Effects of acid-base disturbances on renal handling of magnesium in the dog.
Clearance and micropuncture studies were performed in four groups of acutely thyroparathyroidectomized animals to study the effects of alkalosis and acidosis on the renal handling of magnesium. Our results indicate that chronic metabolic acidosis reduces, whereas acute metabolic alkalosis enhances, magnesium reabsorption. The site within the nephron where absorption of magnesium increases or decreases during acid-base disturbances was beyond the late proximal tubule. Tubular fluid bicarbonate was also measured in these experiments, and the results indicated that magnesium reabsorption in the distal tubule correlated to bicarbonate delivery. However, whether this was a direct or an indirect effect of bicarbonate on magnesium transport could not be delineated.


sEMG Activity in Superimposed Vibration on Suspended Supine Bridge and Hamstring Curl.
Traditionally in strength and conditioning environments, vibration has been transmitted using platforms, barbells, dumbbells, or cables but not suspension devices. This study aimed to examine the effects on the lower limb of applying superimposed vibration on a suspension device. Twenty-one physically active men and women performed supine bridge and hamstring curl exercises in three suspended conditions (non-vibration, vibration at 25 Hz, and vibration at 40 Hz). In each exercise condition, the perceived exertion scale for resistance exercise (OMNI-Res) was registered, and the electromyographic signal was assessed for gastrocnemius (medialis and lateralis), biceps femoris, semitendinosus, gluteus maximus, and rectus femoris. A linear mixed model indicated a significant fixed effect for vibration at 25 Hz and 40 Hz on muscle activity in suspended supine bridge (p < 0.05), but no effect for suspended hamstring curl (p > 0.05). Likewise, the Friedman test showed a significant main effect for vibration at 25 Hz and 40 Hz in suspended supine bridge (p < 0.05) but not for suspended hamstring curl (p > 0.05) on OMNI-Res. Post hoc analysis for suspended supine bridge with vibration at 25 Hz showed a significant activation increase in gastrocnemius lateralis (p = 0.008), gastrocnemius medialis (p = 0.000), semitendinosus (p = 0.003) activity, and for semitendinosus under 40 Hz condition (p = 0.001) compared to the non-vibration condition. Furthermore, OMNI-Res was significantly higher for the suspended supine bridge at 25 Hz (p = 0.003) and 40 Hz (p = 0.000) than for the non-vibration condition. Superimposed vibration at 25 Hz elicits a higher neuromuscular response during the suspended supine bridge, and the increase in vibration frequency also raises the OMNI-Res value.


Facilitation of the isometric maximum voluntary contraction with traction. A test of PNF predictions.
Mean rectified electromyographic activity in vastus lateralis (VL) was recorded with surface electrodes during several Ss isometric maximum voluntary contractions performed in the PNF pattern of flexion-abduction-internal rotation, with the subject supine. The effects of longitudinally applied traction forces were compared in a within subject design employing latin square and counterbalanced presentation. Consistent with predictions, as traction force increased the group mean EMG showed a statistically significant increase. A brief survey using force platform measurements indicated that trained physical therapists tended to apply equal or greater forces than the 20 lb maximum used in the experiment.


The educational and psychosocial needs of students with additional provisions during COVID-19 in Greece: Parents' perspectives against schools' crisis management.
The sudden breakdown of educational and care services following the COVID-19 outbreak caused severe implications to the educational and psychosocial well-being of students with additional needs. The present study investigates the perspectives of parents of students requiring additional provisions in relation to the schools' responsiveness against their children's educational and psychosocial needs during the COVID-19 pandemic, with a focus on (non-) applied inclusive and empowerment practices of parenthood. A sample of 125 parents in Greece filled out a self-reported questionnaire providing information on four main themes: school organisation in accordance with the COVID-19 measures; distance education; support on transition from quarantine and remote education back to school; and parental empowerment. The data revealed that most of the participating parents felt poorly supported during the pandemic. The feeling of being left alone in supporting their children and in fully meeting their personal needs and emotions was also identified. The demographics of the participating parents with children with additional needs revealed an experiences mosaic in relation to the parents' level of education, the number of children who were present in their households, the children's gender as well as their level of school education (preschool- and primary school-aged or secondary school-aged pupils) and attendance of the school programme in regular or special schools. Data suggest that regular and special schools in Greece, as orchestrated by the Ministry of Education, deployed practices that left students requiring additional provisions unsupported in relation to their educational and psychosocial needs while their parents felt disempowered during the whole period of the COVID-19 pandemic. A range of implications on a more effective support for families and their children with additional needs in alignment with the principles of inclusive education is detailed and discussed. The focus of research on the schools' responsiveness to the needs of students requiring additional provisions from the perspective of their parents is of critical importance as it may offer valuable insights pertaining to the school's inclusive policy practices and the promotion of empowering parent partnerships during crisis times. The knowledge gained by exploring parents' experiences will contribute significantly to inform modifications and changes in education delivery in crisis times so as school, as a social system, become more inclusive, supportive, and effective for pupils with additional needs. So far, little attention has been paid to the above-mentioned issues. In the current paper, the parents perspectives were explored through a self-reported questionnaire to reflect on the way schools responded to theirs and their children's educational and psychosocial needs during the COVID-19 pandemic. Most of the participating parents felt poorly supported. The feeling of being left alone in supporting their children and in fully meeting their personal needs and emotions was also identified. The demographics of the participating parents with children requiring additional provisions revealed an experiences mosaic in relation to the parents' level of education, the number of children who were present in their households, the children's gender as well as their level of school education (preschool and primary school or secondary school education) and attendance of the school programme in regular or special schools. A range of implications on a more effective support for families and their children with additional needs in alignment with the principles of inclusive education is detailed and discussed.


Urogenital tuberculosis in children.
The clinical and radiological features of 16 children with urogenital tuberculosis are reviewed. The possibility of urinary tract involvement should be considered in all children with evidence of past or active pulmonary tuberculosis, or who are primary contacts.


[Diego Rivera: a great master and a didactic and discerning medical historian].
Diego Rivera is one of the artistic giants of the 20th century. His many original creations included landscapes, portraits and large murals created in both Mexico and the United States. Rivera ventured into many styles-cubism, naturalism and narrative realism-with great success. Rivera's murals build on those of the Renaissance, pre-historic and colonial civilizations of Mexico. Biological and medical topics and their history form an important concern in Rivera's work, present in many of his murals in a highly informative and creative manner. His two History of Cardiology murals present an original and comprehensive account of the developments of this medical specialty from pre-historic to modern times. His History of Medicine in Mexico (The people demands health) mural is a creatively and vigorously fashioned and highly dynamic and synthetic vision of the relationships between pre-historic and modern medicine in Mexico and its social foundations. Medical topics such as vaccines and vaccination, embryology and surgery are inventively and accurately presented in the large mural, Detroit Industry. The trigger and impetus for the concern of Rivera for these topics of life and death, and the exceedingly ground-breaking way he presents them, appear to stem from his rational materialism, his concern for collective wellbeing, his belief in progress through scientific developments and political action and his commitment to understand Mexican and American history.


An individual's skin stiffness predicts their tactile discrimination of compliance.
Individual differences in tactile acuity have been correlated with age, gender and finger size, whereas the role of the skin's stiffness has been underexplored. Using an approach to image the 3-D deformation of the skin surface during contact with transparent elastic objects, we evaluate a cohort of 40 young participants, who present a diverse range of finger size, skin stiffness and fingerprint ridge breadth. The results indicate that skin stiffness generally correlates with finger size, although individuals with relatively softer skin can better discriminate compliant objects. Analysis of contact at the skin surface reveals that softer skin generates more prominent patterns of deformation, in particular greater rates of change in contact area, which correlate with higher rates of perceptual discrimination of compliance, regardless of finger size. Moreover, upon applying hyaluronic acid to soften individuals' skin, we observe immediate, marked and systematic changes in skin deformation and consequent improvements in perceptual acuity in differentiating compliance. Together, the combination of 3-D imaging of the skin surface, biomechanics measurements, multivariate regression and clustering, and psychophysical experiments show that subtle distinctions in skin stiffness modulate the mechanical signalling of touch and shape individual differences in perceptual acuity. KEY POINTS: Although declines in tactile acuity with ageing are a function of multiple factors, for younger people, the current working hypothesis has been that smaller fingers are better at informing perceptual discrimination because of a higher density of neural afferents. To decouple relative impacts on tactile acuity of skin properties of finger size, skin stiffness, and fingerprint ridge breadth, we combined 3-D imaging of skin surface deformation, biomechanical measurements, multivariate regression and clustering, and psychophysics. The results indicate that skin stiffness generally correlates with finger size, although it more robustly correlates with and predicts an individual's perceptual acuity. In particular, more elastic skin generates higher rates of deformation, which correlate with perceptual discrimination, shown most dramatically by softening each participant's skin with hyaluronic acid. In refining the current working hypothesis, we show the skin's stiffness strongly shapes the signalling of touch and modulates individual differences in perceptual acuity.


Antimicrobial activity of Hemidesmus indicus, Ficus bengalensis and Pterocarpus marsupium roxb.
The antimicrobial activity of Hemidesmus indicus, Ficus bengalensis and Pterocarpus marsupium roxb was evaluated against pathogenic bacteria Stahylococcus aureus, Pseudomonas aeruginosa and Klebsiella pneumonia in an in vitro condition. Aqueous extracts from roots of H. indicus and barks of F. bengalensis and P. marspium roxb were tested for antimicrobial activity using the zone of inhibition method and also screened for phytochemicals. The aqueous extract of P. marsupium roxb inhibited growth of bacteria with the minimal inhibitory concentration ranging from 0.04 mg to 0.08 mg and extracts of F. bengalensis and H. indicus showed inhibition at the range of 0.04 mg to 0.1 mg against the bacteria tested. The susceptibility of bacterial pathogens was in the order of S. aureus, K. pneumoniae and P. aeruginosa. The antimicrobial activity of plant extracts was synergistic with antibiotics tested. Results of the present study suggest that the aqueous extracts of H. indicus, F. bengalensis and P. marspium roxb has significant antibacterial activity against pathogenic bacteria.


Psychological stress and cytokine production in multiple sclerosis: correlation with disease symptomatology.
Psychological variables such as perceived stress appear to play a role in symptom onset or disease exacerbation in multiple sclerosis (MS). The authors sought to determine if perceived stress is indeed associated with the expression of pro-inflammatory cytokines and disease symptoms in individuals with MS. To do so, the authors examined the relationships among disease symptomatology, perceived stress, and cytokine production from peripheral blood mononuclear cells in 42 outpatients with MS and 36 normative controls. The authors drew peripheral blood from all subjects prior to the completion of a series of psychological instruments. The authors measured stress using the Perceived Stress scale and negative mood with the Profile of Mood States. Disease symptoms were measured using the Multiple Sclerosis Symptom Checklist. Cytokine production was induced separately by lipopolysaccharide and a combination of phytohemagglutinin and phorbol-12-myristate-13-acetate. In MS subjects, the induced production of interleukin (IL)-6 and IL-10 positively correlated with psychological stress, mood disturbance, and disease symptomatology. In contrast, psychological stress in control subjects significantly correlated with level of tumor necrosis factor-alpha (TNF-α), and mood disturbance correlated with levels of TNF-α and interferon-gamma. As well, compared to controls, MS subjects exhibited a significant fourfold increase in the production of IL-12. There is, in those with MS, a pattern of IL-6 and IL-10 production that correlates significantly with perceived stress and disease symptomatology.


Open, Laparoscopic, and Robotic Inguinal Hernia Repair: Outcomes and Predictors of Complications.
The robotic approach to an inguinal hernia has not been compared head to head with the open and laparoscopic techniques in randomized controlled trials. Furthermore, long-term outcomes for robotic inguinal hernia repair (RHR) are lacking. In this study, we compared laparoscopic inguinal hernia repair (LHR) and RHR with open inguinal hernia repair (OHR) in veteran patients performed by surgeons most familiar with each approach. A retrospective single-institution analysis of 1299 inguinal hernia repairs performed at the VA North Texas Health Care System between 2005 and 2017 was undertaken. Three surgeons performed the operations, each an expert in one approach, and there was no crossover in techniques. A total of 1100 OHRs, 128 LHRs, and 71 RHRs were performed. Univariable analysis was undertaken to determine associations between techniques and outcomes (OHR versus LHR; OHR versus RHR; LHR versus RHR). Setting complications as a dependent variable, multivariable analyses were undertaken to determine an association with complications as well as independent predictors of complications. Patient demographics were similar among groups except for age that was higher in the OHR cohort. The average follow-up was 5.2 ± 3.4 y. In the present report, recurrence was associated with a higher rate in the RHR versus OHR (5.6% versus 1.7%; P < 0.02), but not in the LHR versus OHR (3.9% versus 1.9%; P = 0.09). Inguinodynia was more likely to occur in both the LHR and RHR compared with the OHR (9.4% and 14.1 versus 1.5%; both P's < 0.001). Urinary retention was also more common in the LHR and RHR than in the OHR (5.5% and 5.6% versus 1.8%, both P's < 0.05) as was the rate of overall complications (34.4% and 38.0% versus 11.2%, both P's < 0.001). Multivariable regression analysis showed femoral hernias, ASA, serum albumin, operative room time, a recurrent hernia, and the minimally invasive approaches were independent predictors of overall complications. Outcomes in the OHR cohort were, in general, superior compared with both the LHR and RHR. However, these strategies should be viewed as complementary. The best approach to an inguinal hernia repair rests on the specific expertise of the surgeon.


Persistent fetal superficial middle cerebral vein: an anatomical study.
The superficial middle cerebral vein (SMCV) drains the venous blood from most of the superolateral surface of the brain and drains typically into the cavernous sinus as mentioned in standard textbooks. But the drainage of the SMCV is variable as indicated by various radiological studies. Although variations in the drainage of the SMCV exist, there is a shortage in the literature providing cadaveric evidence for the same. The present study was designed to identify the variations in the drainage pattern of the SMCV in fetal cadavers. During the dissection of formalin-fixed full-term fetuses, deviation in the drainage of the SMCV was observed in five out of 30 cases. In three out of 30 specimens (10%), SMCV was observed draining into superior petrosal sinus; and in two specimens (6.6%) into the transverse sinus. In the remaining specimens, the SMCV drained directly into the cavernous sinus. Knowledge of the variations noted in the present study is essential, not only for diagnosing several diseases involving the cavernous sinus or paracavernous sinuses but also in surgeries of paracavernous sinus lesions and endovascular treatment of arteriovenous fistulas. The SMCV and superior petrosal sinus can be a venous refluxing route in patients with arteriovenous fistulas.


Midfoot Fusion Using Superconstructs for the Charcot Foot: Current Techniques and Complications.
Neuroarthropathy of the foot and ankle presents a series of challenges. The treating physician faces a perfect storm of pathomechanics, deformity, and medical comorbidities. Successful treatment requires a systematic approach in diagnosis, nonsurgical management, surgical management, and long-term maintenance of the affected extremity. Nonsurgical care of the Charcot foot remains the mainstay of treatment and is successful in most cases. Surgery has become more accepted for patients with severe deformity. The concept of a superconstruct has been introduced to describe modern surgical techniques and implants that have been developed since the early 2000s where stability and durability are maximized. A superconstruct is defined by four factors: (1) fusion is extended beyond the zone of injury to bridge the area of bony dissolution; (2) aggressive bone resection is performed to allow for adequate reduction of deformity without undue tension on the soft- tissue envelope; (3) stronger implants are used than for nonneuropathic fusion procedures, including some specifically developed for fixation of the Charcot foot; and (4) the devices are applied in a position that maximizes mechanical stability to allow the implants to become load sharing. It is important to review the current techniques and implants used in fusion of the neuropathic midfoot and discuss the expected outcomes and complications based on the authors' experience.


The pluripotency regulator Oct4: a role in somatic stem cells?
Since its discovery as a critical regulator of pluripotency in embryonic stem (ES) cells and the inner cells mass of the developing blastocyst, the Pou domain-containing transcription factor Oct4 has become a proxy for "stemness" in numerous studies of somatic stem cells as its presence is often taken as evidence of pluripotency in these cells. Recent studies, however, have demonstrated that not only is Oct4 dispensable for maintaining potency in somatic stem cell compartments, but also that the methods applied to detect Oct4 and the interpretation of the resulting data may be flawed. Here we contrast pathways known to govern pluripotency in embryonic stem cells with those in adult stem cells and critically discuss the concept of pluripotency in adult stem cells of the mammalian soma.


A high-efficiency superhydrophobic plasma separator.
To meet stringent limit-of-detection specifications for low abundance target molecules, a relatively large volume of plasma is needed for many blood-based clinical diagnostics. Conventional centrifugation methods for plasma separation are not suitable for on-site testing or bedside diagnostics. Here, we report a simple, yet high-efficiency, clamshell-style, superhydrophobic plasma separator that is capable of separating a relatively large volume of plasma from several hundred microliters of whole blood (finger-prick blood volume). The plasma separator consists of a superhydrophobic top cover with a separation membrane and a superhydrophobic bottom substrate. Unlike previously reported membrane-based plasma separators, the separation membrane in our device is positioned at the top of the sandwiched whole blood film to increase the membrane separation capacity and plasma yield. In addition, the device's superhydrophobic characteristics (i) facilitates the formation of well-defined, contracted, thin blood film with a high contact angle; (ii) minimizes biomolecular adhesion to surfaces; (iii) increases blood clotting time; and (iv) reduces blood cell hemolysis. The device demonstrated a "blood in-plasma out" capability, consistently extracting 65 ± 21.5 μL of plasma from 200 μL of whole blood in less than 10 min without electrical power. The device was used to separate plasma from Schistosoma mansoni genomic DNA-spiked whole blood with a recovery efficiency of >84.5 ± 25.8%. The S. mansoni genomic DNA in the separated plasma was successfully tested on our custom-made microfluidic chip by using loop mediated isothermal amplification (LAMP) method.


Characterization of the block of sodium channels by phenytoin in mouse neuroblastoma cells.
The interaction of phenytoin (DPH) with membrane ionic channels of cultured N1E-115 neuroblastoma cells was studied. The single suction pipette technique was used for voltage clamp and intracellular perfusion. When the cells were held at -80 mV for periods of 1 min or more, DPH (20-100 microM) inhibited inward sodium current in a dose-dependent manner (resting block); resting block was relieved by hyperpolarizing cells to -100 mV for 1 min. A hyperpolarizing shift of the slow inactivation curve for the Na current was induced by DPH and can explain the effect of holding potential on the resting block. The fast Na inactivation curve, however, was not affected. During repetitive pulsing the DPH-induced inhibition of Na current was enhanced (conditioned block). Conditioned block was both voltage- and frequency-dependent. Conditioning pulses to potentials which do not appreciably open Na channels also produced conditioned block; prolongation of conditioning pulses even to durations longer than the time for maximal steady-state inactivation of the Na current progressively increased the extent of conditioned block, suggesting that DPH can interact with inactivated and closed Na channels. The time course of recovery from voltage-dependent inactivation of sodium current during conditioned block was both slowed and exhibited voltage dependence. Recovery occurred faster when membrane potential during the recovery period was more negative. We conclude that DPH blocks Na channels both by increasing the fraction of channels in an inactivated state and by delaying the transition from inactivated to closed but available channels. This effect is enhanced by depolarizing membrane potential and increasing the frequency of stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)


A Monte Carlo simulation model of mammographic imaging with x-ray sources of finite dimensions.
A simulation model of mammographic x-ray sources with finite size has been developed. The model is based on Monte Carlo methods and it takes into account the electron penetration inside the anode, the anode geometry and material, as well as the resulting heel effect and the spectral and spatial distribution of x-rays. This x-ray source simulation model has been embedded into an earlier developed simulation package of a mammography unit. The main outputs of this model are Monte Carlo generated images that correspond to the irradiation of properly designed phantoms. In this way it is possible to make studies of the influence of x-ray source characteristics on MTF. This paper presents the development of the mammographic x-ray source model, accompanied by a set of simulation studies concerning the influence of magnification effects as well as that of the x-ray spatial and spectral distribution on the mammographic spatial resolution for a certain magnification factor (m = 1.4). The validity level of the model, as well as its limitations and perspectives, rise through comparisons with experimental and theoretical data.


Cytokines and BMP-4 promote hematopoietic differentiation of human embryonic stem cells.
Human embryonic stem cells (hESCs) randomly differentiate into multiple cell types during embryoid body (EB) development. To date, characterization of specific factors capable of influencing hematopoietic cell fate from hESCs remains elusive. Here, we report that the treatment of hESCs during EB development with a combination of cytokines and bone morphogenetic protein-4 (BMP-4), a ventral mesoderm inducer, strongly promotes hematopoietic differentiation. Hematopoietic progenitors of multiple lineages were generated from EBs and were found to be restricted to the population of progeny expressing cell surface CD45. Addition of BMP-4 had no statistically significant effect on hematopoietic differentiation but enabled significant enhancement in progenitor self-renewal, independent of cytokine treatment. Hematopoietic commitment was characterized as the temporal emergence of single CD45+ cells first detectable after day 10 of culture and was accompanied by expression of hematopoietic transcription factors. Despite the removal of cytokines at day 10, hematopoietic differentiation of hESCs continued, suggesting that cytokines act on hematopoietic precursors as opposed to differentiated hematopoietic cells. Our study establishes the first evidence for the role of cytokines and BMP-4 in promoting hematopoietic differentiation of hESC lines and provides an unprecedented system to study early developmental events that govern the initiation of hematopoiesis in the human.


A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis.
The 18 kDa translocator protein (TSPO) is increasingly used to study brain and spinal cord inflammation in degenerative diseases of the CNS such as multiple sclerosis. The enhanced TSPO PET signal that arises during disease is widely considered to reflect activated pathogenic microglia, although quantitative neuropathological data to support this interpretation have not been available. With the increasing interest in the role of chronic microglial activation in multiple sclerosis, characterising the cellular neuropathology associated with TSPO expression is of clear importance for understanding the cellular and pathological processes on which TSPO PET imaging is reporting. Here we have studied the cellular expression of TSPO and specific binding of two TSPO targeting radioligands (3H-PK11195 and 3H-PBR28) in tissue sections from 42 multiple sclerosis cases and 12 age-matched controls. Markers of homeostatic and reactive microglia, astrocytes, and lymphocytes were used to investigate the phenotypes of cells expressing TSPO. There was an approximate 20-fold increase in cells double positive for TSPO and HLA-DR in active lesions and in the rim of chronic active lesion, relative to normal appearing white matter. TSPO was uniformly expressed across myeloid cells irrespective of their phenotype, rather than being preferentially associated with pro-inflammatory microglia or macrophages. TSPO+ astrocytes were increased up to 7-fold compared to normal-appearing white matter across all lesion subtypes and accounted for 25% of the TSPO+ cells in these lesions. To relate TSPO protein expression to ligand binding, specific binding of the TSPO ligands 3H-PK11195 and 3H-PBR28 was determined in the same lesions. TSPO radioligand binding was increased up to seven times for 3H-PBR28 and up to two times for 3H-PK11195 in active lesions and the centre of chronic active lesions and a strong correlation was found between the radioligand binding signal for both tracers and the number of TSPO+ cells across all of the tissues examined. In summary, in multiple sclerosis, TSPO expression arises from microglia of different phenotypes, rather than being restricted to microglia which express classical pro-inflammatory markers. While the majority of cells expressing TSPO in active lesions or chronic active rims are microglia/macrophages, our findings also emphasize the significant contribution of activated astrocytes, as well as smaller contributions from endothelial cells. These observations establish a quantitative framework for interpretation of TSPO in multiple sclerosis and highlight the need for neuropathological characterization of TSPO expression for the interpretation of TSPO PET in other neurodegenerative disorders.


Progesterone-Based Therapy Protects Against Influenza by Promoting Lung Repair and Recovery in Females.
Over 100 million women use progesterone therapies worldwide. Despite having immunomodulatory and repair properties, their effects on the outcome of viral diseases outside of the reproductive tract have not been evaluated. Administration of exogenous progesterone (at concentrations that mimic the luteal phase) to progesterone-depleted adult female mice conferred protection from both lethal and sublethal influenza A virus (IAV) infection. Progesterone treatment altered the inflammatory environment of the lungs, but had no effects on viral load. Progesterone treatment promoted faster recovery by increasing TGF-β, IL-6, IL-22, numbers of regulatory Th17 cells expressing CD39, and cellular proliferation, reducing protein leakage into the airway, improving pulmonary function, and upregulating the epidermal growth factor amphiregulin (AREG) in the lungs. Administration of rAREG to progesterone-depleted females promoted pulmonary repair and improved the outcome of IAV infection. Progesterone-treatment of AREG-deficient females could not restore protection, indicating that progesterone-mediated induction of AREG caused repair in the lungs and accelerated recovery from IAV infection. Repair and production of AREG by damaged respiratory epithelial cell cultures in vitro was increased by progesterone. Our results illustrate that progesterone is a critical host factor mediating production of AREG by epithelial cells and pulmonary tissue repair following infection, which has important implications for women's health.


Effects of Silver Nanoparticles on Physiological and Proteomic Responses of Tobacco (Nicotiana tabacum) Seedlings Are Coating-Dependent.
The harmful effects of silver nanoparticles (AgNPs) have been confirmed in many organisms, but the mechanism of their toxicity is not yet fully understood. In biological systems, AgNPs tend to aggregate and dissolve, so they are often stabilized by coatings that influence their physico-chemical properties. In this study, the effects of AgNPs with different coatings [polyvinylpyrrolidone (PVP) and cetyltrimethylammonium bromide (CTAB)] on oxidative stress appearance and proteome changes in tobacco (Nicotiana tabacum) seedlings have been examined. To discriminate between the nanoparticulate Ag form from the ionic one, the treatments with AgNO3, a source of Ag+ ions, were also included. Ag uptake and accumulation were found to be similarly effective upon exposure to all treatment types, although positively charged AgNP-CTAB showed less stability and a generally stronger impact on the investigated parameters in comparison with more stable and negatively charged AgNP-PVP and ionic silver (AgNO3). Both AgNP treatments induced reactive oxygen species (ROS) formation and increased the expression of proteins involved in antioxidant defense, confirming oxidative stress as an important mechanism of AgNP phytotoxicity. However, the mechanism of seedling responses differed depending on the type of AgNP used. The highest AgNP-CTAB concentration and CTAB coating resulted in increased H2O2 content and significant damage to lipids, proteins and DNA molecules, as well as a strong activation of antioxidant enzymes, especially CAT and APX. On the other hand, AgNP-PVP and AgNO3 treatments induced the nonenzymatic antioxidants by significantly increasing the proline and GSH content. Exposure to AgNP-CTAB also resulted in more noticeable changes in the expression of proteins belonging to the defense and stress response, carbohydrate and energy metabolism and storage protein categories in comparison to AgNP-PVP and AgNO3. Cysteine addition significantly reduced the effects of AgNP-PVP and AgNO3 for the majority of investigated parameters, indicating that AgNP-PVP toxicity mostly derives from released Ag+ ions. AgNP-CTAB effects, however, were not alleviated by cysteine addition, suggesting that their toxicity derives from the intrinsic properties of the nanoparticles and the coating itself.


Development of difluoromethyl-ornithine and Bowman-Birk inhibitor as chemopreventive agents by assessment of relevant biomarker modulation: some lessons learned.
A major goal in the development of chemopreventive agents has been to develop markers that reflect the underlying process of carcinogenesis and which are modulatable by the agent under study. An important application of such markers will be to select cohorts that are at elevated risk for cancer development, which should allow use of smaller sample sizes in definitive phase III trials as well as shorter duration (and lower cost), without loss of statistical power. Susceptibility and surrogate end-point biomarkers are particularly important in this respect. Intermediate markers are probably best assessed in terms of proportionate rather than relative risk. The systematic development of difluoromethylornithine for use in chemoprevention against human cancer has involved pilot, phase IIa and IIb trials using participants with prior colonic polyps as the study group. A unique feature of the phase IIa study was the use of a dose de-escalation design which allowed selection of the lowest effective non-toxic dose of difluoromethylornithine. The phase IIb trial now in progress is using a combination of sulindac with difluoromethylornithine; the rationale for selection of markers for this study and for a randomized phase III registration trial is discussed. We also review the findings in phase I and IIa trials of Bowman-Birk inhibitor concentrate, in which patients with measurable oral leukoplakia are the study group.


Prevalence and factors associated with spontaneous closure of congenital ventricular septal defects.
Most of congenital ventricular septal defects evolve towards spontaneous closure of different mechanisms depending on their location. To determine the prevalence and factors associated with spontaneous closure of congenital ventricular septal defects. We conducted a retrospective study of 1000 patients diagnosed with congenital ventricular septal defects in our department from January 2000 to December 2017. After an average follow-up of 52.65 months (± 76.93 months), 183 (18.88%) of ventricular septal defects closed spontaneously. The average time for spontaneous closure was 45.78 months (76.34 months). 30.77% of trabecular ventricular septal defects (p<0.05) and 16.93% of perimembranous defects closed spontaneously (p=0.17). 28.5% of perimembranous defects associated with aneurysm formation versus 17.4% of those without associated aneurysm evolved to spontaneous closure (p<0.05). 65.6% of spontaneous closure occured during the first 3 years of life. In multivariate analysis, trabecular site [OR=2.85; CI (2.05-3.97)] and aneurysms of membranous septum [OR=1.9; CI (1.41-2.8)] were independent factors associated with spontaneous closure of defects. The highest VSD closure rate was observed during the first three years of life. Trabecular site and aneurysms tissue of membranous septum were found as independent factors associated with spontaneous closure.


Highly sensitive acetylene detection based on multi-pass retro-reflection-cavity-enhanced photoacoustic spectroscopy and a fiber amplified diode laser.
In this paper, a multi-pass retro-reflection-cavity-enhanced photoacoustic spectroscopy (PAS) based gas sensor is reported for the first time. The multi-pass retro-reflection-cavity consisted of two right-angle prisms and was designed to reflect the laser beam to pass through the photoacoustic (PA) cell four times, which improved the acetylene (C2H2)-PAS sensor signal level significantly. The optical power of a near-infrared distributed feedback (DFB) diode laser emitting a continuous wave (CW) was amplified to 1000 mW with an erbium-doped fiber amplifier. The background noise was reduced with wavelength modulation spectroscopy (WMS) and 2nd harmonic demodulation techniques. The linear optical power and concentration response of such a PAS sensor were investigated, and the experimental results showed excellent characteristics. When the integration the time of the sensor system was set to 1 s, the minimum detection limit (MDL) for C2H2 detection was 8.17 ppb, which corresponds to a normalized noise equivalent absorption coefficient (NNEA) of 1.84 × 10-8 cm-1W/√Hz. The long-term stability of such a multi-pass retro-reflection-cavity-enhanced PAS based C2H2 sensor was evaluated by an Allan deviation analysis. It was demonstrated that the multi-pass retro-reflection-cavity-enhanced PAS sensor had an excellent stability. An MDL of 600 ppt was achieved when the integration time was set to ~1000 s. It was verified that the method of multi-pass retro-reflection-cavity-enhanced PAS with an amplified laser source improved the sensor performance significantly. If an appropriate cavity design with increasing reflection times is used, the MDL of such a PAS-based sensor can be further improved.


Laser-Printed, Flexible Graphene Pressure Sensors.
While the outstanding properties of graphene have attracted a lot of attention, one of the major bottlenecks of its widespread usage is its availability in large volumes. Laser printing graphene on polyimide films is an efficient single-step fabrication process that can remedy this issue. A laser-printed, flexible pressure sensor is developed utilizing the piezoresistive effect of 3D porous graphene. The pressure sensors performance can be easily adjusted via the geometrical parameters. They have a sensitivity in the range of 1.23 × 10-3 kPa and feature a high resolution with a detection limit of 10 Pa in combination with an extremely wide dynamic range of at least 20 MPa. They also provide excellent long-term stability of at least 15 000 cycles. The biocompatibility of laser-induced graphene is also evaluated by cytotoxicity assays and fluorescent staining, which show an insignificant drop in viability. Polymethyl methacrylate coating is particularly useful for underwater applications, protecting the sensors from biofouling and shunt currents, and enable operation at a depth of 2 km in highly saline Red Sea water. Due to its features, the sensors are a prime choice for multiple healthcare applications; for example, they are used for heart rate monitoring, plantar pressure measurements, and tactile sensing.


Immunocompetent cells from the lower respiratory tract of normal human lungs.
Subpopulations of lymphocytes in the broncho-alveolar air spaces of normal human lungs were compared with those in peripheral blood. Bone marrow-derived (bursal-equivalent) cells (B cells) were identified by complement receptors (EAC rosettes) and by surface immunoglobulin. Thymus-derived lymphocytes (T cells) were identified by their proliferative response to mitogens and the E rosette technique. Cells in lung air spaces were recovered from eight healthy nonsmoking volunteers by segmental lavage with the flexible bronchofiberscope. On the average, macrophages constituted 78% and lymphocytes 17% of the cells in the aspirates. B cells detected by surface immunoglobulin and complement receptors equaled 22% and 15% of lung lymphocytes, respectively. The distribution of lung B cells into heavy chain immunoglobulin classes revealed IgM and IgG to be the predominant classes, with mean values of 14.5% and 9.3%, respectively; the corresponding value for IgA was 5%. A comparable order of frequency (IgM greater than IgG greater than IgA) was observed for purified peripheral blood lymphocytes in the same and other control subjects. T cells comprised the majority (47%) of identifiable lung lymphocytes by the E rosette method. The presence of lung T cells was also corroborated by their proliferative response to mitogens (phytohemagglutinin and concanavallin A), but the response was less than that of equal numbers of peripheral blood lymphocytes from the same subjects. The B/T cell ratio for lung lymphocytes was comparable to results with peripheral blood lymphocytes in the same subjects, but a higher proportion of lung lymphocytes could not be identified as either T or B cells. It is postulated that lung lymphocytes participate in the local immune defenses of the lung.


Proteasome inhibitors in glioblastoma.
Glioblastomas (GBM) are the tumors originating from the star shaped supportive cells in brain known as astrocytes. These tumors are highly cancerous as they have the ability to proliferate very quickly. New therapeutic strategies are being developed worldwide to fight against deadly GBM, which has median survival time of just 14 months. Proteasome inhibition is an upcoming strategy for GBM. Proteasome inhibition has shown promising results in cancers such as myeloma. However, in the recent past this form of therapy has also shown positive results in brain tumors in the form of elevated apoptosis. We searched the electronic database PubMed for pre-clinical as well as clinical controlled trials reporting importance of proteasome inhibitors during GBM. It was observed clearly that this approach is evolving and has been observed to be promising therapeutic avenue against GBM. Thus, the present review aims to enlighten the present views on use of proteasome inhibition strategy in the case of GBM.


Absolute Binding Energies of Core Levels in Solids from First Principles.
A general method is presented to calculate absolute binding energies of core levels in metals and insulators, based on a penalty functional and an exact Coulomb cutoff method in the framework of density functional theory. The spurious interaction of core holes between supercells is avoided by the exact Coulomb cutoff method, while the variational penalty functional enables us to treat multiple splittings due to chemical shift, spin-orbit coupling, and exchange interaction on equal footing, both of which are not accessible by previous methods. It is demonstrated that the absolute binding energies of core levels for both metals and insulators are calculated by the proposed method in a mean absolute (relative) error of 0.4 eV (0.16%) for eight cases compared to experimental values measured with x-ray photoemission spectroscopy within a generalized gradient approximation to the exchange-correlation functional.


A miRNA signature for defining aggressive phenotype and prognosis in gliomas.
Gliomas represent a disparate group of tumours for which there are to date no cure. Thus, there is a recognized need for new diagnostic and therapeutic approaches based on increased understanding of their molecular nature. We performed the comparison of the microRNA (miRNA) profile of 8 WHO grade II gliomas and 24 higher grade tumours (2 WHO grade III and 22 glioblastomas) by using the Affymetrix GeneChip miRNA Array v. 1.0. A relative quantification method (RT-qPCR) with standard curve was used to confirm the 22 miRNA signature resulted by array analysis. The prognostic performances of the confirmed miRNAs were estimated on the Tumor Cancer Genome Atlas (TCGA) datasets. We identified 22 miRNAs distinguishing grade II gliomas from higher grade tumours. RT-qPCR confirmed the differential expression in the two patients' groups for 13 out of the 22 miRNAs. The analysis of the Glioblastoma Multiforme (GBM) and Lower Grade Glioma (LGG) datasets from TCGA demonstrated the association with prognosis for 6 of those miRNAs. Moreover, in the GBM dataset miR-21 and miR-210 were predictors of worse prognosis in both univariable and multivariable Cox regression analyses (HR 1.19, p = 0.04, and HR 1.18, p = 0.029 respectively). Our results support a direct contribution of miRNAs to glioma cancerogenesis and suggest that miR-21 and miR-210 may play a role in the aggressive clinical behaviour of glioblastomas.


Automated Parameter Extraction Of ScAlN MEMS Devices Using An Extended Euler-Bernoulli Beam Theory.
Magnetoelectric sensors provide the ability to measure magnetic fields down to the pico tesla range and are currently the subject of intense research. Such sensors usually combine a piezoelectric and a magnetostrictive material, so that magnetically induced stresses can be measured electrically. Scandium aluminium nitride gained a lot of attraction in the last few years due to its enhanced piezoelectric properties. Its usage as resonantly driven microelectromechanical system (MEMS) in such sensors is accompanied by a manifold of influences from crystal growth leading to impacts on the electrical and mechanical parameters. Usual investigations via nanoindentation allow a fast determination of mechanical properties with the disadvantage of lacking the access to the anisotropy of specific properties. Such anisotropy effects are investigated in this work in terms of the Young's modulus and the strain on basis of a MEMS structures through a newly developed fully automated procedure of eigenfrequency fitting based on a new non-Lorentzian fit function and subsequent analysis using an extended Euler-Bernoulli theory. The introduced procedure is able to increase the resolution of the derived parameters compared to the common nanoindentation technique and hence allows detailed investigations of the behavior of magnetoelectric sensors, especially of the magnetic field dependent Young's modulus of the magnetostrictive layer.


Calculating the binding free energies of charged species based on explicit-solvent simulations employing lattice-sum methods: an accurate correction scheme for electrostatic finite-size effects.
The calculation of a protein-ligand binding free energy based on molecular dynamics (MD) simulations generally relies on a thermodynamic cycle in which the ligand is alchemically inserted into the system, both in the solvated protein and free in solution. The corresponding ligand-insertion free energies are typically calculated in nanoscale computational boxes simulated under periodic boundary conditions and considering electrostatic interactions defined by a periodic lattice-sum. This is distinct from the ideal bulk situation of a system of macroscopic size simulated under non-periodic boundary conditions with Coulombic electrostatic interactions. This discrepancy results in finite-size effects, which affect primarily the charging component of the insertion free energy, are dependent on the box size, and can be large when the ligand bears a net charge, especially if the protein is charged as well. This article investigates finite-size effects on calculated charging free energies using as a test case the binding of the ligand 2-amino-5-methylthiazole (net charge +1 e) to a mutant form of yeast cytochrome c peroxidase in water. Considering different charge isoforms of the protein (net charges -5, 0, +3, or +9 e), either in the absence or the presence of neutralizing counter-ions, and sizes of the cubic computational box (edges ranging from 7.42 to 11.02 nm), the potentially large magnitude of finite-size effects on the raw charging free energies (up to 17.1 kJ mol(-1)) is demonstrated. Two correction schemes are then proposed to eliminate these effects, a numerical and an analytical one. Both schemes are based on a continuum-electrostatics analysis and require performing Poisson-Boltzmann (PB) calculations on the protein-ligand system. While the numerical scheme requires PB calculations under both non-periodic and periodic boundary conditions, the latter at the box size considered in the MD simulations, the analytical scheme only requires three non-periodic PB calculations for a given system, its dependence on the box size being analytical. The latter scheme also provides insight into the physical origin of the finite-size effects. These two schemes also encompass a correction for discrete solvent effects that persists even in the limit of infinite box sizes. Application of either scheme essentially eliminates the size dependence of the corrected charging free energies (maximal deviation of 1.5 kJ mol(-1)). Because it is simple to apply, the analytical correction scheme offers a general solution to the problem of finite-size effects in free-energy calculations involving charged solutes, as encountered in calculations concerning, e.g., protein-ligand binding, biomolecular association, residue mutation, pKa and redox potential estimation, substrate transformation, solvation, and solvent-solvent partitioning.


The negative effect of repeated equine chorionic gonadotropin treatment on subsequent fertility in Alpine goats is due to a humoral immune response involving the major histocompatibility complex.
In dairy goats, the use of eCG as a convenient hormone for the induction of ovulation is necessary for out-of-season breeding and artificial insemination. However, repeated eCG treatments are followed by decreased fertility in goats inseminated at a fixed time after treatment. In this report, we show the presence of anti-eCG antibodies in plasma of treated goats. A 500 IU eCG injection induces a humoral response, with variable concentrations of anti-eCG antibody being produced in individual goats. The analysis of successive anti-eCG immune responses over several years has demonstrated the existence of different populations of goats, defined as low, medium, and high responders. By the use of two caprine microsatellites located inside (OLADRB) and outside (BM1258) the major histocompatibility complex (MHC), a significant association (p < 0.05) between the anti-eCG antibody response and some MHC-DRB alleles was found. Goats with high antibody concentrations at the time of eCG injection (> 2.5 microg/ml) exhibited a much lower kidding rate than did other females (41.3% vs. 66.7%). Lower fertility of these goats, inseminated at a fixed time after eCG treatment, might be due to the observed delay in estrus occurrence and the preovulatory LH surge.


Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes.
Low-risk myelodysplastic syndrome (MDS) with normal cytogenetics accounts for approximately 50% of MDS patients. There are no pathognomonic markers in these cases and the diagnosis rests on cytomorphologic abnormalities in bone marrow and/or peripheral blood. Affymetrix high-resolution single-nucleotide polymorphism (SNP) genotyping microarrays allow detection of cytogenetically cryptic genomic aberrations. We have studied 119 low-risk MDS patients (refractory anemia [RA] = 22; refractory cytopenia with multilineage dysplasia [RCMD] = 51; refractory anemia with ringed sideroblasts [RARS] = 12; refractory cytopenia with multilineage dysplasia with ringed sideroblasts [RCMD-RS] = 12; 5q- syndrome = 16; refractory anemia with excess blasts [RAEB] = 6) using SNP microarrays to seek chromosomal markers undetected by conventional cytogenetics. Loss of heterozygosity (LOH) detected by 50K arrays was verified using 250K and 500K arrays. We demonstrate the presence of uniparental disomy (UPD) in 46%, deletions in 10%, and amplifications in 8% of cases. Copy number (CN) changes were acquired, whereas UPDs were also detected in constitutional DNA. UPD on 4q was identified in 25% of RARS, 12% of RCMD with normal cytogenetics, 17% of RAEB, and 6% of 5q- syndrome cases. Univariate analysis showed deletions (P = .04) and International Prognostic Scoring System (IPSS; P < .001) scores correlated with overall survival; however, on multivariate analysis only IPSS scores retained prognostic significance (P < .001). We show, for the first time, that SNP microarray analysis in low-risk MDS patients reveals hitherto unrecognized UPD and CN changes that may allow stratification of these patients for early therapeutic interventions.


Assessment of in vivo response to preoperative chemotherapy and radiation therapy as a predictor of survival in patients with soft-tissue sarcoma.
Current histologic methods for staging soft-tissue sarcomas are based on histologic criteria such as number of mitoses or nuclear and cytoplasmic morphology, without taking into account the inherent biologic variability of tumors within a given histologic classification. This study demonstrated that patients whose tumors were effectively destroyed by preoperative chemotherapy and radiation therapy had an improved prognosis compared to patients whose tumors did not respond to the therapy. Four-year survival for the group that responded was 82%, compared to only 55% for the group that had a poor response. The response to preoperative chemotherapy and radiation therapy did not predict an improved sensitivity to postoperative adjuvant therapy, since the addition of postoperative chemotherapy in the high-responding group did not improve survival. Our results indicate that grade III soft-tissue sarcomas are a heterogeneous population of tumors with varying degrees of innate biologic aggressiveness and sensitivity to radiation therapy and chemotherapy, despite their apparently similar histologic appearance.


Occupancy of phosphorylation sites in pyruvate dehydrogenase phosphate complex in rat heart in vivo. Relation to proportion of inactive complex and rate of re-activation by phosphatase.
The [gamma-32P]ATP-back-titration method of estimating occupancy in vivo of the three phosphorylation sites in the pyruvate dehydrogenase complex was improved in precision by specific analysis with trypsin/formic acid, by more effective prevention of site-2 dephosphorylation during purification with NaF, and by other refinements. Disproportionation of phosphorylated complexes during purification was excluded. With this improved method it was shown that the relationship between occupancy of sites and the proportion of complex in the inactive form in rat heart in vivo is closely similar to that measured directly in heart mitochondria by incorporation of [32P]Pi. In the heart in vivo (as in mitochondria), occupancy of site 1 correlated linearly with the proportion of inactive complex. Occupancy of sites 2 and 3 only approached equivalence to that of site 1 when 99% of the complex was inactive (starved or diabetic rats). When 70% or less of the complex was inactive (resting or exercising fed normal rats), occupancy of sites 2 and 3 was minimal (3 less than 2) relative to site 1. The initial rate of re-activation by phosphatase of phosphorylated complex from hearts of resting or exercising fed normal rats was approximately three times that of complex from 48 h-starved rats.


[Anticancer propaganda: myth or reality?].
The authors raise a very important problem of anticancer propaganda aimed at the early detection of cancer to be solved nowadays by means of screening and constructive interaction between oncologists and the public. To increase the level of knowledge of the population in this area it is necessary to expand the range of its adequate awareness of tumor diseases. Only joint efforts can limit the destructive effect of cancer on people's minds, so that every person would be responsible for his own health, clearly understanding the advantages of early visit to a doctor. This once again highlights the need of educational work with the public, motivational nature of which allows strengthening the value of screening in the whole complex of measures to fight cancer.


Selection of optimized microwindows for atmospheric spectroscopy.
In atmospheric Fourier transform spectroscopy so-called microwindows are usually analyzed for retrieval of trace constituents rather than the spectrum as a whole. These microwindows, which are sets of consecutive spectral grid points, contain one or more prominent transitions of the target species, whereas it is desirable for the signal of interfering species to be minimum. An objective, quantitative method is presented to optimize the microwindow boundaries with respect to random errors, signal of interfering species, other parameter and systematic errors and to select optimum microwindows with respect to their associated retrieval errors. Case studies for N(2)O microwindows are performed for a spaceborne limb emission experiment to assess the dependence of the optimum microwindow width on the retrieval concept.


Green Fabrication of Ultrathin Co3O4 Nanosheets from Metal-Organic Framework for Robust High-Rate Supercapacitors.
Two-dimensional cobalt oxide (Co3O4) is a promising candidate for robust electrochemical capacitors with high performance. Herein, we use 2,3,5,6-tetramethyl-1,4-diisophthalate as a recyclable ligand to construct a Co-based metal-organic framework of UPC-9, and subsequently, we obtain ultrathin hierarchical Co3O4 hexagonal nanosheets with a thickness of 3.5 nm through a hydrolysis and calcination process. A remarkable and excellent specific capacitance of 1121 F·g-1 at a current density of 1 A·g-1 and 873 F·g-1 at a current density of 25 A·g-1 were achieved for the as-prepared asymmetric supercapacitor, which can be attributed to the ultrathin 2D morphology and the rich macroporous and mesoporous structures of the ultrathin Co3O4 nanosheets. This synthesis strategy is environmentally benign and economically viable due to the fact that the costly organic ligand molecules are recycled, reducing the materials cost as well as the environmental cost for the synthesis process.


Metabolic profiling of Pseudomonas aeruginosa demonstrates that the anti-sigma factor MucA modulates osmotic stress tolerance.
Metabolic footprinting has shown enormous potential as a phenotyping tool and we are interested in applying it to understand the physiology of the opportunistic pathogen Pseudomonas aeruginosa during its chronic infection of the lungs of cystic fibrosis patients. The selection pressures of surviving in the CF lung environment lead to genetic adaptations of the bacterium. A common adaptation is mutation of the mucA gene, resulting in a loss-of-function mutation to the anti-sigma factor MucA, which leads to a mucoid phenotype as a consequence of the overproduction of the extracellular polysaccharide alginate. However, apart from the mucoid phenotype little is known about the overall metabolic and physiological changes caused by mucA mutation. We investigated the pleiotropic metabolic effects of this mutation using time-resolved metabolic footprinting (extracellular metabolomics), and found changes in the levels of various metabolites associated with osmotic tolerance, including glycine-betaine, trehalose and glutamate. Physiological experiments confirmed that the isogenic mucA22 mutant is less resistant to osmotic stress than the parental PA01 wild-type strain, but only in the stationary phase of growth. Quantitative comparison of the endometabolome of the cells showed differences in the accumulation of osmoprotective metabolites by the wild-type and mucA22 mutant strains, suggesting a switch in osmo-protectant preference from glycine-betaine to trehalose.


Purification and partial characterization of peroxidase from human term placenta of non-smokers: metabolism of benzo(a)pyrene-7, 8-dihydrodiol.
Peroxidase (Donor: H(2)O(2)oxidoreductase EC 18.104.22.168) from human term placentae of non-smokers was purified to homogeneity by a combination of NH(4)Cl extraction, affinity chromatography, (NH(4))(2)SO(4)precipitation, ion-exchange and gel filtration chromatography. The homogeneity of purified human placental peroxidase (HTPP) was confirmed by gel filtration, reverse phase high performance liquid chromatography (HPLC) and SDS-PAGE. Peroxidase was found to be a membrane bound enzyme. A high concentration of NH(4)Cl (1.2 m) was needed to extract and solublize the enzyme. Removal of the salt resulted in irreversible precipitation of the enzyme. The protein exhibited a molecular mass of 126 000 kDa according to gel filtration and approximately 60 000 kDa by SDS-PAGE, indicating that the peroxidase is a homodimer. The purified peroxidase showed an optimum pH range of 7 to 8.5 and the K(m)for H(2)O(2)and guaiacol were found to be 0.08 m m and 10.0 m m, respectively. The purified peroxidase oxidized several substrates, namely potassium iodide, tetramethyl benzidine, guaiacol, ortho dianisidne and tyrosine. The enzyme was resistant to thermal denaturation up to 70 degrees C and also to chaotropic agents, guanidinium chloride and urea. Spectral properties indicated the presence of Soret band at 433 which shifted to 451 nm on complexation with cyanide. The circular dichroism studies showed that HTPP has a predominantly helical secondary structure. The enzyme showed similarities to the myeloperoxidase with regard to spectral and catalytical properties but differed significantly in amino acid composition, the R(z)value and molecular mass. Purified HTPP differed from eosinophil peroxidase in all physico-chemical properties indicating that it is not of eosinophil origin, but may represent a distinct, constitutive peroxidase in human placenta. Further, purified peroxidase catalyzed oxidation of benzo(a)pyrene-7, 8-dihydrodiol in presence of tyrosine and hydrogen peroxide to BP-tetrols, the hydrolytic products of BP-diol-epoxides, demonstrating the ability of peroxidase in bioactivation of benzo(a)pyrene in human placenta.


Profiling Expression Strategies for a Type III Polyketide Synthase in a Lysate-Based, Cell-free System.
Some of the most metabolically diverse species of bacteria (e.g., Actinobacteria) have higher GC content in their DNA, differ substantially in codon usage, and have distinct protein folding environments compared to tractable expression hosts like Escherichia coli. Consequentially, expressing biosynthetic gene clusters (BGCs) from these bacteria in E. coli frequently results in a myriad of unpredictable issues with protein expression and folding, delaying the biochemical characterization of new natural products. Current strategies to achieve soluble, active expression of these enzymes in tractable hosts, such as BGC refactoring, can be a lengthy trial-and-error process. Cell-free expression (CFE) has emerged as 1) a valuable expression platform for enzymes that are challenging to synthesize in vivo, and as 2) a testbed for rapid prototyping that can improve cellular expression. Here, we use a type III polyketide synthase from Streptomyces griseus, RppA, which catalyzes the formation of the red pigment flaviolin, as a reporter to investigate BGC refactoring techniques. We synergistically tune promoter and codon usage to improve flaviolin production from cell-free expressed RppA. We then assess the utility of cell-free systems for prototyping these refactoring tactics prior to their implementation in cells. Overall, codon harmonization improves natural product synthesis more than traditional codon optimization across cell-free and cellular environments. Refactoring promoters and/or coding sequences via CFE can be a valuable strategy to rapidly screen for catalytically functional production of enzymes from BCGs. By showing the coordinators between CFE versus in vivo expression, this work advances CFE as a tool for natural product research.


Trends in Prescription Opioids Detected in Fatally Injured Drivers in 6 US States: 1995-2015.
To assess the time trends in prescription opioids detected in fatally injured drivers. We analyzed 1995 to 2015 Fatality Analysis Reporting System data from California, Hawaii, Illinois, New Hampshire, Rhode Island, and West Virginia of toxicological tests for drivers fatally injured within 1 hour of a crash (n = 36 729). We used the Cochran-Armitage test for trend to assess the statistical significance of changes in the prevalence of prescription opioids detected in these drivers over time. The prevalence of prescription opioids detected in fatally injured drivers increased from 1.0% (95% confidence interval [CI] = 0.5, 1.4) in 1995 to 7.2% (95% CI = 5.7, 8.8) in 2015 (Z = -9.04; P < .001). Prescription opioid prevalence was higher in female than in male drivers (4.4% vs 2.9%; P < .001). Of the drivers testing positive for prescription opioids, 30.0% had elevated blood alcohol concentrations (≥ 0.01 g/dL), and 66.9% tested positive for other drugs. The prevalence of prescription opioids detected in fatally injured drivers has increased in the past 2 decades. The need to assess the effect of increased prescription opioid use on traffic safety is urgent.


The gut microbiome of horses: current research on equine enteral microbiota and future perspectives.
Understanding the complex interactions of microbial communities including bacteria, archaea, parasites, viruses and fungi of the gastrointestinal tract (GIT) associated with states of either health or disease is still an expanding research field in both, human and veterinary medicine. GIT disorders and their consequences are among the most important diseases of domesticated Equidae, but current gaps of knowledge hinder adequate progress with respect to disease prevention and microbiome-based interventions. Current literature on enteral microbiomes mirrors a vast data and knowledge imbalance, with only few studies tackling archaea, viruses and eukaryotes compared with those addressing the bacterial components.Until recently, culture-dependent methods were used for the identification and description of compositional changes of enteral microorganisms, limiting the outcome to cultivatable bacteria only. Today, next generation sequencing technologies provide access to the entirety of genes (microbiome) associated with the microorganisms of the equine GIT including the mass of uncultured microbiota, or "microbial dark matter".This review illustrates methods commonly used for enteral microbiome analysis in horses and summarizes key findings reached for bacteria, viruses and fungi so far. Moreover, reasonable possibilities to combine different explorative techniques are described. As a future perspective, knowledge expansion concerning beneficial compositions of microorganisms within the equine GIT creates novel possibilities for early disorder diagnostics as well as innovative therapeutic approaches. In addition, analysis of shotgun metagenomic data enables tracking of certain microorganisms beyond species barriers: transmission events of bacteria including pathogens and opportunists harboring antibiotic resistance factors between different horses but also between humans and horses will reach new levels of depth concerning strain-level distinctions.


Functional heterogeneity of parietal cells along the pit-gland axis.
The gastric epithelium forms numerous short pits continuous with long tubular glands divisible into isthmus neck, and base regions. Parietal cells are produced in the isthmus and migrate down to the neck and base regions as they mature and age. Stimulation of parietal cells is manifested by translocation of H(+)-K(+)-adenosinetriphosphatase-rich tubulovesicles (TV) from the cytoplasm into the secretory-apical (SA) membrane. In this study we used rabbit isolated gastric glands to examine the physiological responses of parietal cells to graded levels of stimulation. Quantitative morphometry was used to evaluate parietal cell response along the longitudinal axis of the gland. Acid secretion as estimated by [14C]aminopyrine uptake was well correlated with parallel enzymatic and immunoblot assays for the redistribution of H(+)-K(+)-ATPase from TV to SA membranes. These responses also correlated well with morphological transformations of parietal cells within the isthmus and neck regions of the gastric gland; however, parietal cells in the base of the gland showed very little morphological change in response to any of the stimuli used. The poor responsiveness of basal parietal cells is in agreement with observations of intact mucosa and suggests that older parietal cells may serve some function other than acid secretion.


Suppression of in vitro neutrophil function by feline leukaemia virus (FeLV) and purified FeLV-p15E.
Feline neutrophils (PMN) were isolated and exposed to ultraviolet light-inactivated feline leukaemia virus (UV-FeLV) and purified envelope component p15E (FeLV-p15E). Functional capacity of exposed PMN was measured in vitro utilizing the chemiluminescence (CL) response. PMN exposed to UV-FeLV demonstrated depressed CL responses to Ca2+-ionophore A23187 and latex particles. However, FeLV-p15E produced significant suppression in the CL response to A23187 but failed to produce significant alterations in response to latex particles. The data indicate that FeLV-p15E may, in part, be responsible for increased morbidity and mortality among FeLV-infected cats through suppression of the PMN population.


Expression of endothelin-B receptors by glia in vivo is increased after CNS injury in rats, rabbits, and humans.
Previous studies have demonstrated that neonatal cultures of astrocytes express functional endothelin (ET) receptors. To determine if similar ET receptors are expressed by adult glia we used 125I-ET-1 to examine the expression of ET receptors both in vivo in the normal and transected optic nerves of the rabbit and rat and in vitro in cultures of astrocytes, microglia, or oligodendrocytes. Additionally, we examined the expression of ET receptors in the human optic nerve. Moderate levels of ET(B) receptors were identified in the rabbit and rat forebrain, whereas in the normal rabbit, rat, and human optic nerves a low density of ET(B) receptors was observed, mainly in association with glial fibrillary acidic protein + (GFAP+) astrocytes. After unilateral optic nerve transection, or damage to the retina, the density of glial ET(B) receptors in the optic nerve is significantly increased in all species examined. Thus, at 7 days posttransection there is a significant increase in ET(B) receptors, and by 90 days posttransection the density of ET(B) receptors in the rabbit or rat optic nerve was among the highest of any area in the central nervous system (CNS). Primary cultures of astrocytes or microglia, but not oligodendrocytes, express 125I-ET-1 binding sites. These data demonstrate that in the normal CNS, astrocytes express low but detectable levels of ET(B) receptors, and, after CNS injury, both astrocytes and microglia express high levels of ET(B) receptors. ET(B) receptors provide a therapeutic target for regulating glial proliferation and the release of neurotrophic factors from glia that occur in response to neuronal injury.


Identification and genomic distribution of gypsy like retrotransposons in Citrus and Poncirus.
Transposable elements might be importantly involved in citrus genetic instability and genome evolution. The presence of gypsy like retrotransposons, their heterogeneity and genomic distribution in Citrus and Poncirus, have been investigated. Eight clones containing part of the POL coding region of gypsy like retrotransposons have been isolated from a commercial variety of Citrus clementina, one of the few sexual species in Citrus. Four of the eight clones might correspond to active elements given that they present all the conserved motifs described in the literature as essential for activity, no in-frame stop codon and no frame-shift mutation. High homology has been found between some of these citrus elements and retroelements within a resistance-gene cluster from potato, another from Poncirus trifoliata and two putative resistance polyproteins from rice. Nested copies of gypsy like elements are scattered along the Citrus and Poncirus genomes. The results on genomic distribution show that these elements were introduced before the divergence of both genera and evolved separately thereafter. IRAPs based on gypsy and copia types of retrotransposons seem to distribute differently, therefore gypsy based IRAPs prove a new, complementary set of molecular markers in Citrus to study and map genetic variability, especially for disease resistance. Similarly to copia-derived IRAPs, the number of copies and heterozygosity values found for gypsy derived IRAPs are lower in Poncirus than in Citrus aurantium, which is less apomictic and the most usual rootstock for clementines until 1970.


Inhibition of the olfactory cyclic nucleotide gated ion channel by intracellular calcium.
When olfactory receptor neurons are exposed to sustained application of odours, the elicited ionic current is transient. This adaptation-like effect appears to require the influx of Ca2+ through the odour-sensitive conductance; in the absence of extracellular Ca2+ the current remains sustained. Odour transduction proceeds through a G-protein-based second messenger system, resulting finally in the direct activation of an ion channel by cyclic AMP. This channel is one possible site for a negative feedback loop using Ca2+ as a messenger. In recordings of single cyclic AMP gated channels from olfactory receptor neurons, the open probability of the channel in saturating cAMP concentrations was dependent on the concentration of intracellular Ca2+. It could be reduced from 0.6 in 100 nm Ca2+ to 0.09 in 3 microM Ca2+. However, as neither the single channel conductance nor the mean open time were affected by Ca+ concentration, this does not appear to be a mechanism of simple channel block. Rather, these results suggest that intracellular Ca2+ acts allosterically to stabilize a closed state of the channel.


Comparing on-site to off-site biomass collection for Dehalococcoides biomarker gene quantification to predict in situ chlorinated ethene detoxification potential.
Biostimulation and bioaugmentation have emerged as constructive remedies for chlorinated ethene-contaminated aquifers, and a link between Dehalococcoides (Dhc) bacteria and chlorinated ethene detoxification has been established. To quantify Dhc biomarker genes, groundwater samples are shipped to analytical laboratories where biomass is collected on membrane filters by vacuum filtration for DNA extraction and quantitative real-time PCR analysis. This common practice was compared with a straightforward, on-site filtration approach to Sterivex cartridges. In initial laboratory studies with groundwater amended with known amounts of Dhc target cells, Sterivex cartridges yielded one-third of the total DNA and 9-18% of the Dhc biomarker gene copies compared with vacuum filtration. Upon optimization, DNA yields increased to 94 +/- 38% (+/-SD, n = 10), and quantification of Dhc biomarker genes exceeded the values obtained with the vacuum filtration procedure up to 5-fold. Both methods generated reproducible results when volumes containing >10(4) total Dhc target gene copies were collected. Analysis of on-site and off-site biomass collection procedures corroborated the applicability of the Sterivex cartridge for Dhc biomarker quantification in groundwater. Ethene formation coincided with Dhc cell titers of >2 x 10(6) L(-1) and high (i.e., >10(5)) abundance of the vinyl chloride reductive dehalogenase genes vcrA and/or bvcA; however, high Dhc cell titers alone were insufficient to predict ethene formation. Further, ethene formation occurred at sites with high Dhc cell titers but low or no detectable vcrA or bvcA genes, suggesting that other, not yet identified vinyl chloride reductive dehalogenases contribute to ethene formation. On-site biomass collection with Sterivex cartridges avoids problems associated with shipping groundwater and has broad applicability for biomarker monitoring in aqueous samples.


Coping Strategies Utilized by Emergency Department Providers During the COVID-19 Pandemic.
COVID-19 has exposed health care workers to new stressors; emergency department providers are at risk of increased stress. It is unknown how coping strategies are utilized by this group during a pandemic. A cross-sectional survey incorporating the Brief COPE inventory was deployed to residents, fellows, faculty, and physician assistants at a single US academic emergency department in the spring (April 2020 - May 2020) and winter (December 2020 - January 2021). Scores for 14 individual coping strategies, as well as approach (positive) and avoidant (negative) coping categories, were measured, and utilization of these coping strategies was compared with respect to the provider's role, sex, the number of people living at home, presence of pets and/or children at home, and stress level. The response rate was 58/103 (56.3%) and 50/109 (45.9%) for the spring and winter distributions, respectively. In the spring, 70.6% of responders reported increased stress vs 66% in the winter. Overall utilization of coping strategies increased slightly between spring and winter for approach coping (32.22 to 32.64) and avoidant coping (20.95 to 21.73). Resident physicians utilized less approach coping and more avoidant coping when compared to faculty/fellows. Substance use overall had a relatively low score, which increased slightly between spring and winter distributions (2.93 to 3.04). Approach coping was frequently utilized among ED providers during the COVID-19 pandemic study period. Resident physicians had higher utilization of avoidant coping strategies compared to faculty/fellows and could benefit from targeted wellness interventions during times of increased stress.


The effect of pro-ecological procedures and insect foraging on the total content of phenol compounds in winter wheat.
In laboratory conditions, the effect of pro-ecological procedures (application of effective microorganisms and Asahi SL biostimulator) and foraging by insects [cereal leaf beetle (Oulema melanopa L.) and bird cherry-oat aphid (Rhopalosiphum padi (L.)] on the total content of phenolic compounds in winter wheat, was studied. Correlations between the total content of phenolic compounds (determined by the Folin-Ciocalteau colorimetric method) expressed as the amount of pyrogallol in wheat plants: undamaged, damaged by O. melanopa, damaged by R. padi, the length of feeding scar left by cereal leaf beetle and the number of pricks made by actively feeding insects of bird cherry-oat aphid were analysed. The wheat was treated by EM inoculant and a biostimulator. The mode of application of the preparations used had a significant effect on level the total phenolic compounds in the undamaged wheat and the wheat exposed to foraging by the above-mentioned insects. The plants not exposed to insects foraging contained greater amounts of phenolic compounds than those exposed to the insects. The correlation between the total content of phenols in the wheat damaged by the insects in the 'no-choice' conditions, proved insignificant.


The impact of labial fixed appliance orthodontic treatment on patient expectation, experience, and satisfaction: an overview of systematic reviews.
Patient perception with fixed appliance orthodontic treatment is important to improve oral health-related quality of life. The main objective of this study was to evaluate the impact of labial fixed appliance orthodontic care on patient perception before, during, and after the treatment. Relevant systematic reviews investigating patient perception with fixed appliance orthodontic treatment were identified by searching electronic databases: MEDLINE via OVID (1946 to 31 December 2018), EMBASE (1974 to 31 December 2018), AMED (Allied and Complementary Medicine Database; 1985 to November 2018), PubMed (inception to 31 December 2018), Web of Science (1900 to 2018), and PsychINFO (1806 to 31 December 2018). Ongoing systematic reviews were searched using Prospero and a grey literature search was undertaken using Google Scholar and OpenGrey (www.opengrey.eu/). No language restriction was applied. Only studies investigating patient perception of fixed appliance orthodontic treatment were included. Screening, quality assessment [using the AMSTAR 2 tool (A Measurement Tool to Assess Systematic Reviews)], and data extraction were performed by two authors independently. Information was categorized and narratively synthesized for the key findings. A total of 163 articles investigating patient expectation, experience, and satisfaction with conventional ligation labial fixed orthodontic appliances were obtained. Of these, 152 observational or interventional studies were excluded, resulting in 11 eligible systematic reviews. Two were excluded as earlier reports of a Cochrane review. The quality of the reviews was variable (critically low, low, and moderate). The findings were as follows: aesthetics represents a primary motive for orthodontic treatment; a temporary deterioration in the quality of life occurs during the initial phases of treatment; gender and ethnicity factors do not have an impact on patient perception of treatment; and a positive relationship between orthodontist-patient-parent is important to achieve patient compliance and satisfaction. There is a lack of high-quality studies in terms of systematic reviews and meta-analyses for assessing patient perception with fixed appliance orthodontic treatment. The aesthetic impact of malocclusion is the main motive for seeking orthodontic treatment. Quality of life reduces during the initial stages of orthodontic treatment but improves in the later stages of treatment. Assessment before, during, and after orthodontic treatment is necessary to comprehensively assess patient perception at all stages of care. CRD42019122653. None to declare.


Teaching family medicine residents about care of adults with intellectual and developmental disabilities.
Adults with intellectual and developmental disabilities (IDD), a group with complex health problems and inequities in access to health care, look to family physicians for primary care. To enable residents to learn and demonstrate competencies that are unique to the care of adults with IDD with minimal extra time and resources required of the residency program. In their regular family medicine teaching practices, residents undertake planned encounters with adults with IDD involving comprehensive health assessments with physical examinations. Tools to implement the Canadian guidelines for primary care of adults with IDD are available to support the residents in their encounters. Background information in the form of self-learning and small group learning resources, field notes with rubrics to assess residents' development of competencies, and faculty development resources are also available. It is important to include such planned clinical experiences in family medicine residency curricula because people with IDD have special needs that are difficult to learn about in other settings. It is a benefit to residents to have patients and families actively contributing to teaching.


[Smoking and lung infection].
Tobacco smoke exposure leads to development of structural and immunological changes in the lungs. These changes favour development on inflammation in the respiratory tract. Cigarette smoking is a substantial risk factor for important bacterial and viral infections.


What matters when managing childhood fever in the emergency department? A discrete-choice experiment comparing the preferences of parents and healthcare professionals in the UK.
Fever among children is a leading cause of emergency department (ED) attendance and a diagnostic conundrum; yet robust quantitative evidence regarding the preferences of parents and healthcare providers (HCPs) for managing fever is scarce. To determine parental and HCP preferences for the management of paediatric febrile illness in the ED. Ten children's centres and a children's ED in England from June 2018 to January 2019. 98 parents of children aged 0-11 years, and 99 HCPs took part. Nine focus-groups and coin-ranking exercises were conducted with parents, and a discrete-choice experiment (DCE) was conducted with both parents and HCPs, which asked respondents to choose their preferred option of several hypothetical management scenarios for paediatric febrile illness, with differing levels of visit time, out-of-pocket costs, antibiotic prescribing, HCP grade and pain/discomfort from investigations. The mean focus-group size was 4.4 participants (range 3-7), with a mean duration of 27.4 min (range 18-46 min). Response rates to the DCE among parents and HCPs were 94.2% and 98.2%, respectively. Avoiding pain from diagnostics, receiving a faster diagnosis and minimising wait times were major concerns for both parents and HCPs, with parents willing-to-pay £16.89 for every 1 hour reduction in waiting times. Both groups preferred treatment by consultants and nurse practitioners to treatment by doctors in postgraduate training. Parents were willing to trade-off considerable increases in waiting times (24.1 min) to be seen by consultants and to avoid additional pain from diagnostics (45.6 min). Reducing antibiotic prescribing was important to HCPs but not parents. Both parents and HCPs care strongly about reducing visit time, avoiding pain from invasive investigations and receiving diagnostic insights faster when managing paediatric febrile illness. As such, overdue advances in diagnostic capabilities should improve child and carer experience and HCP satisfaction considerably in managing paediatric febrile illness.


Agglomeration Effect of Medical Education: Based on the Web of Science Database.
By retrieving the 1900-2016 medical education-related essays from the web of science database, UCINET software was used to build the national cooperation network and its nested visualization software, and NetDraw was used to visualize the country cooperation networks in different time windows. We found that international medical education papers began to show exponential growth until 1945 and international cooperation did not begin to become dense until 1961. With the increasing number of participating countries in international medical education, the cooperation factions formed more complicated. The intensity of international cooperation between the United States, Britain and other major international medical education powers has been declining from 1991 to 2016. Between Brazil and China, during 1996-2016, the center of cooperation network has been on the rise for a long time, and the intensity of Canada's cooperation in medical education research has been on the rise for nearly 25 years. The center of international medical education is gradually being transferred from the United States to Canada.


Effects of Chronic NAD Supplementation on Energy Metabolism and Diurnal Rhythm in Obese Mice.
Adequate nicotinamide adenine dinucleotide (NAD) content in hypothalamic neurons is critical for the maintenance of normal energy balance and circadian rhythm. In this study, the beneficial metabolic effects of chronic NAD supplementation on diet-induced obesity and obesity-related disruption of diurnal rhythms were examined. C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks and received an intraperitoneal injection of either saline or NAD (1 mg/kg/day) for the last 4 weeks. The control mice were fed a chow diet and injected with saline for the same period. Body weights were monitored daily. Daily rhythms of food intake, energy expenditure, and locomotor activity were measured at the end of NAD treatment. The effect of NAD treatment on the clock gene Period 1 (PER1) transcription was also studied. Chronic NAD supplementation significantly attenuated weight gain in HFD-fed obese mice. Furthermore, NAD treatment recovered the suppressed rhythms in the diurnal locomotor activity patterns in obese mice. In addition, exogenous NAD supply rescued cellular NAD depletion-induced suppression of PER1 transcriptional activity in hypothalamic neuron cells as well as blunted daily fluctuations of hypothalamic arcuate nucleus PER1 expression in obese mice. NAD supplementation showed therapeutic effects in obese mice with altered diurnal behaviors.


Resting State Brain Activity During Long-Term Dry Immersion.
The purpose of this work was to investigate the brain's rhythmic activity during a simulated microgravity condition (namely dry immersion). During dry immersion, which lasted for 5 d, nine subjects (healthy men, 20 to 29 yr of age) were individually placed in a tub (2.2 × 1.1 × 0.85 m) filled with water (temperature was kept constant at about 33°C). Subject floated in the tub without bodily support in the supine horizontal position, but isolated from the water by waterproof material. Resting state EEGs were registered at the fourth or fifth day of dry immersion. Under the control conditions, resting state EEGs were registered while subjects laid in a supine position on a couch. Compared to the control condition, EEG power in the alpha range (8-13 Hz) was greater in dry immersion; this effect was distributed across the whole scalp. No effects of dry immersion were found for the beta, delta, or theta frequency bands. The results of the study, similar to those obtained in a real spaceflight, indicate that support withdrawal is an important contributor to brain activity alterations in weightlessness.Lazarev IE, Tomilovskaya ES, Kozlovskaya IB. Resting state brain activity during long-term dry immersion. Aerosp Med Hum Perform. 2018; 89(7):642-647.


Managing gastric varices.
Gastric varices (GV) are a type of ectopic varix, which is a natural portosystemic shunt occurring in response to an increase in intrahepatic vascular resistance, mostly commonly from portal hypertension. GV are present in up to 20% of patients with portal hypertension. Although oesophageal varices are more common than GV, and oesophageal variceal bleeding (EVB) happens more often than gastric variceal bleeding (GVB), GVB tends to be more severe, to have higher associated hospital costs, length of stay, higher rebleeding rates and have higher mortality. Mortality rates associated with variceal bleeding range from 6% in EVB to 20%-55% in GVB. Risk factors for GV haemorrhage include location, size, severity of liver failure, presence of variceal red spots, and presence of HCC (hepatocellular carcinoma). This manuscript will review endoscopic and non-endoscopic treatment of GV.


Purtscher-Like Retinopathy Associated with Anorexia Nervosa.
A 21-year-old girl presented with acute painless vision loss in her right eye. There was no remarkable ocular history and she had a history of anorexia nervosa. At presentation best-corrected visual acuities were counting fingers from 2 meters and 20/20, in the right and left eyes, respectively. Slit lamp examination result was normal. Fundus examination revealed multiple cotton wool spots and intraretinal hemorrhages surrounding the optic disc and macula in the right eye. Fluorescein angiography showed capillary filling defect and leakage from optic disc in the late phase of the angiogram. One week later best-corrected visual acuities remained the same in both eyes with similar fundus appearance. One month after initial presentation visual acuity was 20/20 in both eyes with no abnormality in fundus appearance.


Cholangiocyte biology.
Cholangiocytes are increasingly recognized as biologically important because of the diversity of cellular processes in which they participate. Collectively, these processes define normal function and, when disturbed, account for abnormalities that cause disease. Advances in animal models of disease, sophistication of technology in imaging, and gene silencing have allowed progress in defining the roles that cholangiocytes play in signaling; transport of water, ions, and solutes; and alterations that result in cholestasis. The pace of advances in technology justifies a yearly summary to identify the most important developments in cholangiocyte biology. The main areas of recent progress include insights into the molecular mechanisms of hormone-induced bile secretion, development of new experimental models, and a better understanding of the mechanisms of cholestasis. Understanding the normal components and key biologic processes in cholangiocytes responsible for the regulation of ductal bile secretion is an initial and required step in generating hypotheses relevant to disease. With regard to the pathologic relevance of this work, cholestatic liver diseases represent a broad group of hepatobiliary disorders with which hepatologists must deal. In addition to genetic defects, the study of the normal and altered trafficking of cholangiocyte transport systems involved in bile secretion may provide a molecular correlate for the functional changes that occur in cholestasis. Crucial to this understanding is the ongoing development of experimental models and techniques to answer key hypothesis-driven questions. Additionally, the collegial sharing and exchange of novel concepts, ideas, reagents, and probes promotes positive advances in the field.


The MaPLE device of Saha Institute of Nuclear Physics: construction and its plasma aspects.
The Magnetized Plasma Linear Experimental (MaPLE) device is a low cost laboratory plasma device at Saha Institute of Nuclear Physics fabricated in-house with the primary aim of studying basic plasma physics phenomena such as plasma instabilities, wave propagation, and their nonlinear behavior in magnetized plasma regime in a controlled manner. The machine is specially designed to be a versatile laboratory device that can provide a number of magnetic and electric scenario to facilitate such studies. A total of 36 number of 20-turn magnet coils, designed such as to allow easy handling, is capable of producing a uniform, dc magnetic field of about 0.35 T inside the plasma chamber of diameter 0.30 m. Support structure of the coils is planned in an innovative way facilitating straightforward fabrication and easy positioning of the coils. Further special feature lies in the arrangement of the spacers between the coils that can be maneuvered rather easily to create different magnetic configurations. Various methods of plasma production can be suitably utilized according to the experimental needs at either end of the vacuum vessel. In the present paper, characteristics of a steady state plasma generated by electron cyclotron resonance method using 2.45 GHz microwave power are presented. Scans using simple probe drives revealed that a uniform and long plasma column having electron density approximately 3-5x10(10) cm(-3) and temperature approximately 7-10 eV, is formed in the center of the plasma chamber which is suitable for wave launching experiments.


[Metabolism of synthetic corticosteroid esters in man (author's transl)].
Metabolism of water-soluble synthetic corticosteroid esters, hydrocortisone hemisuccinate (H-H); hydrocortisone phosphate (HP), prednisolone hemisuccinate (P-H), prednisolone phosphate (P-P), dexamethasone phosphate (D-P) and dexamethasone sulfate (D-S) was studied by i.v. administration of steroids in a dose of 100 mg to 6 healthy volunteers and consequtive urine collections over 24 hrs. Uniary metabolites were separated into free, glucuronide, sulfate and "unhydrolyzed" fractions and measured by means of Porter-Silber (P-S) reaction and isonicotinic acid (INH) reaction. In H-H, H-P and D-S, glucuronide conjugates constituted the largest fraction of P-S positive metabolites in 24 hr-urine. In contrast, P-H, P-P and D-P were excreted mainly as free metabolites. Small but variable portions were found as sulfate and "unhydrolized" conjugates. Time course study revealed that, in H-H, H-P and D-S, the free/glucuronide ratio of P-S positive metabolites decreased progressively or remained low throughout the collection periods, whereas in P-H, P-P and D-P the ratio increased markedly in the 4--12 hr period. For all steroids, the INH/P-S ratio was found to be high in the free fraction and low in the glucuronide fraction; the tendency was especially marked in P-H, P-P and d-p. INH-positive metabolites were also predominant in the sulfate and "unhydrolyzed" fractions. The results indicate that the metabolism of synthetic corticosteroids, in general, is characterized by diminised rate of ring A reduction followed by glucuronide conjugation and compensatory increase in free metabolites, the bulk of which consists of ring A intact, C-20 reduced metabolites. 6-Hydroxylated metabolites may also be increased. Conjugation with sulfuric acid occurs but to a small extent. The consistent presence of "unhydrolyzed" metabolites suggests that portions of esters can be excreted unsplitted. It is also noted that the structure of steroid moieties and type of esters were important factors determining the quantitative and qualitative difference in their metabolic fates.