles through transglutaminase-catalyzed bioconjugation.
Enterokinase (EK) is one of the most popular enzymes for the in vitro cleavage of fusion proteins due to its high degree of specificity for the amino-acid sequence (Asp)4-Lys. Enzyme reusability is desirable for reducing operating costs and facilitating the industrial application of EK. In this work, we report the controlled, site-specific and covalent cross-linking of an engineered EKLC on amine-modified magnetic nanoparticles (NH2-MNPs) via microbial transglutaminase-catalyzed bioconjugation for the development of the oriented-immobilized enzyme, namely, EKLC@NH2-MNP biocatalyst. Upon the site-specific immobilization, approximately 90% EKLC enzymatic activity was retained, and the biocatalyst exhibited more than 85% of initial enzymatic activity regardless of storage or reusable stability over a month. The EKLC@NH2-MNP biocatalyst was further applied to remove the His tag-(Asp)4-Lys fusion partner from the His tag-(Asp)4-Lys-(GLP-1)3 substrate fusion protein, result suggested the EKLC@NH2-MNP possessed remarkable reusability, without a significant decrease of enzymatic activity over 10 cycles (P > 0.05). Supported by the unique properties of MNPs, the proposed EKLC@NH2-MNP biocatalyst is expected to promote the economical utilization of enterokinase in fusion protein cleavage.


Urethral Foreign Bodies: Clinical Presentation and Management.
To review a single institution's 15-year experience with urethral foreign bodies, including evaluation, clinical findings, and treatment. In total, 27 patients comprising 35 episodes of inserted urethral foreign bodies were reviewed at Cook County Hospital between 2000 and 2015. Retrospective chart review was performed to describe the clinical presentation, rationale for insertion, management, recidivism, and sequelae. Median patient age was 26 (range 12-60). Twenty-six patients (97 %) were male, 1 was female (3%). Items inserted included pieces of plastic forks, spoons, metal screws and aluminum, pieces of cardboard or paper, staples, writing utensils such as pens and pencils, as well as coaxial cable and spray foam sealant. Reported reasons for insertion were self-stimulation, erectile enhancement, and attention seeking. Presenting symptoms included dysuria, gross hematuria, urinary retention, urinary tract infection, and penile discharge. The most common technique for removal was manual extraction with extrinsic pressure (n = 19, 54%). Other methods include endoscopic retrieval (n = 8, 23%), open cystotomy (n = 1, 3%), and voiding to expel the foreign body (n = 7, 20%). Postremoval complications included urinary tract infection (n = 7), sepsis (n = 4), urethral false passage (n = 5), laceration (n = 5), and stricture (n = 1). We present the largest single-institutional series of urethral foreign bodies to date. Urethral foreign body insertion is a relatively rare occurrence and, commonly, is a recurrent behavior. Urethral trauma related to foreign body insertion is associated with significant risk of infection and urethral injury with long-term sequelae.


A short parameter-fitting routine for compartmental models.
We have developed a program of 298 FORTRAN statements which obtains the inter-pool exchange rates and other parameters of a compartmental system, working directly from the time course of tracer activity after a bolus injection. The fitting problem - data and model - is specified by the user in a natural syntactic style. The program calculates least-squares estimates, confidence limits and intercorrelation estimates for the fitted parameters. Its small size and conceptual simplicity make the program a powerful practical tool for analyzing tracer studies.


Multimodal CME for surgeons and pathologists improves colon cancer staging.
Optimal treatment of localized colorectal cancer (CRC) depends on accurate retrieval and assessment of lymph nodes (LN) in the resected specimen. Formal CE, informal opinion leadership and reinforcing strategies aimed at pathologists and surgeons to improve LN assessment were implemented. In the pre-intervention period a median of 8 lymph nodes were assessed in making a designation of Stage II CRC (n = 115). Thirty months later (post-intervention period) the median number of LN reported in Stage II CRC increased to 18 (n = 41), p < 0.001. A durable improvement in staging was realized through a multipronged change initiative aimed at both surgeons and pathologists.


Breakage risk of different sacroiliac screws in unilateral sacral fractures a finite element analysis.
To compare the breakage risk of lengthened sacroiliac screws and ordinary sacroiliac screws to treat unilateral vertical sacral fractures and provide a reference for clinical application. A finite element model of Tile C pelvic ring injury (unilateral type Denis II fracture of the sacrum) was produced. The sacral fractures were fixed with a lengthened sacroiliac screw and ordinary sacroiliac screw in 6 types of models. The maximal von Mises stresses and stress distributions of the two kinds of screws when standing on both feet were measured and compared. The maximal von Mises stress of the lengthened screw was less than that of the ordinary screw. Compared with ordinary screw, the stress distribution in the lengthened screw was more homogeneous. The breakage risk of screws fixed in double segments is lower than that of screws fixed in single segments, the breakage risk of lengthened screws is lower than that of ordinary screws, and the breakage risk of screws fixed in S2 segments is lower than that of screws fixed in S1 segments.


Genetics of antigen processing and presentation.
Immune response to disease requires coordinated expression of an army of molecules. The highly polymorphic MHC class I and class II molecules are key to control of specificity of antigen presentation. Processing of the antigen, to peptides or other moieties, requires other sets of molecules. For classical class I, this includes TAP peptide transporters, proteasome components and Tapasin, genes which are encoded within the MHC. Similarly, HLA-DO and -DM, which influence presentation by HLA class II molecules, are encoded in the MHC region. Analysis of MHC mutants, including point mutations and large deletions, has been central to understanding the roles of these genes. Mouse genetics has also played a major role. Many other genes have been identified including those controlling expression of HLA class I and class II at the transcriptional level. Another genetic approach that has provided insight has been the analysis of microorganisms, including viruses and bacteria that escape immune recognition by blocking these antigen processing and presentation pathways. Here, we provide a brief history of the genetic approaches, both traditional and modern, that have been used in the quest to understand antigen processing and presentation.


DFT study the water-gas shift reaction over Cu/α-MoC surface.
Cu-based catalysts have been widely used for water-gas shift reaction (WGS, CO + H2O → CO2 + H2), and α-MoC support also shows the good performance for the reaction. Therefore, WGS reaction is systematically studied over Cu/α-MoC by using density functional theory (DFT). DFT result shows the strong metal-support interaction between Cu and α-MoC(111) support. As a result, an extensive tensile strain is introduced in the Cu lattice due to α-MoC support, and Cu 3d band center shifts to Fermi level. However, the strong metal-support interaction does not lead to significant polarization of the Cu/α-MoC surface due to the less charge transfer from Mo to Cu. For the WGS reaction, small Cu particles on α-MoC(111) are likely to facilitate the reaction. At the interface of Cu-α-MoC(111), oxygen stabilizes the dissociated *H, which is benefit of H2O scission. Then, the activity increases compared with Cu(111) surface. In general, small Cu particles on α-MoC support also have good activity for WGS reaction compared with Au deposition on α-MoC. Graphical abstract.


Chronic treatment with amitriptyline produces supersensitivity to nicotine.
The authors used a thermoregulation paradigm to evaluate effects of amitriptyline (AMI) on the sensitivity of a nicotinic mechanism involved in the regulation of core temperature in rats. Treatment with this tricyclic was associated with a significant increase in the hypothermic response to nicotine. Supersensitivity persisted for a minimum of 7.5 days following the last dose of AMI, and a significant proportion of animals displayed increased sensitivity after 14.5 days of abstinence. Implications for the mechanism of action of AMI are highlighted.


Spontaneous rupture of a pancreatic acinar cell carcinoma presenting as an acute abdomen.
Pancreatic acinar cell carcinoma is a rare malignant pancreatic neoplasm. To the best of our knowledge, there has been no report on spontaneous rupture of acinar cell carcinoma. A 39-year-old Azari male presented with a history of sudden onset, acute epigastric pain of 12-h duration. Eight hours later the patient's general condition rapidly deteriorated, blood pressure was decreased to 90/70mm/Hg and heart rate was increased to 120beat/min. Emergent abdominal computed tomography scan showed a well-defined hypo-dense, necrotic mass, measured 12cm×12cm that was originating from the uncinate process of pancreas with marked free peritoneal fluid and extensive haziness of retroperitoneal and mesenteric fat compatible with marked bleeding. Emergent abdominal operation was performed and histopathology revealed acinar cell carcinoma of the pancreas. Pancreatic acinar cell carcinoma (ACC) usually presents with abdominal pain, nausea and vomiting. To best of our knowledge, no report has been made of spontaneous rupture of ACC. Pancreatic carcinoma may present as acute abdomen due to rupture of underlying neoplasm.


Vascular differentiation of multipotent spermatogonial stem cells derived from neonatal mouse testis.
We previously reported the successful establishment of embryonic stem cell (ESC)-like multipotent spermatogonial stem cells (mSSCs) from neonatal mouse testis. Here, we examined the ability of mSSCs to differentiate into vascular endothelial cells and smooth muscle cells, and compared to that of mouse ESCs. We used real-time reverse transcriptase polymerase chain reaction and immunohistochemistry to examine gene expression profiles of mSSCs and ESCs during in vitro vascular differentiation. Both mSSCs and ESCs exhibited substantial increase in the expression of mesodermal markers, such as Brachyury, Flk1, Mesp1, Nkx2.5, and Islet1, and a decrease in the expression of pluripotency markers, such as Oct3/4 and Nanog during the early stage of differentiation. The mRNA levels of vascular endothelial (VE)-cadherin and CD31 gradually increased in both differentiated mSSCs and ESCs. VE-cadherin- or CD31-positive cells formed sprouting branch-like structures, as observed during embryonic vascular development. At the same time, vascular smooth muscle cell-specific markers, such as myocardin and α-smooth muscle actin (SMA), were also highly expressed in differentiated mSSCs and ESCs. Immunocytochemical analysis revealed that the differentiated cells expressed both α-SMA and SM22-α proteins, and exhibited the intracellular fibril structure typical of smooth muscle cells. Overall, our findings showed that mSSCs have similar vascular differentiation abilities to those of ESCs, suggesting that mSSCs may be an alternative source of autologous pluripotent stem cells for vascular regeneration.