Mothers' reports of infant crying and soothing in a multicultural population.
To investigate the prevalence of infant crying and maternal soothing techniques in relation to ethnic origin and other sociodemographic variables. A questionnaire survey among mothers of 2-3 month old infants registered at six child health clinics in Amsterdam, the Netherlands. A questionnaire on sociodemographic characteristics and crying behaviour was completed for 1826 of 2180 (84%) infants invited with their parents to visit the child health clinics. A questionnaire on soothing techniques was also filled out at home for 1142 (63%) of these infants. Overall prevalences of "crying for three or more hours/24 hour day" "crying a lot", and "difficult to comfort" were 7.6%, 14.0%, and 10.3%, respectively. Problematic infant crying was reported by 20.3% of the mothers. Of these infants, only 14% met all three inclusion criteria. Problematic crying occurred less frequently among girls, second and later born children, Surinamese infants, and breast fed infants. Many mothers used soothing techniques that could affect their infant's health negatively. Shaking, slapping, and putting the baby to sleep in a prone position were more common among non-Dutch (especially Turkish) mothers than among Dutch mothers. Poorly educated mothers slapped their baby more often than highly educated mothers. Mothers' reports of infant crying and soothing varied sociodemographically. Much harm may be prevented by counselling parents (especially immigrants) on how and how not to respond to infant crying. Health education should start before the child's birth, because certain soothing techniques could be fatal, even when practised for the first time.


[Prophylaxis of cytomegalovirus infection in liver transplantation].
CMV prevention strategies in liver transplant recipients should be stratified according to serological status. In donor (D)-/recipient (R)- combinations, no prophylaxis or preemptive therapy is recommended. In the remaining combinations, the most widely used strategies are universal prophylaxis and preemptive therapy. Both strategies are effective compared with placebo but have not been compared with each other in well-designed clinical trials. Preemptive therapy is the preferred strategy in low-risk patients while prophylaxis is the most widely used option in those at high-risk. Delayed CMV disease is an adverse consequence of universal prophylaxis. Prolongation of prophylaxis from 100 to 200 days does not reduce the incidence of CMV disease. CMV-specific cell mediated immunity, facilitated by preemptive therapy and delayed by prophylaxis, has a therapeutic effect by reducing CMV replication. The drug of choice in both strategies is valganciclovir but the duration and dose differ. When preemptive therapy is used, viremia monitoring is required for the first 4 months. The technique of choice is quantitative polymerase chain reaction. Given the lack of conclusive data, the choice of one or other strategy in these patients should be individualized in each patient and center according to the available resources and possibilities of follow-up.


Growth and mortality of individual plants as a function of "available area".
We looked at the relationship between "available area", as defined by Thiessen polygons around individual plants, and plant size and mortality in even-aged green-house populations of Lapsana communis L. Polygon area was a good predictor of plant weight in these populations. After nine weeks growth, just prior to the onset of self-thinning, the dry weight of plants was directly proportional to the square root of polygon area. After the onset of selfthinning, plant weight appeared to be directly related to polygon area to the 3/2 power. Plants in small polygons were much more likely to die than those in larger areas. Thinning changed the frequency distribution of polygon sizes from highly skewed and unequal to normal and more equal, while inequality in surviving plant sizes did not appear to be affected by thinning.


A mutual response between surface temperature and black carbon mass concentration during the daytime.
The mutual response between surface temperature and the mass concentration of regional black carbon (BC) aerosols has still remained far from understanding due to its complex nature. A detailed analysis presented in this study using long-term data indicates a significant pattern of mutual response between surface temperature and BC in restricted background weather conditions (water vapor, cloud cover and wind speeds). The analysis shows that a fall in surface temperature which naturally occurs daily after the sunrise, leads to the development of a stronger inversion in the near-surface level and this, in turn, contributes to the enhancement of BC fumigation peak. Further, the enhanced fumigation peak (especially during pre-monsoon) is found positively influencing the mid-day temperature rise possibly due to the immediate impact of the direct radiative forcing of BC aerosols. These observations lead us to consider a hypothesis that 'an extra fall in the morning hour surface temperature contributes to the enhancement of BC fumigation peak and can degrade the morning hour air quality which gives positive feedback to the mid-day temperature rise over a region'. A substantial in situ data [over Gadanki (13.5°N, 79.2°E)] along with MERRA-2 and ERA-5 data are used in this methodical analysis. Moreover, the validity of the hypothesis has been tested over other locations. Regional weather and seasonal cycle are found to have apparent interference with the feature of the observed mutual response pattern. The results from this study clearly indicate that the approach used, can be executed location independently.


Carbon composite-PVC based membrane coated platinum electrode for chromium determination.
A new synthesized 1-(2-(1H-imidazole-1-yl)-1-(4-methoxyphenyl)ethylidene)-2-phenyl hydrazine has been used as an ionophore in carbon composite-PVC coated platinum electrode for fabrication of chromium(III)-selective sensor. The homogenization procedure of membrane mixture was performed by applying of the ultrasound in this respect. The sensor shows a good Nernstian slope of 19.62 ± 0.45 mV decade(-1) in a wide linear range concentration of 8.4 × 10(-8)-1.0 × 10(-2)M and a detection limit of 6.8 × 10(-8)M for Cr(NO(3))(3). The proposed electrode has a short response time of about 10s and is reproducible and stable for a period of at least 2 months. The performance of the sensor is pH independent in the pH range of 3.3-5.9 and it also works well in partially non-aqueous medium. The electrode has good selectivity relative to variety of metal ions. The practical analytical utility of the electrode is demonstrated by measurement of Cr(III) quantitatively in multivitamin, mineral water and also as an indicator electrode in the potentiometric titration of chromium (III) against EDTA.


[Analysis of pulsed bioelectric activity of rabbit cerebral cortex in response to low-intensity microwave radiation].
In experiments on 22 rabbits the influence of a pulse microwave irradiation on extracellular activity of separate nervous cells of sensorimotori and occipital areas of a cortex brain is shown. The reaction could consist in activation or in braking frequency of the discharges, that was connected to frequency impulsation in an initial background. The researched mode of a microwave irradiation (1.5 GHz, duration of a pulsed-0.4 microsecond, frequency of their recurrence 1000 Hz, DFEpulsed-300 microW/sm2) had a corrigizing action.


Default mode network subsystem alterations in bipolar disorder during major depressive episode.
Default mode network (DMN) has been widely reported to be altered in bipolar disorder during major depressive episode (BDD). Recent studies supported the idea that DMN is not an unitary system, but composed of smaller and distinct functional subsystems. The current study aimed to investigate the abnormal functional connectivity (FC) patterns of DMN subsystems in BDD. Seed-based FC method was applied to extract 11 DMN components in resting-state functional magnetic resonance imaging data acquired from 40 patients with BDD and 63 demographically matched healthy controls. Patients showed reduced FC between precuneus and all three DMN subsystems. Additionally, in the midline core, patients revealed increased FC between posterior cingutate cortex (PCC) seed and lateral orbitofrontal cortex. In the dorsomedial prefrontal cortex and medial temporal lobe subsystems, patients demonstrated increased FC with sensorimotor, visual, and salience network regions. Furthermore, the abnormal FC between the PCC seed and precuneus was correlated with high pessimism. Our sample size is relatively small, limiting the power to detect subtle group differences and significant correlations between brain connectivity and clinical variables. In addition, most of our patients have been treated with medications. Our findings revealed the abnormal FC patterns of DMN subdivision circuits and highlighted these abnormalities were associated the pathological mechanisms in BDD.


Soil acidity determines the effectiveness of an organic amendment and a native bacterium for increasing soil stabilisation in semiarid mine tailings.
Unstable mine tailings are vulnerable to water and air erosion, so it is important to promote their surface stabilisation in order to avoid the spread of heavy metals. In a greenhouse experiment, we assessed the effect of the addition of Aspergillus niger-treated sugar beet waste and inoculation with a native bacterium, Bacillus cereus, on the stabilisation of soil aggregates of two acidic, semiarid mine tailings, with different acidity degree, during watering and drying periods. Organic amendment raised the pH of both the moderately and highly acidic tailings, whereas the bacterial inoculation increased this parameter in the former. Only the amendment addition increased soil water-soluble carbon in both tailings compared with their controls, under either watering or drying conditions. Both the amendment and B. cereus enhanced water-soluble carbohydrates. Both treatments increased dehydrogenase activity and aggregate stability, particularly in the moderately acidic tailing under drying conditions. After soil drying, aggregate stability was increased by the amendment (about 66% higher than the control soil) and by the bacterium (about 45% higher than the control soil) in the moderately acidic tailing. The effectiveness of these treatments as structure-stabilisation methods for degraded, semiarid mine ecosystems appears to be restricted to tailings of moderate acidity.


Application of combined three-dimensional bone and soft tissue model. A case report.
This article describes a new application in three-dimensional modelling. By adding the contours of important soft tissue structures to the bone contours, it is possible to produce a combined bone and soft tissue model. The advantages of this technique are shown in a patient suffering from a parapharyngeal tumour. The model not only enabled the precise localisation of the tumour in relation to the surrounding bone, but also identified important structures like the internal carotid artery in relation to the tumour.


Shift Change: From ICU Nurse to ICU Patient.
A post-childbirth emergency and a new understanding of the comforting presence of nurses.


Evaluation of an improved centrifugal casting machine.
A Type III gold alloy, a silver-palladium alloy, and a base metal alloy were cast in two different centrifugal casting machines. With the number of complete cast mesh squares as an indicator of castability, the Airspin casting machine produced superior castings with all three alloys. The base metal alloy produced the greatest number of complete squares with both casting machines.


Estimation of the biophase concentration of noradrenaline at presynaptic alpha 2-adrenoceptors in brain slices.
The aim of the present study was to determine the local concentrations of noradrenaline existing at presynaptic alpha 2-adrenoceptors during electrical pulse train stimulation of brain slices at different frequencies. The experiments are based on the assumption that the concentration of released noradrenaline at the alpha 2-adrenoceptors exerting a certain autoinhibition should be equal to the concentration of exogenous noradrenaline causing the same inhibition under conditions in which any influence of the released transmitter is excluded. In order to avoid autoinhibition, hippocampus and cortex slices of the rabbit and the rat, prelabelled with [3H]noradrenaline and superfused in presence of an uptake inhibitor, were electrically stimulated using 4 pulses delivered at 100 Hz (POP stimulation). Exogenous noradrenaline diminished the overflow of tritium elicited by POP stimulation in a concentration-dependent manner. In rabbit brain tissues the EC50 value and maximum inhibition of noradrenaline release were found to be approximately 6 nmol/l and more than 95%, respectively, whereas in rat tissues the corresponding values were between 20 and 30 nmol/l and approximately 90%. When electrical stimulation was performed with trains of 36 pulses delivered at 0.1, 0.3 or 3 Hz in absence or presence of an uptake inhibitor, the alpha 2-adrenoceptor antagonist yohimbine (1 or 10 mumol/l) enhanced the evoked tritium overflow in a manner which was dependent on the frequency of stimulation and on blockade of the re-uptake mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)


The Expression of Glutaminases and their Association with Clinicopathological Parameters in the Head and Neck Cancers.
The increased glutamine metabolism is a characteristic feature of cancer cells. The interconversion between glutamine and glutamate is catalyzed by two glutaminase isoforms, GLS1 and GLS2, which appear to have different roles in different types of cancer. We investigated for the first time the protein expression of GLS1 and GLS2, and their correlation with advanced clinicopathological parameters in head and neck cancers. Consecutive slides from a tissue microarray comprised of 80 samples ranging from normal to metastatic were stained immunohistochemically for GLS1, GLS2, HIF-1α or CD147. Following analysis by two expert pathologists, we carried out a statistical analysis of the scores. GLS1 and GLS2 were found to be upregulated at the protein level in head and neck tumours compared to normal tissues, and this increased expression correlated positively (GLS1) and negatively (GLS2) with tumor grade, indicating a shift of expression between GLS enzyme isoforms based on tumor differentiation. Increased expression of GLS1 was associated with high CD147 expression, and elevated GLS2 expression was associated with both high CD147 and high HIF-1α expressions. The correlation of the GLS1 and GLS2 with HIF-1α or CD147 was strongly associated with more advanced clinicopathological parameters. The increased expression of GLS1 and GLS2 may be explored as a new treatment for head and neck cancers.


Association of abnormal coronary microcirculatory function with impaired response of longitudinal left ventricular function during adenosine stress echocardiography in untreated hypertensive patients.
Coronary microcirculation is disturbed in hypertensive patients. We investigated the association of coronary flow reserve (CFR) with the response of left ventricular (LV) function as assessed by tissue Doppler imaging (TDI) during adenosine stress echocardiography in never-treated hypertensive patients. We studied 90 hypertensive patients and 30 control subjects, matched for age and sex, by adenosine stress echocardiography. We measured: (i) CFR, E and A Doppler, S', E', A' mitral annulus velocities with TDI, as well as the E'/A' ratio and the E/E' ratio before and during adenosine infusion (ii) the %changes of the measured indices between baseline and adenosine infusion. After adenosine infusion, there was an increase in S', E', and A' in all patients and controls (P < 0.05). Compared with controls and patients with CFR ≥ 2.5, patients with CFR <2.5 showed a smaller increase in S' (28.6 vs. 30.0 vs. 11.1%, F for interaction = 14.592) and E' (33.3 vs. 33.3 vs.1.5%, F = 28.927) as well as a decrease in E'/A' (9.2 vs. 6.4% vs. -20.0%, F = 5.128) and an increase in E/E' (-6.1 vs. -1.6 vs. 30.5%. F = 12.780) after adenosine infusion (P < 0.05 for all comparisons). CFR was independently related to %changes of TDI parameters (regression coefficient b = 0.576 for S'; b = 0.517 for E'; b = 0.473 for E'/A'; b = -0.520 for E/E', respectively, P < 0.001). By the receiver operating curve, a CFR <2.5 predicted the median changes of all measured TDI markers, with a sensitivity and specificity over 70% (AUC >75%, P < 0.05). An abnormal response of the LV longitudinal function during adenosine stress echocardiography is related to impaired CFR in untreated hypertensive patients.


Open heart surgery in the first 24 hours of life.
The results of open heart surgery in infants have steadily improved. The performance of corrective surgery very early in life has thereby been encouraged. We report four patients who underwent successful surgical correction within 24 h of birth. Two patients with total anomalous pulmonary venous drainage and one patient with pulmonary atresia and intact septum were corrected with the aid of profound hypothermia by the combined surface and bypass cooling technique. Cardiopulmonary bypass alone was used for the fourth patient with aortic stenosis. The usual surgical techniques can be applied successfully to infants even within 24 h of life.


Serum stem cell growth factor for monitoring hematopoietic recovery following stem cell transplantation.
Stem cell growth factor (SCGF) is a novel cytokine for primitive hematopoietic progenitor cells. Although it has burst-promoting activity and granulocyte/macrophage colony-promoting activity in vitro, its significance in hematopoiesis in vivo has not been elucidated. In this study, we have established enzyme-linked immunosorbent assay (ELISA) to quantify human SCGF and measured serum cytokines in normal volunteers and 27 patients undergoing stem cell transplantation (SCT), including six autologous and 21 allogeneic transplants. SCGF levels gradually increased after SCT regardless of graft-versus-host disease or type of transplant. The maximum level of SCGF was observed during the rapid granulocyte recovery phase in patients subjected to an autologous transplantation, and during the granulocyte stabilization phase in allogeneic patients. SCGF levels in PBSCT patients began to rise earlier than in BMT patients. Two patients with no increment of SCGF after SCT showed delayed engraftment. The source of SCGF was further analyzed by RT-PCR and we found that SCGF was highly expressed in bone marrow (BM) CD34(+) and CD34(-)CD33(+) cells, but not in BM CD34(-)CD33(-) cells, BM stromal cells and peripheral blood cells. The cell population expressing SCGF in BM possess the colony-forming cell activity. Therefore, serum SCGF can be an indicator of hematopoietic recovery following SCT.


Teratogenic effects in mouse fetuses subjected to the concurrent in utero exposure to miconazole and metronidazole.
The potential interactivity of the antimicrobials miconazole and metronidazole in the induction of teratogenic effects was investigated in the present study. Drugs were injected at 60 mg/kg either individually or in combination to pregnant mice on gestation day (GD) 8, 9, or 10. Teratological assessments were carried out on GD 18. A potent teratogenic interaction resulted from miconazole-metronidazole co-administration, causing an increment in axial skeletal defects incidence. While, the individual exposure to miconazole or metronidazole produced axial skeletal defects at frequencies that did not exceed 5.6% in the various treatment groups, the percentage of fetuses with malformed skeleton reached 26% after co-exposure on GD 8 or GD 9. No significant synergism was noted when drugs were co-administered on GD 10. This study shows that a teratogenic interaction can result from miconazole-metronidazole concomitant exposure.


[Alkaptonuric ochronosis - rare cause of bilateral meniscopathy (author's transl)].
Bilateral meniscus lesions without an adequate trauma are rare. We observed a patient with such an injury caused by alkaptonuric ochronosis. Radiographs revealed a calcifying degeneration of the intervertebral disks and osteoarthritic alterations of the large joints. The surgeon should think of this disease finding a yellow brown discoloration of the cartilage at arthrotomy.


Possible impact of continuous drainage after minimally invasive partial nephrectomy.
Postoperative management of minimally invasive partial nephrectomy (MIPN) without drain placement is common, but the effects on patients are unclear. We investigated the impact of no drain placement after MIPN. We retrospectively studied 194 consecutive patients who underwent laparoscopic and robotic partial nephrectomy at one academic center. The study group included 46 evaluable patients without drain placement. The quantity of postoperative fluid collection in the perirenal space was calculated using computed tomography. The preoperative and postoperative serum concentrations of total protein, albumin, neutrophils, lymphocytes, monocytes numbers, and C-reactive protein (CRP) levels in the blood were compared between groups. Drains were placed in 148 (76.3 %) patients who underwent MIPN. The remaining 46 (23.7 %) patients did not have drain placement. Although the average total quantity of fluid discharged from the drain was 214 mL, the average fluid remaining in the perirenal space did not significantly differ with or without drain placement (20.3 vs. 16.8 mL, p = 0.64). The decrease in serum total protein and albumin was significantly greater with drain placement than without (total protein: 18.9 vs. 12.2 %, p < 0.001; and albumin: 24.7 vs. 22 %, p = 0.038). No drain placement also caused markedly greater decreases in lymphocytes and monocytes than did drain placement, whereas neutrophils and CRP did not differ based on drain placement. Analysis of the quantity of fluid collection showed little need for routine drain placement. Not placing a drain after MIPN prevented serum protein loss and possibly accelerated wound-healing immune responses.


Acute multifocal hemorrhagic retinal vasculitis.
The authors present a series of seven patients with acute visual loss associated with mild anterior uveitis, multifocal retinal vasculitis, retinal capillary nonperfusion, retinal hemorrhage, disc swelling, and vitreitis. Oral prednisone was of some benefit in these patients and oral acyclovir was generally ineffective. Neovascular complications including retinal, disc, choroidal, and iris new vessels were common, requiring photocoagulation in five patients. Horseshoe tears developed in two patients in zones of uninvolved retina but retinal detachment did not occur. The etiology remains unknown, although it may represent either a localized ocular form of Behçet's disease or other systemic syndrome, infection with a herpes group virus other than zoster varicella virus, or a manifestation of an undefined infectious agent.


Sickle cell disease: the proportion of liganded haemoglobin needed to prevent crises.
In an attempt to predict the likelihood of successfully treating sickle cell disease by increasing haemoglobin S (HbS) oxygen affinity, two liganded derivatives of Hb S have been studied in an in vitro system that measures deoxy-Hb S polymerization. The participation of these liganded forms in the polymers has been quantitated in terms of an exclusion factor that relates their behaviour to that of deoxy-Hb S. Carbonmonoxy-Hb S has an oxy-Hb-like conformation and did not participate significantly in the polymerization. It was calculated that 30% carbonmonoxy-Hb S would have to be maintained in vivo to prevent sickling. Met-Hb S has a conformational equilibrium intermediate between oxy- (or carbonmonoxy-) and deoxy-Hb S and behaved in a similarly intermediate manner with regard to deoxy-Hb S polymerization. 60% met-Hb S would be needed to prevent in vivo sickling. It is concluded that stabilizing the oxy(R)-conformation is a potentially useful way of preventing sickling, and that a level of 30% R-state Hb S would have to be maintained for this to be successful.


[Role of keratinocytes in preservation of oral mucosa epithelium integrity. Part I].
Functions of oral mucosa epithelium in preservation of homeostasis have been presented. Characteristic features that distinguish epithelial cells from the other somatic cells influencing mechanical resistance of oral epithelium and creating selective chemical barrier have been described. The participation of keratinocytes in selected phases of wound healing process has been analyzed.


Biodiversity loss underlies the dilution effect of biodiversity.
The dilution effect predicts increasing biodiversity to reduce the risk of infection, but the generality of this effect remains unresolved. Because biodiversity loss generates predictable changes in host community competence, we hypothesised that biodiversity loss might drive the dilution effect. We tested this hypothesis by reanalysing four previously published meta-analyses that came to contradictory conclusions regarding generality of the dilution effect. In the context of biodiversity loss, our analyses revealed a unifying pattern: dilution effects were inconsistently observed for natural biodiversity gradients, but were commonly observed for biodiversity gradients generated by disturbances causing losses of biodiversity. Incorporating biodiversity loss into tests of generality of the dilution effect further indicated that scale-dependency may strengthen the dilution effect only when biodiversity gradients are driven by biodiversity loss. Together, these results help to resolve one of the most contentious issues in disease ecology: the generality of the dilution effect.


Scalable integration of hybrid high-κ dielectric materials on two-dimensional semiconductors.
Two-dimensional (2D) semiconductors are promising channel materials for next-generation field-effect transistors (FETs). However, it remains challenging to integrate ultrathin and uniform high-κ dielectrics on 2D semiconductors to fabricate FETs with large gate capacitance. We report a versatile two-step approach to integrating high-quality dielectric film with sub-1 nm equivalent oxide thickness (EOT) on 2D semiconductors. Inorganic molecular crystal Sb2O3 is homogeneously deposited on 2D semiconductors as a buffer layer, which forms a high-quality oxide-to-semiconductor interface and offers a highly hydrophilic surface, enabling the integration of high-κ dielectrics via atomic layer deposition. Using this approach, we can fabricate monolayer molybdenum disulfide-based FETs with the thinnest EOT (0.67 nm). The transistors exhibit an on/off ratio of over 106 using an ultra-low operating voltage of 0.4 V, achieving unprecedently high gating efficiency. Our results may pave the way for the application of 2D materials in low-power ultrascaling electronics.


Doppler echocardiography and cardiac pacing.
There is a need for a non-invasive method to evaluate the hemodynamic consequences of pacing. The value of Doppler echocardiography in assessing relative changes in stroke volume and cardiac output is reviewed. We present preliminary observations illustrating the potential value of Doppler echocardiography in cardiac pacing.


Habitat use by singing voles and tundra voles in the southern Yukon.
We investigated how far competitive interactions influence the use of habitats and relative abundance of two species of Microtus in the southwestern Yukon. We worked in the ecotone between alpine tundra and subalpine shrub tundra where populations of singing voles (Microtus miurus) and tundra voles (M. oeconomus) overlap little.We removed tundra voles from shrub tundra on one live-trapping area to look at the effect on the contiguous population of singing voles in alpine tundra. The removal of tundra voles did not affect the distribution or relative abundance of singing voles. The spatial distribution of these species and their movements within habitats suggest that they have a strong habitat preference.Populations of small mammals in the area are extremely dynamic and the relative importance of competitive interactions may change as density varies. At present we have no evidence that competition affects habitat use in M. miurus.


A machine learning-based comparative analysis of surrogate models for design optimisation in computational fluid dynamics.
Complex computer codes are frequently used in engineering to generate outputs based on inputs, which can make it difficult for designers to understand the relationship between inputs and outputs and to determine the best input values. One solution to this issue is to use design of experiments (DOE) in combination with surrogate models. However, there is a lack of guidance on how to select the appropriate model for a given data set. This study compares two surrogate modelling techniques, polynomial regression (PR) and kriging-based models, and analyses critical issues in design optimisation, such as DOE selection, design sensitivity, and model adequacy. The study concludes that PR is more efficient for model generation, while kriging-based models are better for assessing max-min search results due to their ability to predict a broader range of objective values. The number and location of design points can affect the performance of the model, and the error of kriging-based models is lower than that of PR. Furthermore, design sensitivity information is important for improving surrogate model efficiency, and PR is better suited to determining the design variable with the greatest impact on response. The findings of this study will be valuable to engineering simulation practitioners and researchers by providing insight into the selection of appropriate surrogate models. All in all, the study demonstrates surrogate modelling techniques can be used to solve complex engineering problems effectively.


Guilt in alcohol use: A systematic review.
For decades, alcohol use disorder has been investigated in an attempt to understand its processes and implications. However, among all of the factors involved in alcohol use disorder, the role of guilt in alcohol use remains poorly explained, with many contradictory results. Therefore, the purpose of this review is to conduct a systematic analysis of the literature from 1990 to 2022 to review the studies investigating the link between guilt and alcohol consumption. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method, 31 studies were included in this review. The results of this work enable to highlight the plurality of guilt that has been studied in the literature. Grouped in two categories: state guilt and trait guilt, they seem to have diverse implications towards alcohol use or misuse. Guilt proneness seems to act as a protective factor towards alcohol use, except for the few studies conducted on a clinical population. Numerous studies indicated that state guilt is deleterious toward alcohol use, even if some results are contradictory. Furthermore, this work allows us to shed light on the limits of the studies currently carried out, and thus to propose new directions for future studies.


Cosmetovigilance survey: are cosmetics considered safe by consumers?
Cosmetics are largely diffused substances topically applied to wash, to perfume or to improve the look, nevertheless the number of reported adverse reactions is very low, probably because of underreporting. This could be due to self-diagnosis and self-medication that is common in the presence of not severe reactions. In fact adverse reactions to cosmetics are generally not serious and frequently related to skin alterations. The aim of our study was to assess, through a questionnaire supplied by community pharmacists to the customers, the prevalence and characteristic of adverse cosmetic events (ACEs) reported by interviewed and the consequent measures adopted. To this aim ten Naples' community pharmacies were involved and pharmacists agreed to submit a specific questionnaire to all the customers of the pharmacy for two weeks between 9:00 a.m.-01:00 p.m. and 04:00 p.m.-08:00 p.m. from 1 to 15 June. The subjects interviewed were 4373, of them 845 refused to fill the questionnaire. Females responding to the questionnaire were 2716 and males 812. The 98.5% of the respondents reported to use cosmetics. Cosmetic users who experienced at least one ACE were 848 and 18.2% of them reported more than one event. Total adverse cosmetic events reported were 1507. A significant higher prevalence of adverse cosmetic events in women was observed, since the 26.5% of female cosmetic users experienced an adverse cosmetic event, whereas the percent was 17.4 for males. Concerning the type of adverse event, the 95.9% was a cutaneous event, whereas systemic events accounted for 4.1%. Among cutaneous reactions burning and itching were the most prominent and accounted for 36.3 and 32.9%, respectively. The most frequently reported systemic event was headache (40.3%) followed by nausea (24.2%). Product change (45.7%) and product suspension (39.6%), were the main specific measures adopted in the presence of ACEs. The general practitioner or the pharmacist were consulted only in the 6.8 and 6.3% of the episodes, respectively. In the 56.5% of the episodes consultation was not requested, whereas in the 26% a specialist was consulted. In conclusions our results, although supply information about ACEs and the consequent measures adopted by consumers of a restricted geographical area suggest that, due to the large use of these products and the relative high incidence of reported ACEs, the problem of cosmetic related injuries and the need of a system able to report, collect and evaluate them, cannot be ignored.


Visual phenomena following light coagulation in central serous retinopathy (CSR).
A report on three patients with illustrations of their visual anomalies following light coagulation for their CSR disease is presented. The correspondence of the phenomena illustrated with the ophthalmoscopically visible fundus changes prove their objective origin.


Computed EEG topography in acute stroke.
The potential for clinical application of computed EEG topography (CET) has been known since 1978. However, studies relating to the focal brain lesions are few. We have studied 19 cases of acute stroke involving the cerebral hemispheres. CET and EEG were recorded as soon as possible, usually within 1-3 days of onset. Repeat maps were recorded at 1 wk. Symptoms, neurologic exam, routine EEG and CT scan were compared with the CET of power spectral and flash evoked potential data. Statistical criteria were also applied. Good correlation was noted between CET and EEG and CT. Occasionally, CET was noted to provide information beyond EEG or CT. These early studies suggest a potential utility for CET in the early diagnosis of stroke.


Mobile phase influence on electrospray ionization for the analysis of smokeless powders by gradient reversed phase high-performance liquid chromatography-ESIMS.
The solution parameters associated with gradient elution reversed phase high-performance liquid chromatography (HPLC) were characterized by evaluating the electrospray ionization mass spectrometry (ESIMS) response of selected smokeless powder additives. Using direct liquid infusion, the positive ion ESIMS responses were determined for three general classes of powder constituents: dialkylphthalate acid esters, N,N'-dialkyl-N,N'-diphenyl urea based stabilizers and nitroso-, nitro-, and dinitro- derivatives of diphenylamine. The relative ESIMS intensities of the powder components were investigated as a function of three solution parameters: ammonium acetate concentration, pH, and percent methanol. The effect of the ammonium acetate concentration demonstrates that the electrolyte is required for efficient ionization and the ESIMS intensity was optimal at a concentration of 2mM for the selected compounds, except 2,4'-dinitrodiphenylamine. The aqueous solution pH, corresponding to the available protons in solution, did not have a significant effect on the ESIMS intensity of the analytes. The percent methanol was evaluated with both decreasing and constant electrolyte concentrations to demonstrate the effects of droplet stability and ion transfer into the gas phase. These findings were applied to the analysis of the selected smokeless powder additives using HPLC-ESIMS to illustrate increased sensitivity for the protonated molecules.


Easy and computer-time-saving implementation of the van der Pauw method including anisotropy and probe positioning correction factors using approximate closed-form analytical functions.
Measurements in a van der Pauw configuration often require the use of complicated mathematical expressions or implicit relations, which may be computer-time-consuming or tedious to implement in a given software. Thus, a closed-form expression is often desirable. We propose to approximate these relations by closed-form analytical functions using only basic operators that can be easily implemented. We present explicitly the functions and the numerical values of their parameters for the cases of standard van der Pauw measurement, anisotropic resistivities, and the probe position correction factor. The discrepancy with the exact values is smaller than 10-5, which is sufficient for practical purposes.


Incidental Alcohol Appearances in Advertisements on City Buses in Manhattan, New York City: A Descriptive Study.
This paper describes incidental exposure to alcohol in advertisements on buses in Manhattan, New York City. From April to July 2019, researchers observed advertisements on all bus lines in Manhattan and coded the content of these advertisements, including the kinds of products and services advertised and whether alcoholic beverages or images were present. Despite a ban on direct alcohol beverage advertising within the Metropolitan Transit Authority in 2017 (and expanded in 2019), almost one in five of the 136 advertisements observed (n = 25) included incidental exposure to images of alcohol portrayed in a favorable way and/or associated with well-known movie stars and television personalities. Advertisements on city buses are unlike any other, as they traverse the city streets and create considerable exposure to residents, including youth. This study demonstrates that banning advertisements for alcohol will not necessarily restrict favorable images containing alcohol and that youth continue to be exposed to these images.


Incidence of neural tube defects in the least-developed area of India: a population-based study.
Hospital-based records from major cities of India, where roughly a quarter of the population resides, identified the frequency of neural tube defects (NTDs) as ranging from 3.9 to 8.8 per 1000 births, but the incidence in rural areas is unknown. We did a population-based door-to-door survey of mothers living in remote clusters of villages in Balrampur District in Uttar Pradesh, a region ranked as the least-developed area in India. The data showed that the incidence of NTDs was 6.57-8.21 per 1000 livebirths, which is among the highest worldwide. India's Ministry of Health needs to produce a strategy to reduce the incidence of such defects.


Enhanced Oral Bioavailability of β-Caryophyllene in Healthy Subjects Using the VESIsorb® Formulation Technology, a Novel Self-Emulsifying Drug Delivery System (SEDDS).
β-Caryophyllene (BCP), a common constituent of many spice and food plants, is gaining increased attention due to recent research identifying numerous potential health benefits. Due to limited oral bioavailability observed in preclinical models, the described benefits of BCP may be maximized by using a suitable delivery system. Additionally, human pharmacokinetics (PK) remain unknown. This study evaluates the relative oral bioavailability of BCP formulated in a self-emulsifying drug delivery system (SEDDS) based on VESIsorb® formulation technology (BCP-SEDDS) compared to BCP neat oil. Hence, a randomized, double-blind, cross-over design, single oral dose study (100 mg BCP) in 24 healthy subjects (12 men/12 women) was performed under fasting conditions. Pharmacokinetic parameters were analyzed from individual concentration-time curves. The data show that BCP-SEDDS resulted in a 2.2/2.0-fold increase in AUC0-12h/AUC0-24h and a 3.6-fold increase in Cmax compared to BCP neat oil. Moreover, BCP was absorbed faster from BCP-SEDDS (Tmax: 1.43 h) compared to BCP neat oil (Tmax: 3.07 h). Gender analysis revealed that there is no significant difference between men and women for both the investigated formulations and all investigated PK endpoints. In conclusion, BCP-SEDDS offers a well-tolerated and effective oral delivery system to significantly enhance the oral bioavailability of BCP in humans.


Production of superoxide ions by leukocytes of the American alligator (Alligator mississippiensis).
This study was conducted to characterize the production of superoxide ions by leukocytes in whole blood of the American alligator (Alligator mississippiensis). We used WST-1, a tetrazolium salt which can be reduced to a water-soluble formazan compound with high molar absorptivity at 438 nm, to probe the production of superoxide by alligator leukocytes. Incubation of alligator whole blood with WST-1 resulted in a time- and concentration-dependent increase in absorbance of the plasma at 438 nm. The reduction of WST-1 was inhibited in a concentration-dependent manner by superoxide dismutase, an enzyme that catalyzes the reduction of superoxide to peroxide, confirming that the reduction of WST-1 was due to the presence of superoxide. Treatment of whole blood with nitrotetrazolium blue (NBT) resulted in the staining of heterophils and monocytes, enforcing the idea that that the production of superoxide is due to the presence of leukocytes, and not other blood cell components. It is interesting to note that the production of superoxide by the alligator leukocytes required no external stimulation while human leukocytes must be stimulated with an immunological challenge before producing superoxide. This is the first report of the production of superoxide as an innate immune mechanism in crocodilians.


Embryogenesis of Xyleborus ferrugineus (Fabr.) (Coleoptera, Scolytidae). I. External morphogenesis of male and female embryos.
A description of the external morphogenesis of male and female embryos of X. ferrugineus, derived from in vivo observation, is presented here. The embryogenesis of this beetle is typical of the Coleoptera, and is also similar in most respects to the generalized insect plan. Observed unusual aspects of X. ferrugineus embryogenesis include the precocious formation of primordial g/rm cells and their temporary exclusion from somatic blastoderm; the precocious in situ delineation of gnathal metameres, the closing of the gastral groove beginning at both ends and proceeding towards its middle, the formation of several paired lateral amnio-serosal folds, the formation of cellular processes between the amnion and serosa, and the absorption of the thoracic limbs to produce an apodous larva. The embryonic developmental picture provided here, and the previously established means of rearing X. ferrugineus in controlled laboratory culture jointly provide a promising basis for the further use of this insect in developmental studies.


Preoperative breast magnetic resonance imaging and contralateral breast cancer occurrence among older women with ductal carcinoma in situ.
Although preoperative magnetic resonance imaging (MRI) can detect mammographically occult contralateral breast cancers (CBCs) among women with ductal carcinoma in situ (DCIS), the impact of MRI on the incidence of subsequent CBC events is unclear. We examined whether MRI use decreases CBC occurrences and detection of invasive disease among women who develop a CBC. Utilizing the Surveillance, Epidemiology, and End Results-Medicare dataset, we assessed overall, synchronous (<6 months after primary cancer diagnosis), and subsequent (≥6 months after diagnosis, i.e., metachronous) CBC occurrence in women aged 67-94 years diagnosed with DCIS during 2004-2009, with follow-up through 2011. We applied a matched propensity score approach to compare the stage-specific incidence rate of CBC according to MRI use. Our sample consisted of 9166 beneficiaries, 1258 (13.7 %) of whom received preoperative MRI. After propensity score matching, preoperative MRI use was significantly associated with a higher synchronous CBC detection rate (108.6 vs. 29.7 per 1000 person-years; hazard ratio [HR] = 3.65; p < .001) with no significant differences in subsequent CBC rate (6.7 vs. 6.8 per 1000 person-years; HR = 0.90; p = .71). The 6-year cumulative incidence of any CBC (in situ plus invasive) remained significantly higher among women undergoing MRI, compared with those not undergoing MRI (9 vs. 4 %, p < .001). Women undergoing MRI also had a higher incidence of invasive CBC (4 vs. 3 %, p = .04). MRI use resulted in an increased detection of synchronous CBC but did not prevent subsequent CBC occurrence, suggesting that many of the undetected CBC lesions may not become clinically evident.


Tension-type headache as the unique pain experience of a patient with congenital insensitivity to pain.
Congenital insensitivity to pain (CIP) is a rare clinical syndrome characterized by dramatic impairment of pain perception since birth and is generally caused by a hereditary sensory and autonomic neuropathy (HSAN) with loss of the small-calibre, nociceptive nerve fibres. We report the case of a 32-year-old woman with CIP and a presumptive diagnosis of HSAN type V, who experienced physical pain for the first and unique time in her life shortly after the sudden loss of her brother. This patient had sustained innumerable painless injuries during childhood, including bone fractures and severe burns. The only pain she ever felt consisted in an intense headache, which took place in a context of strong emotional overload and anxiety, 3 weeks after her younger brother died suddenly in a car accident. The description of this inaugural episode of headache fulfilled the diagnostic criteria of episodic tension-type headache. This case strongly suggests that the transcription of the grief of bereavement into physical pain may sometimes occur independently of the peripheral mechanisms of nociception and despite the lack of previous pain experience. In the light of recent experimental data showing that the same neural mechanisms that regulate physical pain may also control the expression of separation distress and the feeling of social exclusion, this unique case helps to better understand why some patients may feel physically hurt after the loss of someone they love.


Inferior vena cava oxygen saturation monitoring after the Norwood procedure.
Superior vena cava oxygen saturation monitoring in the early postoperative period after the Norwood procedure (NP) has been associated with improved survival and decreased adverse events (AE). There is no data describing inferior vena cava saturation (Sivo2) monitoring after NP. We sought to investigate the utility of intermittent Sivo2 monitoring after NP and to assess the correlation of Sivo2 with renal near-infrared spectroscopy (rNIRS). We hypothesized failure to achieve Sivo2 greater than 45% within the first 4 hours after NP is predictive of AE, and that rNIRS correlates with Sivo2. A retrospective study of 26 consecutive NP patients who received postoperative management with Sivo2 monitoring according to a strict protocol was conducted. Primary outcome was AE, defined as cardiopulmonary resuscitation, extracorporeal membrane oxygenation, death before discharge, or residual surgical defects. Ten (38%) patients had one or more AE; mortality was 23%. On admission to the cardiac intensive care unit, patients with AE had lower Sivo2 (45% ± 9.4% versus 62% ± 12.0%; p < 0.001) and lower rNIRS (56 ± 6.5 versus 77 ± 7.2; p < 0.001). At 4 hours, 90% of AE patients had an Sivo2 less than 45% versus 6% of non-AE patients. Both Sivo2 and rNIRS were highly predictive of AE: the area under the receiver-operating characteristic curve was greater than 0.86 and 0.95, respectively. Two hours after admission, an Sivo2 less than 45% predicted AE with a specificity of 93%, a sensitivity of 70%, and a positive predictive value of 82%. The Sivo2 was strongly correlated with rNIRS (r = 0.81). Intermittent Sivo2 can be used to guide early postoperative NP management; rNIRS is an accurate continuous, noninvasive surrogate for Sivo2. An Sivo2 of less than 45% in the first 4 hours after the NP is predictive of AE.


Induction of micronuclei by bleomycin in G0 human lymphocytes: I. Dose-response and distribution.
The cytokinesis-block micronucleus assay was used to investigate the induction of chromosomal damage by bleomycin in G0 human lymphocytes. A dose-dependent increase in the frequency of micronuclei was observed in binucleate cells, and the frequency approached 0.5 micronuclei per cell at the highest dosage tested. The distribution of micronuclei among cells was overdispersed, rather than fitting a Poisson distribution. Even at the highest dosage, more than two-thirds of the cells did not contain micronuclei, while some cells were highly damaged, containing more than 4 micronuclei per cell.


Yield optimization, physicochemical characterizations, and antioxidant properties of food grade agar from Gracilaria tenuistipitata of Cox's Bazar coast, Bangladesh.
The present study was aimed at investigating the optimization of extraction variables for food grade quality agar from Gracilaria tenuistipitata, so far, the first study on Bangladeshi seaweed. Water (native)- and NaOH (alkali)-pretreated agars were comparatively analyzed by several physicochemical parameters. All extraction variables significantly affected the agar yield in both extraction conditions. Alkali-pretreated agar provided a better yield (12-13% w/w) and gel strength (201 g/cm2) in extraction conditions as followed by 2% NaOH pretreatment at 30°C for 3 h, seaweed to water ratio at 1:150, and extraction temperature at 100°C for 2 h. Gelling and melting temperatures, color, and pH values of both agars were found to be comparable with commercial agar. Significantly higher sulfate contents including organic and inorganic and total carotenoids were reported in native (3.14% and 1.29 μg/mL) than that in alkali-pretreated agar (1.27% and 0.62 μg/mL). FTIR spectrum demonstrated the purity of the agar as characterized by the stronger relative intensity with higher degree of conversion of L-galactose 6-sulfate to 3,6-anhydrogalactose in alkali pretreatment group than that of native ones. Moreover, antioxidant activity (% DPPH scavenging) was observed and confirmed by IC50 values of 5.42 and 9.02 mg/mL in water- and alkali-pretreated agars, respectively. The results suggested that agar from G. tenuistipitata with optimized alkali extraction conditions could promote cost-effective yield with improved physicochemical characteristics and biofunctional values upon consumption by the consumers as food materials.


Measurement device for ankle joint kinematic and dynamic characterisation.
The paper describes a measurement device for obtaining the kinematic characterisation and isometric loading of ankle joints under different working conditions. Non-invasive, in vivo experiments can be conducted with this experimental apparatus, the potential of which could be usefully exploited in basic biomedical research, prosthesis design, clinical applications, sports medicine and rehabilitation. The device determines the 3D movement of the foot with respect to the shank and evaluates the torques and moments around the three articular axes in relation to any desired angular position of the ankle complex. When integrated with superficial electromyographic techniques and electrical stimulation, it allows the assessment of the functionality of the lower leg in both mechanical and myo-electrical terms. The paper reports the main mechanical and electronic features of the device (high linearity; maximum moment ranges +/- 300 Nm for flexion-extension, +/- 35 Nm for both pronation-supination and internal-external rotation; angular ranges: +/- 100 degrees of dorsi-plantar flexion, +/- 50 degrees of internal-external rotation and prono-supination; linear ranges: +/- 25 mm along each axis). Results from a healthy volunteer, under voluntary or stimulated conditions, helped in testing its operatability, reliability, robustness, repeatability and effectiveness. Preliminary simplified protocols have been also applied to 20 healthy volunteers, and the main results were 80.8 +/- 11.9 degrees of internalexternal rotation, 46.2 +/- 9.1 degrees of prono-supination and 74.6 +/- 13.1 degrees of flexion-extension. Torques and moments were normalised with respect to a body mass index of 30. The maximum plantar flexion moment (57.5 + 21.3 Nm) was measured with the foot at 150 of dorsal flexion; the maximum dorsal flexion moment (50.2 + 20.3 Nm) was measured with the foot at 150 of plantar flexion.


Cell death pathology: cross-talk with autophagy and its clinical implications.
Autophagy is a self-digesting mechanism that cells adopt to respond to stressful stimuli. Morphologically, cells dying by autophagy show multiple cytoplasmic double-membraned vacuoles, and, if prolonged, autophagy can lead to cell death, "autophagic cell death". Thus, autophagy can act both as a temporary protective mechanism during a brief stressful episode and be a mode of cell death in its own right. In this mini-review we focus on recent knowledge concerning the connection between autophagy and programmed cell death, evaluating their possible implications for therapy in pathologies like cancer and neurodegeneration.


Specific high affinity binding of human interleukin 1 beta by Caf1A usher protein of Yersinia pestis.
Understanding the interaction of Yersinia pestis with the key components of the immune system is important for elucidation of the pathogenesis of bubonic plague, one of the most severe and acute bacterial diseases. Here we report the specific, high affinity binding (Kd = 1.40 x 10(-10) M +/- 0.14 x 10(-10)) of radiolabelled human interleukin 1 beta (hIL-1 beta) to E. coli cells carrying the capsular f1 operon of Y. pestis. Caf1A outer membrane usher protein was isolated to greater than 98% purity. Competition studies with purified Caf1A, together with immunoblotting studies, identified Caf1A as the hIL-1 beta receptor. Competition between Caf1 subunit and hIL-1 beta for the same or an overlapping binding site on Caf1A was demonstrated. Relevance of these results to the pathogenesis of Y. pestis and other Gram negative bacterial pathogens with homologous outer membrane usher proteins is discussed.


Histone acetyltransferase HAT4 modulates navigation across G2/M and re-entry into G1 in Leishmania donovani.
Histone acetyltransferases impact multiple processes. This study investigates the role of histone acetyltransferase HAT4 in Leishmania donovani. Though HAT4 was dispensable for survival, its elimination decreased cell viability and caused cell cycle defects, with HAT4-nulls experiencing an unusually long G2/M. Survival of HAT4-nulls in macrophages was also substantially compromised. DNA microarray analysis revealed that HAT4 modestly regulated the expression of only a select number of genes, thus not being a major modulator of global gene expression. Significantly, cdc20 was among the downregulated genes. To ascertain if decreased expression of cdc20 was responsible for HAT4-null growth and cell cycle defects we expressed LdCdc20 ectopically in HAT4-nulls. We found this to alleviate the aberrant growth and cell cycle progression patterns displayed by HAT4-nulls, with cells navigating G2/M phase and re-entering G1 phase smoothly. HAT4-nulls expressing LdCdc20 ectopically showed survival rates comparable to wild type within macrophages, suggesting that G2/M defects were responsible for poor survival of HAT4-nulls within host cells also. These are the first data analyzing the in vivo functional role of HAT4 in any trypanosomatid. Our results directly demonstrate for the first time a role for Cdc20 in regulating trypanosomatid G2/M events, opening avenues for further research in this area.


Toxicology of avermectins and milbemycins (macrocylic lactones) and the role of P-glycoprotein in dogs and cats.
The macrocyclic lactones (MLs) are parasiticides able to kill a wide variety of arthropods and nematodes. They have a high margin of safety for labeled indications, and ivermectin has become the best-selling antiparasitic in the world. Dogs of certain breeds and mixtures of those breeds have a defect in the ABCB1 gene (formerly MDR1 gene) that results in a lack of functional P-glycoprotein, which leads to accumulation of the MLs in the central nervous system and a higher risk of adverse effects when exposed. There is no specific antidote for ML toxicosis so the most important part of treatment is good supportive care.


Impaired interferon-α expression in plasmacytoid dendritic cells in asthma.
Toll-like receptor (TLR)-7-associated rhinovirus (RV) activation is involved in the pathogenesis of asthma. Plasmacytoid dendritic cells (pDCs) are the main interferon-α-producing cells against viruses. To determine whether asthmatic patients and control subjects differ in terms of interferon-α expression in pDCs under TLR-7 or RV stimulation. pDCs were identified in BDCA-2+ and HLA-DR+ peripheral blood mononuclear cells. Interferon-α expression of pDCs was analyzed after TLR-7 stimulation with or without interleukin 4 (IL-4)/IL-13 pretreatment. Interferon-α expression was also analyzed after RV stimulation over periods of 24, 48, or 96 h with or without IL-4 pretreatment. RV detection and molecular typing were assayed from throat swabs. Following TLR-7 stimulation, the expression of intracellular interferon-α was higher in the pDCs of normal subjects than those of asthmatic patients; however, pretreatment with IL-4 was shown to reduce this effect. After 48- and 96-h RV stimulation, we observed a notable increase in the production of interferon-α of pDCs in normal subjects but not in asthmatic patients. Baseline interferon-α expression in pDCs and the incidence of asthma exacerbation to emergency was higher among the 13% of patients identified as rhinovirus+ than among their RV counterparts. Our study discovered the response to TLR-7 stimulation in pDCs was compromised and the sustainability of interferon-α expression to RV stimulation was reduced in pDCs of asthmatic patients, which provide further evidence of defective innate response and subspeciality to RV infection in asthma. The high exacerbation history founded in RV+ patients agrees with these findings. Further research is required for the modulatory effect of IL-4 on TLR-7 stimulated pDCs.


[Characteristics of nucleic acid biosynthesis in the activation of erythroid cell proliferation due to prolonged gamma irradiation].
Most important differences were detected in the nucleic acid metabolism in the rat spleen with increasing proliferation of erythroid cells under the effect of long-term gamma-irradiation and acute hemolytic anemia. It is assumed that humoral regulation pathways and molecular mechanisms of changes in erythropoiesis depend upon haemopoietic stem cell pool.


Bacteria Isolated From Equine Uteri in The United Arab Emirates: A Retrospective Study.
The United Arab Emirates (UAE) presents a unique environment in which to breed horses with a non-physiological breeding season coupled with high temperatures and humidity for much of the year. This study aimed to describe bacterial isolates from the uteri of mares in the UAE and compare them to those reported elsewhere in the world. Bacterial antibiotic resistance was also analyzed to give a starting point for future monitoring. A total of 2,022 swabs taken over five breeding seasons from the endometrium (n = 1,350) or from uterine lavages (n = 672) were submitted for microbiological culture and antibiotic sensitivity testing. At 48 hours post-inoculation 616 of 2,022 (30.5%) of cultures showed microbial growth from which 690 isolates were identified. Most positive plates (548 of 616; 89%) grew one isolate; 68 cultures had two (62 of 616; 10.1%) or three (6 of 616; 1%) isolates. The most frequently isolated bacteria were β-hemolytic Streptococcus (36.5%; 252 of 690), E. coli (10.6%; 73 of 690), P. aeruginosa (10.1%; 70 of 690), K. pneumoniae (8.8%; 61 of 690) and Aeromonas hydrophila (4.1%; 28 of 690). The lowest level of antibiotic susceptibility for all isolates was shown by trimethoprim-sulphonamide (36.4%; 198 of 544), with amikacin showing the highest (76.1%; 271 of 356). A significant decrease in susceptibility to doxycycline, enrofloxacin, and erythromycin, but a significant increase for amoxicillin with clavulanic acid, was seen for β-hemolytic Streptococcus. Decreasing susceptibility of trimethoprim-sulphonamide between two time periods was seen for E. coli. Compared to other studies UAE-based mares had a high incidence of P. aeruginosa and K. pneumoniae isolates, whereas E. coli was represented far less frequently as an isolate.


Failure in the rate adaptation of the atrial refractory period: its relationship to vulnerability.
We evaluated the relationship of rate-dependent changes in atrial refractoriness to atrial vulnerability in 39 patients. Vulnerability was considered present when sustained atrial tachyarrhythmias, lasting longer than 1 minute, could be provoked with one to three extra stimuli. Adaptation of atrial refractory period duration to rate was defined as: normal: steep rate reduction with a linear correlation slope value of 0.08 or more; non-adaptation: absence of rate reduction, the slope value being 0 to 0.01; poor adaptation: slight reduction with rate, the slope having values of 0.02 to 0.07. Increased vulnerability was demonstrable in 16 of 17 patients with non-adaptation of the effective refractory period (ERP), and in 10 of 10 with a similar defect of the functional refractory period (FRP); in the intermediate category (poor adaptation) the results for ERP and FRP were 7/11 and 5/6. By way of contrast when both measurements showed normal adaptation, vulnerability was elicited in 2/9 patients. The significance between these groups showed P less than 0.005. Of 17 patients with atrial arrhythmia by Holter, 14 showed poor or non-adaptation of the ERP. It is suggested that poor or absent rate adaptation of the atrial refractory period, and a propensity to atrial fibrillation or flutter, constitute a clinical entity not previously described.


'Air hunger' from increased PCO2 persists after complete neuromuscular block in humans.
The tolerance of totally curarized subjects for prolonged breath hold is viewed by many as evidence that respiratory muscle contraction is essential to generate the sensation of breathlessness. Although conflicting evidence exists, none of it was obtained during total neuromuscular block. We completely paralyzed four normal, unsedated subjects with vecuronium (a non-depolarizing neuromuscular blocker). Subjects were mechanically ventilated with hyperoxic gas mixtures at fixed rate and tidal volume. End-expiratory PCO2 (PETCO2) was varied surreptitiously by changing inspired PCO2. Subjects rated their respiratory discomfort or 'air hunger' every 45 sec. At low PETCO2 (median 35 Torr) they felt little or no air hunger. When PETCO2 was raised (median 44 Torr) all subjects reported severe air hunger. They had reported the same degree of air hunger at essentially the same PETCO2 before paralysis. When questioned afterwards all subjects said the sensation could be described by the terms 'air hunger', 'urge to breathe', and 'shortness of breath', and that is was like breath holding. They reported no fundamental difference in the sensation before and after paralysis. We conclude that respiratory muscle contraction is not important in the genesis of air hunger evoked by hypercapnia.


Effect of educational intervention based on health belief model on accident prevention behaviours in mothers of children under 5-years.
As the public health problems, accidents are the most important causes of child mortality. The present study aimed to determine the effect of educational intervention based on health belief model on accident prevention behaviors in mothers of children under 5-years of age. This quasi-experimental study was conducted on 200 mothers in Fasa city who were purposefully selected and randomly divided into two groups of intervention and control. Data collection tools were demographic characteristics and health belief model questionnaire. Questionnaires were completed twice before and 3 months after the intervention. After the pre-test, the educational intervention was performed through 6 sessions of 30-35 min in a WhatsApp group. Data were analyzed using SPSS 22 through Chi-square test, independent t-test and paired t-test (p = 0.05). The mean age of mothers in the experimental and control groups was 30.14 ± 4.35 and 31.08 ± 4.31 years. Mean score of awareness, perceived sensitivity, perceived severity, perceived benefits, perceived self-efficacy, cues to action, and accident prevention behaviors significantly increased 3 months after the intervention. This study showed the effectiveness of educational intervention based on health belief model on accident prevention behaviors in mothers of children under 5-years of age.


What do we still need to know about transposable element Ac?
Transposable elements, originally discovered by Barbara McClintock, have been shown to occur in many if not all organisms. Their roles as selfish DNA (probable), as a major agent in evolution (unlikely) and as agents for the response to genomic stress (unclear) are discussed. Among the problems presently addressed are the mechanism of transposition and the regulation of transposition rate. The latter seems to differ in the Ac element of Zea mays compared to other transposable elements. The tendency of Ac transposase to form large aggregates is described, and the possible involvement of these aggregates in the control of the transposition rate is discussed.


A combination of curcumin and oligomeric proanthocyanidins offer superior anti-tumorigenic properties in colorectal cancer.
Combining anti-cancer agents in cancer therapies is becoming increasingly popular due to improved efficacy, reduced toxicity and decreased emergence of resistance. Here, we test the hypothesis that dietary agents such as oligomeric proanthocyanidins (OPCs) and curcumin cooperatively modulate cancer-associated cellular mechanisms to inhibit carcinogenesis. By a series of in vitro assays in colorectal cancer cell lines, we showed that the anti-tumorigenic properties of the OPCs-curcumin combination were superior to the effects of individual compounds. By RNA-sequencing based gene-expression profiling in six colorectal cancer cell lines, we identified the cooperative modulation of key cancer-associated pathways such as DNA replication and cell cycle pathways. Moreover, several pathways, including protein export, glutathione metabolism and porphyrin metabolism were more effectively modulated by the combination of OPCs and curcumin. We validated genes belonging to these pathways, such as HSPA5, SEC61B, G6PD, HMOX1 and PDE3B to be cooperatively modulated by the OPCs-curcumin combination. We further confirmed that the OPCs-curcumin combination more potently suppresses colorectal carcinogenesis and modulated expression of genes identified by RNA-sequencing in mice xenografts and in colorectal cancer patient-derived organoids. Overall, by delineating the cooperative mechanisms of action of OPCs and curcumin, we make a case for the clinical co-administration of curcumin and OPCs as a treatment therapy for patients with colorectal cancer.


Innervation and behaviour of ectopic limbs in Xenopus.
The hindlimb bud of Xenopus tadpoles was replaced with a forelimb bud, or vice versa, prior to axon invasion of the limb. Ectopic hindlimbs supported 94% as many brachial motoneurons as the remaining forelimb, and ectopic forelimbs supported 46% as many lumbar motoneurons as the remaining hindlimbs, on average, after the period of motoneuron death. The patterns of movement of ectopic limbs were characteristic of the innervating spinal cord segments, and not the limbs. The anatomical patterns of nerve trunks were characteristic of the ectopic limbs, and not the sources of innervation. HRP transport studies showed a resemblance between the locations of lumbar motoneurons supplying ectopic forelimb muscles and those supplying the homologous muscles of the hindlimb. It was concluded that motoneurons could survive the period of cell death following connection to muscles for which their patterns of activity were inappropriate, and the projections to ectopic limb muscles were specific although the nerve paths within the limbs were different.


Carbamazepine-induced acute cholangitis.
We report the case of a patient with carbamazepine-induced cholestasis in whom histologic examination showed acute cholangitis. This type of lesion broadens the spectrum of carbamazepine-induced liver injury which also includes granuloma and hepatocellular necrosis. Its association with marked hypereosinophilia suggests that carbamazepine may cause acute cholangitis through an immunoallergic mechanism.


[Group 2A idiopathic parafoveal telangiectasis].
Two cases of group 2A idiopathic parafoveal telangiectasis associated with abnormal glucose metabolism are reported with the typical sings of this disease as well as a foveal vitelliform lesion in one patient, an infrequent association. Group 2A idiopathic parafoveal telangiectasis are a disease with well characterized clinical signs, being some very infrequent such as a vitelliform maculopathy. Its pathogenesis seems to be linked to some alterations in the parafoveal capillary network endothelial cells. These alterations are similar to those that appear in the beginning of the diabetic retinopathy.


Cardiovascular pharmacology of ACC-9089--a novel, ultra-short-acting, beta-adrenergic receptor antagonist.
The beta-adrenergic receptor blocking properties of ACC-9089 were studied in isolated cardiac and tracheal tissues from guinea pigs and in anesthetized dogs. The compound was a potent, nonselective beta-blocker in isolated tissues (atrial pA2 8.01; tracheal pA2 8.16). ACC-9089 was without intrinsic sympathomimetic action and caused direct cardiac depression only at concentrations that were four orders of magnitude higher than its pA2. In anesthetized dogs, ACC-9089 produced steady-state beta-blockade within 20 min of initiation of 3-h intravenous infusions. Recovery from beta-blockade occurred rapidly following termination of infusion (80% recovery in 17 +/- 2 min after 1.2 microgram/kg/min). Intravenous infusion of ACC-9089 caused dose-dependent inhibition of heart rate responses to sympathetic nerve stimulation and inhibition of isoproterenol-induced decreases in perfusion pressure in a perfused hindlimb preparation. The compound (a) did not produce alpha-blockade; (b) had no direct effect on hindlimb vascular resistance; and (c) did not alter hemodynamic variables in catecholamine-depleted dogs. The results indicate that ACC-9089 is a novel, ultra-short-acting beta-blocker that does not possess direct cardiovascular effects beyond those expected as a result of beta-blockade.


Ultrastructural localization of acetylcholinesterase in the synganglion of the tick, Dermacentor variabilis (Say).
Light- and electron-microscopic enzyme cytochemistry was used to localize acetylcholinesterase (AChE) activity in the synganglion (brain) of the tick Dermacentor variabilis. High AChE activity was observed throughout the neuropil as well as adjacent to most neuronal perikarya. Intracellular activity was not observed by light microscopy. By electron microscopy, reaction product was localized at the plasma membrane of glia and neurons. Enzyme activity was not associated with the olfactory globuli neurons. In other types of neurons, small amounts of reaction product were observed in the Golgi apparatus and nuclear envelope. Large neurosecretory neurons contained activity that appeared to be associated with deep invaginations of the plasma membrane as well as intracellular membranes. AChE activity was also associated with processes of both neurons and glia. In most peripheral nerves AChE activity was associated with virtually all axons. Clearly then, AChE is associated with glia and non-cholinergic neurons as well as with presumed cholinergic neurons. The widespread localization and large amounts of AChE in the tick brain exceeds that reported for other invertebrates and vertebrates. As has been suggested for other animals, AChE in the tick brain may have functions in addition to its known role in cholinergic neurotransmission.


Integrated Assessment of Water Environmental Health Risk through Drinking Water Ingestion in Lhasa River Basin: Quantitative Analysis and Environmental Significance.
An integrated assessment of water environmental health risk through drinking water ingestion in Lhasa River has been implemented. The health risks caused by different pollutants in different age groups (children, juvenile and adult groups) are in the order of 10-8 ~ 10-7, 10-7 ~ 10-5 and 10-13 ~ 10-8 a-1, respectively. The total health risks for all age groups are lower than the International Commission on Radiation Protection recommended value and the U.S. Environmental Protection Agency recommended value at all points except LS4, LS12 and LS13. The total health risk levels in different age groups at most points are class III or II, which means that there are low or negligible negative effect in these points and age groups. It is more important to monitor the arsenic concentration. The water environment quality protecting in Lhasa River Basin must be consistent with the clear water and blue sky protecting in Tibet Autonomous Region and the national ecological security barrier construction on the Tibetan Plateau.


Induction of apoptosis by vitamin D metabolites and analogs in a glioma cell line.
Gliomas are the most common malignant tumors in brain. Recent studies demonstrate the capacity of 1alpha,25(OH)2D3 to specifically induce cell death (apoptosis) in model glioma cell lines and in primary cultures from tumor tissue, but not in primary astrocytes. In spite of this promising activity, a broad therapeutic application of vitamin D metabolites and analogs is still restricted because of their poor bioavailability and their hypercalcemic actions. Compared to 1alpha,25(OH)2D3, its natural 3alpha-epimer exhibits far higher metabolic stability and a reduced calcemic effect. Focusing on a possible therapeutic advantage of the 3alpha-conformation, we have examined the apoptotic potential of a representative set of vitamin D analogs, each of them in the 3alpha- and 3beta-conformation, and of natural vitamin D metabolites in the rat C6 glioma cell line. Exposure of these cells to the synthetic analogs resulted in all cases in a pronounced reduction of cell density (tested by incorporation of neutral red) and induction of apoptosis, monitored by staining nuclei with Hoechst 33258 dye and by following DNA fragmentation by capillary electrophoresis. The 3alpha-epimers showed equivalent or even higher activity on C6 cells than their respective 3beta forms. For their potent effects on growth and apoptosis of tumor cells and their high metabolic stability combined with a low calcemic potential, we speculate that these 3a-epimers could provide advantages for a prospective treatment of glioma.


New Advances in Chromosome Architecture.
Our knowledge of the "architecture" of chromosomes has grown enormously in the past decade. This new insight has been enabled largely through advances in interdisciplinary research methods at the cutting-edge interface of the life and physical sciences. Importantly this has involved several state-of-the-art biophysical tools used in conjunction with molecular biology approaches which enable investigation of chromosome structure and function in living cells. Also, there are new and emerging interfacial science tools which enable significant improvements to the spatial and temporal resolution of quantitative measurements, such as in vivo super-resolution and powerful new single-molecule biophysics methods, which facilitate probing of dynamic chromosome processes hitherto impossible. And there are also important advances in the methods of theoretical biophysics which have enabled advances in predictive modeling of this high quality experimental data from molecular and physical biology to generate new understanding of the modes of operation of chromosomes, both in eukaryotic and prokaryotic cells. Here, I discuss these advances, and take stock on the current state of our knowledge of chromosome architecture and speculate where future advances may lead.


Clinical Experience Using a Monofilament Fiber Cleansing and Debriding Technology for Various Skin Conditions.
Gentle skin cleansing and exfoliation and the use of moisturizers as an adjunct to medical treatment should be part of the prevention, treatment, and maintenance of cutaneous conditions such as acne vulgaris (acne) psoriasis, and xerosis. A monofilament fiber debriding technology (MFDT) is used for effective, safe, and rapid skin cleansing and exfoliation and debris, slough, and biofilm removal. The current review addresses the clinical experience using MFDT for various cutaneous conditions that require cleansing or exfoliation or both and how to combine it with medical treatment. A literature review explored clinical insights into the role of skin cleansing and exfoliation for patients with various dermatological conditions. The searches yielded 29 publications, 7 guidelines/algorithms, 13 reviews, 8 clinical studies, and one in vitro study. Mechanical cleansing using a device can be helpful; however, avoid injury of the skin as it may result in thickening of the epidermis leading to hyperkeratosis and disruption of the skin barrier. Clinical experience with MFDT for acne, psoriasis, atopic dermatitis, and xerosis is discussed. Additionally, MFDT was used to exfoliate hyperkeratosis, actinic keratosis, and traumatic skin tattoos. Mechanical cleansing using MFDT was shown to be safe and beneficial for skin cleansing and exfoliation of various cutaneous conditions; however, only anecdotal evidence or small studies are available to support its use for these conditions. J Drugs Dermatol. 2022;21(11):1173-1180. doi:10.36849/JDD.6261.


Record completeness and data concordance in an anesthesia information management system using context-sensitive mandatory data-entry fields.
Use of an anesthesia information management system (AIMS) does not insure record completeness and data accuracy. Mandatory data-entry fields can be used to assure data completeness. However, they are not suited for data that is mandatory depending on the clinical situation (context sensitive). For example, information on equal breath sounds should be mandatory with tracheal intubation, but not with mask ventilation. It was hypothesized that employing context-sensitive mandatory data-entry fields can insure high data-completeness and accuracy while maintaining usability. A commercial off-the-shelf AIMS was enhanced using its built-in VBScript programming tool to build event-driven forms with context-sensitive mandatory data-entry fields. One year after introduction of the system, all anesthesia records were reviewed for data completeness. Data concordance, used as a proxy for accuracy, was evaluated using verifiable age-related data. Additionally, an anonymous satisfaction survey on general acceptance and usability of the AIMS was performed. During the initial 12 months of AIMS use, 12,241 (99.6%) of 12,290 anesthesia records had complete data. Concordances of entered data (weight, size of tracheal tubes, laryngoscopy blades and intravenous catheters) with patients' ages were 98.7-99.9%. The AIMS implementation was deemed successful by 98% of the anesthesiologists. Users rated the AIMS usability in general as very good and the data-entry forms in particular as comfortable. Due to the complexity and the high costs of implementation of an anesthesia information management system it was not possible to compare various system designs (for example with or without context-sensitive mandatory data entry-fields). Therefore, it is possible that a different or simpler design would have yielded the same or even better results. This refers also to the evaluation of usability, since users did not have the opportunity to work with different design approaches or even different computer programs. Using context-sensitive mandatory fields in an anesthesia information management system was associated with high record completeness rate and data concordance. In addition, the system's usability was rated as very good by its users.


[The deployment of digital services across the 92 Nord health territory].
E-pathway territories are defined to promote the use of digital tools in order to improve the flow of patient pathways. To ensure the successful implementation of these services, all players need to adapt their practices but there also needs to be a change in professional culture.


Gentianella acuta improves TAC-induced cardiac remodelling by regulating the Notch and PI3K/Akt/FOXO1/3 pathways.
Cardiac remodelling mainly manifests as excessive myocardial hypertrophy and fibrosis, which are associated with heart failure. Gentianella acuta (G. acuta) is reportedly effective in cardiac protection; however, the mechanism by which it protects against cardiac remodelling is not fully understood. Here, we discuss the effects and mechanisms of G. acuta in transverse aortic constriction (TAC)-induced cardiac remodelling in rats. Cardiac function was analysed using echocardiography and electrocardiography. Haematoxylin and eosin, Masson's trichrome, and wheat germ agglutinin staining were used to observe pathophysiological changes. Additionally, real-time quantitative reverse transcription polymerase chain reaction and western blotting were used to measure protein levels and mRNA levels of genes related to myocardial hypertrophy and fibrosis. Immunofluorescence double staining was used to investigate the co-expression of endothelial and interstitial markers. Western blotting was used to estimate the expression and phosphorylation levels of the regulatory proteins involved in autophagy and endothelial-mesenchymal transition (EndMT). The results showed that G. acuta alleviated cardiac dysfunction and remodelling. The elevated levels of myocardial hypertrophy and fibrosis markers, induced by TAC, decreased significantly after G. acuta intervention. G. acuta decreased the expression of LC3 II and Beclin1, and increased p62 expression. G. acuta upregulated the expression of CD31 and vascular endothelial-cadherin, and prevented the expression of α-smooth muscle actin and vimentin. Furthermore, G. acuta inhibited the PI3K/Akt/FOXO1/3a pathway and activated the Notch signalling. These findings demonstrated that G. acuta has cardioprotective effects, such as alleviating myocardial fibrosis, inhibiting hypertrophy, reducing autophagy, and blocking EndMT by regulating the PI3K/Akt/FOXO1/3a and Notch signalling pathways.


Binding of cholecystokinin-8 (CCK-8) peptide derivatives to CCKA and CCKB receptors.
The structural requirements for the selective binding of cholecystokinin-8 (CCK-8)-related peptides to peripheral (CCKA) receptors are not sufficiently understood. In this study, the interaction of a series of newly shortened analogues of CCK-8 with both receptor subtypes was analyzed by displacement studies using [3H]-CCK-8 and 125I-Bolton-Hunter (BH)-CCK-8 as radioligands. The pentapeptide derivative of CCK-8, succinyl-Tyr (SO3H)-Met-Gly-Trp-Met-phenethylamide, was found to bind selectively with high affinity to the CCKA receptor. The replacement of Met28 and/or Met31 by norleucine and of L-Trp30 by its D-analogue had no significant effect on the binding properties of the peptide. Further C-terminal shortening resulted in a drastic loss of affinity and selectivity of the CCK receptor binding.


β2-adrenergic stimulation potentiates spontaneous calcium release by increasing signal mass and co-activation of ryanodine receptor clusters.
It is unknown how β-adrenergic stimulation affects calcium dynamics in individual RyR2 clusters and leads to the induction of spontaneous calcium waves. To address this, we analysed spontaneous calcium release events in green fluorescent protein (GFP)-tagged RyR2 clusters. Cardiomyocytes from mice with GFP-tagged RyR2 or human right atrial tissue were subjected to immunofluorescent labelling or confocal calcium imaging. Spontaneous calcium release from single RyR2 clusters induced 91.4% ± 2.0% of all calcium sparks while 8.0% ± 1.6% were caused by release from two neighbouring clusters. Sparks with two RyR2 clusters had 40% bigger amplitude, were 26% wider, and lasted 35% longer at half maximum. Consequently, the spark mass was larger in two- than one-cluster sparks with a median and interquartile range for the cumulative distribution of 15.7 ± 20.1 vs 7.6 ± 5.7 a.u. (P < .01). β2-adrenergic stimulation increased RyR2 phosphorylation at s2809 and s2815, tripled the fraction of two- and three-cluster sparks, and significantly increased the spark mass. Interestingly, the amplitude and mass of the calcium released from a RyR2 cluster were proportional to the SR calcium load, but the firing rate was not. The spark mass was also higher in 33 patients with atrial fibrillation than in 36 without (22.9 ± 23.4 a.u. vs 10.7 ± 10.9; P = .015). Most sparks are caused by activation of a single RyR2 cluster at baseline while β-adrenergic stimulation doubles the mass and the number of clusters per spark. This mimics the shift in the cumulative spark mass distribution observed in myocytes from patients with atrial fibrillation.


High-frequency oscillations in human respiratory electromyograms during voluntary breathing.
Electromyograms (EMGs) from respiratory muscles were obtained from human subjects during voluntarily controlled breathing. In 10 studies on 6 subjects EMGs were recorded from the right and left lower ventrolateral surface of the rib cage while the subject emphasized the use of his diaphragm for breathing. Simultaneous samples of the 2 EMG signals of 256-ms duration were obtained once per inspiration (in either the first of second half of inspiration) from each of 30 consecutive breaths using a laboratory minicomputer. Individual power spectra for the 2 EMG signals, and the squared coherence spectrum between them, were calculated. From the coherence spectrum common high-frequency oscillations could be identified within two frequency ranges: 70-100 Hz and 20-50 Hz. Peaks at similar frequencies were identified in both early-inspiratory and late-inspiratory EMG signals. Similar experiments were done on 3 subjects from whom an esophageal diaphragm EMG was obtained as well. The coherence spectrum between the esophageal EMG and the right rib cage surface EMG again demonstrated the presence of common high-frequency oscillations in the same frequency ranges as above. Evidence of these oscillations was not usually apparent in the power spectra. When ECG signal components were allowed to contaminate some of the EMG data samples, the coherence spectrum could be altered considerably, leading to inappropriate conclusions regarding the presence or absence of high-frequency oscillations. It is hypothesized that these high-frequency oscillations are similar to those described in nerve recordings from previous studies on anesthetized and decerebrate cats and dogs and a mechanism for their expression in EMG signals is proposed. The coherence spectrum is a very sensitive method for detecting related signal components in two signals. That high-frequency oscillations can be detected using the less sensitive techniques of autocorrelation and power spectral analysis in some animal preparations may reflect an enhancement of these oscillations in those preparations.


Extracellular vesicles from pluripotent stem cell-derived mesenchymal stem cells acquire a stromal modulatory proteomic pattern during differentiation.
Mesenchymal stem/stromal cells (MSCs) obtained from pluripotent stem cells (PSCs) constitute an interesting alternative to classical MSCs in regenerative medicine. Among their many mechanisms of action, MSC extracellular vesicles (EVs) are a potential suitable substitute for MSCs in future cell-free-based therapeutic approaches. Unlike cells, EVs do not elicit acute immune rejection, and they can be produced in large quantities and stored until ready to use. Although the therapeutic potential of MSC EVs has already been proven, a thorough characterization of MSC EVs is lacking. In this work, we used a label-free liquid chromatography tandem mass spectrometry proteomic approach to identify the most abundant proteins in EVs that are secreted from MSCs derived from PSCs (PD-MSCs) and from their parental induced PSCs (iPSCs). Next, we compared both datasets and found that while iPSC EVs enclose proteins that modulate RNA and microRNA stability and protein sorting, PD-MSC EVs are rich in proteins that organize extracellular matrix, regulate locomotion, and influence cell-substrate adhesion. Moreover, compared to their respective cells, iPSCs and iPSC EVs share a greater proportion of proteins, while the PD-MSC proteome appears to be more specific. Correlation and principal component analysis consistently aggregate iPSCs and iPSC EVs but segregate PD-MSC and their EVs. Altogether, these findings suggest that during differentiation, compared with their parental iPSC EVs, PD-MSC EVs acquire a more specific set of proteins; arguably, this difference might confer their therapeutic properties.


Pathology of Struma Ovarii: A Report of 96 Cases.
Thyroid tissue is a relatively frequent component of mature teratoma and can occur in 5-20 % of cases. Struma ovarii is defined as ovarian goiter which comprises either entirely or predominantly thyroid tissue (>50 %). This also includes cases of mature teratoma with less than 50 % thyroid tissue but harboring thyroid-associated malignancy. A total of 118 patients with mature teratoma containing thyroid tissue were identified at our institution (1989 to 2014). Ninety-six cases were diagnosed struma ovarii, including 10 cases of papillary thyroid carcinoma, 1 case of highly differentiated follicular carcinoma of ovarian origin (HDFCO), 5 cases of strumal carcinoid, and 80 cases of struma ovarii (53 cases of thyroid-only struma ovarii). Six cases had diffuse adenomatous hyperplasia, and seven cases had focal adenomatous hyperplasia. There was no recurrence on follow-up except one of the papillary thyroid carcinomas. Concurrent primary ovarian lesions included: serous cystadenoma--3, mucinous cystadenoma--4, Brenner tumor--3, thecoma--2, ovarian fibroma--1, and focal hilus cell hyperplasia--4 cases. In this series, papillary thyroid carcinoma and strumal carcinoid were the most common well-differentiated neoplasm/malignancies arising in struma ovarii; these demonstrate a minimal or no aggressive clinical behavior.


Acute cardiovascular effects of (+)-nantenine, an alkaloid isolated from Platycapnos spicata, in anaesthetised normotensive rats.
This is the first study of the in vivo potential activity of (+)-nantenine (a natural aporphinoid alkaloid) on the rat cardiovascular system. In anaesthetized normotensive rats, acute intravenous ( i. v.) administration of (+)-nantenine (3 - 6 mg/kg) produced a dose-dependent fall in mean arterial pressure (MAP), accompanied by a significant decrease in heart rate (HR). In addition, (+)-nantenine (5 mg/kg i. v.) did not modify the cardiovascular effects induced by angiotensin II (0.2 microg/kg i. v.) and the selective alpha (2)-adrenoceptor agonist B-HT 920 (0.2 mg/kg i. v.) [unlike nifedipine (0.8 mg/kg i. v.) and yohimbine (1 mg/kg i. v.), respectively] but markedly attenuated [like prazosin (0.2 mg/kg i. v.)] the hypertension evoked by phenylephrine (PE, 25 microg/kg, i. v.), a selective alpha (1)-adrenergic receptor agonist and, like ketanserin (1 mg/kg i. v.), the second phase (rise in MAP) of the cardiovascular response caused by 5-hydroxytryptamine (5-HT, 0.3 mg/kg i. v.). On the other hand, pre-treatment of anaesthetised rats with NG-nitro- L-arginine ( L-NOARG, 5 mg/kg i. v.) did not significantly affect the cardiovascular effects of (+)-nantenine. These results indicate that the hypotension and bradycardia elicited by this aporphine alkaloid in anaesthetised normotensive rats seem to be due, at least in part, to a combined alpha (1)-adrenergic and 5-HT (2A) receptor blockade but not to the release of nitric oxide (NO) from vascular endothelium, to an alpha (2)-adrenoceptor antagonism or to a calcium antagonist activity. Abbreviations. BP:blood pressure HR:heart rate 5-HT:5-hydroxytryptamine i. v.:intravenous L-NOARG: NG-nitro- L-arginine MAP:mean arterial pressure NO:nitric oxide PE:phenylephrine


Laser synovectomy of the knee joint. Experimental results on a new approach to joint surgery.
The clinical impact of laser-assisted synovectomy was investigated in a two-part study consisting of a morphological part with morphometric measurements and an in vivo part using an animal model. A continuous wave Nd:YAG laser (lambda = 1064 nm; power density 18-106 W/mm2; exposure 0.5-5 s) and a XeCl excimer laser (lambda = 308 nm; pulsewidth 20 ns; repetition rate 10-70 Hz; energy density 20-45 mJ/mm2; exposure 10-60 s) were employed in combination with a fused silica fiber with diameters of 600 microns and 800 microns, respectively. In vitro study. Under light microscopy, synovium exposed to Nd:YAG laser energy presents a transitional band (with a mean diameter of 2 mm) with three zones: a carbonized area, a vesicular zone, and a coagulated part. In contrast, pulsed UV-laser irradiation leads only to a narrow transitional zone extending 10-70 microns. Scanning electron microscopy reveals a clear-cut surface following excimer synovectomy, whereas Nd:YAG laser irradiation forms an irregular surface with numerous bursts due to vaporizing activity. In vivo study. Partial synovectomy of the knee joint was performed in two groups of 14 New Zealand white rabbits with a 1064-nm Nd:YAG laser and a 308-nm XeCl excimer laser. Another 14 animals synovectomized in a conventional technique served as a control. Morphological examination and histopathological scoring of the synovial membrane were performed 4 days to 6 months after the operation. The progress of synovial regeneration following excimer laser synovectomy did not differ from observations in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)


Bacteria evolve macroscopic multicellularity by the genetic assimilation of phenotypically plastic cell clustering.
The evolutionary transition from unicellularity to multicellularity was a key innovation in the history of life. Experimental evolution is an important tool to study the formation of undifferentiated cellular clusters, the likely first step of this transition. Although multicellularity first evolved in bacteria, previous experimental evolution research has primarily used eukaryotes. Moreover, it focuses on mutationally driven (and not environmentally induced) phenotypes. Here we show that both Gram-negative and Gram-positive bacteria exhibit phenotypically plastic (i.e., environmentally induced) cell clustering. Under high salinity, they form elongated clusters of ~ 2 cm. However, under habitual salinity, the clusters disintegrate and grow planktonically. We used experimental evolution with Escherichia coli to show that such clustering can be assimilated genetically: the evolved bacteria inherently grow as macroscopic multicellular clusters, even without environmental induction. Highly parallel mutations in genes linked to cell wall assembly formed the genomic basis of assimilated multicellularity. While the wildtype also showed cell shape plasticity across high versus low salinity, it was either assimilated or reversed after evolution. Interestingly, a single mutation could genetically assimilate multicellularity by modulating plasticity at multiple levels of organization. Taken together, we show that phenotypic plasticity can prime bacteria for evolving undifferentiated macroscopic multicellularity.


Advantages of structural similaritiesof the reactants in optical resolution processes.
Advantages and limitations of the use of structurally similar compounds in racemate resolution viadiastereoisomeric salt formation are discussed in this review. An effective conception on "derivativeresolving agents" (use of the optically active derivatives of a racemate as resolving agents)is presented by examples and the method is extended to the homologous series of the derivative resolvingagents and/or achiral additives. A recently developed distillation version of the family approachto optical resolution and the novel, solvent-free resolution methods using a half equivalent amountof resolving agent are also discussed.