Early Cardiac Catheterization Leads to Shortened Pediatric Extracorporeal Membrane Oxygenation Run Duration.
Cardiac catheterization in patients receiving extracorporeal life support (ECLS) has previously been shown to be safe and, in many cases, therapeutic. However, the influence of cardiac catheterization on clinical outcomes in this patient population has not been clearly defined. A single institution, retrospective review of all pediatric cardiac ECLS patients who underwent cardiac catheterization between January 2006 and September 2015 was performed. Eighty-two interventional cardiac catheterization procedures were performed on 74 patients. Catheterization findings directly led to catheterization-based or surgical intervention in 54 (73%) patients. One (1.2%) catheterization-related complication occurred (pulmonary artery rupture), which ultimately resulted in death. Patients who underwent early catheterization (≤72 hours of ECLS initiation) required shorter total duration of ECLS than patients who underwent catheterization >72 hours after ECLS initiation (136 hours vs. 227 hours, P < 0.01). The groups experienced similar rates of interventions based on catheterization findings (72% early cath vs. 74% late cath, P = 0.81). Survival to hospital discharge was higher in the early catheterization group (74% vs. 51%, P = 0.04). In multivariate models adjusting for covariates, early catheterization was associated with a reduction in ECLS duration by approximately 150 hours (P < 0.01). Cardiac catheterization is safe in pediatric ECLS patients and an earlier catheterization is associated with shorter duration of ECLS and improved hospital survival. Diagnostic cardiac catheterization should be considered in patients who remain dependent on ECLS after several days of support.


Reversible ischemia around intracerebral hemorrhage: a single-photon emission computerized tomography study.
A zone of perilesional ischemia has been demonstrated around intracerebral hemorrhage (ICH) in numerous experimental models and in human studies. There is potential for perfusion recovery in the zone of perilesional oligemia around ICH. The authors sought to demonstrate, quantify, and study the chronological evolution of perilesional ischemic change in ICH in humans by measuring cerebral blood flow. Eleven patients with spontaneous supratentorial ICH underwent two technetium-99m hexamethylpropyleneamine oxime single-photon emission computerized tomography (SPECT) scanning, one in the acute stage (within days of ictus) and the other in the late stage (6-9 months postictus). All patients in this study were treated nonsurgically. Methods of SPECT data analysis based on count differences in regions of interest can be difficult to apply to images with large space-occupying lesions such as ICH, because of the distortion of intracranial anatomy, midline shift, and alterations in the three-dimensional (3D) characteristics of the lesion over time (that is, absorption of the hematoma on the later studies). The authors used the following method: the late and early images were registered and aligned to a common 3D orientation and were normalized to maximal counts. The late images were then compared voxel by voxel with the early ones. The region-growing algorithm was used to discern the difference between the two images, outlining voxels in the perihematoma region, with a signal improvement of at least 15% on the late image. Discrete brain regions around the hematoma with at least a 15% improvement in radiotracer uptake (and hence perfusion) in the late images were observed in all cases. The mean volume of brain with a greater than 15% improvement in perfusion between the two studies was 34.8 cm3 (range 7.2-71.3 cm3). These volumes represent regions of the brain that were poorly perfused in the initial studies. This may represent a zone of reversible perilesional oligemia (penumbra) in ICH in humans. This is the first study in which it is documented that some of the perilesional hypoperfused tissue around human ICH regains its perfusion in the long term, leading the authors to suggest that there may be a penumbra in human ICH. Medical or surgical therapeutic interventions could increase the volume of perilesional brain that recovers after the initial insult. The results of this study therefore support the concept that intervention in ICH has the potential to reduce the ultimate neurological deficit and improve outcome.


Harnessing functional segregation across brain rhythms as a means to detect EEG oscillatory multiplexing during music listening.
Music, being a multifaceted stimulus evolving at multiple timescales, modulates brain function in a manifold way that encompasses not only the distinct stages of auditory perception, but also higher cognitive processes like memory and appraisal. Network theory is apparently a promising approach to describe the functional reorganization of brain oscillatory dynamics during music listening. However, the music induced changes have so far been examined within the functional boundaries of isolated brain rhythms. Using naturalistic music, we detected the functional segregation patterns associated with different cortical rhythms, as these were reflected in the surface electroencephalography (EEG) measurements. The emerged structure was compared across frequency bands to quantify the interplay among rhythms. It was also contrasted against the structure from the rest and noise listening conditions to reveal the specific components stemming from music listening. Our methodology includes an efficient graph-partitioning algorithm, which is further utilized for mining prototypical modular patterns, and a novel algorithmic procedure for identifying 'switching nodes' (i.e. recording sites) that consistently change module during music listening. Our results suggest the multiplex character of the music-induced functional reorganization and particularly indicate the dependence between the networks reconstructed from the δ and β H rhythms. This dependence is further justified within the framework of nested neural oscillations and fits perfectly within the context of recently introduced cortical entrainment to music. Complying with the contemporary trends towards a multi-scale examination of the brain network organization, our approach specifies the form of neural coordination among rhythms during music listening. Considering its computational efficiency, and in conjunction with the flexibility of in situ electroencephalography, it may lead to novel assistive tools for real-life applications.


Possible Use of a Safety-Valve with a Foley Catheter During Catheterisation of Male Spinal Cord Injury Patients for Prevention of Urethral Trauma Caused by Inflation of the Catheter Balloon in the Urethra.
We used a safety-valve (Trans-Urethral Catheterisation Safety Valve, Class Medical, Limerick, Ireland) to prevent urethral trauma due to inflation of the anchoring balloon in the urethra during catheterisation of male spinal cord injury patients in a spinal unit. The safety-valve is attached to the balloon channel of a Foley catheter. If the balloon is inflated when it is in the urethra, the pressure valve is activated. Any fluid pushed into the balloon channel leaks out and balloon inflation stops, indicating that the balloon is not inside the bladder. The safety-valve was used in 44 catheterisations. There was leakage of water during three catheterisations. In the first case, the health professional did not inflate and deflate the balloon prior to its use. This "pre-valve inflation" step overcomes the baseline resistance pressure of the balloon and prevents fluid leaking from the valve when the catheter is in the correct position. In the second instance, the valve was found to be defective. In the third case, the catheter had been misplaced; it was removed and repositioned; there was no leakage of water during inflation of the balloon. In one out of 44 catheterisations, the catheter had been misplaced; leakage of water from the safety-valve stopped inflation of the balloon and prevented iatrogenic urethral trauma. The safety-valve may be used during catheterisation of male patients in the spinal unit to prevent urethral trauma caused by inflation of the balloon of Foley catheter in the urethra. However, health professionals should remember the few shortcomings of the catheter safety-valve.


Molecular epidemiology of tuberculosis in Malaysia.
Molecular typing with IS6110 was applied to Mycobacterium tuberculosis isolates from all parts of Malaysia. The degree of clustering increased with patient age, suggesting that reactivation may contribute to clustering. Identical banding patterns were also obtained for isolates from widely separate regions. Therefore, the use of clustering as a measure of recent transmission must be treated with caution. Strains related to the Beijing family were common in Peninsular Malaysia but were less common in Sabah and Sarawak, while a distinct group of strains comprised nearly 40% of isolates from East Malaysia but such strains were rare in Peninsular Malaysia. Single-copy strains, common in South and Southeastern Asia, constituted nearly 20% of isolates from the peninsula but were virtually absent in East Malaysia. The marked geographical difference in the prevailing strains indicates not only a restricted dissemination of M. tuberculosis but also a considerable degree of stability in the banding patterns.


Life-threatening hyponatraemia.
A 31-year-old hypertensive woman was admitted to hospital with palpitations. Her hypertension was treated with bendroflumethiazide, which had been increased from 2.5 to 5 mg daily by her general practitioner about 18 months prior to her admission. She was also on ramipril 10 mg once daily. There were no abnormal findings on examination, and a 12-lead ECG showed sinus rhythm, rate 75, with Q waves in leads V1-V2. Telemetry (over 24 h) showed ventricular bigeminy when she had her typical palpitations. Her admission serum sodium and potassium concentrations were 132 and 3.4 mmol/l, respectively. Immediately prior to planned discharge the following day, she experienced paraesthesiae, weakness, confusion and seizures accompanied by 10 s asystole on the ECG monitor. Her serum sodium had fallen to 120 mmol/l and potassium to 2.3 mmol/l. Bendroflumethiazide and ramipril were discontinued and the patient was restricted to fluids of 1.5 l/24 h. She also received potassium supplements. Her serum sodium concentration rose to normal over 6 days, and she was discharged on feeling well.


Assembly of the isoindolinone core of muironolide A by asymmetric intramolecular Diels-Alder cycloaddition.
The hexahydro-1H-isoindolin-1-one core of muironolide A was prepared by asymmetric intramolecular Diels-Alder cycloaddition using a variant of the MacMillan organocatalyst which sets the C4,C5 and C11 stereocenters.


[Could the expression of L-selectin be an early marker of arterial hypertension and microangiopathy in the course of type 1 diabetes mellitus in juvenile patients?].
Autoreactive T lymphocytes participate in the development of type 1 diabetes mellitus. The migration of T cells is initiated by increased expression of L-selectin on the cellular membrane of lymphocyte. Recently, a correlation between the concentration of sL-selectin and the develop-ment of diabetic retinopathy, atherosclerosis and arterial hypertension was stated. The purpose of this study was to evaluate whether the expression of L-selectin on lymphocytes T alters in the course of the disease -- diabetes lasting less than 5 years and over 5 years; to assess a relationship between the percentage of L-selectin on T cells and the evolution of vascular complications; to elucidate whether the percentage of peripheral blood T lymphocytes expressing L-selectin could be an early marker of angiopathy in juvenile patients. The study was carried out on 60 children and adolescents (aged 9-20) with diagnosed type 1 diabetes: a) (20 n) with the disease lasting <5 years, b) (20 n) with type 1 diabetes lasting >5 years without vascular complications, c) (20 n) with type 1 diabetes and vascular complications (microalbuminuria, arterial hypertension, diabetic retinopathy). The control group consisted of 20 healthy volunteers (aged 6-17). The expression of adhesion molecules has been evaluated by using three-color flow cytometry (Coulter EPICS XL). HbA1c concentration has been analysed by a liquid chromatography technique HPLC-Variant (Bio-Rad). The percentage of T lymphocytes expressing L-selectin was significantly increased in all groups of patients with type 1 diabetes versus healthy controls (p<0.005 and p<0.001, in groups without complications and with angiopathy, respectively). Moreover in patients with diagnosed arterial hypertension the percentage of T lymphocytes expressing L-selectin was higher than in patients in whom arterial hypertension was not developed (p<0.05). In juvenile patients with type 1 diabetes the percentage of T lymphocytes expressing L-selectin was increased independently on the du-ration of the disease. In children with type 1 diabetes and diagnosed vascular complications the highest percentage of T lymphocytes expressing L-selectin was found.


Immunohistochemical analysis of nasal biopsies during rhinovirus experimental colds.
Human rhinoviruses (HRV) are an important cause of upper respiratory tract infection and are etiologically linked with asthma exacerbations. However, the mechanisms of virus-induced inflammation are largely unknown. We examined nasal mucosal biopsies for the presence of an associated inflammatory cellular infiltrate during experimental rhinovirus infection. A group of 21 adult volunteers (10 atopic) had baseline nasal biopsies, followed 2 wk later by inoculation with HRV Serotype 16. Nasal biopsies were taken on Day 4 of the cold and again 6-10 wk later. Infection was documented by symptom scores, viral culture, and seroconversion. The biopsies were fixed in acetone and processed into glycol methacrylate resin for semithin sectioning. Mast cells, eosinophils, lymphocytes, and neutrophils were identified with appropriate monoclonal antibodies and a streptavidin-biotin horseradish peroxidase technique. There were no significant changes in the numbers of inflammatory cells present during the cold or the convalescent period compared with baseline biopsies (Wilcoxon paired, p > 0.05). There were also no differences between normal and atopic groups. We suggest that rhinoviral colds are not associated with increased inflammatory cellularity and that other mechanisms, such as increased mediator release, are responsible for coryzal symptoms.


Pannexins in Acute Kidney Injury.
Acute kidney injury (AKI) is highly prevalent among hospitalized patients and is associated with serious consequences with limited pharmacological treatment options. Pannexin 1 (Panx1) channel is a ubiquitously expressed nonselective membrane transport channel that efficiently effluxes ATP and plays a central role in the progression of inflammatory diseases. Animal models that target Panx1 through pharmacological inhibition or genetic deficiency have better outcomes in minimizing inflammation and associated pathology. Given the involvement of Panx1 at multiple steps of -inflammatory pathology, Panx1 could be a potential therapeutic target in the treatment of AKI. Further research is needed in elaborating the mechanisms and identifying Panx1-specific inhibitor molecules to better understand the role of Panx1 in AKI pathology arising due to diverse insults.


A serotonin malfunction hypothesis by finding clear mutual relationships between several risk factors and symptoms associated with sudden infant death syndrome.
In our recent study allele variants in the promoter of serotonin transporter (5-HTT) gene have been shown as a novel risk factor for sudden infant death syndrome (SIDS). L and XL alleles were more frequent and S allele was less frequent in SIDS victims compared to age-matched controls. Serotonin (5-HT) is suggested as a major agent that is closely involved in the etiology of SIDS. Although many risk factors of SIDS looked mutually unrelated each other, we found in literature many of them other than prone position to change 5-HT levels in the brain. Along with the genetic factors, environmental and temporal factors appear additively to lower the excitatory function of 5-HT to the respiratory center, and finally SIDS might occur. Now the pathophysiological mechanisms and symptoms of SIDS are explained by decreased levels of 5-HT.


Visual scoring of the middle latency response.
Interjudge validity and intrajudge reliability were studied in a task in which three sets of judges (scores) identified middle latency responses under varying conditions of intensity and number of stimuli per response. The results demonstrated that intensity level was the only factor that had a statistically significant effect on the scorers' judgments. As intensity decreased it became increasingly difficult to detect middle latency responses; however, silent controls were clearly identified as response absent. Definite trends were seen for the scorer groups as a function of experience; the experienced groups generally had slightly higher mean confidence levels and percent correct judgments than the naive scorers. Surprisingly, increasing the number of stimuli had no significant effect on the scorers' judgments. Last, intrajudge reliability was high across all scorers for all conditions except at 10 dB SL. Most of the unreliable judgments and difficulty in detection (interjudge validity) occurred at the 10 dB SL.


[Alpha fetoprotein concentration in the amniotic fluid in normal pregnancy and in pregnancy complicated by fetal anomaly].
The authors determined alpha-fetoprotein (AFP) concentration of amniotic fluid samples taken from 351 pregnancies in the 15-23. gestational weeks with the outcome of healthy infants with the use of radioimmunoassay. These values were compared to those of 255 pathological pregnancies, and the sensitivity and specificity of this diagnostic method based on amniotic fluid AFP assay were determined. It has been concluded that if the borderline value between normal and pathological cases is three times greater than median, the specificity of the method is 100%, its sensitivity is 98.5% in anencephaly (exencephaly), 75.0% in ADAM sequence, 70.4% in spina bifida and 55.5 in omphalocele (gastroschisis). Thus amniocentesis is advisable in cases where the risk of the above malformations is above the average and also when the possibility of the malformation cannot be excluded by non-invasive methods.


Impact of dysfunctional maternal personality traits on risk of offspring depression, anxiety and self-harm at age 18 years: a population-based longitudinal study.
The impact of underlying parental psychological vulnerability on the future mental health of offspring is not fully understood. Using a prospective cohort design, we investigated the association between dysfunctional parental personality traits and risks of offspring self-harm, depression and anxiety. The association between dysfunctional parental personality traits (monotony avoidance, impulsivity, anger, suspicion, and detachment), measured in both mothers and fathers when offspring were age 9 years, and risk of offspring depression, anxiety and self-harm at age 18 years, was investigated in a population-based cohort (ALSPAC) from over 8000 parents and children. Higher levels of dysfunctional maternal, but not paternal, personality traits were associated with an increased risk of self-harm, depression, and anxiety in offspring. Maternal associations were best explained by the accumulation of dysfunctional traits. Associations were strongest for offspring depression: Offspring of mothers with three or more dysfunctional personality traits were 2.27 (1.45-3.54, p < 0.001) times as likely to be depressed, compared with offspring of mothers with no dysfunctional personality traits, independently of maternal depression and other variables. The accumulation of dysfunctional maternal personality traits is associated with the risk of self-harm, depression, anxiety in offspring independently of maternal depression and other confounding variables. The absence of associations for equivalent paternal traits makes a genetic explanation for the findings unlikely. Further research is required to elucidate the underlying mechanism. Mothers with high levels of dysfunctional personality traits may benefit from additional support to reduce the risk of adverse psychological outcomes occurring in their offspring.


Camel back shaped Kirkwood-Buff integrals.
Some binary mixtures, such as specific alcohol-alkane mixtures or even water-tbutanol, exhibit two humps "camel back" shaped Kirkwood-Buff integrals (KBIs). This is in sharp contrast with the usual KBIs of binary mixtures having a single extremum. This extremum is interpreted as the region of maximum concentration fluctuations, usually occurs in binary mixtures presenting appreciable micro-segregation, and corresponds to where the mixture exhibits a percolation of the two species domains. In this paper, it is shown that two extrema occur in binary mixtures when one species forms "meta-particle" aggregates, the latter acts as a meta-species, and they have their own concentration fluctuations, hence their own KBI extremum. This "meta-extremum" occurs at a low concentration of the aggregate-forming species (such as alcohol in alkane) and is independent of the other usual extremum observed at mid-volume fraction occupancy. These systems are a good illustration of the concept of the duality between concentration fluctuations and micro-segregation.


Subjective Age and Its Correlates Among Middle-Aged and Older Adults.
The present study evaluates discrepancies in subjective age as reported by middle-age persons (aged 44-64 years) in comparison to older adults (aged 65 years and older), using a multidimensional definition of the concept. A convenience sample of 126 middle-aged and 126 older adults completed subjective age measures (felt age, desired age, and perceived old age), attitudes toward older adults, knowledge about aging, and sociodemographic questionnaires. Overall, participants reported feeling younger than they actually were and wanting to be younger than their chronological age. Perceived mean for old age was about 69 years. Discrepancies in felt age and desired age were significantly larger for the older group compared to the middle-aged group. Regarding perceived old age, compared to the younger group, older adults reported that old age begins at an older age. Findings suggest that middle-aged and older adults' perceptions regarding themselves and regarding old age in general are independent and need, therefore, separate research and practical attention.


Amperometric cell for subcutaneous detection of hydrogen sulfide in anesthetized experimental animals.
Hydrogen sulfide (H2S) is a toxic gas. It has been recognized that H2S evolving in biochemical reactions in living organisms has an important role in different physiologic processes. Nowadays, H2S is known as an endogenous messenger molecule. Natural sulfurous spring water has been proved beneficial in the therapy of diseases of the skin and other organs (Boros et al 2013). In vivo real-time detection of local H2S concentration is an important but challenging task.We developed a two-electrode amperometric cell for selective subcutaneous detection of H2S in anesthetized mice. The cell is a small size implantable gas sensor containing a platinum disc anode and a silver cathode. The selectivity is provided by a membrane permeable only by gases. There is a buffered reversible electrochemical mediator solution in an oxidized form inside the cell. As gaseous H2S penetrates into the cell the mediator is reduced, and +0.4 V versus the reference is employed on the platinum working electrode. The reduced mediator is oxidized on the anode surface. The current provides an analytical signal representing the concentration of H2S.Appropriate shape, size and membrane material were selected, and optimal working parameters--such as mediator concentration, pH and cell voltage--were determined in vitro. The lower limit of detection in the stirred sample solution at pH = 5.5 was as small as 9.4 × 10(-7) M and a dynamic concentration range of 0-6 × 10(-4) M could be achieved.The detecting surfaces of the cell were covered with freshly dissected mouse skin to test dermal H2S permeability. In other experiments, the cell was implanted subcutaneously in an anesthetized mouse and the animal was submerged in a buffer solution containing different concentrations of H2S so that the skin surface over the sensor was covered by the solution. Measurements of subcutaneous H2S concentration were taken. The experiments clearly proved that H2S diffuses through the skin of the live mouse.


[Surgical treatment of nodular and mixed euthyroid goiter].
The results of surgical treatment of 308 patients with nodular and mixed goiter are analysed. Because of increasing incidence of nodular goiter malignization, the extended resection of the thyroid gland versus the previously used sparing resection is suggested. To prevent activation of thyrotropic function of the pituitary body after the operation, we recommended the use of thyroidin. The incidence of disease recurrence was 1.3%, stable hypothyrosis--1.6%.


Studying work practices: a key factor in understanding accidents on the level triggered by a balance disturbance.
Accidents on the level (AOL) rank second amongst the most numerous and serious occupational accidents with days lost in France and are a major health and safety problem in every sector of activity. The case study described in this paper was conducted at a metallurgical company with 300 employees. The aims of this work were dual: 1) to extend the general knowledge required for preventing these accidents; 2) to propose prevention measures to this company. Existing data on company occupational accidents were gathered and analysed to identify a work situation that appeared likely to cause AOL. This work situation was analysed in detail. Several risk factors were identified within this work situation, by way of interviews with 12 operators. These risk factors concerned various dimensions of the work situation, particularly its physical dimension (e.g. templates structure) and organisational dimension (e.g. parts availability). Interviews were conducted, focusing on risk factors perceived by operators and involving allo-confrontations based on accounts of four AOL occurring in this situation. Allo-confrontations were interviews confronting operators with a risk occupational situation that was accidental for one of their colleagues, the latter being absent from the interview. Results highlighted the fact that the work practices implemented are key factors in understanding these accidents. This study underlines the role of work practices in AOL causality and prevention. It also provides explanations associated with various work situation dimensions involving adoption of more or less safe work practices. AOL are serious and frequent in occupational situations. Injury claims analysis and interviews in an industrial company emphasise the specific characteristics of an occupational situation and of prevention actions forming the basis of an intervention. The need for a better understanding of factors affecting work practice is highlighted in relation to research.


Comparison of polymerase chain reaction and immunohistochemistry for the detection of Mycoplasma pulmonis in paraffin-embedded tissue.
The polymerase chain reaction (PCR) is a reliable method of detecting specific DNA sequences. The purpose of this study was to develop a PCR method of detecting Mycoplasma pulmonis in paraffin-embedded tissue sections and to compare the sensitivity of this method with that of the avidin-biotin complex (ABC) immunohistochemistry technique. We infected mice intranasally with 10(7) M. pulmonis and sacrificed them 28 days later. Using a published oligonucleotide primer sequence for M. pulmonis, we examined 8-microns paraffin sections by PCR for a 710 base-pair segment of the genome. A sequential 8-microns paraffin section was stained for M. pulmonis, using standard ABC immunohistochemistry methods. By PCR and dot blot hybridization, 60 of 62 paraffin-embedded lungs were positive for M. pulmonis, whereas only 17 of 62 lungs were positive, using the ABC method. In this study, we demonstrated that PCR of paraffin-embedded tissues followed by dot blot hybridization of the PCR products was much more sensitive than the ABC method in identifying mouse lungs infected with M. pulmonis.


A Novel microCT Method for Bone and Marrow Adipose Tissue Alignment Identifies Key Differences Between Mandible and Tibia in Rats.
Bone homeostasis is influenced by the bone marrow adipose tissue (BMAT). BMAT distribution varies from one anatomical location in the skeleton to another. We developed an advanced microfocus computed tomography imaging and analysis protocol that allows accurate alignment of both the BMAT distribution and bone micro-architecture as well as calculation of the distance of the BMAT adipocytes from the bone surface. Using this protocol, we detected a different spatial BMAT distribution between the rat tibia and mandible: in the proximal metaphysis of the tibia a large amount of BMAT (~ 20% of the total BMAT) was located close to the bone surface (< 20 µm), whereas in the alveolar ridge ~ 30% of the total BMAT was located between 40 and 60 µm from the bone surface. In the alveolar ridge of rats, the trabecular bone volume was 48.3% higher compared to the proximal metaphysis of the tibia (p < 0.0001) and the percentage of adiposity determined to the relative marrow volume was lower (1.5%) compared to the proximal metaphysis of the tibia (9%, p = 0.0002). Interestingly, in the tibia a negative correlation was found between the percentage of adiposity in the total volume and the trabecular thickness (r =- 0.74, p = 0.037). The present study highlights that in comparison to tibial proximal metaphysis, the mandibular bone exhibits a massive trabecular network and a low BMAT content with almost no contact with the bone surface. These findings are of great interest because of the importance of the fat-bone interaction and its potential relevance to several resorptive bone diseases.


Adsorption and isomerization of glyoxal and methylglyoxal at the air/hydroxylated silica surface.
We present results from molecular dynamics simulations coupled with enhanced sampling techniques on the adsorption and isomerization of glyoxal (GL) and methylglyoxal (MG) at the air/hydroxylated silica (α-Quartz) interface. GL and MG are two organic compounds present in the atmosphere as oxidation products of both biogenic and anthropogenic precursors. By adsorption and hydration on liquid droplets or wetted dust particles, they can enable aerosol growth in the atmosphere. Moreover, thanks to the different polar characters of their trans and cis conformers, GL and MG have been suggested as possible molecular switches capable of responding to changes in solvent polarity. Here, we show that the hydroxylated silica surface does not significantly catalyze the trans-to-cis isomerization, but it stabilizes the cis-isomers, indicating a higher interfacial cis/trans relative concentration compared to the gas phase. Moreover, adsorbed GL prefers to lie parallel on the silica surface, while adsorbed MG shows a tilted orientation. In particular, we report the aldehyde group pointing upward (downward) to the gas phase (to the silica surface) in trans-MG (cis-MG). These results will help in the rationalization of upcoming experimental and modeling work on the adsorption of ketonic compounds on dust aerosols, while it clarifies the catalytic role of the solid substrate surface in promoting conformational changes.


Learning theoretical knowledge doesn't have to be boring.
Marta Kankofer was one of a small team that developed teaching materials for veterinary students to allow them to use their cognitive abilities to solve virtual problems. The VetVIP project promotes self-study based on solving problems and aims to increase satisfaction and motivation among second-year students, who find themselves in a theory-heavy stage of the veterinary course.


Role of Coil Embolization during Prostatic Artery Embolization: Incidence, Indications, and Safety Profile☆.
To determine if coil embolization is a safe adjunctive measure to prevent nontarget embolization during prostatic artery embolization (PAE). A retrospective analysis of patients who underwent PAE with coil embolization (cPAE) or without coil embolization (nPAE) between January 2014 and June 2016 was conducted. Adverse events, identified in accordance with SIR guidelines, and procedural variables were compared between the 2 cohorts. Of 122 patients, 32 (26.2%) underwent coil embolization in 39 arteries, with coils placed to prevent nontarget embolization (n = 36), treat prostatic artery extravasation (n = 2), and occlude an intraprostatic arteriovenous fistula (n = 1). Compared with nPAE, cPAE had a nonsignificant increase in dose area product (64,516 μGy·m2 vs 52,100 μGy·m2, P = .053) but significantly longer procedure (160.1 min vs 137.1 min, P = .022) and fluoroscopy (62.9 min vs 46.1 min, P = .023) times. One major complication (urosepsis) occurred in each group (cPAE, 1/32 [3.1%]; nPAE, 1/80 [1.3%]). Both cases resolved after 2 weeks of intravenous antibiotics. A minor ischemic complication (1/32 [3.1%]) occurred in a patient with coil embolization, which manifested as white discoloration of the glans penis and resolved with topical therapy. There were no statistically significant differences in major and minor complications between cohorts at 1-month and 3-month follow-up visits. Although coil embolization leads to increases in procedure and fluoroscopy times, it is a safe adjunctive technique to occlude communications between the prostatic artery and pelvic vasculature to potentially prevent nontarget embolization.


Inhibition of DNA synthesis by protein kinase C-activating phorbol esters in NIH/3T3 cells.
Fibroblast growth factor (FGF) plus insulin induced DNA synthesis in and proliferation of NIH/3T3 cells. The protein kinase C-activating phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), inhibited both the DNA synthesis and cell proliferation induced by FGF plus insulin. The concentration of TPA required for 50% inhibition of the DNA synthesis was about 5 nM. Phorbol-12,13-dibutyrate, another protein kinase C-activating phorbol ester, also inhibited the DNA synthesis but 4 alpha-phorbol-12,13-didecanoate, known to be inactive for this enzyme, was ineffective. DNA synthesis started at about 12 h after the addition of FGF plus insulin. The inhibitory action of TPA on the DNA synthesis was observed when it was added within 12 h after the addition of FGF plus insulin. These results suggest that phorbol esters exhibit an antiproliferative action through protein kinase C activation in NIH/3T3 cells, and that this action of phorbol esters is due to inhibition of the progression from the late G1 to the S phase of the cell cycle.


Maize/peanut intercropping has greater synergistic effects and home-field advantages than maize/soybean on straw decomposition.
The decomposition of plant litter mass is responsible for substantial carbon fluxes and remains a key process regulating nutrient cycling in natural and managed ecosystems. Litter decomposition has been addressed in agricultural monoculture systems, but not in intercropping systems, which produce species-diverse litter mass mixtures. The aim here is to quantify how straw type, the soil environment and their combined effects may influence straw decomposition in widely practiced maize/legume intercropping systems. Three decomposition experiments were conducted over 341 days within a long-term intercropping field experiment which included two nitrogen (N) addition levels (i.e. no-N and N-addition) and five cropping systems (maize, soybean and peanut monocultures and maize/soybean and maize/peanut intercropping). Experiment I was used to quantify litter quality effects on decomposition; five types of straw (maize, soybean, peanut, maize-soybean and maize-peanut) from two N treatments decomposed in the same maize plot. Experiment II addressed soil environment effects on root decomposition; soybean straw decomposed in different plots (five cropping systems and two N levels). Experiment III addressed 'home' decomposition effects whereby litter mass (straw) was remained to decompose in the plot of origin. The contribution of litter and soil effects to the home-field advantages was compared between experiment III ('home' plot) and I-II ('away' plot). Straw type affected litter mass loss in the same soil environment (experiment I) and the mass loss values of maize, soybean, peanut, maize-soybean, and maize-peanut straw were 59, 77, 87, 76, and 78%, respectively. Straw type also affected decomposition in the 'home' plot environment (experiment III), with mass loss values of maize, soybean, peanut, maize-soybean and maize-peanut straw of 66, 74, 80, 72, and 76%, respectively. Cropping system did not affect the mass loss of soybean straw (experiment II). Nitrogen-addition significantly increased straw mass loss in experiment III. Decomposition of maize-peanut straw mixtures was enhanced more by 'home-field advantage' effects than that of maize-soybean straw mixtures. There was a synergistic mixing effect of maize-peanut and maize-soybean straw mixture decomposition in both 'home' (experiment III) and 'away' plots (experiment I). Maize-peanut showed greater synergistic effects than maize-soybean in straw mixture decomposition in their 'home' plot (experiment III). These findings are discussed in terms of their important implications for the management of species-diverse straw in food-production intercropping systems.


Further studies of the engrailed phenotype in Drosophila.
Although most mutations at the engrailed locus of Drosophila cause embryonic death when homozygous, they are viable in clones of cells. We describe the phenotype of such clones in the eye-antenna, proboscis, humerus, wing, legs, and terminalia. When in anterior compartments the clones are normal, but in most posterior compartments they are abnormal and fail to respect the anteroposterior compartment boundary. We find that the yield of engrailed-lethal clones in posterior compartments is often significantly lower than expected, indicating that these clones are lost during development. Mutant clones are abnormal in the analia and rare in the humerus, suggesting that both structures are of posterior provenance. These results support the hypothesis that the engrailed+ gene is required exclusively in cells of posterior compartments to specify their characteristic cell affinities and pattern.


Metabolic activity of hypotonically treated mature boar spermatozoa.
Treatment of washed boar sperm with hypotonic phosphate buffer removed the acrosome, disrupted the cytoplasmic membrane and almost completely separated the heads from the mid piece-tail segment. As assessed by oxygen uptake studies and their ability to oxidize 14C-labelled substrates to 14CO2, hypotonically-treated cells exhibit low glycolytic activity yet mitochondrial activity remains high. Both lactate and glycerol 3-phosphate underwent oxidation and these substrates continued to be metabolized by this preparation which had been stored for up to 10 days at 4 degrees C. Such preparations may be of assistance in the investigation of the biochemistry of boar sperm mitochondria.


Conservative interventions for treating hyperextension injuries of the proximal interphalangeal joints of the fingers.
Immobilisation and early motion (protected or unrestricted) are both used following hyperextension injuries to the proximal interphalangeal (PIP) joint of the finger. To assess the effects of conservative interventions (non-surgical management) for treating hyperextension injuries of the proximal interphalangeal joints of the fingers. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (January 2012), the Cochrane Central Register of Controlled Trials (in The Cochrane Library 2012, Issue 1), MEDLINE (1946 to January Week 2 2012), EMBASE (1980 to 2012 Week 03), CINAHL (1950 to 24 January 2012), PEDro (1929 to March 2012), trial registers and reference lists of articles. Randomised and quasi-randomised studies comparing immobilisation/protected mobilisation/unrestricted mobilisation in participants with PIP joint hyperextension injuries managed non-surgically. Two review authors independently assessed risk of bias and extracted data. There was no pooling of data. Three trials involving 366 people were identified. All three trials, which were over 15 years old, were methodologically flawed with unclear or high risk of bias. None of the studies reported on self assessment of function. One trial compared unrestricted mobility with immobilisation; one trial compared protected mobilisation with immobilisation; and the remaining trial compared immobilisation for one week versus three weeks. None of these trials found statistically significant differences between their intervention groups in various measures of poor outcome, pain and range of movement at six months follow-up. This lack of difference applied at three years for the comparison between unrestricted mobility with immobilisation. There is insufficient evidence from trials testing the need for, and the extent and duration of, immobilisation to inform on the key conservative management decisions for treating hyperextension injuries of the proximal interphalangeal joints.


Activity of the human carcinogens benzidine and 2-naphthylamine in male mouse bone marrow micronucleus assays.
Conflicting reports exist in the literature regarding the activity of the human bladder carcinogens benzidine and 2-naphthylamine in the rodent bone marrow micronucleus assay. These chemicals have therefore been re-evaluated in mouse bone marrow micronucleus assays, and each gave a clear positive response in male mice 24 h after oral dosing of approximately 20% of the 4-day median lethal dose level. Experiments were repeated.


Anti-peptide monoclonal antibodies generated for immuno-multiple reaction monitoring-mass spectrometry assays have a high probability of supporting Western blot and ELISA.
Immunoaffinity enrichment of peptides coupled to targeted, multiple reaction monitoring-mass spectrometry (immuno-MRM) has recently been developed for quantitative analysis of peptide and protein expression. As part of this technology, antibodies are generated to short, linear, tryptic peptides that are well-suited for detection by mass spectrometry. Despite its favorable analytical performance, a major obstacle to widespread adoption of immuno-MRM is a lack of validated affinity reagents because commercial antibody suppliers are reluctant to commit resources to producing anti-peptide antibodies for immuno-MRM while the market is much larger for conventional technologies, especially Western blotting and ELISA. Part of this reluctance has been the concern that affinity reagents generated to short, linear, tryptic peptide sequences may not perform well in traditional assays that detect full-length proteins. In this study, we test the feasibility and success rates of generating immuno-MRM monoclonal antibodies (mAbs) (targeting tryptic peptide antigens) that are also compatible with conventional, protein-based immuno-affinity technologies. We generated 40 novel, peptide immuno-MRM assays and determined that the cross-over success rates for using immuno-MRM monoclonals for Western blotting is 58% and for ELISA is 43%, which compare favorably to cross-over success rates amongst conventional immunoassay technologies. These success rates could most likely be increased if conventional and immuno-MRM antigen design strategies were combined, and we suggest a workflow for such a comprehensive approach. Additionally, the 40 novel immuno-MRM assays underwent fit-for-purpose analytical validation, and all mAbs and assays have been made available as a resource to the community via the Clinical Proteomic Tumor Analysis Consortium's (CPTAC) Antibody (http://antibodies.cancer.gov) and Assay Portals (http://assays.cancer.gov), respectively. This study also represents the first determination of the success rate (92%) for generating mAbs for immuno-MRM using a recombinant B cell cloning approach, which is considerably faster than the traditional hybridoma approach.


Genetically modified mesenchymal stem cells and their clinical potential in acute cardiovascular disease.
Adult mesenchymal stem cells (MSCs) are non-hematopoietic cells with multi-lineage potential to differentiate into various tissues of mesodermal origin. They can be isolated from bone marrow and other tissues and have the capacity to extensively proliferate in vitro. Moreover, MSCs have also been shown to produce anti-inflammatory molecules which can modulate humoral and cellular immune responses. Considering their regenerative potential and immunoregulatory effect, MSC therapy is a promising tool in the treatment of degenerative, inflammatory, and autoimmune diseases. However, the current understanding from results of clinical trials is that MSC-therapy is safe but its therapeutic efficiency needs to be improved. In this article we will focus on options for genetic manipulation of MSCs and on current progress in adapting genetically-modified MSCs for clinical use in acute cardiovascular disease.


The brain and higher mental function.
Critical evaluation of biological theories of psychiatric disorder requires an understanding of current concepts of higher mental function and its related biology. Both the nature of the topic and the rapidity of advances in the field make it difficult to obtain an updated synthesis. Part I of this paper attempts to provide that by reviewing current concepts of the mind/body relationship, emotion, arousal, attention, consciousness and motivation. Part II considers those concepts in relation to recent work on the structure and function of the reticular, limbic and anterior cerebral systems. It is concluded that the model of the limbic system as subserving emotional life could now perhaps be set aside in favour of the model of a core set of chemically identified neurons in the reticular system being necessary but not sufficient to subserve higher mental function whilst also subserving other integrating functions for which no mental terminology is required. The problem of developing an eclectic theory of higher mental function that will embrace these concepts is discussed.


Being in rhythm: dissociative attunement in therapeutic process.
Dissociative attunement is a profound rhythmic encounter in therapeutic treatment. Attunement is a synchronized awareness of implicit knowing that is nonlinear and bidirectional. Empathically attuned clinicians are like microtonal tuning forks. They resonate with a variety of emotional pitches and will resonate with nuanced shifting of emotional tone. This resonance is the basis of dissociative attunement. Concepts such as empathic attunement, affect attunement, "the unthought known," "implicit relational knowing," and "a two-person unconscious" help us to understand unique aspects of projective identification, transference, and countertransference within the dissociative frame. However, "dissociative" attunements are systemically self-emergent moments in which multiple self-states are shared by means other than projection. Using clinical vignettes, I demonstrate how dissociative attunement can paradoxically appear to be misattunement. By synthesizing scientific and theoretical concepts applied to these clinical moments, we can understand dissociative attunement as a therapeutic tool as well as a pathway to vicarious traumatization.


Complexity of implementing a nationwide advance care planning program: results from a qualitative evaluation.
We evaluated Singapore's national advance care planning (ACP) program to understand challenges to its implementation within multiple clinical settings. We conducted focus group discussions (FGDs) with a purposive sample of health care professionals (HCPs) involved in ACP program delivery within acute care hospitals, primary care clinics and nursing homes. FGDs were stratified into three categories based on HCPs' role within the ACP framework-leaders versus facilitators and advocates versus nursing home heads. Using NVivo 11, we analysed data using thematic analysis and Conceptual Framework for Implementation Research. A total of 107 HCPs from 25 organisations participated in 22 FGDs. Findings revealed wide variation in ACP implementation among organisations and identified 12 themes organized within four domains-outer setting (lack of public awareness, shortcomings in inter-organisational partnerships, performance driven policies), inner setting (lack of commitment from organisational leadership, paucity of dedicated resources, absence of an institution-wide ACP culture, lack of physician engagement), characteristics of HCPs (language barriers) and process (inadequate training, complexity of conversations and documentations, challenges to retrieving ACP documents, absence of comprehensive monitoring and evaluation). ACP program implementation is complex and faces multiple health care system challenges. To integrate ACP within routine clinical care, ACP processes should be simplified, training framework be strengthened, physicians be engaged and an ACP supportive culture be created within and outside organisations. Findings will be used to guide ACP implementation within the country and globally.


[Clinical manifestations and mutation study in 16 Chinese patients with Fabry disease].
To investigate the clinical manifestations and to characterize mutations of the GLA gene in Chinese patients with Fabry disease so to enhance the diagnosis of Fabry disease. Sixteen Chinese affected males (from 16 unrelated families) with the classic phenotype of Fabry disease were investigated. The patients were diagnosed by a deficiency of alpha-galactosidase A (alpha-Gal A) activity. All seven exons and the neighboring intronic sequences of GLA gene were analyzed by PCR amplification and automated sequencing. A total of 14 mutations were identified including 12 single-base substitutions (11 missense and 1 nonsense mutations), 1 small deletion and 1 splicing mutation. Eight novel mutations (c.119 C > A, c.275 A > T, c.520T > C, c.547G > C, c.647A > G, c.929T > G, c.1045T > A, IVS1-1G > A) were identified. The novel mutations were not tested by RFLP on 100 GLA alleles in Chinese population, and were highly conservative in mammalian species. Fabry disease is often misdiagnosed in China. There is no hot spot for mutations in Chinese patients. GLA gene mutation analysis is a reliable method to diagnosis for Fabry disease.


A point-of-care test for facing the burden of undiagnosed celiac disease in the Mediterranean area: a pragmatic design study.
We aimed at assessing the factors that can influence results of the dissemination of an already validated, new generation commercial Point-of-Care Test (POCT) for detecting celiac disease (CD), in the Mediterranean area, when used in settings where it was designed to be administered, especially in countries with poor resources. Pragmatic study design. Family pediatricians at their offices in Italy, nurses and pediatricians in Slovenia and Turkey at pediatricians', schools and university primary care centers looked for CD in 3,559 (1-14 yrs), 1,480 (14-23 yrs) and 771 (1-18 yrs) asymptomatic subjects, respectively. A new generation POCT detecting IgA-tissue antitransglutaminase antibodies and IgA deficiency in a finger-tip blood drop was used. Subjects who tested positive and those suspected of having CD were referred to a Celiac Centre to undergo further investigations in order to confirm CD diagnosis. POCT Positive Predictive Value (PPV) at tertiary care (with Negative Predictive Value) and in primary care settings, and POCT and CD rates per thousand in primary care were estimated. At tertiary care setting, PPV of the POCT and 95% CI were 89.5 (81.3-94.3) and 90 (56-98.5) with Negative Predictive Value 98.5 (94.2-99.6) and 98.7% (92-99.8) in children and adults, respectively. In primary care settings of different countries where POCT was performed by a different number of personnel, PPV ranged from 16 to 33% and the CD and POCT rates per thousand ranged from 4.77 to 1.3 and from 31.18 to 2.59, respectively. Interpretation of POCT results by different personnel may influence the performance of POC but dissemination of POCT is an urgent priority to be implemented among people of countries with limited resources, such as rural populations and school children.


Post-traumatic bifid condyle: the pathogenesis analysis.
This study investigated the characteristic of bifid condyle secondary to temporomandibular joint (TMJ) trauma, aiming to analyse the pathogenesis of post-traumatic bifid condyle. Four cases identified as having bifid condyle secondary to TMJ trauma were involved in this study. The relative information extracted from the case records included patients' complaint, history of injury and radiographic appearance, which were used to analyse the characteristic and pathogenesis of post-traumatic bifid condyle. The results indicated that there was a correlation between condylar trauma degree and bifid condylar head appearance after trauma. For severe condylar fracture, it might result in Y-shaped condyle associated with TMJ ankylosis; and condylar groove could be associated with the slight trauma in condyle articulating surface. In conclusion, as a specific entity, post-traumatic bifid condyle may develop in cases with insufficient remodelling capacity after condyle trauma, and it seems that the severity degree of trauma, the site of trauma and its relation to the insertion of the lateral pterygoid muscles are factors associated with the appearance and orientation of bifid condyle.


Single substitution in H3.3G34 alters DNMT3A recruitment to cause progressive neurodegeneration.
Germline histone H3.3 amino acid substitutions, including H3.3G34R/V, cause severe neurodevelopmental syndromes. To understand how these mutations impact brain development, we generated H3.3G34R/V/W knock-in mice and identified strikingly distinct developmental defects for each mutation. H3.3G34R-mutants exhibited progressive microcephaly and neurodegeneration, with abnormal accumulation of disease-associated microglia and concurrent neuronal depletion. G34R severely decreased H3K36me2 on the mutant H3.3 tail, impairing recruitment of DNA methyltransferase DNMT3A and its redistribution on chromatin. These changes were concurrent with sustained expression of complement and other innate immune genes possibly through loss of non-CG (CH) methylation and silencing of neuronal gene promoters through aberrant CG methylation. Complement expression in G34R brains may lead to neuroinflammation possibly accounting for progressive neurodegeneration. Our study reveals that H3.3G34-substitutions have differential impact on the epigenome, which underlie the diverse phenotypes observed, and uncovers potential roles for H3K36me2 and DNMT3A-dependent CH-methylation in modulating synaptic pruning and neuroinflammation in post-natal brains.


Isotope effects on the enzymatic and nonenzymatic reactions of chorismate.
The important biosynthetic intermediate chorismate reacts thermally by two competitive pathways, one leading to 4-hydroxybenzoate via elimination of the enolpyruvyl side chain, and the other to prephenate by a facile Claisen rearrangement. Measurements with isotopically labeled chorismate derivatives indicate that both are concerted sigmatropic processes, controlled by the orientation of the enolpyruvyl group. In the elimination reaction of [4-2H]chorismate, roughly 60% of the label was found in pyruvate after 3 h at 60 degrees C. Moreover, a 1.846 +/- 0.057 2H isotope effect for the transferred hydrogen atom and a 1.0374 +/- 0.0005 18O isotope effect for the ether oxygen show that the transition state for this process is highly asymmetric, with hydrogen atom transfer from C4 to C9 significantly less advanced than C-O bond cleavage. In the competing Claisen rearrangement, a very large 18O isotope effect at the bond-breaking position (1.0482 +/- 0.0005) and a smaller 13C isotope effect at the bond-making position (1.0118 +/- 0.0004) were determined. Isotope effects of similar magnitude characterized the transformations catalyzed by evolutionarily unrelated chorismate mutases from Escherichia coli and Bacillus subtilis. The enzymatic reactions, like their solution counterpart, are thus concerted [3,3]-sigmatropic processes in which C-C bond formation lags behind C-O bond cleavage. However, as substantially larger 18O and smaller 13C isotope effects were observed for a mutant enzyme in which chemistry is fully rate determining, the ionic active site may favor a somewhat more polarized transition state than that seen in solution.


Experiences of agency in historically underrepresented racial and ethnic dental faculty at predominantly white institutions.
Historically underrepresented racial and ethnic (HURE) dentists remain underrepresented in dental education and dental practice, and surprisingly, little is known about the factors that enable them to thrive. The lack of information about their experiences is a critical gap in the literature. The purpose of this critical qualitative study is to describe how HURE dental faculty in predominantly white institutions (PWIs) exercise agency to thrive and advance in academic promotion when faced with challenges and adversity in the workplace. Thirteen semi-structured interviews were conducted in 2021 and 2022 with HURE dental faculty from 10 different institutions. Interviews were audio recorded, transcribed, and analyzed using the construct of agency and tenets of critical race theory to understand how they thrive in their institutions. HURE dental faculty experienced racism as normal from both faculty and students. Racism centered around white faculty guarding access to white spaces, including things that should be open to everyone like meetings and information about promotion. To counter this, HURE faculty engaged in individual agency by fighting for their perspectives to be heard, proxy agency by seeking and building relationships with mentors and colleagues who could use their whiteness to create change, and improvisational agency by going outside their institutions for support. To thrive in PWIs requires HURE faculty to exercise various forms of agency to directly or indirectly advocate for themselves as professionals. These findings have implications for dental leaders to change their existing structures and improve the work environments for HURE dental faculty.


Development of specific human mab's by a small scale electrofusion technique: the influence of some physical and chemical factors on hybridoma yield of human peripheral blood lymphocytes XCB-F7 fusions.
A fusion chamber and an appropriate procedure are described which allow to fuse a sample of 15 to 25 microliters of cell suspension every two minutes. The cells can be observed throughout the process. They are not exposed to mechanical stress after the fusion pulse. Electrofusion between the heteromyeloma line CB-F7 and human mononuclear cells from peripheral blood of immunized donors is shown to provide stable hybridomas producing IgG against tetanustoxin. Pronase treatment, calmodulin, PEG, lanthanum and a number of variations in the fusion conditions were investigated as to whether they influence physical fusion of the cells, hybridoma yield, and immunoglobulin production.


Little or no response to 24-hr water-deprivation of Fos-like immunoreactivity in vasopressinergic magnocellular neurons in the hypothalamus of hereditary microphthalmic rats.
In normal rats, 24-hr water-deprivation was found to cause a significant increase in the plasma concentration of arginine vasopressin (AVP), and marked induction of Fos in the AVP-positive magnocellular neurons in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) of the hypothalamus. On the other hand, 24-hr water-deprivation also caused a significant increase in the plasma AVP concentration in hereditary microphthalmic rats, but much less than in normal rats. Consistent with this, the extent of induction of Fos in the nuclei of the PVN and SON of these rats was lesser than in normal rats. These results suggest that hereditary microphthalmic rats have a defect or decrease in the response to water-deprivation of vasopressinergic magnocellular neurons in the PVN and SON.


Ultrastructure, glutathione and low molecular weight proteins of Penicillium brevicompactum in response to cobalt.
Penicillium brevicompactum highly tolerated cobalt concentrations of 50, 200, 800 and 1000 ppm both through cell wall and intracellular sequestration- immobilization of the metal on/within the cell wall, cell wall thickness, presence of electron-dense deposits inside vacuoles (thiol peptides sequestering cobalt) and in the cytoplasm (cobalt), and presence of matrixed electron-dense deposits, only at 800 and 1000 ppm, were observed. Increased vacuole formation and plasmolysis were also observed. Fraction number 9 of the cell free extract showed maximum cobalt uptake for all the investigated cobalt concentrations. In this fraction, glutathione was only induced at 500, 800 and 1000 ppm. Maximum glutathione concentration supported maximum cobalt uptake at 800 ppm. Low molecular weight protein profiles of fraction number 9 revealed that the presence of cobalt induced the appearance of new proteins that were not detected in the same fraction of the control. These low molecular weight peptides (12-5 KDa) suggest the production of Co-metallothioneins. This is the first report of cobalt-induced glutathione by P. brevicompactum and suggests the possible production of phytochelatins.


Emotion and auditory virtual environments: affect-based judgments of music reproduced with virtual reverberation times.
Emotions are experienced both in real and virtual environments (VEs). Most research to date have focused on the content that causes emotional reactions, but noncontent features of a VE (such as the realism and quality of object rendering) may also influence emotional reactions to the mediated object. The present research studied how noncontent features (different reverberation times) of an auditory VE influenced 76 participants' ratings of emotional reactions and expressed emotional qualities of the sounds. The results showed that the two emotion dimensions of pleasantness and arousal were systematically affected if the same musical piece was rendered with different reverberation times. Overall, it was found that high reverberation time was perceived as most unpleasant. Taken together, the results suggested that noncontent features of a VE influence emotional reactions to mediated objects. Moreover, the study suggests that emotional reactions may be a important aspect of the VE experience that can help complementing standard presence questionnaires and quality evaluations.


Long-term efficacy of psoriasis vulgaris treatments: analysis of treatment with topical corticosteroid and/or vitamin D3 analog, oral cyclosporin, etretinate and phototherapy over a 35-year period, 1975-2010.
Various therapies have been tried for psoriasis. In Japan, biologics began to be used for psoriasis treatment in January 2010. Their clinical efficacy is well known, but biologics cannot be used in all psoriasis patients for reasons such as side-effects and cost. It is necessary to evaluate the effect of long-term psoriasis treatment, but there have been no reports evaluating long-term treatment. Therefore, the outcomes of patients who had been treated at the Tokai University Hospital for more than 5 years, before biological agents were released, were examined. Three categories, classified by initial severity, changes in severity by method of treatment and background characteristics, were investigated. In conclusion, cases of long-term treatment with a combination of topical corticosteroid and topical vitamin D3 analog or oral cyclosporin were found to be effective therapies. Patients with a history of diabetes mellitus or cardiovascular disease of psoriasis were likely to be treatment resistant.


Social justice, federal paternalism, and feminism: breast implants in the cultural context of female beauty.
In April 1992 the Food and Drug Administration (FDA) announced it was restricting the availability of silicone gel-filled breast implants to women enrolled in clinical trials. All candidates for breast reconstruction, but only a "very limited" number of augmentation candidates, would have access to the implants. This policy has been criticized as paternalistic, sexist, and unjustified by scientific data. I examine these charges and conclude that controversy surrounding the scientific data weakens the FDA's paternalistic mandate and that its policy of treating reconstruction and augmentation candidates differently results in increased social injustice and perpetuates cultural biases concerning female beauty and women's rights to control their bodies. I also argue that these cultural biases shape women's subjective experience of their physical selves and should not, contrary to some feminist arguments, be viewed as precluding their giving informed consent to breast surgery.


Gastrointestinal Impedance Spectroscopy to Detect Hypoperfusion During Hemorrhage.
Changes in tissue impedance (Ω) have been proposed as early signs of impaired tissue perfusion. We hypothesized that hemorrhage may induce early changes in alimentary tract tissue impedance and that these can be detected by impedance spectroscopy. We evaluated impedance spectroscopy in an acute hemorrhage model in pigs. Twenty anesthetized pigs were randomized to stepwise hemorrhage to mean arterial blood pressure (MAP) targets of 60 mm Hg, 50 mm Hg, 45 mm Hg, and 40 mm Hg, followed by retransfusion in two steps, or control (n = 10 each). In the end, 500 mL of enteral nutrition was administered in both groups. Ω in four sites (sublingually, esophagus, stomach, proximal jejunum) and cardiac output (Qtot thermodilution), superior mesenteric artery blood flow (QSMA; Doppler ultrasound), and jejunal mucosal blood flow (LDF; laser Doppler) were measured. The bleeding (total volume 838 ± 185 mL; mean ± SD) resulted in progressive hypotension (actual MAP 65 ± 3 mm Hg, 59 ± 4 mm Hg, 55 ± 5 mm Hg, and 46 ± 6 mm Hg) and decrease in Qtot, QSMA, and mucosal LDF. Bleeding did not change Ω in any of the monitoring sites. Retransfusion restored the blood flows to at least baseline levels, again without change in Ω. Enteral nutrition did not alter Ω or any of the blood flows.Five animals (three in the hemorrhage group, two in the control group) had histologically proven acute gastric focal necrosis at the site of It transducer. Gastrointestinal impedance spectroscopy does not detect early changes in tissue perfusion during progressive hemorrhage or retransfusion. Ω spectroscopy is unlikely to provide any additional information of hypovolemia-induced early changes in gastrointestinal perfusion.


Current molecular methods in epidemiological typing of Acinetobacter baumannii.
The emergence of Acinetobacter baumannii during recent decades as an important nosocomial pathogen responsible of worldwide, intensively documented, outbreaks has resulted in a need for effective epidemiological typing methods. Throughout the years, many typing methods for A. baumannii epidemiological studies have been proposed from phenotypic to molecular methods. Currently, the use of phenotypic typing methods have declined considerably and been progressively replaced by molecular methods. In this review, we introduce the current molecular methods available for A. baumannii typing. Each method has its own advantages and disadvantages, and the selection of an appropriate genotyping method depends on studied objectives. This review sheds light on questions in different epidemiological settings and most molecular methods used to fit these objectives.


A systematic evaluation of yeast sample preparation protocols for spectral identifications, proteome coverage and post-isolation modifications.
The importance of obtaining comprehensive and accurate information from cellular proteomics experiments asks for a systematic investigation of sample preparation protocols. In particular when working with unicellular organisms with strong cell walls, such as found in the model organism and cell factory Saccharomyces cerevisiae. Here, we performed a systematic comparison of sample preparation protocols using a matrix of different conditions commonly applied in whole cell lysate, bottom-up proteomics experiments. The different protocols were evaluated for their overall fraction of identified spectra, proteome and amino acid sequence coverage, GO-term distribution and number of peptide modifications, by employing a combination of database and unrestricted modification search approaches. Ultimately, the best protocols enabled the identification of approximately 65-70% of all acquired fragmentation spectra, where additional de novo sequencing suggests that unidentified spectra were largely of too low spectral quality to provide confident spectrum matches. Generally, a range of peptide modifications could be linked to solvents, additives as well as filter materials. Most importantly, the use of moderate incubation temperatures and times circumvented excessive formation of modification artefacts. The collected protocols and large sets of mass spectrometric raw data provide a resource to evaluate and design new protocols and guide the analysis of (native) peptide modifications. SIGNIFICANCE: The single-celled eukaryote yeast is a widely used model organism for higher eukaryotes in which, for example, the regulation of glycolysis is studied in the context of health and disease. Moreover, yeast is a widely employed cell factory because it is one of the few eukaryotic organisms that can efficiently grow under both aerobic and anaerobic conditions. Large-scale proteomics studies have become increasingly important for single-celled model organisms, such as yeast, in order to provide fundamental understanding of their metabolic processes and proteome dynamics under changing environmental conditions. However, comprehensive and accurate cellular proteomics experiments require optimised sample preparation procedures, in particular when working with unicellular organisms with rigid cell walls, such as found in yeast. Protocols may substantially bias towards specific protein fractions, modify native protein modifications or introduce artificial modifications. That lowers the overall number of spectral identifications and challenges the study of native protein modifications. Therefore, we performed a systematic study of a large array of protocols on yeast grown under highly controlled conditions. The obtained outcomes, the collected protocols and the mass spectrometric raw data enable the selection of suitable sample preparation elements and furthermore support the evaluation of (native) peptide modifications in yeast, and beyond.


Pharmacokinetics of cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) in patients with normal and impaired renal function.
cis-Diammine-1,1-cyclobutane dicarboxylate platinum(II) (CBDCA, JM8) is a nonnephrotoxic analogue of cisplatin currently undergoing clinical evaluation. Pharmacokinetic studies have been performed in patients receiving CBDCA (20 to 520 mg/sq m) as a 1-hr infusion without hydration or diuresis. Following the end of the infusion, plasma levels of total platinum and ultrafilterable (Mr less than 50,000) platinum (free platinum) decayed biphasically with first-order kinetics (total platinum t alpha 1/2 = 98 min; t beta 1/2 range, 399 to greater than 1440 min; free platinum t alpha 1/2 = 87 min; t beta 1/2 = 354 min). During the first four hr, binding of platinum to plasma protein was limited (24%), with most of the free platinum in the form of unchanged CBDCA (94%). However, by 24 hr, the majority of platinum was protein bound (87%). The major route of elimination was renal, 65% of the platinum administered being excreted in the urine within 24 hr, with 32% of the dose excreted as unchanged CBDCA. No evidence was found from studies on the renal clearance of free platinum to indicate renal tubular secretion (mean free platinum renal clearance, 69 ml/min). However, the plasma clearance of free platinum did correlate positively with glomerular filtration rates (p = 0.005). None of the pharmacokinetic parameters determined were dose dependent. In vitro studies with plasma and urine demonstrated that, in contrast to cisplatin, CBDCA is a stable complex [t 1/2 - 37 degrees; plasma, 30 hr, and urine (range), 20 to 460 hr]. The differences in the pharmacokinetics of cisplatin and CBDCA may explain why the latter complex is not nephrotoxic.


Developments in the Reactivity of 2-Methylimidazolium Salts.
Unexpected and unusual reactivity of 2-methylimidazolium salts toward aryl-N-sulfonylimines and aryl aldehydes is here reported. Upon reaction with aryl-N-sulfonylimines, the addition product, arylethyl-2-imidazolium-1-tosylamide (3), is formed with moderate to good yields, while upon reaction with aldehydes, the initial addition product (6) observed in NMR and HPLC-MS experimental analysis is postulated by us as an intermediate to the final conversion to carboxylic acids. Studies in the presence and absence of molecular oxygen allow us to conclude that the imidazolium salts is crucial for the oxidation. A detailed mechanistic study was carried out to provide insights regarding this unexpected reactivity.


Investigation and treatment of hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy is a common genetically transmitted disease, defined clinically by the presence of left ventricular hypertrophy in the absence of loading conditions sufficient to cause the observed degree of hypertrophy. The disease has a heterogeneous clinical course, with many patients having few cardiovascular symptoms and others profound exercise limitation and recurrent arrhythmia. The overall annual rate of disease-related complications such as sudden death, end-stage heart failure and fatal stroke is approximately 1-2%, but risk in individual patients varies as a function of age, disease severity and the underlying cause of the hypertrophy. Genetic counselling and clinical risk stratification are relevant for all patients. Subsets of patients require septal alcohol ablation, septal myectomy and implantable cardioverter defibrillators.


The effects of temperature on nickel bioaccumulation and toxicity in the freshwater snail Lymnaea stagnalis.
It is well known that temperature can have important effects on the toxicity of metals (and other contaminants) to aquatic organisms. To date, research has mostly focused on thermal effects on acute metal toxicity, and there is a data gap on thermal effects on chronic metal toxicity to sensitive organisms that are particularly relevant to environmental risk assessment. This latter research is especially needed in the context of increased global temperature and heat waves frequency associated with climate change. We investigated temperature effects on chronic nickel (Ni) bioaccumulation and toxicity to the metal-sensitive freshwater snail Lymnaea stagnalis. In the laboratory, we conducted a series of experiments with juvenile snails that were pre-acclimated to different temperatures since their embryonic stage. We found that temperature and nickel separately had strong effects on juvenile growth rate and survival. Rising temperature from 18 to 26 °C had no noticeable effect on Ni-induced growth inhibition and Ni bioaccumulation in juvenile L. stagnalis exposed over 40 days to 0, 30 and 60 μg L-1 of dissolved Ni. These results agreed with estimates of Ni uptake and elimination rates (ku and ke), which were either unaffected by temperature or increased by similar factors from 18 to 26 °C. On the other hand, a temperature increase from 18 to 26 °C appeared to exacerbate Ni lethality to juvenile snails in the 40-day toxicity test. This exacerbation might have been due to a combination of factors, including detrimental changes in metabolically available Ni pools and/or to sensitization of the organism under sub-optimal temperatures. Overall, our study shows that thermal effects on metal chronic toxicity are complex, with effects that can be response-specific and not directly related to metal toxicokinetic.


Childhood granulomatous periorificial dermatitis with a good response to oral metronidazole.
Childhood granulomatous periorificial dermatitis (CGPD) is a condition included in the spectrum of rosacea and perioral dermatitis that affects prepubescent children. It is characterized by papular eruptions located around the mouth, nose, and eyes that histopathologically show a granulomatous pattern. We report a 9-year-old girl with CGPD who required treatment with an oral antibiotic. Oral metronidazole was administered because of its known efficacy in adult rosacea and its safety in children. The patient responded well to this therapy, showing resolution of the lesions.


[Reference values for maximal midexpiratory flow in black females].
The aim of this publication is to contribute to the establishment of reference values for the forced expiratory flow between 25 and 75% of the vital capacity (FEF25-75) among black females in West Africa. 316 of them, aged between 10 and 70 years, were submitted to this test. They were considered free from cardiopulmonary disease after a questionnaire and clinical examination. FEF25-75 in absolute value was lower than in the white Euro-americans. It increased up to 18-19 years of age, then decreased steadily thereafter. The main equations of regression for the FEF25-75 (l X s-1) were: 10-18 years, 0.177A + 1.058 and 0.157A + 0.826H + 0.005; 19-70 years, -0.028A + 4.211 and -0.025A + 2.206H + 0.512, (where A is the age in years and H the height in metres). The results are compared with the reference values published in Black Africa, Europe and the United States.


Impact of Valve Size on Paravalvular Leak and Valve Hemodynamics in Patients With Borderline Size Aortic Valve Annulus.
Transcatheter heart valve (THV) selection for transcatheter aortic valve implantation (TAVI) is crucial to achieve procedural success. Borderline aortic annulus size (BAAS), which allows a choice between two consecutive valve sizes, is a common challenge during device selection. In the present study, we evaluated TAVI outcomes in patients with BAAS according to THV size selection. We performed a retrospective study including patients with severe aortic stenosis (AS) and BAAS, measured by multi-detector computed tomography (MDCT), undergoing TAVI with self-expandable (SE) or balloon-expandable (BE) THV from the Israeli multi-center TAVI registry. The aim was to evaluate outcomes of TAVI, mainly paravalvular leak (PVL) and valve hemodynamics, in patients with BAAS (based on MDCT) according to THV sizing selection in between 2 valve sizes. In addition, to investigate the benefit of shifting between different THV types (BE and SE) to avoid valve size selection in BAAS. Out of 2,352 patients with MDCT measurements, 598 patients with BAAS as defined for at least one THV type were included in the study. In BAAS patients treated with SE-THV, larger THV selection was associated with lower rate of PVL, compared to smaller THV (45.3 vs. 64.5%; pv = 0.0038). Regarding BE-THV, larger valve selection was associated with lower post-procedural transvalvular gradients compared to smaller THV (mean gradient: 9.9 ± 3.7 vs. 12.5 ± 7.2 mmHg; p = 0.019). Of note, rates of mortality, left bundle branch block, permanent pacemaker implantation, stroke, annular rupture, and/or coronary occlusion did not differ between groups. BAAS is common among patients undergoing TAVI. Selection of a larger THV in these patients is associated with lower rates of PVL and optimized THV hemodynamics with no effect on procedural complications. Additionally, shift from borderline THV to non-borderline THV modified both THV hemodynamics and post-dilatation rates.


Cytochemical changes induced by apholate, tepa and hempa during vitellogenesis in Locusta migratoria.
Proteins (--SS, --SH, and NH2 groups; tyrosine, tryptophan and arginine), DNA, phospholipids and triglycerides showed a progressive decline in the oocytes of Locusta migratoria with increase in doses of apholate, tepa and hempa. Carbohydrates showed a decline only after higher doses of apholate and tepa whereas they were not affected at all with hempa. The pyroninophilia due to RNA in the oocytes decreased in the ooplasm of oocytes slightly, but increased in the cytoplasm and nucleoplasm of follicular epithelial cells with all the chemosterilants. The follicular epithelial cells degenerated in the mature oocytes, and yolk formation was inhibited.


Cold comfort care.
People living in remote rural areas often have difficulty accessing healthcare services, and community and primary care providers are set to be even more important as hospital services become centralised. Rural nurses demonstrate high levels of skill, resilience and ingenuity in bringing care to patients in their own homes.


Model for gas-hydrate equilibrium in porous media that incorporates pore-wall properties.
Naturally-occurring gas hydrates (in permafrost and marine sediments) have the potential to contribute as a carbon-based source to the increasing energy demand. Precise estimates of gas-hydrate global inventory, development of strategies for their exploitation, and evaluation of their environmental impact require models that accurately describe gas-hydrate stability in marine sediments. A model for gas-hydrate equilibrium in porous media, developed from fundamental thermodynamic principles, is proposed and validated against available experimental data. The derivation of the model allowed for the natural incorporation of sediment properties into equilibrium conditions, such as interfacial energies and contact angles between different phases. Model parameters were obtained from independent experiments and fundamental calculations reported in the literature. For the range of pore sizes (3.4-24.75 nm) of different materials reported in the literature, the absolute average deviations (AAD%) between the model predictions and the experimental data are between 0.04% and 2.07%. The wettability of the pore surface affects the shape of the hydrate phase inside the pore and consequently influences the equilibrium pressures of gas-hydrate formed in porous media.


Inactivation of the cellular p53 gene is a common feature of Friend virus-induced erythroleukemia: relationship of inactivation to dominant transforming alleles.
The Friend erythroleukemia virus complex contains no cell-derived oncogene. Transformation by this virus may therefore involve mutations affecting cellular gene expression. We provide evidence that inactivating mutations of the cellular p53 gene are a common feature in Friend virus-induced malignancy, consistent with an antioncogene role for p53 in this disease. We have shown that frequent rearrangements of the p53 gene cause loss of expression or synthesis of truncated proteins, whereas overexpression of p53 protein is seen in other Friend cell lines. We now demonstrate that p53 expression in the latter cells is also abnormal, as a result of missense mutations in regions encoding highly conserved amino acids. Three of these aberrant alleles obtained from cells from different mice were cloned and found to function as dominant oncogenes in gene transfer assays, supporting the view that certain naturally occurring missense mutations in p53 confer a dominant negative phenotype on the encoded protein.


Use of Polymer-Jacketed, Tapered-Tip, Low-Force Guidewires With Composite-Core, Dual-Coil Design as Part of the Antegrade Approach to Coronary Chronic Total Occlusions.
To investigate the impact of novel, polymer-jacketed, tapered-tip, low-force guidewires with composite-core, dual-coil design (Fielder XT-R and Fielder XT-A; Asahi Intecc) on antegrade wire escalation (AWE) crossing of coronary chronic total occlusion (CTO) lesions. From March of 2017 to December 2018, a total of 164 consecutive CTO lesions at a single institution were treated with a primary AWE strategy using either Fielder XT-R or XT-A (XTRA) as the starting wire regardless of lesion characteristics. Success rates, wiring times, and complications were analyzed. The mean Japanese (J)-CTO score was 3.71 ± 1.27, mean PROGRESS-CTO score was 2.46 ± 1.15, and mean PROGRESS-CTO Complications score was 3.9 ± 2.0. Mean CTO length was 25.0 ± 0.5 mm, 48 lesions (29.3%) were previously bypassed, 77 lesions (47.0%) had moderate to severe calcification, and 62 lesions (37.8%) had moderate to severe tortuosity. Antegrade success rates using XTRA wires were 79%, 60%, and 17% of lesions with J-CTO scores of 0-1, 2-3, and 4-5, respectively. In successful antegrade XTRA cases, median wiring times were 6.5 min (interquartile range [IQR], 5.0-11.0 min), 9.0 min (IQR, 4.2-14.0 min), and 12.0 min (IQR, 9.0-15.0 min) for J-CTO scores of 0-1, 2-3, and 4-5, respectively, and differed non-significantly according to J-CTO score (P=.20). Complication rates were low (In-hospital major adverse cardiac event rate, 1.3%) with no wire perforations caused by XTRA wires. Use of Fielder XTRA wires as part of an AWE strategy in CTO percutaneous coronary interventions may facilitate more efficient antegrade lesion crossing and overall procedural success in lesions that have been traditionally challenging to treat using an antegrade-first approach.


Simultaneous protein expression and modification: an efficient approach for production of unphosphorylated and biotinylated receptor tyrosine kinases by triple infection in the baculovirus expression system.
Protein kinases can adopt multiple protein conformations depending on their activation status. Recently, in drug discovery, a paradigm shift has been initiated, moving from inhibition of fully activated, phosphorylated kinases to targeting the inactive, unphosphorylated forms. For identification and characterization of putative inhibitors, also interacting with the latent kinase conformation outside of the kinase domain, highly purified and homogeneous protein preparations of unphosphorylated kinases are essential. The kinetic parameters of nonphosphorylated kinases cannot be assessed easily by standard kinase enzyme assays as a result of their intrinsic autophosphorylation activity. Kinetic binding rate constants of inhibitor-protein interactions can be measured by biophysical means upon protein immobilization on chips. Protein immobilization can be achieved under mild conditions by binding biotinylated proteins to streptavidin-coated chips, exploiting the strong and highly specific streptavidin-biotin interaction. In the work reported here, the cytoplasmic domains of insulin receptor and insulin-like growth factor-1 receptor fused to a biotin ligase recognition sequence were coexpressed individually with the phosphatase YopH and the biotin-protein ligase BirA upon triple infection in insect cells. Tandem affinity purification yielded pure cytoplasmic kinase domains as judged by gel electrophoresis and HPLC. Liquid chromatography-mass spectrometry analysis showed the absence of any protein phosphorylation. Coexpression of BirA led to quantitative and site-specific biotinylation of the kinases, which had no influence on the catalytic activity of the kinases, as demonstrated by the identical phosphorylation pattern upon autoactivation and by enzymatic assay. This coexpression approach should be applicable to other protein kinases as well and should greatly facilitate the production of protein kinases in their phosphorylated and unphosphorylated state suitable for enzymatic and biophysical studies.


Complications after 100 sessions of cone-beam computed tomography-guided lung radiofrequency ablation: a single-center, retrospective experience.
Objective: To evaluate complications after consecutive 100 sessions of cone-beam computed tomography (CBCT)-guided radiofrequency ablation (RFA) of lung tumorsMaterials and methods: A retrospective study was conducted from January 2016 and October 2018. All procedures were performed using a CBCT virtual navigation guidance system, combining three-dimentional CBCT, needle planning software, and real-time fluoroscopy. Complications were evaluated for each RFA session in 63 consecutive patients (31 male, 32 female; mean age 58.0 years) with 121 lung tumors who underwent 100 sessions of CBCT-guided lung ablation with an internally cooled RFA system. Complications were recorded using the Common Terminology Criteria of Adverse Events (CTCAE) 5.0. A major complication was defined as a grade 3 or 4 adverse event.Results: There was no postprocedural mortality. The major and minor complication rates were 5% and 28%, respectively. The major complications were significant pulmonary hemorrhage (1%), large hemothorax requiring drainage (1%), pneumonia treated with antibiotics (2%), and delayed bronchopleural fistula (1%). The minor complications were pneumothorax (15%), hemoptysis (11%), and subcutaneous emphysema (2%). Of the 15 pneumothoraces, percutaneous catheter drainage was required in six sessions. Pneumothorax was more likely to occur if RFA was performed on two or more tumors at one session. Immediate, periprocedural and delayed complications were 23%, 9%, and 1%, respectively.Conclusion: CBCT-guided RFA of lung tumors is a relatively safe procedure with acceptable morbidity.


Collagen-derived peptides modulate CD4+ T-cell differentiation and suppress allergic responses in mice.
Collagen peptides have been widely used as a food supplement. After ingestion of collagen peptides, oligopeptides containing hydroxyproline (Hyp), which are known to have some physiological activities, are detected in peripheral blood. However, the effects of collagen-peptide administration on immune response are unclear. In the present study, we tested the effects of collagen-peptide ingestion on allergic response and the effects of collagen-derived oligopeptides on CD4+ T-cell differentiation. BALB/c mice fed a collagen-peptide diet were immunized with ovalbumin (OVA), and their serum IgE and IgG levels, active cutaneous anaphylaxis, and cytokine secretion by splenocytes were examined. Naive CD4+ T cells were stimulated with anti-CD3 and anti-CD28 in the presence of collagen-derived oligopeptides, and the expression of IFN-γ, IL-4, and Foxp3 was analyzed. In an active anaphylaxis model, oral administration of collagen peptides suppressed serum OVA-specific immunoglobulin E (IgE) production and diminished anaphylaxis responses. In this model, the ingestion of collagen peptides skewed the pattern of cytokine production by splenocytes toward T-helper (Th) type 1 and regulatory T (Treg) cells. In vitro T-helper cell differentiation assays showed that Hyp-containing oligopeptides promoted Th1 differentiation by upregulating IFN-γ-induced signal transducer and activator of transcription 1 (STAT1) signaling. These oligopeptides also promoted the development of Foxp3+ Treg cells in response to antigen stimulation in the presence of TGF-β. Collagen-peptide ingestion suppresses allergic responses by skewing the balance of CD4+ T cells toward Th1 and Treg cells and seems to be a promising agent for preventing allergies and inflammatory diseases.


A Systematic Review of Case Reports of a Rare Dermatological Condition: Elastosis Perforans Serpiginosa.
A systematic review was carried out on a rare dermatological condition affecting papillary dermal tissue fibers of the skin known as elastosis perforans serpiginosa (EPS). The aim of this review was to highlight this skin disease, its association with other medical conditions, and its management. The search was conducted by using the keywords "elastosis perforans serpiginosa" and "case reports" in the databases. A total of 10 case reports were analyzed and presented by the parameters like age, gender, chief complaints, and medical history. The most common causes of EPS were drug-induced and occurred along with the Wilson disease. The study concluded that as EPS is an uncommon disease with few instances, there is a need for further research to analyze randomized controlled trials that have been conducted in relation to the condition.


Glomerular expression of alpha2(IV) and alpha5(IV) chains of type IV collagen in patients with IgA nephropathy.
IgA nephropathy (IgAN) frequently accompanies glomerular basement membrane (GBM) alterations. To clarify the compositional changes of the GBM in IgAN, we examined the glomerular expression of alpha2(IV) and alpha5(IV) chains of type IV collagen in 36 patients with IgAN. Increased expression of the alpha2(IV) chain was observed in the expanded mesangium, and there were segmental sclerotic lesions of glomeruli in which the expression of the alpha5(IV) chain in the GBM was reduced. These lesions were found in 11 out of the 36 patients (30.6%). The patients with these lesions had more proteinuria, lower creatinine clearance and severer histological changes than the patients without them. On the other hand, a partial reduction of alpha5(IV) chain in normal-appearing GBM was observed in 15 out of the 36 patients (41.7%). The patients with this lesion had a longer disease period before biopsy than the patients without it. No other clinical and histological parameters were related to the partial reduction of alpha5(IV) in the GBM. In conclusion, an imbalance of glomerular alpha2(IV) and alpha5(IV) chain expression occurred in IgAN. This may be associated with the morphological changes of glomerular sclerosis and GBM alterations in IgAN. Further studies are required to understand the pathogenesis of the abnormal expression of type IV collagen chains.


How to Build the Plane While Flying: VTE/PE Thromboprophylaxis Clinical Guidelines for COVID-19 Patients.
Over the years, the practice of medicine has evolved from authority-based to experience-based to evidence-based with the introduction of the scientific process, clinical trials, and outcomes-based data analysis (Tebala GD. Int J Med Sci. 2018;15(12):1397-1405). The time required to perform the necessary randomized controlled trials, a systematic literature review, and meta-analysis of these trials to then create, accept, promulgate, and educate the practicing clinicians to use the evidence-based clinical guidelines is typically measured in years. When the severe acute respiratory syndrome novel coronavirus-2 (SARS-nCoV-2) pandemic commenced in Wuhan, China at the end of 2019, there were few available clinical guidelines to deploy, let alone adapt and adopt to treat the surge of coronavirus disease 2019 (COVID-19) patients. The aim of this study is to first explain how clinical guidelines, on which bedside clinicians have grown accustomed, can be created in the midst of a pandemic, with an evolving scientific understanding of the pathophysiology of the hypercoagulable state. The second is to adapt and adopt current venous thromboembolism diagnostic and treatment guidelines, while relying on the limited available observational reporting of COVID-19 patients to create a comprehensive clinical guideline to treat COVID-19 patients.


Ginsenoside Rb1 attenuates intestinal ischemia reperfusion induced renal injury by activating Nrf2/ARE pathway.
Intestinal ischemia reperfusion (IIR) is a serious clinical condition associated with simultaneous multiple organ dysfunction. The aim of this study was to investigate the effects of ginsenoside Rb1 on IIR induced renal injury in mice. An intestinal ischemia reperfusion mouse model was established by superior mesenteric artery (SMA) occlusion for 45 min, followed by reperfusion for 2 h. IIR induced renal injury characterized by increase of BUN, Cr and NGAL in serum, MDA levels and decrease of SOD levels in the renal tissues. Ginsenoside Rb1 (30, 60 mg/kg) given intraperitoneally before reperfusion attennuated renal injury, which was associated with decrease of BUN, Cr and NGAL in serum, MDA levels and increase of SOD levels in the renal tissues. Furthermore, the immunohistochemistry and Western blot data showed that ginsenoside Rb1 dramatically reversed IIR induced renal injury, associated with upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in renal tissues. Our data suggests that ginsenoside Rb1 attenuates acute renal injury induced by intestinal ischemia reperfusion by activating the Nrf2/ARE pathway.


[Study of serum phospholipase A2 activity in bronchial asthmatic patients].
We examined serum PLA2, lipids and platelets in 133 bronchial asthma patients who had not taken any glucocorticoids. Serum PLA2 was measured by radioimmunoassay. Serum PLA2 activity in the bronchial asthma patients was 384.2 +/- 114.7 (pmol/ml/min), and in the control group (healthy subjects) it was 271.7 +/- 53.9; this is a statistically significant difference (p < 0.01). Serum PLA2 of the mixed type was higher than that of the atopic type (p < 0.05) with respect to age, those subjects in their 60s showed statistically higher serum PLA2 values than those in their 20s and 30s (p < 0.05). The serum PLA2 level was statistically higher in a patient with an attack (409.1 +/- 113.9) than without an attack (342.6 +/- 94.3) (p < 0.05). However, there was no significant difference in lipid and platelet levels according to attack status. In conclusion, the serum PLA2 level is not only higher in asthma patients with attacks, but is also higher in asthma patients without attacks when compared to the control group. Therefore, the measurement of serum PLA2 is significant in predicting attacks.


Safety and efficacy of jet anesthesia for bone marrow aspirations.
Aspirations or Jamshidi needle biopsies (n = 287) of bone marrow were performed on children and adolescents with acute leukemia or other malignant disease following the use of a spring-loaded instrument that delivered local anesthetic in a jet spray; 89% of the patients were receiving chemotherapy, 12% were thrombocytopenic, and 23% of the 269 patients who were afebrile at the time of the procedure were severely neutropenic. None of these patients had an infection or a hemorrhage as a complication of the procedure. We conclude that not only is this procedure safe, but it is also much less painful than the traditional method of local anesthetic infiltration using a syringe and needle.