From a synthetic, microporous, compliant, biodegradable small-caliber vascular graft to a new artery.
Microporous, compliant, biodegradable vascular grafts prepared from physical mixtures of polyurethane and poly(L)lactide acid can function as temporary scaffolds for the regeneration of a new arterial wall. In this overview article, the basic ideas behind the properties and construction of these grafts, the basic mechanisms of regeneration, and the scope, limitations, and further prospectives of the use of these biodegradable grafts are reviewed and discussed among literature.


Influence of drought stress and mycorrhizal (Funneliformis mosseae) symbiosis on growth parameters, chlorophyll fluorescence, antioxidant activity, and essential oil composition of summer savory (Satureja hortensis L.) plants.
Drought stress unfavorably influences the growth and physiological traits of plants in the arid and semi-arid regions of the world. This study aimed to determine the effects of arbuscular mycorrhiza fungi (AMF; Funneliformis mosseae) inoculation on the physiological and biochemical responses of summer savory (Satureja hortensis L.) under different irrigation regimes. The first factor was different irrigation regimes, including no drought stress (100% field capacity; FC), moderate drought stress (60% FC), and severe drought stress (30% FC); the second factor included the plants without AMF (AMF0) and with AMF inoculation (AMF1). The results showed that better values, higher plant height, shoot mass (fresh and dry weight), relative water content (RWC), membrane stability index (MSI), photosynthesis pigments, Fv, Fm, Fv/Fm, and total soluble proteins were obtained in the plants inoculated with AMF. The highest values were obtained for plants with no drought stress, then the plants subjected to AMF1 under 60% FC, and the lowest ones for plants under 30% FC without AMF inoculation. Thus, these properties are reduced under moderate and severe drought stress. At the same time, the utmost activity of superoxide dismutase (SOD), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), and the highest malondialdehyde (MDA), H2O2, proline, and antioxidant activity (TAA) were achieved for 30% FC + AMF0. It was also found that AMF inoculation improved essential oil (EO) composition, also as EO obtained from plants under drought stress. Carvacrol (50.84-60.03%) was the dominant component in EO; γ-terpinene (19.03-27.33%), p-cymene, α-terpinene, and myrcene, were recognized as other important components in EO. The higher carvacrol and γ-terpinene contents were obtained from summer savory plants with AMF inoculation and the lowest for plants without AMF and under 30% FC. According to the present findings, using AMF inoculation could be a sustainable and eco-friendly approach to improve physiological and biochemical characteristics and the essential oil quality of summer savory plants under water shortage conditions.


Effects of stress on drug-induced yawning: constant vs. intermittent stress.
Effects of stress on drug-induced yawning: Constant vs. intermittent stress. PHYSIOL BEHAV 58(1) 181-184, 1995.--Experiment 1 tested whether chronic exposure to immobilization, foot shock or forced swimming would result in suppression of apomorphine-, pilocarpine-, and physostigmine-induced yawning. Immobilization caused suppression of yawning, whereas foot shock and swimming resulted in increased number of yawns. Since interstressor interval was long in the two latter stressors, animals could have recovered and the increase in yawning could be due to the last (acute) exposure to stress. In Experiment 2 we recorded the number of yawns induced by pilocarpine in animals exposed to 1 h of swimming or foot shock. No differences between control and acutely stressed animals were detected. These results suggest that yawning is differently altered by constant and intermittent stressors (i.e., diminished by constant and increased by intermittent stress).


Tremella polysaccharides-coated zein nanoparticles for enhancing stability and bioaccessibility of curcumin.
The purpose of the present research was to examine the ability of Tremella polysaccharide (TP) to stabilize zein nanoparticles (zein NPs) and appraise the performance of zein/Tremella polysaccharide nanoparticles (zein/TP NPs) in terms of encapsulating and delivering curcumin. In this study, the zein/TP NPs were fabricated based on the anti-solvent precipitation method, which were used to protect and deliver curcumin. The results suggested that TP could be deposited on the surface of zein NPs by virtue of electrostatic interaction, so as to improve the hydrophilicity of zein, provide better protection for curcumin and assemble more stable nanoparticles. Compared with zein NPs (54.73%), the zein/TP NPs exhibited higher encapsulation efficiency of curcumin (93.34%) and excellent re-dispersibility. Furthermore, the retention rate of curcumin encapsulated in zein/TP NPs reached 80.78% and 90.74% after UV irradiation and 80 °C heat treatment for 2 h, respectively, which proved that the addition of TP significantly improved the stability of curcumin. Meanwhile, in vitro digestion study demonstrated that the bioaccessibility of curcumin encapsulated in zein/TP NPs increased by 37.36% compared with in zein NPs. Therefore, the zein/TP NPs may be served as an effective and potential carrier for the delivery of nutraceuticals.


Terpolymers from Borane-Initiated Copolymerization of Triphenyl Arsonium and Sulfoxonium Ylides: An Unexpected Light Emission.
The first synthesis of well-defined poly[(phenylmethylene-co-methylpropenylene)-b-methylene, [(C1-co-C3)-b-C1], terpolymers was achieved by one-pot borane-initiated random copolymerization of ω-methylallyl (C3 units, chain is growing by three carbon atoms at a time) and benzyltriphenylarsonium (C1 units, chain is growing by one carbon atom at a time) ylides, followed by polymerization of sulfoxonium methylide (C1 units). Other substituted arsonium ylides, such as prenyltriphenyl, propyltriphenyl and (4-fluorobenzyl)triphenyl can also be used instead of benzyltriphenylarsonium. The obtained terpolymers are well-defined, possess a predictable molecular weight and low polydispersity (Mn,NMR =1.83-9.68×103 g mol-1 , Đ=1.09-1.22). An unexpected light emission phenomenon was discovered in these non-conjugated terpolymers, as confirmed by fluorescence and NMR spectroscopy. This phenomenon can be explained by the isomerization of the double bonds of allylic monomeric units along the chain of the terpolymers (isomerization-induced light emission).


Provision of critical care services for the obstetric population.
Management of the peripartum patient is a challenging aspect of critical care that requires consideration of both the physiological changes associated with pregnancy as well as the well-being of the foetus. In the UK, for every maternal death, approximately 118 near-miss events or severe acute maternal morbidities (SAMMs) occur. While a dedicated anaesthetic cover is usually provided on larger labour wards in the UK and US, a close communication with intensive care and other medical specialties must still be maintained. Medical outreach teams and early warning scores may help facilitate the early identification of clinical deterioration and prompt treatment. Ultimately level of care is allocated according to the clinical need, not the location, which may be a designated room, a normal labour room or a recovery area. Specialist obstetric units that provide high-dependency care facilities show lower rates of maternal transfer to critical care units and improved continuity of care before and after labour. The benefits of obstetric high-dependency units (HDUs) are likely to be determined by a number of logistic aspects of the hospital organisation, including hospital size and available resources. There remains a striking contrast in the burden of maternal mortality and morbidity and intensive care unit (ICU) resources between high- and low-income countries. The countries with the highest maternal mortality rates have the lowest number of ICU beds per capita. In under-resourced countries, patients admitted to ICUs tend to have higher illness severity scores, suggesting delayed admission to the ICU. The appropriate training of midwives is essential for successful HDUs located within labour wards.


EMG-based detection of muscle fatigue during low-level isometric contraction: effects of electrode configuration and blood flow restriction.
This study assessed muscle fatigue during low-level contraction, which is sometimes difficult to observe. Surface EMG signals were recorded with monopolar and bipolar configurations during low-level isometric muscle contraction under a blood flow restriction condition (BFR condition) and a non-blood flow restriction condition (CON condition). As indices of fatigue, center frequency (CF) of the power spectral density (PSD) of the surface EMG and rating of perceived exertion (RPE) with the Borg CR-10 Scale were used. Results suggested that the monopolar configuration, which has a wider detection area relative than the bipolar one, was well suited for obtaining wave slowing accompanied by muscle fatigue. In addition, the monopolar configuration could detect differences in muscle condition in the BFR and CON conditions.


Identifying the Co-Curing Effect of an Accelerated-Sulfur/Bismaleimide Combination on Natural Rubber/Halogenated Rubber Blends Using a Rubber Process Analyzer.
The rheometer curing curves of 50/50 blends of natural rubber (NR) and two different halogenated rubbers with a combination of conventional accelerated sulfur (CV) and 3 phr of a bismaleimide (MF3) at 170 °C indicates that a co-curing reaction has been taken place between NR and the halogenated rubbers via Diels-Alder reaction. To further confirm whether the co-curing reaction has taken place in the early stage of curing, a complex test methodology was applied with the help of a rubber process analyzer. In this test, the blends with CV and with CVMF3 were subjected to cure at 170 °C for a predetermined time so that both the CV and CVMF3 cured blends will have the same magnitude of curing torque. It is then cooled down to 40 °C and the storage modulus (G') was evaluated as a function of strain from 0.5% to 100% at a constant frequency of 1 Hz. The results reveal that the blends cured with CVMF3 exhibit a higher G' due to the enhanced network strength because of the formation of bismaleimide crosslinks than the same cured with only the CV system. The swelling resistance and the mechanical properties of the blends cured with CVMF3 were significantly higher than those cured with only the CV system.


Clinical variety and prognosis of intracranial arachnoid cysts in children.
Arachnoid cysts (AC) occur in different intracranial locations. Management and prognosis depend on the clinical presentation and treatment guidelines do not exist. With this study, we want to demonstrate the clinical variety of arachnoid cysts in children and place a focus on outcome factors in operated cases. This retrospective study of a consecutive single unit series of children, who underwent AC surgery between January 2010 and September 2019, provides demographic, clinical, imaging data, and information about surgical treatment and outcome. Overall, 63 patients (71.4 male) underwent surgery. Mean age was 50 months (0-191). Mean follow-up was 40 months (0-121). Eighty-one percent of patients presented with symptoms/signs of raised ICP. Focal neurological deficits were present in 15.9%, headache in 11.1% of children. Galassi cysts represented the predominant type (30.2%), followed by suprasellar (14.3%), quadrigeminal (12.7%), retrocerebellar, CPA and midline (each 11.1%), and hemispheric cysts (7.9%). Endoscopic and microsurgical fenestrations were performed in 27% and 58.7%, stent or shunt insertion in 6.3%/57.9% of the cases. In 33.3% of the cases one and in 12.7%, a second reintervention became necessary. Reoperation rate was significantly higher in children < 1 year (p = 0.003). Cyst volume decreased in 85.7%. Seventy percent of the patients were symptom free, 5% suffered from headache, and 22% from developmental disorders. All focal neurological symptoms resolved. Complication rate and outcome are depending on age and cyst location. Recurrence and revision rates are significantly higher in young infants (p = 0.003). Midline cysts with CCA are associated with developmental disorders.


Monte Carlo simulation of gamma-ray spectra from natural radionuclides recorded by a NaI detector in the marine environment.
The GEANT4 Monte Carlo code has been used to simulate gamma-ray spectra of natural radionuclides collected by a NaI scintillation detector immersed in seawater. The gamma-rays emitted from the decay of (40)K, and the series of (232)Th and (238)U, were used to describe the radioactive water source around the NaI crystal. The simulated gamma-ray spectra were compared with real data recorded in situ by a newly constructed NaI spectrometer and were found to be in good agreement. The NaI spectrometer was calibrated in the laboratory in a water tank, before its deployment in seawater. Activity concentrations were deduced from the gamma-ray spectra and discussed in comparison with results from the literature.


Selected pyrethroid insecticides stimulate glutamate uptake in brain synaptic vesicles.
We aimed to ascertain whether pyrethroid insecticides could influence the vesicular transport of the excitatory amino acid glutamate. The incubation of rat cortical synaptic vesicles with resmethrin and permethrin, consistently stimulated both ATP-dependent and -independent uptake of [3H]glutamate, while not evoking depletion of its vesicular content. Both processes were counteracted by valinomycin, a dissipator of the transmembrane potential gradient (deltapsi(sv)). Meanwhile, the vesicular influx of 36Cl- anions was impaired by pyrethroid concentrations which did not affect the ATP-dependent uptake of [14C]methylamine, as a marker for the proton gradient (deltapH). Thus, the stimulation of glutamate transport appeared to involve mainly the deltapsi(sv). A self-attenuating effect of selected pyrethroids on putatively enhanced excitatory transmission in severe intoxication is suggested.


Modification of dopamine and norepinephrine metabolism in the rat brain by monoamine oxidase inhibitors.
The treatment of Sprague-Dawley rats with monoamine oxidase (MAO) inhibitors (pargyline, tranylcypromine) profoundly affects dopamine (DA) and norepinephrine (NE) metabolism in the brain. In these rats injection of L-dopa led to large increases in norepinephrine (NE), normetanephrine (NMN) and 3-methoxytyramine (3-MT) in brain tissues. The response of MAO-inhibited rats to L-dopa contrasted sharply with those not treated with the MAO inhibitor; the latter showed no change in NE, NMN and 3-MT after similar administration of L-dopa. The increase of NE in pargyline-treated rats correlated closely with that of DA in the hypothalamus and in the brain stem. This response was greatly diminished in rats previously treated with the neurotoxin 6-hydroxydopamine, but was restored when the treatment with 6-hydroxydopamine was accompanied by desimipramine. This suggests that noradrenergic neurons were the origin of the NE response. The NMN and 3-MT increases occurring only in the rats treated with a MAO inhibitor were highly correlated. The results suggested that MAO inhibitor may affect entry of DA into catecholaminergic storage where NE synthesis takes place and from where DA is released.


Rheumatoid-like joint lesions in rabbits injected intravenously with bovine serum.
Rheumatoid-like synovial lesions have been produced experimentally in 21% of rabbits receiving intravenous injections of bovine serum by various regimens. They were characterized by lining cell hyperplasia, accumulations, often follicular, of lymphocytes and plasma cells just under the lining layer, sometimes with extensive fibroplasia and pannus formation with cartilage erosion.


Sex Differences in Immunometabolism: An Unexplored Area.
The last three decades have seen a growing interest in research in the field of immunometabolism, likely because of promising discoveries made in this field. This includes demonstration of the crucial roles of cellular metabolism in the regulation of functional plasticity of various immune cells, their cross talk with major metabolic tissues (and consequently in the regulation of metabolic homeostasis) at the systemic level, and their potential in improving the efficacy of current immunotherapy or developing new therapeutics for a variety of metabolic and immune diseases (Lee YS, Wollam J, Olefsky JM, Cell 172:22-40, 2018). Surprisingly, sex differences, which are integral to metabolic and immune health and disease, have received a short shrift from researchers in this field. The purpose of this chapter in this protocols book in the Immunometabolism: Methods in Molecular Biology series is to bring attention to this understudied, but crucial, feature of immunometabolism within the scientific community. Sex differences in adipose (and by extension, metabolic) and immune functions are pervasive in metabolic and immune health and disease; it is likely that a better insight into them may open new research directions to better capitalize on the promising discoveries made in this field, and thereby contribute to the development of sex-based precision medicine. It is counterintuitive to ignore a fundamental aspect of immunometabolism, and thereby limit our ability to capitalize on its promising features in improving or maintaining health, and for the therapeutic targeting of associated diseases. Here we briefly discuss the potential drivers and touch upon some unanswered questions in sex differences in immunometabolism, especially those that require attention from the scientific community.


Anatomical correlates of rhythmical slow wave activity (theta) in the hippocampal formation of the cat.
The topography of spontaneous and hypothalamically induced hippocampal rhythmical slow wave activity (theta) was studied acutely in cats anesthetized with urethane. Tracking and depth profile analysis using microelectrodes showed two amplitude maxima of theta activity approximately 180 degrees out of phase separated by a null zone. One amplitude peak was located in stratum oriens of CA1 (maximum amplitude 1.2 mV) and the other peak in stratum moleculare of the fascia dentata (maximum amplitude 1.9 mV). The null zone was localized to stratum radiatum, just ventral to the CA1 pyramidal cells. The two 'generator' hypothesis of theta activity was discussed in relation to similar findings for other species. Pharmacological results were interpreted as supporting the view that there is an ascending cholinergic input mediating theta in the urethanized cat.


A rat yolk-sac antigen defined by monoclonal antibodies.
The distribution of a rat yolk-sac antigen (Rat YSA-I) as defined by a monoclonal antibody raised against rat yolk-sac carcinoma cells is described. The antigen is present on rat yolk-sac carcinomas, on visceral yolk-sac endoderm and on embryonal endoderm of 9-day-old embryos. It is not present on a variety of rat tumors other than yolk-sac carcinomas and not detectable on pre-implantation embryos, inner cell mass and fetal endoderm. Rat YSA-I differs from alpha-fetoprotein and Forssman antigen and is species-specific. In adult rats the only cells displaying this antigen are the spermatozoa and certain cells of the spermatogenic lineage.


Relapse following emergency treatment for acute asthma: can it be predicted or prevented?
We prospectively followed 314 children discharged from a children's hospital emergency department (ED) following an asthma attack, to identify risk, factors for relapse, i.e. a second ED visit for asthma within the next 10 days. Parents were surveyed concerning their child's past medical history, drugs received prior to the index visit, triggering factors, physician availability, parental anxiety, and sociodemographic variables. Data on severity of the attack, emergency treatment, response to treatment and drugs prescribed on discharge were extracted from the medical record. Ninety-six of the 314 children (31%) relapsed, most (68%) within 24 hours. Using multiple logistic regression, a predictive model was developed on 211 patients ("test sample"). The best model contained two variables: (1) the number of ED visits for acute asthma in the previous year (odds ratio [OR] = 2.4 for 4 or more vs fewer visits, 95% CI = 1.3-4.4) and (2) the intake of an oral short-acting theophylline preparation during the course of the acute treatment (OR = 0.4, 95% CI = 0.2-0.7). The sensitivity, specificity and positive predictive values of this model for predicting relapse were 73, 53, and 40%, respectively. When applied to a second randomly selected "validation sample" of 103 children, sensitivity was 73%, specificity 50%, and PPV 41%, thus indicating the stability of the model. The model identifies the number of ED visits in the previous year as an important risk factor for relapse. It also suggests that oral short-acting theophylline may still have a role in the treatment of patients in whom the contribution of inflammation to airway obstruction is minimal.


Transcription of 5S RNA by RNA polymerase III from genomic bovine DNA templates.
RNA polymerase III in an extract of HeLa cells transcribes RNA 5S in size from genomic bovine DNA template. This RNA represents a major fraction of the RNA synthesized. 5S RNA is not transcribed from bovine chromatin at equivalent concentrations and RNA the size of tRNA or tRNA precursor is not detected. At low UTP concentrations RNA slightly smaller in size than 5S is synthesized in addition to 5S RNA.


Pseudosyndactyly - an inflammatory and fibrotic wound healing disorder in recessive dystrophic epidermolysis bullosa.
A genetic blistering skin disease, recessive dystrophic epidermolysis bullosa (RDEB), is marked by severe wound healing defects and finger contractures. The purpose of this investigation was to elucidate the mechanisms of impaired wound healing and pseudosyndactyly occurring in RDEB patients by studying the role of known inflammation and fibrosis markers in RDEB pseudosyndactyly tissue. We studied the expression of the fibrosis and/or inflammation markers tenascin-C, α-smooth muscle actin, transforming growth factor-β1, interleukin-1β, and interleukin-6 in scarring and nonscarring tissue from healthy donors and RDEB patients by semiquantitative real time-PCR and, where applicable, by immunoblots. Furthermore, the distribution pattern of α-smooth muscle actin and tenascin-C were assessed by immunofluorescence microscopy. Based on mRNA and protein analysis, we found upregulation of tenascin-C, interleukin-1β, and interleukin-6 - but not of transforming growth factor-β1 - in recessive dystrophic epidermolysis bullosa scar samples taken from pseudosyndactyly hands. Unexpectedly, α-smooth muscle actin was not upregulated. Our results confirm inflammation and fibrosis in recessive dystrophic epidermolysis bullosa, especially in scars, suggesting major roles for these processes in pseudosyndactyly. Our data therefore suggests the potential use of antiinflammatory and antifibrotic drugs in the prevention of pseudosyndactyly.


Brief report: The impact of the COVID-19 pandemic on health behaviors in adolescents with Autism Spectrum Disorder.
There is concern that the COVID-19 pandemic may negatively affect health behaviors in youth, especially youth diagnosed with Autism Spectrum Disorder (ASD). The purpose of this paper was to examine changes in physical activity, screen-time, and sleep in adolescents with ASD due to the COVID-19 pandemic. Nine adolescents with ASD completed surveys measuring physical activity, screen-time, and sleep duration prior to and during the pandemic. A significant decrease in days of physical activity (4.17 vs 2.27; p = 0.0006), and a significant increase in hours of both weekday (3.69 vs 6.25; p = 0.007) and weekend screen-time (5.94 vs. 7.39; p = 0.004) was observed during the pandemic. No changes regarding sleep duration was observed. Although preliminary, results suggest that physical activity and screen-time may be negatively affected by the COVID-19 outbreak in youth with ASD. The development of interventions to promote health behaviors in ASD populations during long periods of less-structured time (quarantine) should be considered.


An acromegaly case treated with clomiphene citrate: add-on treatment in primary medical therapy.
Acromegaly is a disease with various comorbidities and hypogonadism is a common comorbidity in patients with acromegaly. Herein, we aim to present our experience with clomiphene citrate in a patient with acromegaly accompanied by hypogonadism, who declined surgery. A 40-year-old male patient with impaired fasting glucose, hyperlipidemia, and psychosis and who complained of increasing tongue growth, snoring, enlargement of the hands, spacing between the teeth, and loss of libido for the last 6 years was followed up. Acromegaly was diagnosed, with high levels of insulin-like growth factor-1 (IGF-1) and a pituitary neuroendocrine tumor measuring 11 mm; the patient had concomitant hypogonadism. Lanreotide was started as the initial primary medical treatment. Clomiphene citrate was added to the patient's treatment. The patient, whose IGF-1 level was high during follow-up, did not want to use the intramuscular testosterone esters for hypogonadism. In the third month of clomiphene citrate treatment, IGF-1 normalization was achieved and the patient's total testosterone level increased. Biochemical control is not always achieved with somatostatin receptor ligands and dopamine agonists in the treatment of acromegaly. Therefore, we support the use of clomiphene citrate (CC) as a cost-effective oral add-on treatment option in selected hypogonadal acromegaly cases.


How amenable is type 2 diabetes treatment for precision diabetology? A meta-regression of glycaemic control data from 174 randomised trials.
There are two prerequisites for the precision medicine approach to be beneficial for treated individuals. First, there must be treatment heterogeneity; second, in the case of treatment heterogeneity, we need to detect clinical predictors to identify people who would benefit from one treatment more than from others. There is an established meta-regression approach to assess these two prerequisites that relies on measuring the variability of a clinical outcome after treatment in placebo-controlled randomised trials. Our aim was to apply this approach to the treatment of type 2 diabetes. We performed a meta-regression analysis using information from 174 placebo-controlled randomised trials with 178 placebo and 272 verum (i.e. active treatment) arms including 86,940 participants with respect to the variability of glycaemic control as assessed by HbA1c after treatment and its potential predictors. The adjusted difference in log(SD) values between the verum and placebo arms was 0.037 (95% CI: 0.004, 0.069). That is, we found a small increase in the variability of HbA1c values after treatment in the verum arms. In addition, one potentially relevant predictor for explaining this increase, drug class, was observed, and GLP-1 receptor agonists yielded the largest differences in log(SD) values. The potential of the precision medicine approach in the treatment of type 2 diabetes is modest at best, at least with regard to an improvement in glycaemic control. Our finding of a larger variability after treatment with GLP-1 receptor agonists in individuals with poor glycaemic control should be replicated and/or validated with other clinical outcomes and with different study designs. The research reported here received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Two datasets (one for the log[SD] and one for the baseline-corrected log[SD]) to reproduce the analyses from this paper are available on https://zenodo.org/record/7956635 .


Establishing comprehensive oral assessments for children with safeguarding concerns.
The dental profession is well placed to contribute important information in child protection cases but no previous research has been reported that assesses the volume or impact of this information. Comprehensive oral assessment clinics were introduced and established as an integral part of comprehensive medical assessments for children with welfare concerns in Greater Glasgow and Clyde. An assessment protocol and standardised paperwork for comprehensive oral assessments were developed to enhance information sharing and patient access to appropriate care. Two cases are presented and discussed to demonstrate the value of dental input.


Characteristics of carbonaceous aerosols derived from long-term high-resolution measurements at a high-altitude site in the central Himalayas: radiative forcing estimates and role of meteorology and biomass burning.
Simultaneous observations (2014-2017) of organic carbon (OC) and elemental carbon (EC) are made over a high-altitude site (Nainital, 29.4°N, 79.5°E, 1958 m a.m.s.l) in the central Himalayas, and the role of long-range transport, meteorology and biomass burning is studied. There are only a few online and simultaneous observations of OC and EC over South Asia and none in the high-altitude Himalayan region. This work presents the first diurnal variations with a unimodal pattern in both OC and EC at the Himalayan site. Such a diurnal pattern is in contrast with the bimodal pattern observed at any continental polluted site. Clear seasonal variations in OC and EC were seen with a primary maximum during spring and a secondary maximum in autumn/winter. OC and EC concentrations are observed to be as high as 65.8 μg/m3 and 12 μg/m3, in May, respectively. Concentration weighted trajectory (CWT)-assisted analysis shows that the biomass burning in northern India is one of the major sources for the springtime maximum even at this high-altitude site. The coinciding rise in OC/EC ratio from 4.6 to 7.9, along with fire events, further convinces that the enhancement in the concentrations is due to the biomass burning at distant regions and long-range transport of air masses influencing this high-altitude site. A poor covariation between OC-EC and the boundary-layer height during autumn and winter suggests that secondary maxima in OC and EC are most likely due to local sources, e.g. household burning for heating during this cold period when the temperature drops sharply after October and remains low until February. The higher temporal resolution of online measurements reveals that swiftly varying meteorological parameters change the OC-EC concentrations at diurnal scales. Back-air trajectory-assisted analysis of residence time and its relationship with OC and EC confirms the increase in their concentration in slow-moving air masses. The observed diurnal variations of EC are utilized to estimate the radiative forcing and shown that the atmospheric radiative forcing during the afternoon is about 70% higher than the forenoon one. It is envisaged that this dataset with diurnal observations of OC and EC would be an important input for studying the radiation budget and source apportionment over this high-altitude region.


Accuracy of plasma turbidity measurement for determining fat intolerance during total parenteral nutrition.
The accuracy of plasma turbidity measurements in predicting ability to metabolise intravenous fat emulsions during total parenteral nutrition was studied in 35 adult surgical patients. Plasma turbidity, expressed as a light scattering index (LSI), was determined by nephelometry and compared with measured triglyceride (TG) concentrations. A poor coefficient of correlation was found between LSI and TG (r = 0.52). The sensitivity and specificity of LSI in predicting TG concentration were 19% and 96% respectively. This indicates that the measurement of LSI is more useful in ruling out hypertriglyceridaemia than in detecting it. Consequently, clinical tolerance of intravenous fat emulsion cannot be monitored by measuring plasma turbidity. In order to avoid metabolic complications which may occasionally occur during intravenous nutritional therapy including fat emulsion, determination of plasma TG levels at timed intervals are recommended.


Time spent in the emergency department and mortality rates in severely injured patients admitted to the intensive care unit: An observational study.
The aim of this study was to identify the determinants of a shorter emergency department time (EDt) in patients with severe trauma (STPs) admitted to the intensive care unit and determine whether EDt influences mortality. A prospective observational study of STPs (2005-2007) was conducted. With the variables available from the ED, 2 multiple logistic regression models (MLRM) were created: one for the factors associated with EDt less than or equal to median and the other with mortality. A total of 243 patients were included. The mean age was 43 years; 76% were male. The overall mortality rate was 20%. The median EDt was 120 minutes. The independent factors that were associated with the MLRM for an EDt of 120 minutes or less included age less than 60 years, mechanical ventilation, severe traumatic brain injury, and a trauma and injury severity score of 20 or higher. The MLRM for mortality was age greater than 60 years, mechanical ventilation, traumatic brain injury and shock. An EDt of 120 minutes or less was associated with an increased risk of death in the univariate analysis but not in the MLRM. Patients in the ED with indicators of high trauma severity have a reduced EDt but a higher mortality rate. Advanced age increases both mortality and EDt. With the factors included in the model, EDt was not an independent factor for mortality in STPs.


True-FISP MRI in diagnosis of postoperative hernia recurrence: a brief report.
A 24-year-old man underwent laparoscopic mesh repair of a right direct inguinal hernia which had recurred after previous surgery 3 months previously. A large swelling was noted in the right groin 4 h postoperatively, which was reduced initially but recurred within 24 h. A differential diagnosis of postoperative recurrence versus hematoma was considered, and patient was referred for imaging. The patient was imaged using different modalities including B-mode ultrasonography, computed tomography (CT) of the pelvis, and True-FISP magnetic resonance imaging (true imaging with steady-state precession MRI). Initial focused ultrasound (US) [corrected] was suggestive of but equivocal for recurrence. Subsequent non-contrast CT of the region followed by rapid sequence (true-FISP) MRI confirmed the presence of bowel in the inguinal canal. Imaging has a role in the diagnosis of postoperative hernia recurrence in cases where there is a clinical diagnostic dilemma, especially MRI using true-FISP sequence, which is acquired in seconds, is a non-ionising radiation modality and does not have inter operator variability.


[Clinical trial of a combination of human lymphoblastoid interferon (HLBI), melphalan and prednisolone (HLBI-MP) in multiple myeloma].
Six patients with multiple myeloma were treated with HLBI-MP regimen; HLBI 300 X 10(4)U/day daily, Melphalan 4 mg/day p.o. from day 1 to 4 and prednisolone 20 mg/day p.o. from day 1 to 4. Two patients had been refractory to a combination chemotherapy consisting of vincristine, cyclophosphamide, prednisolone and/or adriamycin, while the other 4 patients had been previously untreated. With the HLBI-MP regimen, 3 of 6 patients showed clinical effects. Among the two patients previously treated, one showed an improvement in performance status and the other disappearance of plasmacytoma, respectively. One previously untreated patient showed more than 50% reduction of M-protein. Slight to moderate leukocytopenia was found in all cases, but this was controlled without need for cessation of HLBI. HLBI-MP regimen is thus expected to be useful in the clinical management of patients with multiple myeloma.


Microsphere-based suspension array for simultaneous recognition and quantification of multiple cancer-associated miRNA via DNAzyme-Mediated signal amplification.
Herein, a novel suspension array of polystyrene (PS) beads for simultaneous recognition and quantification of multiple cancer-associated microRNAs (miRNAs) using flow cytometry has been reported. The suspension array contained three moieties, streptavidin-modified PS beads, biotin-labeled substrate strands (17S) of the 17-8 DNAzyme and two split DNAzyme parts (PA, PB). 17S was labeled with 6-carboxyfluorescein (FAM) and Dabcyl on both sides of the ribonucleic acid. Once the target miRNAs appear, they can bind with the corresponding PA and PB to form an active secondary structure of DNAzyme. The active DNAzyme can cleave 17S and remove Dabcyl from the bead's surface, thus recovering the FAM's fluorescence intensity. Furthermore, the released target miRNA can autonomously move to the neighboring inactive DNAzyme for further cleavage, thus amplifying the fluorescence signal. Therefore, the target miRNAs can be quantified by reading the fluorescence intensity output from flow cytometry. The PS beads-based suspension array for the target miRNA in buffer shows good selectivity and high sensitivity. Via binding with a different pair of PA and PB, this suspension sensor array has successfully typed and quantified cancer-associated miRNAs of miR-21, miR-155, miR-335, and miR-122 in buffer and serum conditions.


Intravitreal Bevacizumab and Cardiovascular Risk in Patients with Age-Related Macular Degeneration: Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Studies.
Intravitreal bevacizumab (IVTB) is used to treat age-related macular degeneration (ARMD), although its use is off-label and its cardiovascular safety has not been unequivocally established. Our objective was to assess the cardiovascular safety of IVTB in patients with ARMD. We conducted a systematic review and meta-analysis of published randomized controlled trials (RCTs) and observational studies. Of the 2028 non-duplicate records, five RCTs versus ranibizumab (N = 3038, 12/24 months), four RCTs comparing different regimens (N = 809, 12/23 months), one RCT versus pegaptanib, photodynamic therapy (PDT), or sham (N = 131, 12 months), and three observational studies versus PDT, ranibizumab, or pegaptanib (~150,000 or 1666 patients/12 months and 317 patients/1-2 years, respectively) had a low risk of bias/high quality and ≥20 patients per arm with ≥6 months and ≥3 injections of treatment. RCT-based comparisons with PDT or pegaptanib are negligible. Observational data have not demonstrated differences [all-cause mortality, myocardial infarction (MI), stroke], but the level of evidence is "very low" (imprecise, indirect). RCT-based comparisons with ranibizumab did not demonstrate differences regarding some outcomes, although certain point estimates were at the level of a relevant harm/benefit [all-cause mortality odds ratio (OR) 1.103, 95 % confidence interval (CI) 0.641-1.898; vascular mortality OR 1.380, 95 % CI 0.476-3.997; MI OR 0.551, 95 % CI 0.265-1.146; stroke OR 0.657, 95 % CI 0.260-1.660; transitory ischemic attack OR 1.536, 95 % CI 0.444-5.313; atherothrombotic events (ATEs) OR 1.007, 95 % CI 0.641-1.593; venous thromboembolism OR 2.325, 95 % CI 0.963-5.612] or suggested a higher risk with bevacizumab (hypertension OR 7.512, 95 % CI 1.056-52.3), but estimates were based on sparse data, were extremely imprecise, and commonly exhibited considerable heterogeneity/inconsistency. The level of evidence per outcome was "low" or "very low". Observational data did not demonstrate difference (all-cause mortality, MI, stroke), or suggested a higher risk with bevacizumab (ATE), but were imprecise and indirect (level of evidence "very low"). RCT-based comparisons of different IVTB regimens suffered from the same limitations. Published data on IVTB in AMRD provide only a low level of evidence on its cardiovascular safety and do not support any finite conclusions.


Effect of surgical face mask wearing on tear film in women with a high body mass index.
Due to the COVID-19 pandemic, wearing a face mask has become an essential measure to reduce the rate of virus spreading. The aim of the study was to assess the effect of wearing a surgical face mask for a short period on the tear film parameters in subjects with a high body mass index (BMI). Twenty-five females with a high BMI (31.4 ± 5.5 kg/m2) aged 18-35 years (22.7 ± 4.6 years) participated in the study. In addition, a control group consisting of 25 females (23.0 ± 6.7 years) with a high BMI (29.9 ± 4.1 kg/m2) participated in the study in which no mask was worn. The standardized patient evaluation of eye dryness (SPEED) questionnaire was completed first, followed by the phenol red thread (PRT) and tear ferning (TF) tests, before wearing the face mask. The subjects wore the face mask for 1 hour, and the measurements were performed again immediately after its removal. For the control group, the measurements were performed twice with one hour gap. Significant (Wilcoxon test, p < 0.05) differences were found between the SPEED scores (p = 0.035) and the PRT measurement (p = 0.042), before and after wearing the surgical face mask. The PRT scores have improved after wearing the surgical face mask, while the dry eye symptoms detected by the SPEED questionnaire have increased. On the other hand, no significant (Wilcoxon test, p = 0.201) differences were found between the TF grades before and after wearing a surgical face mask. For the control group, no significant (Wilcoxon test, p > 0.05) differences were found between the two scores from the SPEED questionnaire and the PRT, and TF tests. Wearing a surgical face mask for a short duration leads to a change in volume and quality of tears as well as dry eye symptoms in women with a high BMI.


Semaphorin5A expression in the developing chick telencephalon.
In the present study, we analyzed the expression of Semaphorin5A (Sema5A), a gene implicated in axon guidance and many other processes of neuronal development, in the developing chick telencephalon. By using a heterologous mouse probe and in situ hybridization techniques, we showed distinct patterns of Sema5A expression within the chick telencephalon. In early development, Sema5A was present in pallial regions, mainly in the neuroepithelium and in the deep mantle of ventral and lateral pallia, and in the subpallium. As development proceeds, some ventral pallial derivatives maintained a moderate to strong Sema5A expression, whereas other lateral or dorsal pallial derivatives showed low to moderate expression of Sema5A. The overall expression of Sema5A during development in the chick telencephalon was similar to that reported in mouse. Moreover, the expression of Sema5A in mesencephalic, diencephalic, and telencephalic centers related to the tectofugal system suggests an important role of this gene in the development.


Use of SMS text messaging to improve outpatient attendance.
To evaluate the effect of appointment reminders sent as short message service (SMS) text messages to patients' mobile telephones on attendance at outpatient clinics. Cohort study with historical control. Royal Children's Hospital, Melbourne, Victoria. Patients who gave a mobile telephone contact number and were scheduled to attend any of five outpatient clinics (dermatology, gastroenterology, general medicine, paediatric dentistry and plastic surgery) in September (trial group) or August (control group), 2004. Failure to attend (FTA) rate compared between the group sent a reminder and those who were not. 2151 patients were scheduled to attend a clinic in September; 1382 of these (64.2%) gave a mobile telephone contact number and were sent an SMS reminder (trial group). Corresponding numbers in the control group were 2276 scheduled to attend and 1482 (65.1%) who gave a mobile telephone number. The FTA rate for individual clinics was 12%-16% for the trial group, and 19%-39% for the control group. Overall FTA rate was significantly lower in the trial group than in the control group (14.2% v 23.4%; P < 0.001). The observed reduction in failure to attend rate was in line with that found using traditional reminder methods. The ease with which large numbers of messages can be customised and sent by SMS text messaging, along with its availability and comparatively low cost, suggest it may be a suitable means of improving patient attendance.


Expanded Demographics for the Tillaux Fracture in Patients Receiving Feminizing Hormone Therapy A Case Report.
We present the case of a transgender female patient who had been undergoing feminizing hormone therapy for several years and sustained a Tillaux fracture despite being older than the expected age range for females with this injury pattern. Despite work focused on understanding physeal closure, the molecular signals governing this phenomenon remain incompletely described. This case study illustrates that physeal closure may be delayed in patients undergoing sex hormone therapy with associated transitional fractures possibly occurring later than would be expected for the transitional gender. Additional work is necessary to clarify the direct effect of sex hormonal therapy on physeal homeostasis.


The patient's perspective on stereotactic body radiation therapy (SBRT) vs. surgery for treatment of early stage non-small cell lung cancer (NSCLC).
We investigated the patient's perspective on SBRT for treatment of stage I NSCLC and compared the patient's perspective of SBRT to that of surgery. IRB approval was obtained to contact patients who had received SBRT for stage I NSCLCs. Patients were asked questions inquiring into their knowledge of SBRT and how their SBRT experience compared to their original expectations. Patients who had undergone prior surgery for a previously diagnosed stage I NSCLC were asked questions comparing their experience between SBRT and surgery. Frequencies of these reported measures were calculated and analysis was done using Fisher's exact test. 102 patients were contacted with 91 (89%) participating. Among all patients, prior to their radiation oncology consultation, 56% had no knowledge of SBRT and 58% believed SBRT to be as effective as resection. After consultation, 98.9% did not believe they were getting an inferior treatment with SBRT. 92.3% of patients reported less side effects, 59.3% reported SBRT to be more convenient and 87.9% reported SBRT to be less anxiety provoking than compared to their original expectations. Among patients with prior lung surgery (N=39), compared to surgery, 100% reported an easier recovery, less treatment related anxiety and less caregiver strain with SBRT. Overall, 79.5% were more satisfied with SBRT than surgery and 89.7% would have rather had SBRT than surgery as it was performed for their prior NSCLC. Actual experiences with SBRT are overwhelmingly superior compared to patient expectations. Patients with prior lung surgery reported significantly more satisfaction with SBRT.


Pharmacokinetics and bioequivalence study of irbesartan tablets after a single oral dose of 300 mg in healthy Thai volunteers.
Pharmacokinetics and bioequivalence of 300 mg irbesartan tablets were studied in 26 healthy Thai male volunteers. A single oral dose of one 300 mg tablet of the test product and the reference product was given to each volunteer according to a randomized two-way crossover design with 1-week wash out period. Blood samples were collected at predetermined time intervals until 72 hours post dose and irbesartan concentration was quantified with a validated HPLC method. Individual plasma irbesartan concentration-time profile was analyzed for pharmacokinetic parameters. Maximum plasma concentrations (Cmax) of 3,617.19 and 3,295.77 ng/mL for test and reference, respectively, were achieved. Areas under the plasma concentration-time curve; AUC0-t and AUC0-∞ were 15,304.65 and 15,638.90 ng×h/mL for test and 15,389.21 and 15,730.34 ng×h/mL for reference. The median tmax was 1.50 hours and 1.25 hours for test and reference, respectively. Plasma elimination half-lives (t1/2) were 7.35 hours and 8.09 hours for test and reference, respectively. Primary pharmacokinetic parameters Cmax, AUC0-t, and AUC0-∞ were tested parametrically by analysis of variance (ANOVA), and it revealed no statistically significant difference (defined as p < 0.05) between the corresponding Cmax, AUC0-t, and AUC0-∞ with respect to sequence, volunteers, period and formulation. The 90% confidence intervals for the ratio of test and reference product of the parameters Cmax, AUC0-t, and AUC0-∞ were within 80 - 125% (100.13 - 121.40% for Cmax, 90.83 - 106.86% for AUC0-t and 91.11 - 106.55% for AUC0-∞). The two products were bioequivalent in terms of both rate and extent of drug absorption into systemic circulation.


A comparative ethno-botanical study of Cholistan (an arid area) and Pothwar (a semi-arid area) of Pakistan for traditional medicines.
The present study is intended to compare and document the therapeutic flora, their remedial use, and the traditional knowledge used frequently by the residents of the Cholistan desert and Pothwar (Potohar) Plateau of Punjab, Pakistan. The old endemic remedies of these areas are diminishing due to lack of qualitative and quantitative research. The data was generated by unstructured-interviews, informal meetings, open-ended conversations and group discussions with local people and traditional health healers of the study area. Reported literature was also utilized. The study recorded a list of various medicinal plants used as traditional medicines by local people. Total 86 numbers of plant species belonging to 38 families and 67 plant species belonging to 29 families have been reported in the Pothwar and Cholistan respectively. Only 10.5% of similar plant species were present in the studied areas. The investigation revealed that the local people of study areas inherit a rich traditional knowledge but there is great danger of losing this wealth of knowledge in the near future. Documentation of the knowledge exclusively from desert area of Cholistan, Pakistan is unique information in its nature. The study presents the undocumented knowledge worth recognition that will not only help in conservation of medicinal plant species but will highlight the pharmacological capacity for improved human healthcare regarding many common ailments.


A geometrical model of vertical translation and alar ligament tension in atlanto-axial rotation.
While allowing the greatest range of axial rotation of the entire spine with 40° to each side, gradual restraint at the extremes of motion by the alar ligaments is of vital importance. In order for the ligaments to facilitate a gradual transition from the neutral to the elastic zone, a complex interaction of axial rotation and vertical translation via the biconvex articular surfaces is essential. The aim of this investigation is to establish a geometrical model of the intricate interaction of the alar ligaments and vertical translatory motion of C1/C2 in axial rotation. Bilateral alar ligaments including the odontoid process and condylar bony entheses were removed from six adult cadavers aged 65-89 years within 48 h of death. All specimens were judged to be free of abnormalities with the exception of non-specific degenerative changes. Dimensions of the odontoid process and alar ligaments were measured. Graphical multiplanar reconstruction of atlanto-axial rotation was done in the transverse and frontal planes for the neutral position and for rotation to 40° with vertical translation of 3 mm. The necessary fibre elongation of the alar ligaments in the setting with and without vertical translation of the atlas was calculated. The mean diameter of the odontoid process in the sagittal plane was 10.6 mm (SD 1.1). The longest fibre length was measured from the posterior border of the odontoid enthesis to the posterior border of the condylar enthesis with an average of 13.2 mm (SD 2.5) and the shortest between the lateral (anterior) border odontoid enthesis and the anterior condylar enthesis with an average of 8.2 mm (SD 2.2). In graphical multiplanar reconstruction of atlanto-axial rotation to 40° without vertical translation of C1/C2, theoretical alar fibre elongation reaches 27.1% for the longest fibres, which is incompatible with the collagenous structure of the alar ligaments. Allowing 3 mm caudal translation of C1 on C2 at 40° rotation, as facilitated by the biconvex atlanto-axial joints, reduces alar fibre elongation to 23.3%. The biconvex configuration of the atlanto-axial joints is an integral feature of the functionality of upper cervical spine as it allows gradual vertical translation of the atlas against the axis during axial rotation, with gradual tensing of the alar ligaments. Vertical translation on its own, however, does not explain the tolerance of the alar ligaments towards the maximum of 40° of rotation and is most likely synergistic with the effects of the coupled motion of occipitocervical extension during rotation.


Acid-sensitive prodrugs of Doxorubicin.
The endosomal and/or lysosomal pathway of macromolecules, as well as the slightly acidic extracellularenvironment in solid tumors, form the rationale for designing carrier-linked prodrugs with pH-dependentlinkers. In the past 20 years, a spectrum of acid-sensitive doxorubicin prodrugs has been developedwith antibodies, serum proteins, and synthetic polymers. For a number of these, a convincingproof of concept has been obtained preclinically, showing an enhanced therapeutic efficacy of theprodrugs compared to free doxorubicin in tumor models. Clinically, the (6-maleimidocaproyl)-hydrazonederivative of doxorubicin, which binds either to the monoclonal antibody BR96 or to endogenous albumin,has been evaluated in clinical trials.


Cast-treated distal radius fractures: a prospective cohort study of radiological outcomes and their association with impaired calcaneal bone mineral density.
We hypothesized that treating distal radius fractures with cast only or closed reduction and cast is associated with high malunion risk and that the risk is higher in patients with low bone mineral density (BMD). We prospectively studied 130 patients aged 40 years or older with distal radius fractures treated with cast only (87 patients) or closed reduction and cast (43 patients). Radiographs were obtained before treatment, after reduction (in the closed reduction group), and at 1 year. We measured calcaneal BMD with DXA scanner and calculated T scores. We calculated radiological changes from baseline (initial radiographs in cast only and post-reduction radiographs in closed reduction patients) to 1 year. We assessed the relationship between BMD status (normal, osteopenia or osteoporosis) and baseline-to-1-year worsening in volar tilt, ulnar variance, and radial inclination with analysis of covariance adjusting for baseline radiological values. We used receiver operating characteristic (ROC) analysis to determine the ability of T scores to distinguish patients with severe malunion (dorsal tilt >25° and/or ulnar variance ≥5 mm) from those with less severe or no malunion. In both treatment groups, baseline radiological variables had deteriorated at 1 year, more in the closed reduction group. Compared to patients with normal BMD, those with osteoporosis had significantly greater worsening in volar tilt and radial inclination but did not differ in ulnar variance worsening. Severe malunion was found in 34 fractures (26 %, 15 in cast only group); T scores had a modest ability in distinguishing severe malunion (area under ROC curve 0.67, 95 % CI 0.56-0.78, p = 0.003). Closed reduction and cast is not an effective treatment for distal radius fractures if radiological graphic outcomes are considered. There is a higher risk of malunion involving dorsal and radial tilt in patients with osteoporosis. Calcaneal BMD measurement may have some benefit in predicting the risk of severe malunion.


Effect of dual inhibition of apoptosis and autophagy in prostate cancer.
Targeting multiple anti-apoptotic proteins is now possible with the small molecule BH3 domain mimetics such as ABT-737. Given recent studies demonstrating that autophagy is a resistance mechanism to multiple therapeutic agents in the setting of apoptotic inhibition, we hypothesized that hydroxychloroquine (HCQ), an anti-malarial drug that inhibits autophagy, will increase cytotoxicity of ABT-737. Cytotoxicity of ABT-737 and HCQ was assessed in vitro in PC-3 and LNCaP cells, and in vivo in a xenograft mouse model. The role of autophagy as a resistance mechanism was assessed by siRNA knockdown of the essential autophagy gene beclin1. ROS was measured by flow cytometry, and mitophagy assessed by the mCherry-Parkin reporter. Induction of autophagy by ABT-737 was a mechanism of resistance in prostate cancer cell lines. Therapeutic inhibition of autophagy with HCQ increased cytotoxicity of ABT-737 both in vitro and in vivo. ABT-737 induced LC-3 and decreased p62 expression by immunoblot in cell lines and by immunohistochemistry in tumors in vivo. Assessment of ROS and mitochondria demonstrated that ROS production by ABT-737 and HCQ was a mechanism of cytotoxicity. We demonstrated that autophagy inhibition with HCQ enhances ABT-737 cytotoxicity in vitro and in vivo, that LC-3 and p62 represent assessable markers in human tissue for future clinical trials, and that ROS induction is a mechanism of cytotoxicity. These results support a new paradigm of dual targeting of apoptosis and autophagy in future clinical studies.


Governing stem cell research in California and the USA: towards a social infrastructure.
Owing to the restrictive human embryonic stem cell (hESC) policies of the US government, the question of whether to pursue human embryonic stem cell experiments has dominated the ethical and political discourse concerning such research. Explicit attention must now turn to problems of implementing the research on a large scale: in the 2004 US elections, California voters approved a state initiative for stem cell research, earmarking $3 billion in direct spending over 10 years. This article explores three ethical and political problem areas emerging out of the California program, the resolution of which will help set the trajectory of hESC research in the US and abroad, and then proposes an institutional approach to help address them: a network of public stem cell banks in the US that feature transparent and shared governance.


Antibodies to the most tightly bound proteins in eukaryotic DNA. Formation of immuno-complexes with 'nuclear matrix' components.
Chromosomal DNA is associated with polypeptides covalently bound to internal DNA ends. Since these polypeptides can only be released from chromosomal DNA by enzymes or other agents hydrolysing phosphodiester bonds they were termed 'the most tightly bound' (MTB) polypeptides in DNA. Antibodies developed against the MTB polypeptides are shown to form immunocomplexes with major 'nuclear matrix' polypeptides as well as with polypeptides which are still associated with 'nuclear matrix' DNA isolated by means of SDS/proteinase K and phenol. Immuno-complex formation is revealed by immunoblotting and by indirect immunofluorescence. Thus, since MTB polypeptides, major 'nuclear matrix' polypeptides and 'nuclear matrix' DNA-associated polypeptides share common antigenic sites they can be considered to be identical or at least closely related. This suggests that a fraction of distinct 'nuclear matrix' polypeptides is either transiently or permanently linked to DNA by covalent bonds. Consistently, isolated eukaryotic 'bulk' DNA is inevitably associated with residual 'nuclear matrix' polypeptides.


Diagnostic accuracy of apparent diffusion coefficient values combined with γ-glutamyl transpeptidase-to-platelet ratio parameters for predicting hepatitis B-related fibrosis.
The accuracy of non-invasive liver fibrosis diagnosis based on the apparent diffusion coefficient (ADC) value combined with the γ-glutamyl transpeptidase-to-platelet ratio (GPR) model to predict the stage of hepatitis B-related fibrosis has not been reported. This study aimed to evaluate the diagnostic efficacy of ADC value combined with GPR for liver fibrosis grading. The data of 180 patients with chronic hepatitis B (CHB) diagnosed by liver biopsy were analyzed. The ADC value, GPR, and their combination were assessed in different cirrhosis stages using receiver operating characteristic curve analysis to evaluate their value in diagnosing liver fibrosis. We observed that liver fibrosis stages were inversely associated with ADC values (r=-0.691, P<0.001), and positively associated with GPR (r=0.502, P<0.001). The area under the curve for diagnostic efficacy of ADC values, GPR, and their combination for F≥2 liver fibrosis was 0.831, 0.749, and 0.858, respectively, and for F≥3 was 0.872, 0.771, and 0.903, respectively. The diagnostic cutoffs of the combination for each stage were -7.07, -12.21 and -37.75, respectively. The combined diagnostic tool of ADC and GPR may improve the accuracy of hepatitis B-related liver fibrosis diagnosis, especially for F≥3.


Physical activity and cardiovascular risk factors: effect of advice from an exercise specialist in Australian general practice.
To determine whether provision of individualised physical activity advice by an exercise specialist in general practice is effective in modifying physical activity and cardiovascular risk factors in older adults. Randomised controlled trial of individualised physical activity advice, reinforced at three and six months (intervention) versus no advice (control). Two general practices in Adelaide, South Australia, 1996. 299 adults aged 60 years or more who were healthy, sedentary and living in the community. Changes to physical activity (frequency and duration of walking and vigorous exercise), selected cardiovascular risk factors (blood pressure, body weight, serum lipid levels) and quality of life over 12 months. Self-reported physical activity increased over the 12 months in both groups (P < 0.001). The increase was greater for the intervention than the control group for all measures except time spent walking (P < 0.05). More intervention than control participants increased their intention to exercise (P < 0.001). Serum levels of total and low-density lipoprotein cholesterol and triglycerides fell significantly over the 12 months to a similar extent in the two groups. No other significant changes in cardiovascular risk factors were seen. Quality-of-life scores decreased over the 12 months. The decrease was significantly greater among intervention than control women, but not men, for emotional well-being (P = 0.02), physical well-being (P = 0.04) and social functioning (P = 0.04). Provision of general practice-based physical activity advice reinforced three-monthly produced a sustained increase in self-reported physical activity. However, there were no associated changes in clinical measures of cardiovascular risk factors and minimal changes in quality-of-life measures.


Electrophysiological properties of the follicle wall in the pig ovary.
The transmural potential difference and short-circuit current of the porcine Graafian follicle have been measured in an attempt to test whether antral fluid accumulates as a result of active transport of salt. The values obtained by mounting explants of follicle wall in Ussing chambers were close to zero and the specific electrical resistance was only 59 delta.cm2. The elemental composition of the follicular fluid was similar to that of ovarian venous plasma with the exception of follicular Na+ which was slightly more abundant. Bicarbonate concentrations were slightly lower in follicular fluids. These findings were interpreted as evidence that the follicular wall is a leaky epithelium and, therefore, any charge resulting from net ion transport will be shunted along low resistance paracellular pathways.


Hidradenitis suppurativa and social disadvantage: A nationwide administrative data study of the French hospitalized population.
A lower socioeconomical status (SES) has been reported in patients suffering from hidradenitis suppurative (HS). However, limitations in the available studies prevent drawing definitive conclusions. The objective of this study was to assess the SES of HS patients using a specific SES indicator, the French DEPrivation index (FDep), specifically designed and validated for the French population. This cross-sectional cohort study compared the HS hospitalized population with the general hospitalized population without HS. Data were extracted from the French national hospital discharge database, an exhaustive database on all reimbursed hospital stay in the country with a rolling 10-year history (2012-2021). We included all patients aged 7-75 years with at least one stay in a French hospital. A 1:40 propensity score matching, adjusted for age, sex, smoking status and obesity, was performed to create 2 groups of comparable patients. Subgroup analysis was done in the minor (7-17 years) and major (25-75 years) populations independently. In the overall population, we identified 33,880 patients with HS and 24,445,337 patients without HS. After propensity score matching, logistic regression showed a significant association between HS and social disadvantage. There is a 22.5% increased risk of developing HS for individuals being in quintile 5 (the most disadvantaged quintile) versus quintile 1 (the least disadvantaged quintile) (p < 0.0001). After propensity score matching, the logistic regression showed no association between HS and social disadvantage in the 7-17 subgroup. In this minor population, an association between HS and social disadvantage was observed when propensity score matching was performed on age and sex only. We demonstrate a significant association between HS and low SES in the adult population. In children between 7 and 17, low SES was associated with obesity and tobacco consumption, but not with HS when the populations were matched on these confounding factors.


The beginnings of urban ambulance service in the United States and England.
Urban ambulance systems emerged in the second half of the 19th century as an outgrowth of military experiences in both Europe and America. Developing first in cities such as Cleveland and New York, these systems quickly adapted to the urban environment, and modifications in ambulance construction and procedures soon followed. Since first-aid texts for urban ambulances were rare, military texts on battlefield medicine were adapted to emergency medicine in civilian accidents.


Thymosin α1 protects from CTLA-4 intestinal immunopathology.
The advent of immune checkpoint inhibitors has represented a major boost in cancer therapy, but safety concerns are increasingly being recognized. Indeed, although beneficial at the tumor site, unlocking a safeguard mechanism of the immune response may trigger autoimmune-like effects at the periphery, thus making the safety of immune checkpoint inhibitors a research priority. Herein, we demonstrate that thymosin α1 (Tα1), an endogenous peptide with immunomodulatory activities, can protect mice from intestinal toxicity in a murine model of immune checkpoint inhibitor-induced colitis. Specifically, Tα1 efficiently prevented immune adverse pathology in the gut by promoting the indoleamine 2,3-dioxygenase (IDO) 1-dependent tolerogenic immune pathway. Notably, Tα1 did not induce IDO1 in the tumor microenvironment, but rather modulated the infiltration of T-cell subsets by inverting the ratio between CD8+ and Treg cells, an effect that may depend on Tα1 ability to regulate the differentiation and chemokine expression profile of DCs. Thus, through distinct mechanisms that are contingent upon the context, Tα1 represents a plausible candidate to improve the safety/efficacy profile of immune checkpoint inhibitors.


Autonoetic consciousness in Alzheimer's disease: neuropsychological and PET findings using an episodic learning and recognition task.
This study aims to map in patients with mild Alzheimer's disease (AD) the correlations between resting-state brain glucose utilization measured by FDG-PET and scores reflecting autonoetic consciousness in an episodic learning and recognition task. Autonoetic consciousness, that gives a subject the conscious feeling to mentally travelling back in time to relive an event, was assessed using the Remember/Know (R/K) paradigm. AD patients provided less R responses (reflecting autonoetic consciousness) and more K ones (indicating the involvement of noetic consciousness) than healthy controls. Correct recognitions associated with a R response correlated with the metabolism of frontal areas bilaterally whereas those associated with a K response mainly correlated with the metabolism of left parahippocampal gyrus and lateral temporal cortex. These data show that recollection is impaired in AD and recognition is more based on a feeling of familiarity than in controls. In addition, the findings of our correlative approach indicate that the impairment of episodic memory is mainly subserved by the dysfunction of frontal areas and of the hippocampal region.


Chiral characterization of deprenyl-N-oxide and other deprenyl metabolites by capillary electrophoresis using a dual cyclodextrin system in rat urine.
A chiral capillary electrophoresis method has been developed for the simultaneous separation of the enantiomers of deprenyl and eight of its metabolites, among them the recently described metabolite deprenyl-N-oxide. Although heptakis-(2,6-di-O-methyl)-beta-cyclodextrin (DIMEB) was suitable for the enantioresolution of deprenyl and its dealkylated derivatives, the enantiomers of deprenyl-N-oxide were just partly resolved. Carboxymethyl-beta-cyclodextrin (CMBCD) in as low as 2 mM concentration was capable of the enantiomer separation of all the nine examined compounds, however co-migration of 1R,2S-(-)-norephedrine and 1R,2R-(-)-pseudoephedrine, as well as 1S,2R-(+)-ephedrine and R-(-)-amphetamine was observed. This problem could be overcome by the use of a dual cyclodextrin system containing 4 mM DIMEB in addition to 2 mM CMBCD; simultaneous separation of all the compounds could be achieved. The optimized method was used for the analysis of rat urine samples after 10 days of treatment of animals with either R-(-)- or S-(+)-deprenyl. The stereospecific biotransformation of both deprenyl enantiomers was confirmed, and the stereoselectivity of N-oxide formation was demonstrated.


Interacting partners of AMPA-type glutamate receptors.
Glutamate is the principal excitatory neurotransmitter in the brain. The alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic (AMPA) receptors, as one of several types of endogenous ionotropic glutamate receptors, mediate the fast excitatory synaptic transmission that is essential for information processing and integration in the mammalian brain. Modifications of AMPA receptors are assumed to be the molecular basis underlying learning and memory, and impairments of AMPA receptors cause certain neurological diseases, including epilepsy, autism spectrum disorders, and Alzheimer's disease. Thus, extensive studies have been conducted, and these have revealed a complex protein-protein network controlling the expression, trafficking, and function of AMPA receptors in neurons. Here, we summarize the interacting partners of AMPA-type glutamate receptors and the functional implications of these interactions.


CL 316, 243 mediated reductions in blood glucose are enhanced in RIP140-/- mice independent of alterations in lipolysis.
The β-3 adrenergic agonist CL 316, 243 acutely lowers blood glucose through a mechanism thought to involve fatty-acid induced insulin release. The purpose of this study was to determine if ablation of the nuclear receptor, receptor-inactivating protein 140 (RIP140), altered this response. Here, we used a single injection of CL 316, 243 (1 mg/kg) and found that whole body RIP140-/- mice had a greater decline in blood glucose over 2 h. This occurred alongside increased hexokinase II (HKII) protein content in adipose tissue and skeletal muscle, but independent of changes in circulating insulin or indices of lipolysis. These data indicate that RIP140 has a unique role in the acute effect of β-3 adrenergic receptor activation using CL 316, 243.


Quantitative study of the changes in brain white matter before and after radiotherapy by applying multi-sequence MR radiomics.
To analyse the changes in brain white matter before and after radiotherapy (RT) by applying multisequence MR radiomics features and to establish a relationship between the changes in radiomics features and radiation dose. Eighty-eight patients with brain tumours who had undergone RT were selected in this study, and MR images (T1, T1+C, T2FLAIR, T2, DWI, and ASL) before and after RT were obtained. The brain white matter was delineated as an ROI under dose gradients of 0-5 Gy, 5-10 Gy, 10-15 Gy, 15-20 Gy, 20-30 Gy, 30-40 Gy, and 40-50 Gy. The radiomics features of each ROI were extracted, and the changes in radiomics features before and after RT for different sequences under different dose gradients were compared. At each dose gradient, statistically significant features of different MR sequences were mainly concentrated in three dose gradients, 5-10 Gy, 20-30 Gy, and 30-40 Gy. The T1+C sequence held the most features (66) under the 20-30 Gy dose gradient. There were 20 general features at dose gradients of 20-30 Gy, 30-40 Gy, and 40-50 Gy, and the changes in features first decreased and then increased following dose escalation. With dose gradients of 5-10 Gy and 10-15 Gy, only T1 and T2FLAIR had general features, and the rates of change were - 24.57% and - 29.32% for T1 and - 3.08% and - 10.87% for T2FLAIR, respectively. The changes showed an upward trend with increasing doses. For different MR sequences that were analysed under the same dose gradient, all sequences with 5-10 Gy, 20-30 Gy and 30-40 Gy had general features, except the T2FLAIR sequence, which was concentrated in the FirstOrder category feature, and the changes in features of T1 and T1+C were more significant than those of the other sequences. MR radiomics features revealed microscopic changes in brain white matter before and after RT, although there was no constant dose-effect relationship for each feature. The changes in radiomics features in different sequences could reveal the radiation response of brain white matter to different doses.


Mechanisms of autophagy and endoplasmic reticulum stress in the reversal of platinum resistance of epithelial ovarian cancer cells by naringin.
Our previous studies showed that naringin (Nar) can effectively reverse the cisplatin resistance of ovarian cancer cells. This study aims to explore the potential mechanism by which Nar reverses cisplatin resistance in ovarian cancer. The proliferative activity of cells was evaluated using CCK8 and cell clone formation assays. Autophagic flux in cells was evaluated via LC3B immunofluorescence and monodansylcadaverine (MDC) staining. The expression levels of autophagy, endoplasmic reticulum (ER) stress, and apoptosis-related proteins were detected via Western blotting. Autophagy and ER stress were regulated using siATG5, siLC3B, rapamycin (Rap), chloroquine (CQ), 4-phenylbutyric acid (4-PBA), and thapsigargin (TG). siATG5 and siLC3B are short interfering RNAs (siRNAs) used to knock down the expression of ATG5 and LC3B genes, respectively. Nar inhibited autophagy in SKOV3/DDP cells by activating the PI3K/AKT/mTOR pathway. And Nar increased the levels of ER stress-related proteins, namely, P-PERK, GRP78, and CHOP, and promoted apoptosis in SKOV3/DDP cells. Moreover, treatment with the inhibitor of ER stress alleviated apoptosis induced by Nar in SKOV3/DDP cells. In addition, compared to cisplatin or naringin alone, the combination of Nar and cisplatin significantly reduced the proliferative activity of SKOV3/DDP cells. And siATG5, siLC3B, CQ or TG pretreatment further inhibited the proliferative activity of SKOV3/DDP cells. Conversely, Rap or 4-PBA pretreatment alleviated the cell proliferation inhibition caused by Nar combined with cisplatin. Nar not only inhibited the autophagy in SKOV3/DDP cells by regulating the PI3K/AKT/mTOR signalling pathway, but also promoted apoptosis in SKOV3/DDP cells by targeting ER stress. Nar can reverse the cisplatin resistance in SKOV3/DDP cells through these two mechanisms.


Ethambutol-induced hyperuricaemia.
A prospective study involving 134 cases of pulmonary tuberculosis was conducted to determine the incidence and severity of ethambutol-induced hyperuricaemia. The cases were randomly allocated to two groups: one group (71 cases) received ethambutol (20 mg/kg bodyweight/day) streptomycin and isoniazid (SHE), the other group (60 cases) received streptomycin, isoniazid and thioacetazone (SHT). All the cases were hospitalized. A significant rise in serum uric acid levels was found in 66% of SHE patients during the first 60-90 days of treatment, but there was no such change in the SHT patients. In one patient who received ethambutol generalized arthralgia developed and in another acute gouty arthritis was observed. In both cases, symptoms abated when ethambutol was withdrawn and reappeared when it was resumed.


Joining of linear plasmid DNA is reduced and error-prone in Bloom's syndrome cells.
A linearized, replicating, shuttle vector plasmid, pZ189, was used to measure in vivo DNA joining ability of cells from patients with the cancer-prone, immunodeficient, chromosome breakage disorder, Bloom's syndrome (BS). The BS cell lines we studied were reported to contain reduced in vitro activity of DNA ligase I. We assessed in vivo joining ability by transfecting linear plasmids with overlapping or blunt ends (produced by EcoRI or StuI) into BS and normal fibroblast or lymphoblast host cells and measuring the amount of re-joined, replicated plasmids by their ability to transform bacteria. With plasmids having either overlapping or blunt ends we found a 1.3- to 3-fold lower (P less than 0.05) joining efficiency in BS cells than in the normal cells. The mutation frequency of the recovered plasmids was measured by screening for function of the suppressor tRNA contained in pZ189, for plasmid size, for presence of restriction sites, or by DNA sequencing. The spontaneous mutation frequency with the circular plasmid was 0.05-0.08% with both BS cell lines, values 2- to 21-fold higher (P less than 0.03) than with the normal cell lines. The mutation frequency with the linear plasmid passaged through both BS cell lines was 21-52%, values 1.4- to 5.4-fold higher (P less than 0.001) than with the normal lines. Detailed analysis of 210 recovered plasmids revealed an increase (P less than or equal to 0.001) in deletions, insertions or complex mutations at the joining sites, and in point mutations with the EcoRI cut plasmid with the BS cells in comparison to the normal cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular Mechanisms and Current Treatment Options for Cancer Cachexia.
Cancer cachexia is a condition marked by functional, metabolic, and immunological dysfunctions associated with skeletal muscle (SM) atrophy, adipose tissue loss, fat reduction, systemic inflammation, and anorexia. Generally, the condition is caused by a variety of mediators produced by cancer cells and cells in tumor microenvironments. Myostatin and activin signaling, IGF-1/PI3K/AKT signaling, and JAK-STAT signaling are known to play roles in cachexia, and thus, these pathways are considered potential therapeutic targets. This review discusses the current state of knowledge of the molecular mechanisms underlying cachexia and the available therapeutic options and was undertaken to increase understanding of the various factors/pathways/mediators involved and to identify potential treatment options.


Urachal adenocarcinoma: A case report and review of the literature.
The urachus is a canal between the allantois and the early fetal bladder. Urachal carcinoma is a rare and aggressive type of bladder cancer. This cancer usually presents at an advanced stage. We report a 70-year-old patient with malignant transformation of urachal cyst several years later. The patient was treated with partial cystectomy and adjuvant radiotherapy. A review of the published literature is also presented.


Combined non-surgical treatment for Paget-Schröetter syndrome: a case report.
Paget-Schröetter syndrome is an uncommon form of venous thrombosis, which is related to thoracic outlet syndrome. Axillary-subclavian vein thrombosis typically presents in healthy young adults. We present this case of particular interest because it indicates that a combined treatment involving thrombolysis, anticoagulation therapy, rehabilitation, and elastic compression sleeves can be a valid non-surgical alternative for some patients with Paget-Schröetter syndrome. This report describes a case of a 38-year-old white woman, a swimmer, who presented with a sudden episode of swelling and pain in her right upper extremity. After duplex ultrasound diagnosis of venous thrombosis, computed tomography (CT) showed extrinsic compression of the vessel. Catheter-directed thrombolysis was performed in the first 24 hours, followed by anticoagulant therapy with bemiparin at a dose of 7500 IU/24 hours for the first week, and then reduced to 3500 IU/24 hours for the next 3 months. After treatment there was restoration of her venous flow and she returned to work 2 weeks later. Anticoagulant treatment was continued for 3 months; decompression surgery was not performed. At 6 months she was asymptomatic. Combined treatment involving thrombolysis, anticoagulant therapy, rehabilitation, and elastic compression sleeves may be a valid non-surgical alternative for a selected subset of patients with Paget-Schröetter syndrome.


ZIP10 drives osteosarcoma proliferation and chemoresistance through ITGA10-mediated activation of the PI3K/AKT pathway.
The zinc transporters Zrt- and Irt-related protein (ZIP/SLC39) are overexpressed in human tumors and correlate with poor prognosis; however, their contributions to carcinogenesis and chemoresistance in osteosarcoma (OS) remain unclear. We collected 64 OS patient tissues with (n = 12) or without (n = 52) chemotherapy. The expression levels of ZIP10 were measured by immunohistochemistry and applied to prognostic analysis. ZIP10 was knocked down or overexpressed in OS cell lines to explore its effect on proliferation and chemoresistance. RNA sequencing, quantitative real-time PCR, and western blotting analysis were performed to explore ZIP10-regulated downstream target genes. A xenograft mouse model was established to evaluate the mechanisms by which ZIP10 modulates chemoresistance in OS cells. The expression of ZIP10 was significantly induced by chemotherapy and highly associated with the clinical outcomes of OS. Knockdown of ZIP10 suppressed OS cell proliferation and chemoresistance. In addition, ZIP10 promoted Zn content-induced cAMP-response element binding protein (CREB) phosphorylation and activation, which are required for integrin α10 (ITGA10) transcription and ITGA10-mediated PI3K/AKT pathway activation. Importantly, ITGA10 stimulated PI3K/AKT signaling but not the classical FAK or SRC pathway. Moreover, overexpression of ZIP10 promoted ITGA10 expression and conferred chemoresistance. Treatment with the CREB inhibitor 666-15 or the PI3K/AKT inhibitor GSK690693 impaired tumor chemoresistance in ZIP10-overexpressing cells. Finally, a xenograft mouse model established by subcutaneous injection of 143B cells confirmed that ZIP10 mediates chemotherapy resistance in OS cells via the ZIP10-ITGA10-PI3K/AKT axis. We demonstrate that ZIP10 drives OS proliferation and chemoresistance through ITGA10-mediated activation of the PI3K/AKT pathway, which might serve as a target for OS treatment.


[Dermorphins--a natural opioids with unique primary structure that determines their biological specificity].
Based on the authors' and published data, the spectrum of biological activities of dermorphins was theoretically analyzed for the first time from the viewpoint of specific structural features of their molecule that determine selective affinity to mu-opiate receptors. It was shown that specific distribution of dermorphins and corresponding opiate receptors in tissues and organs, especially in the CNS structures, determines the role of dermorphins in the regulation of functions of the most important physiological systems.


Validity and Reliability of Semiautomatic Ocular Cycloposition Measurement With Spectralis Optical Coherence Tomography.
Disc-fovea angle determined by fundus photography (P-DFA) is considered the gold standard for cycloposition assessment. Fovea-to-disc alignment (FoDi) software of the spectral-domain optical coherence tomography (SD-OCT) (Spectralis) also measures the DFA (O-DFA) based on subject fixation and offers important clinical advantages. This study aimed to analyze the validity and reliability of measuring cycloposition using OCT and to determine its performance in eyes with poor foveal definition. Validity and reliability analysis. In 60 eyes with normal foveal definition and 32 eyes with poorly defined fovea, ocular cycloposition was assessed by 2 observers using 5 fundus photographs and 5 FoDi analyses each. Patients were repositioned after every capture. Cycloposition assessed by O-DFA was 7.6 ± 3.5-degrees, and P-DFA was 7.9 ± 3.8-degrees. The concordance between methods was good (intraclass correlation coefficient [ICC], 0.71), with absolute differences ranging from zero to 4-degrees in 85% of the subjects. The precision was 1.4-degrees for O-DFA and 3.0-degrees for P-DFA. Repeatability and reproducibility were excellent in both techniques. In the group of patients with poor foveal definition, the precision of P-DFA changed from 3.0-degrees to 4.8-degrees, whereas the O-DFA remained stable. OCT had a good agreement with the fundus photography method. O-DFA showed better precision than P-DFA. O-DFA repeatability and reproducibility were excellent and unconditioned by foveal status.


Quantitative assessment and characterization of glenoid bone loss in a spectrum of patients with glenohumeral osteoarthritis.
Eccentric posterior bone loss and associated glenoid retroversion represent challenges to glenoid placement during total shoulder arthroplasty. This bone loss can lead to poor stability and perforation of the glenoid during arthroplasty. The purpose of this study was to evaluate the morphology of glenoid bone loss for a spectrum of osteoarthritis patients using 3D computed tomography imaging and simulation software. This study included 29 patients with glenohumeral osteoarthritis treated with shoulder arthroplasty. Three-dimensional reconstruction of preoperative CT images was performed. Glenoid bone loss was measured at ten, vertically equidistant axial planes along the glenoid surface at four distinct anterior-posterior points on each plane. The images were fitted with modeled pegged glenoid implants to predict glenoid perforation. The 3D maps demonstrated greatest average bone loss posteriorly in the AP plane at the central axis of the glenoid in the SI plane. The average amount of bone loss was 3.85 mm. Walch A2 and B1 shoulders showed more central bone loss, while Walch B2 shoulders displayed more posterior and inferior bone loss. Patients with predicted peg perforation displayed significantly greater bone loss than those without predicted peg perforation (p = 0.037). Peg perforation was most common in Walch B2 shoulders occurring in the posterior direction involving the central and posterior-inferior peg. These data demonstrate an anatomic pattern of glenoid bone loss for different classes of glenohumeral arthritis. These findings can be used to develop various models of glenoid bone loss to guide surgeons, predict failures, and develop better glenoid implants. This study has been approved by the Cleveland Clinic IRB: Number 6235.


Factors affecting couples' adjustment to recurrent breast cancer.
The purpose of this study was to identify factors that affect the adjustment of women and their husbands to recurrent breast cancer and to examine the mutual effect that partners have on one another. An exploratory study was designed to determine the relationship between four predictor variables (support, uncertainty, symptom distress, hopelessness) and women's and husbands' adjustments. The sample consisted of 155 subjects; 81 women, who had a first recurrence of breast cancer, and 74 husbands. Multiple standardized instruments with established reliability and validity were used to measure the study variables. The independent variables were measured with the Social Support Questionnaire, the Mishel Uncertainty in Illness Scale, McCorkle Symptom Distress Scale and the Beck Hopelessness Scale. The dependent variable, psychosocial adjustment, was measured with the Brief Symptom Inventory and the Psychosocial Adjustment to Illness Scale. The results indicated that the independent variables accounted for 43% of the variance in women's distress and 32% of the variance in husbands' distress; they also explained 66% of the variance in women's role adjustment problems and 57% of the variance in husbands' role problems. Symptom distress and hopelessness accounted for the most variance in women's and husbands' levels of adjustment. A significant and positive relationship was found between women's and husbands' adjustment scores, indicating that partners have a mutual influence on one another. The findings suggest that there are multiple factors that influence couples' adjustment to recurrent breast cancer, and that these factors need to be taken into consideration when planning care for women and their partners.


Ectopic expression of CYP24A1 circular RNA hsa_circ_0060927 in uterine leiomyomas.
As a novel class of non-coding RNAs, the role of circular RNAs (circRNAs) in tumor biogenesis and progression has been proved in a number of human tumors; however, up to now, the relation between circRNAs and uterine leiomyomas (ULM) remains unclear. In this study, we have estimated the expression level of CYP24A1 hsa_circ_0060927 in uterine leiomyoma and adjacent tissues considering the mediator complex subunit 12 gene (MED12) mutation profile by quantitative real-time polymerase chain reaction (qRT-PCRs). Using Sanger sequencing method, somatic mutations in the MED12 exon 2 were detected in 14 (35.90%) ULM samples, including 10 (71.43%) missense mutations and 4 (28.57%) in-frame deletions. Our results revealed that hsa_circ_0060927 was ectopically expressed in 33.33% of ULM tissues; although, this expression was independent of the MED12 mutation profile in the ULM samples. Present results provide primary evidence for the role of circular RNAs in the leiomyoma development; however, further studies are essential to confirm the importance of these molecules as potential biomarkers for diagnosis and/or prognosis in ULM.


Depression of plasma gelsolin level during acute liver injury.
Human plasma contains two actin-binding proteins, plasma gelsolin and vitamin D-binding protein. These proteins are considered to play an important role in the disposition of actin derived from injured tissue. To evaluate this actin-scavenger system, gelsolin concentrations were measured in serial plasma samples obtained from patients with acute liver injury using an enzyme-linked immunosorbent assay. Plasma gelsolin levels in 43 healthy persons were 226 +/- 52 micrograms/mL. They were markedly reduced to 80 +/- 40 micrograms/mL in 14 patients with an early stage of acute hepatitis and returned to normal levels of 232 +/- 38 micrograms/mL as the disease resolved. Moreover, they showed a significant negative correlation with serum aminotransferase and bilirubin levels. In 7 patients with hepatocellular carcinoma, plasma gelsolin levels rapidly decreased from 182 +/- 42 to 87 +/- 41 micrograms/mL after transcatheter arterial embolization therapy. Because plasma gelsolin is not a hepatic protein, the decreased levels are considered to depend exclusively on the extent of actin leakage from the injured liver.


Structural basis for molecular interactions involving MRG domains: implications in chromatin biology.
MRG15 is a member of the mortality family of transcription factors that targets a wide variety of multiprotein complexes involved in transcription regulation, DNA repair, and alternative splicing to chromatin. The structure of the apo-MRG15 MRG domain implicated in interactions with diverse proteins has been described, but not in complex with any of its targets. Here, we structurally and functionally characterize the interaction between MRG15 and Pf1, two constitutively associated subunits of the histone deacetylase-associated Rpd3S/Sin3S corepressor complex. The MRG domain adopts a structure reminiscent of the apo state, whereas the Pf1 MRG-binding domain engages two discrete hydrophobic surfaces on the MRG domain via a bipartite motif comprising an α-helix and a segment in an extended conformation, both of which are critical for high-affinity interactions. Multiple MRG15 interactors share an FxLP motif in the extended segment, but equivalent sequence/helical motifs are not readily evident, implying potential diversity in MRG-recognition mechanisms.


Role of transmembrane domains in the functions of B- and T-cell receptors.
The antigen receptors on the surface of B- and T-lymphocytes are complexes of several integral membrane proteins, essential for their proper expression and function. Recent studies demonstrated that transmembrane (TM) domains of the components of these receptors play a critical role in their association and function. It was specifically demonstrated that in many cases point mutations in the TM domains can partially or completely disrupt the receptor surface expression and function. Here we review studies of the TM domains of B- and T-cell receptors. Furthermore, we use a novel method, PHDtopology, to provide estimates of the exact locations and lengths of the TM domains of the subunit components of these receptors. Most previous studies used single residue hydrophobicity as a criterion for determining the position and length of the TM domains. In contrast, PHDtopology utilizes a system of neural networks and the evolutionary information contained in multiple alignments of related sequences to predict the location, length, and orientation of transmembrane helices. Present results significantly differ from most published estimates of the TM domains of the B- and T-cell receptor components, primarily in the length of the TM domains. These results may lead to modification of putative TM motifs and re-interpretation of the results of studies using mutated TM domains. The availability of PHDtopology on the Internet would make it a valuable tool in the future studies of the TM domains of integral membrane proteins.


Harmonic radiation contribution and X-ray transmission at the Small Quantum Systems instrument of European XFEL.
Transmission measurements of the soft X-ray beamline to the Small Quantum Systems (SQS) scientific instrument at the SASE3 undulator of European XFEL are presented. Measurements are reported for a wide range of photon energies (650 eV to 2400 eV), using X-ray gas monitors as well as a bolometric radiometer. The results are in good agreement with simulations for the beam transport and show a transmission of up to 80% over the whole photon energy range. The contribution of second- and third-harmonic radiation of the soft X-ray undulator is determined at selected photon energies by performing transmission measurements using a gas absorber to provide variable attenuation of the incoming photon flux. A comparison of the results with semi-analytic calculations for the generation of free-electron laser pulses in the SASE3 undulator reveals an influence of apertures along the beam transport on the exact harmonic content to be accounted for at the experiment. The second-harmonic content is measured to be in the range of 0.1% to 0.3%, while the third-harmonic contributed a few percent to the SASE3 emission. For experiments at the SQS instrument, these numbers can be reduced through specific selections of the mirror reflection angles.


Material transport within specialised ciliary shafts on Rhabdopleura zooids.
The surface of the Rhabdopleura zooid is ciliated. The cilia of the cephalic shield and tentacles have paddle-like swellings of the shaft. These swellings are usually about 0.6-1 micron in diameter and most frequently found in the distal 1-2 micron of the ciliary shaft. Others are found in other positions along the length of the cilium and it is suggested that at least some of these swellings represent material transport within the cilium. Paddle shaped cilia are probably more efficient than normal cilia in moving water and food particles. If these cilia are involved in the building of the tubular coenecium then their distribution suggests that the tentacles as well as the cephalic shield are actively involved in tube building.


Genome scan of systemic biomarkers of vascular inflammation in the Framingham Heart Study: evidence for susceptibility loci on 1q.
Vascular inflammation plays a central role in atherosclerosis and inflammatory biomarkers predict risk of cardiovascular disease (CVD). Thus, finding genes that influence systemic levels of inflammatory biomarkers may provide insights into genetic determinants of vascular inflammation and CVD. We conducted variance-component linkage analyses of blood levels of four biomarkers of vascular inflammation [C-reactive protein (CRP), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1)] in 304 extended families from the Framingham Heart Study, using data from a 10cM genome scan. We computed p-values by a permutation approach. Heritability estimates ranged from 14% (IL-6) to 44% (MCP-1) after log transforming and adjusting for covariates. Significant linkage to MCP-1 was found on chromosome 1 (LOD=4.27 at 186cM; genome-wide p=0.005), in a region containing inflammatory candidate genes such as SELE, SELP (E- and P-selectin) and CRP. Other linkage peaks with LOD scores >2 were found for MCP-1 on chromosome 1 (LOD=2.04 at 16cM; LOD=2.34 at 70cM) and chromosome 17 (LOD=2.44 at 22cM) and for sICAM-1 on chromosome 1 at 229cM (LOD=2.09) less than 5cM from the interleukin-10 (IL10) gene. Multiple genes on chromosome 1 may influence inflammatory biomarker levels and may have a potential role in development of CVD.