Building the Concept of Nurturing Resilience.
Children and adolescents are faced with ubiquitous daily stressors. When faced with various stressors, they will either recover or stay distressed. For those unable to recover, acute daily stressors have potential to turn chronic with long term negative mental health outcomes. Nurturing resilience is one way to prevent distress from turning to mental health disorders. With the ability of adolescents and children to access nurses with various specialties, it is imperative nurses understand the nuances of resilience and the core elements to nurture resilience in youth. The purpose of building the concept of nurturing resilience is to clarify the meaning of this concept in children and adolescents, develop a conceptual definition of nurturing resilience, and provide a conceptual model of nurturing resilience based on the building process. The concept was formulated utilizing Liehr and Smith's practice-based approach to concept building. Concept building defines nurturing resilience as developing secure connections with another to support self-acceptance that aids in tempering reactivity when faced with environmental hardships. Resilience is a protective mechanism which keeps youth balanced while promoting positive mental health when faced with adversities by allowing one to bounce back after adversity to an original, fundamental state. Understanding patterns and processes of resilience enables nurses to nurture resilience. Nurturing resilience provides adolescents and children the ability to change in response to difficult circumstances; in turn, mental distress is reduced, and mental health of youth are optimized.


The Association of Erectile Dysfunction and Cardiovascular Disease: A Systematic Critical Review.
Despite strong association between erectile dysfunction (ED) and cardiovascular disease (CVD), there is a paucity of clear clinical guidelines detailing when and how to evaluate for ED in patients with known CVD, or vice versa. This systematic review discuss the role of cardiologists and urologists in the characterization of risk and management of CVD in the setting of ED, as well as contrasting the current evaluation of CVD and ED from the standpoint of published consensus statements. A comprehensive literature review utilizing MEDLINE®, the Cochrane Library® Central Search, and the Web of Science was performed to identify all published peer-reviewed articles in the English language describing ED and CVD across various disciplines. There is strong consensus that men with ED should be considered at high risk of CVD. Available risk assessment tools should be used to stratify the coronary risk score in each patient. The 2012 Princeton III Consensus Conference expanded on existing cardiovascular recommendations, proposing an approach to the evaluation and management of cardiovascular risk in men with ED and no known CVD. This systematic review highlights the similarities and differences of the existing clinical guidelines and recommendations regarding assessment and management of ED and CVD, as well as the pathophysiological linkage between ED and CVD, which may permit physicians, including urologists, to perform opportunistic screening and initiate secondary prophylaxis with regard to cardiovascular risk factors, particularly in young, nondiabetic men with ED.


Plasminogen enhances neuritogenesis on laminin-1.
Proteins of the plasminogen activation system are broadly expressed throughout the nervous system, and key roles for these proteins in neuronal function have been demonstrated. Recent reports have established that plasminogen is synthesized in neuroendocrine tissues, making this protein and the proteolytic activity of the product of its activation, plasmin, available at sites separated anatomically from circulating, hepatocyte-derived plasminogen. Results with plasminogen-deficient humans and mice suggest a role for plasminogen in neuritogenesis. To elucidate the role of the plasminogen activation system in these processes, the function of plasminogen during neuritogenesis and neurite outgrowth was studied. It is shown here that plasminogen participates in neuritogenesis, as plasmin inhibitors reduced both neurite outgrowth and neurite length in PC-12 cells. The addition of exogenous plasminogen enhanced neurite outgrowth and neurite length in both PC-12 cells and primary cortical neurons. The proteolytic activity of plasmin was required, since mutation of the catalytic serine residue completely abolished the stimulatory activity. Furthermore, mutation of the lysine binding site within kringle 5 of the plasminogen molecule also reduced the neuritogenic activity of plasminogen. Additionally, we demonstrate that plasminogen specifically bound to laminin-1, the interaction resulted in increased plasminogen activation by tissue-type plasminogen activator, and was dependent on a functional lysine binding site within plasminogen kringle 5. Moreover, during NGF-induced neuritogenesis, laminin-1 was degraded, and this cleavage was catalyzed by plasmin. This study provides the first direct evidence that plasminogen participates in neurite outgrowth and also suggests that laminin-1 degradation by plasmin contributes to the process of neuritogenesis.


Challenges and opportunity in the era of quantitative echocardiography.
The advancement of echocardiography in the past two decades is more than downsizing of the machines and improvement of image quality, but introduction of new imaging modalities leading to the ability of performing quantitative analysis. This function is greatly facilitated by the integration of echo machines with high performance computers, software programming and establishment of workstation for offline analysis. Today, echo examination is more than estimation of ejection fraction (EF) and patterns of left ventricular (LV) diastolic dysfunction. Echosonographers are facing a large number of quantitative parameters for interpretation. In newer imaging modalities such as tissue Doppler imaging, speckle tracking, 3-dimensional echocardiography and 3D-transoesophageal echocardiography, quantitative echocardiographic assessment has important roles. These have brought many opportunities but also challenges in our echo practice.


Nitrogen removal properties in a continuous marine anammox bacteria reactor under rapid and extensive salinity changes.
Salinity tolerance is one of the most important factors for the application of bioreactors to high-salinity wastewater. Although marine anammox bacteria (MAB) might be expected to tolerate higher salinities than freshwater anammox bacteria, there is little information on the effects of salinity on MAB activity. This study aimed to reveal the nitrogen removal properties in a continuous MAB reactor under conditions of rapid and extensive salinity changes. The reactor demonstrated stable nitrogen removal performance with a removal efficiency of over 85% under salinity conditions ranging from 0 to 50 g/L NaCl. The reactor performance was also well maintained, even though the salinity was rapidly changed from 30 to 50 g/L and from 30 to 0 g/L. Other evidence suggested that the seawater medium used contained components essential for effective MAB performance. Bacterial community analysis using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) showed that planctomycete UKU-1, the dominant MAB species in the inoculum, was the main contributor to anammox activity under all conditions. The PCR-DGGE using a universal bacterial primer set showed different DNA band patterns between the reactor biomass sample collected under conditions of 75 g/L NaCl and all other conditions (0, 30, 50 and freshwater-medium). All DNA sequences determined were very similar to those of bacterial species from marine environments, anaerobic environments, or wastewater-treatment facilities.


Treatment of gastric lesions in horses with pectin-lecithin complex.
This study compared the study of a pectin-lecithin complex (Pronutrin) on gastric ulcer healing during an 11 day period in 2 groups of 12 horses each. Twenty-four horses suffering from gastric lesions of differing severity were selected from a larger group of clinical cases on the basis of gastroscopic examination. Both gastric mucosal erosions as well as gastric ulcers were found in the 2 mucosal regions (pars nonglandularis and pars glandularis). The gastric mucosal lesions occurred predominantly in the pars nonglandularis in the vicinity of the margo plicatus. The 24 horses were divided equally into a treated group (Group A) and a control group (Group B). Twelve horses in Group A received Pronutrin, in a dose of 300 g/horse/day over a period of 10 days, whereas horses in Group B received no active substance. Gastroscopic examination was performed on Days 0 and 11. The degree of severity of the gastric erosions or gastric ulcers was evaluated independently in the 2 mucosal regions with the aid of a scoring system. Group A horses showed good acceptance of the product and no side effects were recorded. After the 10 day treatment phase, Group A showed a marked reduction in gastric mucosal lesions or disappearance of lesions, while untreated horses showed no change or, even, a deterioration on Day 11. Statistical calculation of efficacy revealed a highly significant reduction in gastric mucosal lesions in the pars nonglandularis and a significant reduction in gastric mucosal lesions in the pars glandularis in the treated horses. It would appear, however, that the treatment period of 10 days was too short, since the gastric mucosal lesions had often not completely healed in all horses. The results of this study in 24 horses with gastric lesions suggest that a pectin-lecithin complex can have a beneficial effect on the healing of gastric ulcers.


Control of 1,3-cyclohexadiene photoisomerization using light-induced conical intersections.
We have studied the photoinduced isomerization from 1,3-cyclohexadiene to 1,3,5-hexatriene in the presence of an intense ultrafast laser pulse. We find that the laser field maximally suppresses isomerization if it is both polarized parallel to the excitation dipole and present 50 fs after the initial photoabsorption, at the time when the system is expected to be in the vicinity of a conical intersection that mediates this structural transition. A modified ab initio multiple spawning (AIMS) method shows that the laser induces a resonant coupling between the excited state and the ground state, i.e., a light-induced conical intersection. The theory accounts for the timing and direction of the effect.


[Surgical treatment of pertrochanteric femoral benign tumors in children].
Disclosure of the tumor area intertrochanteric femur occurs mostly at the time of pathological fracture. Detection of changes can also be made in conjunction with x-ray of the hip joint such as the hip injury. The purpose of this study was to present the treatment of benign tumors of the intertrochanteric area in children and adolescents. From 1. 01. 2002 to 31. 12. 2009 13 patients were treated with benign tumors of the femur intertrochanteric area, including 10 with pathological fractures in the background. Average age was 9.8 years (5-13 years). There were 11 boys and 2 girls. The procedure was performed with resection of the tumor,histopathology, allogenic bone grafting, the femur was fixed using locked plate (10 patients) or angular plate (3 patients). The mean observation time was 62 months (24-94 months). Histopathology examination showed a simple cyst in 7 patients, aneurysmal cyst in 2 patients, and fibrous dysplasia of bone in 4 patients. Bone consolidation was achieved in 10 patients after an average of 4 months (3-5 months) after surgery, as determined by X-ray examination and clinical examination. In 3 cases there was a recurrence of the tumor, 2 patients with fibrous dysplasia after 4 months and 6 months after surgery were found in X-ray partial resorption of bone graft >25%, and 1 patient after 4 months presented fatigue fracture at Adams angle. After re-treatment complete bone consolidation was achieved in this group after an average of 4 months (2.5-5 months) from the second surgery. 1 patient with aneurysmal cyst in 11 month after surgery, presented femoral infection, sequestrum and plate were surgically removed, antibiotic therapy was used and the inflammatory process was stopped. Surgical treatment of benign tumors of the intertrochanteric area of the femur gives good results if it is carried out by a complex surgery (resection of the tumor - bone graft - osteosynthesis).


A method to detect residual confounding in spatial and other observational studies.
Residual confounding is challenging to detect. Recently, we described a method for detecting confounding and justified it primarily for time-series studies. The method depends on an indicator with 2 key characteristics: (1) it is conditionally independent (given measured exposures and covariates) of the outcome, in the absence of confounding, misspecification, and measurement errors; and (2) like the exposure, it is associated with confounders, possibly unmeasured. We proposed using future exposure levels as the indicator to detect residual confounding. This choice seems natural for time-series studies because future exposure cannot have caused the event, yet they could be spuriously related to it. A related question addressed here is whether an analogous indicator can be used to identify residual confounding in a study based on spatial, rather than temporal, contrasts. Using directed acyclic graphs, we show that future air pollution levels may have the characteristics appropriate for an indicator of residual confounding in spatial studies of environmental exposures. We empirically evaluate performance for spatial studies using simulations. In simulations based on a spatial study of ambient air pollution levels and birth weight in Atlanta, and using ambient air pollution 1 year after conception as the indicator, we were able to detect residual confounding. The discriminatory ability approached 100% for some factors intentionally omitted from the model, but was very weak for others. The simulations illustrate that an indicator based on future exposures can have excellent ability to detect residual confounding in spatial studies, although performance varied by situation.


Truly Distributed Finite-Time Attitude Formation-Containment Control for Networked Uncertain Rigid Spacecraft.
This article addresses the finite-time attitude formation-containment control problem for networked uncertain rigid spacecraft under directed topology. A unified distributed finite-time attitude control framework, based on the sliding-mode control (SMC) principle, is developed. Different from the current state of the art, the proposed attitude control method is suitable for not only the leader spacecraft but also the follower spacecraft, and only the neighbor state information among spacecraft is required, allowing the resulting control scheme to be truly distributed. Furthermore, the proposed method is inherently continuous, which eliminates the undesired chattering problem. Such features are deemed favorable in practical spacecraft applications. In addition, upon using the proposed neuro-adaptive control technique, the attitude formation-containment deployment can be achieved in finite time with sufficient accuracy, despite the involvement of both the uncertain inertia matrices and external disturbances. The effectiveness of the developed control scheme is confirmed by numerical simulations.


Administration of Albumin Solution Increases Serum Levels of Albumin in Patients With Chronic Liver Failure in a Single-Arm Feasibility Trial.
Infections are life-threatening to patients with acute decompensation and acute-on-chronic liver failure (AD/ACLF). Patients with AD/ACLF have prostaglandin E2-mediated immune suppression, which can be reversed by administration of albumin; infusion of 20% human albumin solution (HAS) might improve outcomes of infections. We performed a feasibility study to determine optimal trial design, assess safety, and validate laboratory assessments of immune function to inform design of a phase 3 trial. We performed a prospective multicenter, single-arm, open-label trial of 79 patients with AD/ACLF and levels of albumin lower than 30 g/L, seen at 10 hospitals in the United Kingdom from May through December 2015. Patients were given daily infusions of 20% HAS, based on serum levels, for 14 days or until discharge from the hospital. Rates of infection, organ dysfunction, and in-hospital mortality were recorded. The primary end point was daily serum albumin level during the treatment period. Success would be demonstrated if 60% achieved and maintained serum albumin levels at or above 30 g/L on at least one third of days with recorded levels. The patients' mean model for end-stage disease score was 20.9 ± 6.6. The primary end point (albumin ≥30 g/L on at least one third of days recorded) was achieved by 68 of the 79 patients; 75% of administrations were in accordance with suggested dosing regimen. Mean treatment duration was 10.3 days (104 ± 678 mL administered). There were 8 deaths and 13 serious adverse events, considered by the independent data-monitoring committee to be consistent with those expected. Twelve of 13 patients that developed either respiratory or cardiovascular dysfunction (based on ward-based clinical definitions) as their only organ dysfunction were alive at 30 days compared with 1 of 3 that developed renal dysfunction. Only 1 case of brain dysfunction was recorded. In a feasibility trial, we found that administration of HAS increased serum levels of albumin in patients with AD/ACLF. The dosing regimen was acceptable at multiple sites and deemed safe by an independent data-monitoring committee. We also developed a robust system to record infections. The poor prognosis for patients with renal dysfunction was confirmed. However, patients with cardiovascular or respiratory dysfunction had good outcomes, which is counterintuitive. Severe encephalopathy appeared substantially under-reported, indicating that ward-based assessment of these parameters cannot be recorded with sufficient accuracy for use as a primary outcome in phase 3 trials. Trial registration no: EudraCT 2014-002300-24 and ISRCTN14174793.


Ergodicity and scars of the quantum cat map in the semiclassical regime.
We study the quantum localization effect of the cat map manifested in the motions of statistical ensembles. Specifically, the coarse-grained entropy and time-averaged phase space distributions are investigated. For this purpose, an amended version of the Wigner function on the discretized phase torus is presented. We find that the time average of the coarse-grained Wigner function is scarred (antiscarred) along some short periodic orbits, and the heights (depths) of these scars (antiscars) decrease in a linear way with the Planck constant when the semiclassical limit is approached. The relationship between the scars observed here and those exhibited in the quasienergy eigenstates is discussed.


Ultrasonically activated shears in thyroidectomies: a randomized trial.
To test whether the advantages of the ultrasonically activated shears (UAS) observed in thyroidectomies in a previous matched-pair study could be repeated in a randomized trial. The UAS has been documented, mainly in nonrandomized studies, to be a safe and fast device in video-assisted and conventional surgery. Thyroidectomies and lobectomies performed for benign or malignant thyroid disease between August 1997 and January 1999 were included in this series. Separate randomization, resulting in four sets of envelopes, was done for one consultant endocrine surgeon and for senior residents for both lobectomies and for total thyroidectomies. The operations performed with the UAS were compared with operations performed with the conventional method, using ligatures as the main hemostatic method. Main outcome measures were operating time, postoperative serum calcium level, palsy of the recurrent laryngeal nerve, and amount of intraoperative and postoperative bleeding. Possible bias that could have been caused by imbalance between treatment groups for surgeon experience was tested by two-way analysis of covariance. Thirty-six patients were randomized, 19 to the UAS and 17 to the conventional group. Mean operating time was 99.1 minutes in the UAS group and 134.9 minutes in the conventional group. The average savings in operating time with the UAS was thus 35.8 minutes. There was no difference in complications between the groups. The estimated savings in operating time would have been 1.66 times that observed in this study if the groups had been unbalanced with reference to surgeon experience. The UAS is a usable device in total thyroidectomies and lobectomies.


Digital optical computing with magneto-optic spatial light modulators: a new and efficient multiplication algorithm.
Digital optical computing executed on arrays of binary data can offer parallel processing and multivalued output, which permits more flexibility in algorithm development. The hardware used consists of two computer-controlled magneto-optic spatial-light-modulator arrays in conjunction with a CCD detector array as the computational hardware. Algorithms for binary-processing tasks are presented. We used magneto-optic spatial light modulators for parallel processing in a way that exploits multivalued output. Also, in carrying this evaluation out, we developed a new and efficient multiplication algorithm. Multiplication is an important operation in many digital systems, and the design of fast multipliers is of great interest to computer scientists and engineers. The speed of this computing system is evaluated.


Effect of ambroxol on pneumonia caused by Pseudomonas aeruginosa with biofilm formation in an endotracheal intubation rat model.
Pseudomonas aeruginosa, especially the mucoid phenotype, is responsible for most of the morbidity and mortality in ventilator-associated pneumonia. Although ambroxol is widely used in neonatal lung problems as a mucolytic as well as an antioxidant agent, its anti-infective role is not well demonstrated by studies in vivo. To explore the effect of ambroxol on the biofilms of mucoid P. aeruginosa and on the associated lung infection using a rat model. We developed a rat model of acute lung infection by endotracheal intubation with a tube covered with mucoid P. aeruginosa biofilm. Then, we studied the effect of ambroxol on the biofilm using saline treatment as a control. Subsequently, we studied the microstructure of the biofilm, bacterial count in the tubes and lungs, pathological changes that occurred in the lungs, and the cytokine response. Alteration of the microstructure of the biofilm with ambroxol treatment was demonstrated by scanning electron microscopy. The bacterial counts on the biofilm-covered tube in the ambroxol-treated group were significantly lower than those in the saline-treated group on both post-bacterial challenge days 4 and 7 (p < 0.05). The bacterial counts in lungs of the ambroxol-treated group and of the saline-treated group on post-bacterial challenge day 7 were not significantly different (p > 0.05). The pathological changes in lungs were milder with the effect of ambroxol. The cytokine responses, namely the level of IFN-γ and the ratio of IFN-γ and IL-10, were also reduced with the effect of ambroxol. We demonstrated that the ambroxol treatment could destroy the structure of the biofilm on the tube used for intubation and decrease the bacterial load. Further, the reduced cytokine response and milder pathological changes in lungs in an endotracheal intubation rat model indicate that ambroxol can attenuate the damage caused by biofilm-associated infection in the lung.


A furosemide-sensitive cotransport of sodium plus potassium in the human red cell.
The influxes of Na(+) and K(+) into the human red cell appear to be interrelated. This relationship was investigated under conditions in which either Na(+) or K(+) concentration outside the cell was varied or one cation was replaced by Mg(2+), choline(+), or Li(+). The effects of furosemide on Na(+) and K(+) movements were studied in the presence of ouabain. When ouabain was present, Na(+) influx was higher with K(+) ions externally than with other cations externally. Furosemide inhibited this K(+)-stimulated Na(+) influx, but it had little effect when K(+) was absent. Ouabain-insensitive K(+) influx was stimulated two-fold by external Na(+) compared with other cations. Furosemide also inhibited this stimulation, but it had little effect when Mg(2+) or choline(+) replaced external Na(+). Thus it was confirmed that synergism exists between the ouabain-insensitive influxes of Na(+) and K(+) and it was demostrated that furosemide inhibits this cooperative effect. The ouabain-insensitive influx of both K(+) and Na(+) showed a hyperbolic "saturating" dependence on the external concentration of the transported cation. Furosemide therefore eliminates a saturable component of influx of each cation. The net uptake of Na(+) in the presence of ouabain was stimulated by K(+) ions. A similar effect was observed with red cells, in which Li(+) replaced nearly all the internal Na(+) plus K(+) ions. In these cells, net Na(+) uptake was stimulated by external K(+), and net K(+) uptake was stimulated by external Na(+). Furosemide inhibited this mutual stimulation of net cation entries. The inhibitory action of furosemide was not limited to inward flux and net movement of Na(+) and K(+). Furosemide also inhibited the efflux of Na(+) into Na(+)-free media and the efflux of K(+) into K(+)-free media. It appeared, therefore, that the action of furosemide was not explained by inhibition of exchange diffusion. These data are consistent with an ouabain-insensitive transport process that facilitates the inward cotransport of Na(+) plus K(+)-ions, and that can produce a net movement of both ions. Although this process under some conditions mediates an equal bidirectional flux of both Na(+) and K(+), it cannot be defined as exchange diffusion. The contransport process is inhibited by furosemide.


Prevalence of visceral artery involvement in patients with peripheral artery disease found on run-off MRA.
In patients with peripheral artery disease (PAD), run-off MR-angiography (MRA) is a commonly performed diagnostic test to obtain high-resolution images for evaluation of the arterial system from the aorta through the distal run-off vessels. The aim of this study was to investigate the prevalence of visceral artery involvement (VAI) in patients with PAD and leg symptoms examined with run-off MRA. We retrospectively analyzed 145 patients (median age 68 years, range 27-91) who underwent MRA due to known or suspected PAD at our institution between 2012 and 2018. MRA examinations were re-evaluated for visceral artery stenosis. Patient dossiers were reviewed to determine cardiovascular risk factors, kidney function and Fontaine stage of PAD. Involvement of at least one visceral artery with ≥ 50% diameter stenosis was found in 72 (50%) patients. There were no differences in age, gender, MRA indication, Fontaine stage, levels of C-reactive protein (CRP), cardiovascular risk factors or vascular comorbidities between patients with and without VAI. Renal artery (RA) involvement with ≥ 50% diameter stenosis was observed in 28 (20%) of patients. Patients with involvement of the RA were more likely to suffer from hypertension (79 vs. 54%, p = 0.019) and reduced renal function (glomerular filtration rate 70 vs. 88 mL/min/1.73m2, p = 0.014). Visceral artery stenosis can be seen in half of patients with known or suspected PAD and leg symptoms on run-off MRA. Investigating for RA stenosis in patients with PAD and hypertension and/or impaired renal function may have high diagnostic yield.


Microbial transformation of the anti-diabetic agent corosolic acid.
Biotransformation of corosolic acid (1) by Cochliobolus lunatus and Streptomyces asparaginoviolaceus afforded four metabolites, which were identified by using (1)H NMR, (13)C NMR, DEPT, HSQC, HMBC and NOESY spectral data. Biotransformation of corosolic acid by C. lunatus R.R. Nelson & Haasis CGMCC 3.4381 produced three metabolites: 2α,3β,21β-trihydroxyurs-12-en-28-oic acid (2), 2α,3β,7β,21β-tetrahydroxy-urs-12-en-28-oic acid (3) and 2α,3β-dihydroxy-21-oxours-12-en-28-oic acid (4). Incubation of corosolic acid with growing cultures of S. asparaginoviolaceus CGMCC 4.0175 afforded metabolite 2α,3β,30-trihydroxyurs-12-en-28-oic acid (5). All the metabolites were reported for the first time. The substrate and four metabolites, along with four products obtained previously, were evaluated for their inhibitory effects on α-glucosidase; all the triterpenes tested showed potent inhibitory effects.


Shift work with and without night shifts and breast cancer risk in a cohort study from Finland.
To examine the association of shift work with and without night work with breast cancer among women in the public sector. Using the Finnish Public Sector cohort study (N=33 359, mean age of 40.6 years at baseline), we investigated the associations of shift work and potential confounders with incident breast cancer. Exposure to permanent day work or shift work was defined from first two consecutive surveys from 2000, 2004, 2008 or 2012 and past information on exposure in a subcohort (n=20 786). Incident cases of breast cancer (n=1129) were retrieved from the National Cancer Register and the cohort members were followed to the end of 2016. HR and 95% CI from Cox proportional hazard regression models were calculated. Shift work with and without night shifts was not overall associated with breast cancer. When stratified according to age, both shift work without nights (HR 2.01, 95% CI 1.12 to 3.60) and shift work with nights (OR 2.05, 95% CI 1.04 to 4.01) were associated with an increased risk after a period of 10 years or more follow-up among women aged 50 years or older, when adjusted for age, socioeconomic status, children, smoking, alcohol and body mass index. In a subgroup with past information on exposure to shift work, the increased risk by longer exposure to shift work was not significant. This study provides support for an increased risk of breast cancer among elderly shift workers. However, insufficient information on exposure and intensity of night work may attenuate the risk estimates.


Cardiovascular aspects of menopausal hormone replacement therapy.
Cardiovascular disease is the leading cause of death in postmenopausal women in Western countries. Despite preventive strategies, in the past decades, the incidence of cardiovascular events has shown a decline in men but a rise in women, matching the growth of the population of postmenopausal women. Several epidemiological findings suggest the causative role of ovarian hormone deficiency in the development of cardiovascular disease in women. Observational and randomized studies have suggested that initiation of hormone replacement therapy in early postmenopause could be beneficial from a cardiovascular point of view. Conversely, aging, time since menopause and presence of cardiovascular risk factors or cardiovascular disease may decrease its efficacy and increase the risk of cardiovascular events. It is plausible that the unfavorable effects of the estrogen/progestin combination used in the randomized studies are not related to the hormone preparation per se but rather to the use of hormones in the less receptive group of women, older and with cardiovascular risk factors. Clinical judgement, choice of the right dose and estrogen/progestin combination are of pivotal importance to maximize the beneficial effect of estrogen or estrogen-progestin replacement therapy, especially if given within a reasonably short time after the menopause to those women that need this therapy for the relief of menopausal symptoms. In these women, continuation of estrogen or estrogen-progestin replacement therapy may be beneficial.


Alternative regulatory perspectives of obstetrics and gynaecology.
In addressing whether the field of obstetrics and gynaecology demands internal self-regulation or external state intervention, the authors look at the distinct yet at once interrelated notions of ethics, deontology and law. The distinctness of these concepts relates not only to their optional and/or obligatory natures, but also to the group and/or groups they influence and/or regulate. The interrelated nature of these concepts suggests that they are complimentary paradigms in as much as they collectively form a framework of individual, professional and societal norms. Given the emergence of both legal pluralism and self-regulation over the last two decades, it is believed that neither self-regulation nor state intervention is in itself appropriate. Rather, it is contended that only a pluralistic system--incorporating ethics, deontology (self-regulatory models) and law (state regulatory model) can effectively and comprehensively regulate the medical community so that it may efficaciously and appropriately respond to the continually emerging issues raised by contemporary medicine.


Markers of endothelial activation and atherothrombosis in women with history of preeclampsia or gestational hypertension.
Women who have had preeclampsia (PE) or gestational hypertension (GH) exhibit relatively high rates of circulatory diseases. PE is a disease associated with inflammation and vascular endothelial dysfunction. We therefore hypothesised that women with a history of PE or GH might have abnormal levels of markers of endothelial activation or inflammation, reflecting either an innate predisposition to preeclampsia or changes induced by the eclamptic process. Levels of von Willebrand factor, fibrinogen and C-reactive protein were compared in 392 women with a history of PE between 1951 and 1970, 297 women with a history of GH and 163 matched controls. Although no significant differences between those with either PE or GH and controls were noted, subjects with a history of PE had significantly higher CRP values than those with GH. No significant differences were found when the three groups were compared for von Willebrand factor or fibrinogen. Overall, the data do not support our hypothesis. In addition, our data document increasing von Willebrand factor levels increase with age, which may help explain the age dependent increase in venous or arterial thrombosis. Moderate alcohol consumption was also associated with lower levels of inflammatory markers.


Aqueous skin antisepsis before surgical fixation of open fractures (Aqueous-PREP): a multiple-period, cluster-randomised, crossover trial.
Chlorhexidine skin antisepsis is frequently recommended for most surgical procedures; however, it is unclear if these recommendations should apply to surgery involving traumatic contaminated wounds where povidone-iodine has previously been preferred. We aimed to compare the effect of aqueous 10% povidone-iodine versus aqueous 4% chlorhexidine gluconate on the risk of surgical site infection in patients who required surgery for an open fracture. We conducted a multiple-period, cluster-randomised, crossover trial (Aqueous-PREP) at 14 hospitals in Canada, Spain, and the USA. Eligible patients were adults aged 18 years or older with an open extremity fracture treated with a surgical fixation implant. For inclusion, the open fracture required formal surgical debridement within 72 h of the injury. Participating sites were randomly assigned (1:1) to use either aqueous 10% povidone-iodine or aqueous 4% chlorhexidine gluconate immediately before surgical incision; sites then alternated between the study interventions every 2 months. Participants, health-care providers, and study personnel were aware of the treatment assignment due to the colour of the solutions. The outcome adjudicators and data analysts were masked to treatment allocation. The primary outcome was surgical site infection, guided by the 2017 US Centers for Disease Control and Prevention National Healthcare Safety Network reporting criteria, which included superficial incisional infection within 30 days or deep incisional or organ space infection within 90 days of surgery. The primary analyses followed the intention-to-treat principle and included all participants in the groups to which they were randomly assigned. This study is registered with ClinicalTrials.gov, NCT03385304. Between April 8, 2018, and June 8, 2021, 3619 patients were assessed for eligibility and 1683 were enrolled and randomly assigned to povidone-iodine (n=847) or chlorhexidine gluconate (n=836). The trial's adjudication committee determined that 45 participants were ineligible, leaving 1638 participants in the primary analysis, with 828 in the povidone-iodine group and 810 in the chlorhexidine gluconate group (mean age 44·9 years [SD 18·0]; 629 [38%] were female and 1009 [62%] were male). Among 1571 participants in whom the primary outcome was known, a surgical site infection occurred in 59 (7%) of 787 participants in the povidone-iodine group and 58 (7%) of 784 in the chlorhexidine gluconate group (odds ratio 1·11, 95% CI 0·74 to 1·65; p=0·61; risk difference 0·6%, 95% CI -1·4 to 3·4). For patients who require surgical fixation of an open fracture, either aqueous 10% povidone-iodine or aqueous 4% chlorhexidine gluconate can be selected for skin antisepsis on the basis of solution availability, patient contraindications, or product cost. These findings might also have implications for antisepsis of other traumatic wounds. US Department of Defense, Canadian Institutes of Health Research, McMaster University Surgical Associates, PSI Foundation.


Retrospective ratings of 100 first time-documented stroke patients on the Functional Oral Intake Scale.
This study investigated whether patients originally evaluated on the swallowing portion of the Functional Assessment Measure (SFAM), an instrument that when used independently of the Functional Assessment Measure (FAM) has questionable reliability and validity, would demonstrate clinically and statistically significant gains if measured on an instrument such as the Functional Oral Intake Scale (FOIS), which is valid and reliable. Second, this study questioned how easily the FOIS could be adopted at Rancho Los Amigos National Rehabilitation Center (RLANRC), a rehabilitation facility currently utilising the Functional Independence Measure and the SFAM. Additionally, this research addressed inter-rater reliability, the relationship between the SFAM and FOIS at admission and at discharge, and the clinical and statistical difference in ratings between the two scales. Treatment was given at RLANRC in Downey, California. Subjects for this study consisted of 100 first time-documented acute stroke patients with swallowing disorders. Inter-item correlation, intraclass correlation coefficients and Spearman Rho Correlations were used to establish inter-rater reliability, and descriptive statistics, Spearman Rho Correlations and the Wilcoxon Signed Ranks Test were used to explore relationships between the two scales. It was found that there was high inter-rater reliability, strong significant relationships between the SFAM and FOIS at admission and discharge, and statistically significant differences and clinical change in scores between admission and discharge on the FOIS. The FOIS is a valid and reliable instrument that is similar in design to the SFAM and requires minimal training for implementation. The transition from the SFAM to the FOIS will provide RLANRC with a reliable and valid assessment protocol.


Audit of results of operations for infantile pyloric stenosis in a district general hospital.
Because of the proposal that infants with hypertrophic pyloric stenosis should only be treated by surgeons with an interest in paediatric surgery, we carried out a retrospective study to audit our experience in a district general hospital. Forty six infants over a five year period underwent pyloromyotomy. There were no deaths, and 36 infants (78%) made uneventful recoveries. Perforation of the duodenal mucosa occurred during the operation in 11 patients, and eight complications developed in six of these infants. There were seven wound infections, and two patients had vomiting that lasted four days or longer after their operations. There were no long term feeding problems. The results of this study show that such patients can be successfully treated in district general hospitals, and three areas merit special attention: meticulous surgical technique, the use of prophylactic antibiotics, and early graduated feeding.


A transcriptional inhibitor of TNF-alpha prevents diabetes induced by multiple low-dose streptozotocin injections in mice.
The aim of the present study was to examine the effect of a transcriptional inhibitor of tumour necrosis factor-alpha (TNF-alpha) on the development of diabetes induced by multiple low doses of streptozotocin (STZ) in mice. MDL 201.449A is a novel transcriptional inhibitor of TNF-alpha gene expression and protein production and might therefore be potentially interesting in counteracting diabetes. We have studied the effect of MDL 201,449A on the development of hyperglycaemia and pancreatic insulitis in mice treated with multiple low-dose injections of streptozotocin. It was found that one daily sc injection of MDL 201,449A (25 mg/kg body weight) for 14 days prevented the development of hyperglycaemia following the streptozotocin injections. The mice treated with multiple low-dose injections of streptozotocin became gradually hyperglycaemic, and concomitant treatment with MDL 201,449A significantly reduced this elevation in blood glucose levels. In vitro MDL 201,449A reduced TNF-alpha mRNA levels dose-dependently by 75-80% after ConA stimulation of spleen cells, indicating the efficacy of MDL 201,449A to counteract TNF-alpha mRNA synthesis. These data suggest that transcriptional inhibition of TNF-alpha might be an interesting approach in the prevention of type 1 diabetes.


Olfactory Dysfunction in Patients Infected with 2019 Novel Coronavirus.
The current study aimed at investigating the occurrence and features of olfactory dysfunction in patients with confirmed coronavirus disease 2019 (COVID-19) infection. Patients with laboratory and clinically confirmed COVID-19 infection were enrolled in this longitudinal study. They were managed in either the inpatient or outpatient setting. The demographic, clinical, and outcome data were retrieved from patients' medical records. Olfactory dysfunction features, including the onset pattern, duration, and recovery time were investigated. The visual analog scale (VAS) was utilized as a self-rating subjective measurement of olfactory function. According to the results, the mean age of the patients (n=502) was obtained at 46.8±18.5 years; moreover, 52.4% and 47.6% of cases were female and male, respectively. It was also revealed that 35.4% and 64.5% of the subjects were outpatients and hospitalized, respectively. Based on the findings, 178 (38.4%) subjects had olfactory dysfunction. The mean values of VAS in hyposmic patients were estimated at 2.5±2.5, 8.3 ±2.1, and 9.4±1.6 at the first evaluation, in 2 weeks, and after 1 month of follow-up (P<0.001). The onset of olfactory dysfunction was more suddenly (58.7%). The majority of cases experienced olfactory dysfunction at the same time as other symptoms 72(51.1%). Based on the results, 0.4% of subjects infected with COVID-19 had olfactory dysfunction as an isolated symptom. The olfactory dysfunction was recovered after 2 weeks in 18 (25.3%) anosmic and 37(46.8%) hyposmic patients. Olfactory dysfunction seemed to be an important symptom of COVID-19 infection. The occurrence of this disturbance as a transient self-limited condition was significantly higher among female subjects.


In vivo mapping of DNA topoisomerase II-specific cleavage sites on SV40 chromatin.
The antitumor drug, m-AMSA (4'-(9-acridinylamino)-methanesulfon-m-anisidide), is known to interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II by blocking the enzyme-DNA complex in its putative cleavable state. Treatment of SV40 virus infected monkey cells with m-AMSA resulted in both single- and double-stranded breaks on SV40 viral chromatin. These strand breaks are unusual because they are covalently associated with protein. Immunoprecipitation results suggest that the covalently linked protein is DNA topoisomerase II. These results are consistent with the proposal that the drug action in vivo involves the stabilization of a cleavable complex between topoisomerase II and DNA in chromatin. Mapping of these double-stranded breaks on SV40 viral DNA revealed multiple topoisomerase II cleavage sites. A major topoisomerase II cleavage site was preferentially induced during late infection and was mapped in the DNAase I hypersensitive region of SV40 chromatin.


Breakfast Intake Among Children and Adolescents: United States, 2015-2018.
The American Academy of Pediatrics recommends that children and adolescents consume breakfast for healthier body weights, improved nutrition, better memory, better test scores, and better attention spans (1). This report describes breakfast consumption among children and adolescents by sex, age, race and Hispanic origin, and family income level. Foods and beverages frequently consumed for breakfast, as well as trends in breakfast consumption over the last decade, are also reported.


CsPAO2 Improves Salt Tolerance of Cucumber through the Interaction with CsPSA3 by Affecting Photosynthesis and Polyamine Conversion.
Polyamine oxidases (PAOs) are key enzymes in polyamine metabolism and are related to the tolerance of plants to abiotic stresses. In this study, overexpression of cucumber (Cucumis sativus L.) PAO2 (CsPAO2) in Arabidopsis resulted in increased activity of the antioxidant enzyme and accelerated conversion from Put to Spd and Spm, while malondialdehyde content (MDA) and electrolyte leakage (EL) was decreased when compared with wild type, leading to enhanced plant growth under salt stress. Photosystem Ⅰ assembly 3 in cucumber (CsPSA3) was revealed as an interacting protein of CsPAO2 by screening yeast two-hybrid library combined with in vitro and in vivo methods. Then, CsPAO2 and CsPSA3 were silenced in cucumber via virus-mediated gene silencing (VIGS) with pV190 as the empty vector. Under salt stress, net photosynthetic rate (Pn) and transpiration rate (Tr) of CsPAO2-silencing plants were lower than pV190-silencing plants, and EL in root was higher than pV190-silencing plants, indicating that CsPAO2-silencing plants suffered more serious salt stress damage. However, photosynthetic parameters of CsPSA3-silencing plants were all higher than those of CsPAO2 and pV190-silencing plants, thereby enhancing the photosynthesis process. Moreover, CsPSA3 silencing reduced the EL in both leaves and roots when compared with CsPAO2-silencing plants, but the EL only in leaves was significantly lower than the other two gene-silencing plants, and conversion from Put to Spd and Spm in leaf was also promoted, suggesting that CsPSA3 interacts with CsPAO2 in leaves to participate in the regulation of salt tolerance through photosynthesis and polyamine conversion.


Expression of messenger ribonucleic acids that encode for 3 beta-hydroxysteroid dehydrogenase and cholesterol side-chain cleavage enzyme throughout the luteal phase of the macaque menstrual cycle.
To study further the control of the primate corpus luteum, we obtained corpora lutea from cynomolgus macaques at defined stages of the luteal phase and examined steady state mRNA levels in these corpora lutea by Northern analysis for the two major enzymes involved in progesterone biosynthesis, cytochrome P450 cholesterol side-chain cleavage (P450SCC) and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD). mRNAs for both P450SCC and 3 beta HSD were maximal or near maximal shortly after ovulation and luteinization (days 3-5 of the luteal phase). mRNA for P450SCC exhibited a slight, but nonsignificant (P greater than 0.05) decline throughout the remainder of the luteal phase and was undetectable upon luteal regression. Steady state levels of 3 beta HSD mRNA were significantly lower (P less than 0.05) from corpora lutea removed during the midluteal phase (days 7-8 of the luteal phase) than those in newly formed corpora lutea and declined to 10% of early luteal phase values by days 13-15 of the luteal phase. 3 beta HSD mRNA levels fell to nondetectable values upon luteal regression. These results reveal a paradoxical relationship between the steroidogenic activity of the primate corpus luteum in vivo and the steady state levels of the mRNAs that encode for the major enzymes involved in progesterone biosynthesis. Unlike serum progesterone concentrations, which are very low immediately after ovulation and then rise during the midluteal phase, the steady stale levels of P450SCC mRNA and 3 beta HSD appeared to be maximal or near maximal shortly after ovulation and declined throughout the remainder of the luteal phase. These findings are consistent with the notion that luteal lifespan is set at the time of ovulation and luteinization, and the decline in luteal function may be due in part to decay of specialized luteal cell mRNAs with finite half-lives.


Possibilities of therapeutic manipulation of the gut microbiota.
Human gut microbiota, complex ecosystem of microbes associated with human gut, is essential for the development of the host's immune system and many other physiological functions. Recently, numerous diseases and syndromes were associated with disruption of this ecosystem thus stressing its importance in maintaining the host's health. Growing evidence suggests that by manipulating the gut microbiota, some of these diseases could be treated or even prevented. These manipulations include changes in diet, use of probiotics, prebiotics, antibiotics and fecal microbiota transplantation (FMT). The successes in FMT treatment of recurrent infection of Clostridium difficile led recently to a great interest in extending this treatment modality to other diseases with proven disruption of gut microbiota, such as ulcerative colitis or metabolic syndrome. Key words: Clostridium difficile - dysbiosis - fecal microbial transplantation - microbiota - prebiotics - probiotics.


[Acute respiratory failure caused by inhalation of waterproofing spray fumes].
A 25-year-old woman was admitted to our hospital because of dry cough, slight fever, and severe dyspnea 5 hrs after inhalation of waterproofing spray. She had used the spray indoors near an oil heater, and then had smoked with spray-contaminated fingers. Chest roentgenograms revealed diffuse interstitial shadows mixed with patchy alveolar infiltration, and computed tomographic (CT) scans confirmed diffuse infiltration in both lungs. Marked leukocytosis and severe hypoxemia were noted. A transbronchial lung biopsy performed 4 days later demonstrated extensive alveolitis characterized by edema in alveolar septa and marked neutrophil migration into alveoli as well as alveolar septa. Oxygen therapy and the administration of methylprednisolone (1 g/day) achieved a complete recovery in about 1 week. We speculated that acute lung injury in this patient may have been induced by direct inhalation not only of the waterproofing spray itself, but also of spray by-products resulting from heat-decomposition. When using waterproofing spray, precautions should be taken to avoid inhaling the spray fumes or the more toxic by-products of thermal degradation.


Exclusion of autosomal dominant polycystic kidney disease type II (ADPKD2) from 160 cM of chromosome 1.
Autosomal dominant polycystic kidney disease is a heritable disorder and recent studies have shown genetic heterogeneity, with some, but not all, families showing linkage with markers on chromosome 16p. Members of a large ADPKD family, unlinked to chromosome 16, have been typed for 12 marker loci located on both arms of chromosome 1. Multipoint analysis excluded ADPKD2 from the region between D1S81 (pTHH33) and D1S67 (pHHH106) on the long arm and between Rh and PGM1 on the short arm. This excludes the disease locus from about 61% of chromosome 1.


[Separation and identification of differential protein in the insect-resistant and insect-susceptible mungbean].
In order to find the insect-resistant composition and differentially expressed proteins of mungbean, Jinlv No.7, B20 and Weilv 2117 were used as experimental materials, and the differential proteins and functions of mungbean varieties that are resistant and susceptible to bruchids were compared and analyzed by two dimensional gel electrophoresis (2-DE) and identified by mass spectrometry. Among the samples, 15 protein spots showed a more than 2.5 times reproducible up-regulated, significance 6 of them were successfully identified by the database, and involved three kinds of proteins. They are the alpha and beta subtype 8S globulin, ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBis CO) subunits binding protein and the precursor peptide chains for amylase inhibitor and trypsin inhibitor. The protein expressions of B49 (alpha subtype 8S globulin) and B31 (RuBis CO subunits binding protein) of insect-resistant mungbean were 10 000 and 23 times higher than that of insect-susceptible mungbeans. It stunted the growth and even death of the Callosobruchus chinensis L. that alpha and beta subtype 8S globulin and RuBis CO subunits binding protein and precursor peptide chains for amylase inhibitor and trypsin inhibitor of insect-resistant mungbean, the bruchid resistance effect of these three proteins need to further verified in terms of the quantity and the combined effect.


Can we eliminate severe ovarian hyperstimulation syndrome?
The desire of some couples for children is so strong that they are willing to accept a modicum of risk to treat their infertility. Ideally, assisted reproduction technology practitioners seek a balance between optimum ovarian stimulation and successful treatment outcome with minimal rate of severe ovarian hyperstimulation syndrome (OHSS) or multiple pregnancies. However, despite many years of clinical experience, there are no precise methods to completely prevent severe OHSS, except by withholding the ovulation-inducing trigger of hCG. Individualization of treatment according to the specific risk factor and the specific response in the current cycle with the option of freezing of all embryos, or replacement of only a single embryo, has the potential of reducing the risk and the severity of the syndrome in susceptible cases. We offer a triage aimed at eliminating the occurrence of severe ovarian hyperstimulation syndrome on the basis of several clinical observations, including the role of GnRH antagonist in controlled ovarian stimulation protocols, the option of freezing of all embryos, or replacement of only a single embryo in the blastocyst stage.


Two Pahlavi chapters on medicine.
The medical sciences in Sasanian society, in late Antiquity, constitute a rather neglected field of inquiry. Our most reliable sources for the study of this particular period in the history of science include a number of texts that were written in several older Iranian languages. In the following pages, we offer translations and commentaries on two such texts, written in Middle Persian, dealing with the life sciences. The topics discussed include copulation, pregnancies in various species, lactation, and moral and physical characteristics in the offspring. Placed in juxtaposition, the two texts, furthermore, clarify some of the obscure points in each of them. It is hoped that this preliminary study will help to sketch the path for future studies of the field.


Functional activation of monoamine transporters by luteolin and apigenin isolated from the fruit of Perilla frutescens (L.) Britt.
Monoamine transporters playing major roles in regulating normal and abnormal synaptic activity are associated with various neuropsychological disorders. In spite of the discovery of a series of structurally different monoamine transporter antagonists for the therapy approach, no practical pharmaceutical can act as a transporter activator. Here, we isolated luteolin and apigenin from the fruit of Perilla frutescens (L.) Britt by using an activity-guided extraction technique, and proved that the two compounds possess actions of enhancing monoamine uptake either upon monoamine-transporter transgenic Chinese hamster ovary (CHO) cells or upon wild dopaminergic cell lines, with higher specificity for dopamine (DA) uptake than for norepinephrine (NE)- and serotonin (5HT)-uptake, as well as with more potency and greater efficacy for luteolin than for apigenin. Further, in the transgenic cells, the principal NE/DA uptake activation by luteolin was significantly prevented by respective transporter inhibitor, and the transmitter-uptake-enhancing action was independent of its ligands, which is in support of the compounds as monoamine transporter activators. Furthermore, luteolin evoked a marked disinhibition of cocaine-targeted effect in CHO cells overexpressing dopamine transporter. Thus, luteolin and apigenin function as monoamine transporter activators, which would improve several hypermonoaminergic neuropsychological disorders, especially cocaine dependence, through up-regulating monoamine transporter activity.


Limited thermal acclimation of photosynthesis in tropical montane tree species.
The temperature sensitivity of physiological processes and growth of tropical trees remains a key uncertainty in predicting how tropical forests will adjust to future climates. In particular, our knowledge regarding warming responses of photosynthesis, and its underlying biochemical mechanisms, is very limited. We grew seedlings of two tropical montane rainforest tree species, the early-successional species Harungana montana and the late-successional species Syzygium guineense, at three different sites along an elevation gradient, differing by 6.8℃ in daytime ambient air temperature. Their physiological and growth performance was investigated at each site. The optimum temperature of net photosynthesis (ToptA ) did not significantly increase in warm-grown trees in either species. Similarly, the thermal optima (ToptV and ToptJ ) and activation energies (EaV and EaJ ) of maximum Rubisco carboxylation capacity (Vcmax ) and maximum electron transport rate (Jmax ) were largely unaffected by warming. However, Vcmax , Jmax and foliar dark respiration (Rd ) at 25℃ were significantly reduced by warming in both species, and this decline was partly associated with concomitant reduction in total leaf nitrogen content. The ratio of Jmax /Vcmax decreased with increasing leaf temperature for both species, but the ratio at 25℃ was constant across sites. Furthermore, in H. montana, stomatal conductance at 25℃ remained constant across the different temperature treatments, while in S. guineense it increased with warming. Total dry biomass increased with warming in H. montana but remained constant in S. guineense. The biomass allocated to roots, stem and leaves was not affected by warming in H. montana, whereas the biomass allocated to roots significantly increased in S. guineense. Overall, our findings show that in these two tropical montane rainforest tree species, the capacity to acclimate the thermal optimum of photosynthesis is limited while warming-induced reductions in respiration and photosynthetic capacity rates are tightly coupled and linked to responses of leaf nitrogen.


MiR-216a accelerates proliferation and fibrogenesis via targeting PTEN and SMAD7 in human cardiac fibroblasts.
Heart failure (HF) is a progressive disease with relatively poor prognosis and lacks effective therapy, and the discovery of dysregulated microRNAs (miRNAs) and their role in cardiac fibroblasts have provided a new avenue for elucidating the mechanism involved in HF. Two datasets of GSE53080 and GSE57338 were used to screen the miRNAs profiling and analysis the differentially expressed genes (DEGs) in HF. QRT-PCR was used to detect miR-216a between HF and healthy controls (HC). Cell counting kit-8 (CCK-8) assay and clonogenic assay were used to analyze the effect of proliferation and fibrogenesis. Then dual-luciferase activity assay and western blotting were used to confirm the key mechanism. In this study, the results showed that miR-216a was significantly up-regulated in HF and over-expression of miR-216a promoted proliferation and enhanced the fibrogenesis in the human cardiac fibroblasts (HCF) cells. Phosphatase and tensin homolog (PTEN) and mothers against decapentaplegic homolog 7 (SMAD7) were both validated as the direct target genes of miR-216a, which were confirmed by the dual-luciferase reporter assay. MiR-216a decreased the expression of PTEN and SMAD7 leading to the activation of Akt/mTOR and TGF-βRI/Smad2 in the HCF cells, which might act as a promoter of cardiac fibrosis. Our study might provide a promising approach for the treatment of HF in the future.


Embolisation of arteriovenous malformation of the maxilla.
We describe a 20-year-old male patient who presented with gingival bleeding. Physical examination showed gingival swelling of the right maxilla and loosening of the molar teeth. The initial diagnosis of gingivitis was made, but further examination revealed a lytic lesion of the maxilla. On suspicion of fibrous dysplasia, biopsy was attempted but was unsuccessful due to severe haemorrhage. Further evaluation showed palpable and audible bruit on the gingiva, which caused the suspicion of vascular malformation. Angiography was performed and demonstrated arteriovenous malformation (AVM). Embolisation therapy with polyvinyl alcohol was performed. Post-embolisation angiogram demonstrated complete obliteration of the lesion.


Molecular dynamics simulations of the structure and transport properties of tetra-butylphosphonium amino acid ionic liquids.
Systematic molecular dynamics simulations are used to study the structure, dynamics and transport properties of the ionic liquids composed of the tetra-butylphosphonium ([TBP](+), or [P(C(4)H(9))(4)](+)) cation with six amino acid ([AA](-)) anions. The structural features of these ionic liquids were characterized by calculating the partial site-site radial distribution functions, g(r), and computing the dihedral angle distribution of n-butyl side chains in the [TBP](+) cations. The dynamics of the ionic liquids are described by studying the velocity autocorrelation function (VACF) and the mean-square displacement (MSD) for the centers of mass of the ions at different temperatures. The ionic diffusion coefficients and the electrical conductivities were evaluated from both the Einstein and Green-Kubo methods. The cross-correlation terms in the electric-current autocorrelation functions, which are an indication of the ion pair correlations, are investigated. The cationic transference numbers were also estimated to study the contributions of the anions and cations to the transport of charge in these ionic liquids. We determined the role of the amino acid anion structures on the dynamical behavior and the transport coefficients of this family of ionic liquids. In general, the MSD and self-diffusion coefficients of the relatively heavier non-planar [TBP](+) cations are smaller than those of the lighter amino acid anions. Introducing polar functional groups (acid or amide) in the side chain of [AA](-) decreases the diffusion coefficient and electrical conductivity of AAILs. The major factors for determining the magnitude of the transport coefficients are the chemical functionality and the length of the alkyl side chain of the [AA](-) anion of these [TBP][AA] ionic liquids.


Interrelationship between inflammatory cytokines (IL-1, IL-6, IL-33, IL-37) and acquired immunity.
It is now well-known that interleukins (ILs) play a pivotal role in shaping innate immunity: inflammatory ILs are responsible for all innate aspects of immune response, from the very first vascular reactions to the chronic non-specific response to inflammation; while anti-inflammatory ILs are responsible for keeping adaptive immunity at bay. The interactions between ILs and adaptive immunity have been long considered secondary to the effects on the innate immune system, but in recent years it has appeared more clearly that IL direct interactions with adaptive immunity are extremely important both in physiologic and pathologic immune response. In the present review we analyze the role of inflammatory ILs (IL-1, IL-6, IL-33 and IL-37) on adaptive immunity and briefly discuss the possible therapeutic perspectives of IL-blockade in adaptive immunity disorders.


Quantitative characterization of the carbon/carbon composites components based on video of polarized light microscope.
The components of carbon/carbon (C/C) composites have significant influence on the thermal and mechanical properties, so a quantitative characterization of component is necessary to study the microstructure of C/C composites, and further to improve the macroscopic properties of C/C composites. Considering the extinction crosses of the pyrocarbon matrix have significant moving features, the polarized light microscope (PLM) video is used to characterize C/C composites quantitatively because it contains sufficiently dynamic and structure information. Then the optical flow method is introduced to compute the optical flow field between the adjacent frames, and segment the components of C/C composites from PLM image by image processing. Meanwhile the matrix with different textures is re-segmented by the length difference of motion vectors, and then the component fraction of each component and extinction angle of pyrocarbon matrix are calculated directly. Finally, the C/C composites are successfully characterized from three aspects of carbon fiber, pyrocarbon, and pores by a series of image processing operators based on PLM video, and the errors of component fractions are less than 15%.


X-RAY SEMIOTICS OF ENDOCRINE OPHTHALMOPATHY. PART 2. THE OPTIC NERVE, LACRIMAL GLAND, SUPERIOR OPHTHALMIC VEIN.
Objective: to study the optic nerve, lacrimal gland, and superior ophthalmic vein in patients with different clinical forms of endocrine ophthalmopathy (EOP). Material and methods. 294 patients (559 orbits) with EOP were examined. Hydrodynamic disorders were detected in 43 patients. 46 patients (91 orbits) with mixed or myogenic types of edematous exophthalmos (EE) were diagnosed as having optic neuropathy (ON). Results and discussion. The paper presents the indicators of the optic nerve, lacrimal gland, and superior ophthalmic vein in patients with different clinical forms of EOP. This study provides evidence that ON in patients with EOP is characterized by specific changes in the optic nerve, as shown by computed tomography. It is ascertained that there are volumetric and structural changes in the lacrimal gland in 40.62% of the patients with mixed EE and in 33.89% of those with myogenic EE. Conclusion. The study of the extraocular muscles in patients with ON-complicated EE may confirm that enlargement of the extraocular muscles at the orbital apex plays a major role in the pathogenesis of ON in this disease. The change in the anatomictopographic relationships of the orbit leads to compression of the superior ophthalmic vein, which entails obstruction of blood outflow from the orbit and causes ocular hypertension.


Multicolor CRISPR labeling of chromosomal loci in human cells.
The intranuclear location of genomic loci and the dynamics of these loci are important parameters for understanding the spatial and temporal regulation of gene expression. Recently it has proven possible to visualize endogenous genomic loci in live cells by the use of transcription activator-like effectors (TALEs), as well as modified versions of the bacterial immunity clustered regularly interspersed short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system. Here we report the design of multicolor versions of CRISPR using catalytically inactive Cas9 endonuclease (dCas9) from three bacterial orthologs. Each pair of dCas9-fluorescent proteins and cognate single-guide RNAs (sgRNAs) efficiently labeled several target loci in live human cells. Using pairs of differently colored dCas9-sgRNAs, it was possible to determine the intranuclear distance between loci on different chromosomes. In addition, the fluorescence spatial resolution between two loci on the same chromosome could be determined and related to the linear distance between them on the chromosome's physical map, thereby permitting assessment of the DNA compaction of such regions in a live cell.


An exploratory evaluation of the utility of transcriptional and urinary kidney injury biomarkers for the prediction of aristolochic acid-induced renal injury in male rats.
The predictive value of different urinary and transcriptional biomarkers was evaluated in a proof-of-principle toxicology study in rats using aristolochic acid (AA), a known nephrotoxic agent. Male Wistar rats were orally dosed with 0.1, 1, or 10 mg/kg for 12 days. Urine was collected on days 1, 5, and 12 over 24 hours. Gene expression analysis was also conducted using quantitative real-time polymerase chain reaction and Illumina whole-genome chips. Protein biomarkers (Kim-1, Timp-1, vascular endothelial growth factor, osteopontin, clusterin, cystatin C, calbindin D-28K, β2-microglobulin, α-glutathione S-transferase, GSTY1b, RPA-1, and neutrophil gelatinase-associated lipocalin) were measured in these urine samples. Treatment with AA resulted in a slight dose- and/or time-dependent increase in urinary β2-microglobulin, lipocalin 2, and osteopontin before an increase in serum creatinine or serum urea nitrogen was observed. A strong decrease in urinary calbindin D-28K was also detected. The Compugen Ltd. prediction model scored both the 1- and 10-mg/kg AA dose groups as positive for nephrotoxicity despite the absence of renal histopathological changes. In addition, several previously described transcriptional biomarkers were identified as early predictors of renal toxicity as they were detected before morphological alterations had occurred. Altogether, these findings demonstrated the predictive values of renal biomarkers approved by the Food and Drug Administration, European Medicines Agency, and Pharmaceuticals & Medical Devices Agency in AA-induced renal injury in rats and confirmed the utility of renal transcriptional biomarkers for detecting progression of compound-induced renal injury in rats. In addition, several transcriptional biomarkers identified in this exploratory study could present early predictors of renal tubular epithelium injury in rats.


Low-Latency Haptic Open Glove for Immersive Virtual Reality Interaction.
Recent advancements in telecommunications and the tactile Internet have paved the way for studying human senses through haptic technology. Haptic technology enables tactile sensations and control using virtual reality (VR) over a network. Researchers are developing various haptic devices to allow for real-time tactile sensation, which can be used in various industries, telesurgery, and other mission-critical operations. One of the main criteria of such devices is extremely low latency, as low as 1 ms. Although researchers are attempting to develop haptic devices with low latency, there remains a need to improve latency and robustness to hand sizes. In this paper, a low-latency haptic open glove (LLHOG) based on a rotary position sensor and min-max scaling (MMS) filter is proposed to realize immersive VR interaction. The proposed device detects finger flexion/extension and adduction/abduction motions using two position sensors located in the metacarpophalangeal (MCP) joint. The sensor data are processed using an MMS filter to enable low latency and ensure high accuracy. Moreover, the MMS filter is used to process object handling control data to enable hand motion-tracking. Its performance is evaluated in terms of accuracy, latency, and robustness to finger length variations. We achieved a very low processing delay of 145.37 μs per finger and overall hand motion-tracking latency of 4 ms. Moreover, we tested the proposed glove with 10 subjects and achieved an average mean absolute error (MAE) of 3.091∘ for flexion/extension, and 2.068∘ for adduction/abduction. The proposed method is therefore superior to the existing methods in terms of the above factors for immersive VR interaction.


The administration of a loading dose of aspirin to patients presenting with acute myocardial infarction while receiving chronic aspirin treatment reduces thromboxane A2-dependent platelet reactivity.
Abstract The optimal dose of aspirin for patients presenting with acute myocardial infarction (AMI) while receiving chronic aspirin therapy has not been clearly established. We evaluated whether continued treatment with 100 mg of aspirin or a loading dose (200-500 mg) influences thromboxane A2 (TX) suppression or platelet reactivity. Sixty-four consecutive patients with AMI and 98 healthy subjects (82 aspirin-free and 16 receiving 100 mg daily for a week) were evaluated. Treatment was at the discretion of the attending physician. Collagen (1 µg/ml)-induced TX synthesis, (14)C-serotonin-release, platelet aggregation, and the PFA-100 assay were evaluated. The platelet TX synthesis of patients receiving a loading dose of aspirin was sixfold lower than that of patients receiving 100 mg of aspirin (p<0.005). This was associated with marked reductions in (14)C-serotonin-release and arachidonic-acid-induced aggregation and an increase in the PFA-100 closure time (p<0.01). Categorization of patients according to their TX synthesis (<95% or ≥ 95% inhibition vs. healthy aspirin-free subjects) revealed that 8% of the patients treated with loading doses had a poor response (<95% inhibition) vs. 53% of those treated with 100 mg (p<0.001). Patients with lower TX inhibition had higher serum NT-Pro-BNP (p<0.005), a marker of poor left ventricular systolic function. Administration of a loading dose of aspirin to patients with AMI during existing chronic aspirin treatment induced greater reductions in platelet TX synthesis and TX-dependent platelet reactivity than the continued treatment alone.


Diagnostic Yield and Safety of Computed Tomography-guided Mediastinal Core Needle Biopsies.
Mediastinal masses of various origins can be encountered on imaging in symptomatic or asymptomatic patients. We aimed to evaluate the diagnostic yield and complication rate of computed tomography (CT)-guided mediastinal core needle biopsies in a large population of patients presenting with mediastinal masses and to identify the factors that could influence these results. In total, 293 consecutive CT-guided mediastinal biopsies, performed in 285 patients with equivocal masses at a single center from 2006 to 2011, were included. Lesion characteristics, technical biopsy parameters, final diagnoses, diagnostic yields (number of biopsies that yielded a complete diagnosis divided by the total number of biopsies), and complication rates were recorded. Malignant diagnoses, including lymphoproliferative disorders (N=151, 53%) and lung cancers (N=54, 19%), were established in 233 cases (82%). Benign lesions were found in 52 procedures (18%), including sarcoidosis (N=19, 7%) and infections (N=17, 6%). The overall diagnostic yield was 87% and was lower for lymphoma residual masses (57%) than for initial diagnosis or relapses of known disease (90%). Complications occurred in 21 patients (7%), but only 2 patients (0.7%) required hospitalization for >12 hours. Neither the diagnostic yield nor the complication rate was influenced by the target characteristics or by technical parameters. CT-guided core needle biopsy of equivocal mediastinal masses is a minimally invasive procedure that is effective and safe, even in cases of small targets or targets in challenging locations.


[Influence of temperature and light on the growth and development of Tenodera angustipennis and related preying functional responses].
Tenodera angustipennis was raised under laboratory conditions to study the influence of temperature and light on the growth and development of its nymphs. The functional responses of T. angustipennis to Plutella xylostella (L.) larvae and adults and to Lipaphis erysimi (Kaltenbach) were also studied. The results showed that temperature remarkably affected the growth and development of T. angustipennis, but light did not. The Holling models could well describe the functional responses of T. angustipennis to P. xylostella and L. erysimi.


Registration accuracy in the integration of laser-scanned dental images into maxillofacial cone-beam computed tomography images.
A precision 3-dimensional (3D) head model can be fabricated by integrating a digital dental model into a maxillofacial 3D image. The integration requires accurate registration of 2 image modalities. The aims of this study were to determine the registration errors for implementation of laser-scanned dental images into cone-beam computed tomography (CBCT) scan data and to examine the influence of the registration area on the accuracy of registration. The CBCT scans were obtained from 30 adults, and the maxillofacial 3D images were reconstructed. Maxillary and mandibular dental casts were taken from the same subjects and scanned with a 3D laser scanner. The laser-scanned maxillary and mandibular dentition images were incorporated into the CBCT images of each arch in 3 ways according to the registration area: only the buccal surfaces, only the lingual surfaces, and both the buccal and lingual surfaces. Surface-based registration was performed by using an iterative closest point algorithm, and its errors were evaluated by measuring the 3D Euclidean distances between the surface points on the 2 images. The registration errors ranged from 0.27 to 0.33 mm. The mandibular arch did not show significant differences in registration errors according to the selected area for the registration. The maxillary arch, however, showed significant differences according to the registration area. When the lingual surfaces only were used for registration, the errors were greater than for the other 2 methods. The errors were least when both the buccal and lingual surfaces were used for registration. The results of this study indicate that accuracy in the integration of laser-scanned dental images into the maxillofacial CBCT images increases when a broad area is used for registration.


Synthesis of polycyclic benzonitriles via a one-pot aryl alkylation/cyanation reaction.
A norbornene-mediated palladium-catalyzed tandem alkylation/cyanation sequence is described in which an alkyl-aryl bond and a nitrile-aryl bond are formed in one pot. A variety of sterically hindered, five-, six-, and seven-membered ring benzonitriles were synthesized in good yields from easily accessible starting materials.


Preparation and in vitro performance evaluation of resveratrol for oral self-microemulsion.
The purpose of this study was to improve the solubility of resveratrol (Res) by a self-microemulsifying drug-delivery system (SMEDDS). Through a solubility experiment, the pseudoternary phase diagram and ternary phase diagram were used to optimize the Res SMEDDS formula. The optimum formulation consisted of 5% IPM, 20% PEG400, and 65% Cremophor RH40. The water solubility, stability, in vitro release and antioxidant activity of the Res SMEDDS were characterized. The Res solubility in the SMEDDS was at least 1,000 times compared to that in water. The average droplet size of the microemulsion was 28.00±1.67 nm and uniform distribution. The Res SMEDDS should be stored at low temperature and in the dark to avoid light conditions. Res SMEDDS was able to improve the in vitro release rate of Res, and the in vitro release of Res from Res SMEDDS was significantly faster that of Res powder and unaffected by pH value of media. Antioxidant assays showed that antioxidant activities of Res in Res SMEDDS were unaffected compared to Res powder. Cytotoxicity study indicated that Res SMEDDS at the concentration of less than 100 μM was safe. These results demonstrated the potential use of Res SMEDDS for oral administration of Res.


Nucleosides and nucleotides. 95. Improved synthesis of 1-(2-azido-2-deoxy-beta-D-arabinofuranosyl)cytosine (cytarazid) and -thymine. Inhibitory spectrum of cytarazid on the growth of various human tumor cells in vitro.
Reaction of N3-benzoyl-1-[3,5-O-(tetraisopropyldisiloxan-1,3-diyl)-beta- D- ribofuranosyl]thymine (4a) with diphenyl phosphorazidate, diethyl azodicarboxylate, and triphenylphosphine in tetrahydrofuran afforded N3-benzoyl-1-[2-azido-2-deoxy-3,5-O- (tetraisopropyldisiloxan-1,3-diyl)-beta-D-arabinofuranosyl]t hymine (5a) in good yield. After the sequence of deblocking of 5a gave 1-(2-azido-2-deoxy-beta-D-arabinofuranosyl)thymine (7), it was heated in N,N-dimethylformamide to produce 6,2'-imino-1-(2-deoxy-beta-D-arabinofuranosyl)thymine (8). This reaction disclosed the arabino configuration for 5a. Similarly the N3-benzoyluracil derivative 4b was transformed to the corresponding 2'-"up"-azidouridine derivative 5b, which was further converted to 1-(2-azido-2-deoxy-1-beta-D-arabinofuranosyl)cytosine (1, cytarazid). The antineoplastic activity of 1 was compared with that of ara-C against various human cancer cell lines in vitro.


Intraspecific variation of Haematoloechus floedae Harwood, 1932 (Digenea: Plagiorchiidae), from Rana spp. in North and Central America.
Haematoloechus floedae was originally described from the lungs of Rana catesbeiana in Texas, and later reported in Florida, in the United States. It was proposed to be synonymous with H. breviplexus, H. parviplexus, and H. varioplexus. We obtained specimens of H. floedae from Rana brownorum and R. vaillanti in Yucatán, Mexico; R. cf. forreri and R. taylori in Guanacaste, Costa Rica; and R. catesbeiana in Georgia and California. Some specimens were processed for morphological study; sequences of the 28S of the rDNA and the mitochondrial COI were obtained from several specimens of each population. Phylogenetic analysis of molecular data indicates studied populations constitute a single taxon, different from H. varioplexus, H. breviplexus, and H. parviplexus. Some morphological characters remain constant among populations of H. floedae, and are useful for differentiating this species. These include the oral sucker-pharynx ratio, oral sucker-ventral sucker ratio, ovary and testes shape, extension of uterine longitudinal loops, and extension of vitelline follicles (in fully developed worms). Sequence homogeneity among populations of H. floedae suggests a recent spread, perhaps due to the introduction of R. catesbeiana for culture to the western United States, southeast Mexico, and Costa Rica.


[Karnosfsky index as a mortality predicting factor in patients on home-based enteral nutrition].
Karnofsky Index (KI) is a widely used functional scale developed for oncology patients. It has proved useful as outcome predictor with cancer and geriatric patients. Theoretically, KI could be used to predict mortality in patients with home enteral nutrition (HEN). To determine baseline KI and its 6-month evolution in HEN patients, and to assess its relation with the mortality rate. Observational and prospective study carried out during 2002 and 2003 with tube feeding neurologic and cancer patients followed during 10 months since their HEN programme inclusion. 201 patients were included, 131 (65.2%) with neurological diseases and 70 (34.8%) with neoplasm. There were not significant differences between groups in age, days with HEN and mortality rate at the end of the study period (35.1% in neurologic patients and 40% in cancer ones). 27.1% of cancer patients had resumed full oral nutrition after ten months from the beginning of the study, whereas only 10.7% of neurologic patients did (p < 0.05). In the three measurement phases (initial, past-3 and past-6 months) KI values were higher for cancer patients than for neurologic ones (p < 0.001). In both groups we didn't found statistically significant differences in KI along the three measurements. A significant relation was observed overall between initial KI values and average survival after 10 months (p < 0.001), and an inverse relation was found between the former and mortality rate (p < 0.001). KI is a useful tool to predict mortality rate in cancer and neurologic patients under HEN.


Role of JNK isoforms in the kainic acid experimental model of epilepsy and neurodegeneration.
Chemoconvulsants that induce status epilepticus in rodents have been widely used over the past decades due to their capacity to reproduce with high similarity neuropathological and electroencephalographic features observed in patients with temporal lobe epilepsy (TLE). Kainic acid is one of the most used chemoconvulsants in experimental models. KA administration mainly induces neuronal loss in the hippocampus. We focused the present review inthe c-Jun N-terminal kinase-signaling pathway (JNK), since it has been shown to play a key role in the process of neuronal death following KA activation. Among the three isoforms of JNK (JNK1, JNK2, JNK3), JNK3 is widely localized in the majority of areas of the hippocampus, whereas JNK1 levels are located exclusively in the CA3 and CA4 areas and in dentate gyrus. Disruption of the gene encoding JNK3 in mice renders neuroprotection to KA, since these animals showed a reduction in seizure activity and a diminution in hippocampal neuronal apoptosis. In light of this, JNK3 could be a promising subcellular target for future therapeutic interventions in epilepsy.


Non-mutagenicity of YTR 830 H, a novel beta-lactamase inhibitor.
The Ames test indicated that a novel beta-lactamase inhibitor YTR 830 H, belonging to penicillanic acid sulfone was non-mutagenic for any of the tester strains of Salmonella typhimurium TA 98, TA 100 and TA 102. The test was performed both in the presence and absence of S9 activation mixtures which were prepared from the livers of Aroclor 1254-induced Syrian hamsters.


Near-Infrared Spectroscopy as an Analytical Process Technology for the On-Line Quantification of Water Precipitation Processes during Danhong Injection.
This paper used near-infrared (NIR) spectroscopy for the on-line quantitative monitoring of water precipitation during Danhong injection. For these NIR measurements, two fiber optic probes designed to transmit NIR radiation through a 2 mm flow cell were used to collect spectra in real-time. Partial least squares regression (PLSR) was developed as the preferred chemometrics quantitative analysis of the critical intermediate qualities: the danshensu (DSS, (R)-3, 4-dihydroxyphenyllactic acid), protocatechuic aldehyde (PA), rosmarinic acid (RA), and salvianolic acid B (SAB) concentrations. Optimized PLSR models were successfully built and used for on-line detecting of the concentrations of DSS, PA, RA, and SAB of water precipitation during Danhong injection. Besides, the information of DSS, PA, RA, and SAB concentrations would be instantly fed back to site technical personnel for control and adjustment timely. The verification experiments determined that the predicted values agreed with the actual homologic value.


Phase retrieval with a dual recursive scheme.
Since optical sensors cannot detect the phase information of the light wave, recovering the missing phase from the intensity measurements, called phase retrieval (PR), is a natural and important problem in many imaging applications. In this paper, we propose a learning-based recursive dual alternating direction method of multipliers, called RD-ADMM, for phase retrieval with a dual and recursive scheme. This method tackles the PR problem by solving the primal and dual problems separately. We design a dual structure to take advantage of the information embedded in the dual problem that can help with solving the PR problem, and we show that it is feasible to use the same operator for both the primal and dual problems for regularization. To demonstrate the efficiency of this scheme, we propose a learning-based coded holographic coherent diffractive imaging system to generate the reference pattern automatically according to the intensity information of the latent complex-valued wavefront. Experiments on different kinds of images with a high noise level indicate that our method is effective and robust, and can provide higher-quality results than other commonly-used PR methods for this setup.


IL-27 regulates IL-12 responsiveness of naive CD4+ T cells through Stat1-dependent and -independent mechanisms.
IL-27, a novel heterodimeric cytokine produced by antigen-presenting cells, signals through the T cell cytokine receptor (TCCR)/WSX-1 expressed on naïve CD4+ T cells and natural killer cells. TCCR/WSX-1 deficiency results in delayed T helper type 1 (TH1) development through an unresolved mechanism. We report here that IL-27 stimulation in developing murine T helper cells potently induces the expression of the major TH1-specific transcription factor T-bet and its downstream target IL-12R beta2, independently of IFN gamma. In addition, IL-27 suppresses basal expression of GATA-3, the critical TH2-specific transcription factor that inhibits TH1 development by down-regulating signal transducer and activator of transcription (Stat) 4. IL-27 signaling through TCCR/WSX-1 induces phosphorylation of Stat1, Stat3, Stat4, and Stat5. Stat1 is required for suppression of GATA-3, but T-bet induction by IL-27 can also be mediated through a Stat1-independent pathway. Despite its TH1-like signaling profile, IL-27 is not sufficient to drive the differentiation of CD4+ T cells into IFN gamma-producing cells. Similarly, IL-27 induces T-bet expression in primary natural killer cells, but this does not result in an increase of IFN gamma production or cytotoxic activity. Therefore, although IL-27 is unable to drive IFN gamma production on its own, it plays an important role in the early steps of TH1 commitment by contributing in a paracrine manner to the control of IL-12 responsiveness.


Behavioral Aspects of Phlebotomine Sand Flies Associated with a Case of Cutaneous Leishmaniasis in Atlántico, Northern Colombia.
After the first autochthonous case of cutaneous leishmaniasis was reported in the Atlántico department in the Caribbean region of Colombia, entomological sampling was conducted in the specific areas where the infection might have occurred. CDC traps were installed inside and outside dwellings in the peri-urban and rural areas of a settlement in the municipality of Luruaco. Sampling was performed during the night with protected human bait, and phlebotomine sand flies were actively sampled from potential diurnal resting sites within dwellings. Ten species of the genus Lutzomyia were identified; Lutzomyia evansi was the dominant species (78%) in the rural and peri-urban areas as well as in the different sampled habitats, followed by Lutzomyia panamensis and Lutzomyia gomezi. There was a 100% household infestation by Lu. evansi, and its indoor mean abundance was 13.3 sand flies/CDC trap/night. The indoor mean abundance of Lu. panamensis and Lu. gomezi was only 0.9 and 0.8 sand flies/CDC trap/night, respectively. Female Lu. evansi were collected with protected human bait, mostly in the peridomestic area, with sustained activity during the night and a slight increase in the activity from 19:00 to 23:00 hours. Of the total sand flies captured in the diurnal resting sites, 73.1% were collected from the walls of bedrooms and corresponded to Lu. evansi, Lutzomyia cayennensis cayennensis, and Lutzomyia trinidadensis. Owing to their vectorial importance, the species on which entomological surveillance should be focused are Lu. evansi, Lu. panamensis, and Lu. gomezi. The biting and resting behavior reported in this study will help guide vector prevention and the control of leishmaniasis within the study area.


The prevalence of back pain, hand discomfort, and dermatitis in the US working population.
The purpose of the study was to provide the health care and public health communities with national prevalence estimates of selected conditions in the US working population. National prevalence estimates of self-reported conditions among working people were calculated from data collected for the 1988 Occupational Health Supplement to the National Health Interview Survey. The highest prevalence estimates were found among occupational groups. For example, the prevalence of back pain due to an injury at work among truck drivers was 6.7%; back pain due to repeated activities at work among mechanics and repairers of heavy equipment and machinery was 10.5%; hand discomfort among operators of machines that process metal, plastic, stone, and glass was 23.5%; and dermatitis due to contact with substances at work among physicians, dentists, nurses, pharmacists, and dietitians was 5.6%. A substantial proportion of these conditions among occupational groups with the highest prevalence estimates are occupational in origin. These prevalence estimates identify occupations in which efforts are needed to prevent these conditions.


Pathogenesis of membranous nephropathy.
Membraneous nephropathy is the most common cause of idiopathic nephrotic syndrome in adults. Recent studies of the pathogenesis of the subepithelial glomerular immune deposits that characterize this disease have revealed new mechanisms of glomerular immune deposit formation involving cell surface antigens and have documented the role of the C5b-9 membrane attack complex of complement in mediating renal injury. Understanding these mechanisms may help us understand the pathogenesis of several other immune-mediated diseases and has implications for possible therapeutic interventions in MN.


Role of the Staphylococcus aureus Extracellular Loop of GraS in Resistance to Distinct Human Defense Peptides in PMN and Invasive Cardiovascular infections.
GraS is a membrane sensor in Staphylococcus aureus that induces mprF and dltABCD expression to alter the surface positive charge upon exposure to cationic human defense peptides (HDPs). The sensing domain of GraS likely resides in the 9-residue extracellular loop (EL). In this study, we assessed a hospital-acquired methicillin-resistant S. aureus (HA-MRSA) strain (COL) for the specific role of two distinct EL mutations: F38G (bulk) and D/35/37/41K (charged inversion). Activation of mprF by polymyxin B (PMB) was reduced in the D35/37/41K mutant versus the D35/37/41G mutant, correlating with reduced surface positive charge; in contrast, these effects were less prominent in the F38G mutant but still lower than those in the parent. These data indicated that both electrostatic charge and steric bulk of the EL of GraS influence induction of genes impacting HDP resistance. Using mprF expression as a readout, we confirmed GraS signaling was pH dependent, increasing as pH was lowered (from pH 7.5 down to pH 5.5). In contrast to PMB activation, reduction of mprF was comparable at pH 5.5 between the P38G and D35/37/41K point mutants, indicating a mechanistic divergence between GraS activation by acidic pH versus cationic peptides. Survival assays in human blood and purified polymorphonuclear leukocytes (PMNs) revealed lower survival of the D35/37/41K mutant versus the F38G mutant, with both being lower than that of the parent. Virulence studies in the rabbit endocarditis model mirrored whole blood and PMN killing assay data described above. Collectively, these data confirmed the importance of specific residues within the EL of GraS in conferring essential bacterial responses for MRSA survival in infections.


In Vivo Proof of Biological Safety and Physiological Effects of Orally Ingested Water Containing H2-Filled Ultrafine Bubbles (UFBs).
Owing to their unique physicochemical properties and diverse biological effects, ultrafine bubbles (UFBs) have recently been expected to be utilized for industrial and biological purposes. Thus, this study investigated the biological safety of UFBs in water for living beings in drinking the water with a view to future use in health sciences. In this study, we used H2-filled UFBs (NanoGAS®) that can hold hydrogen in the aqueous phase for a long time. Mice were randomly assigned to one of three groups: those receiving NanoGAS® water, reverse osmosis water, or natural mineral water, and they ingested it ad libitum for one month or three months. As a result, subchronic drinking of NanoGAS® water does not affect either the common blood biochemical parameters or the health of the organs and mucosal membranes. Our results, for the first time, scientifically demonstrated the biological safety of H2-filled UFBs water for subchronic oral consumption.


Chronic obstructive pulmonary disease: Does gender really matter?
Limited data is available on the clinical expression of chronic obstructive pulmonary disease (COPD) from India. The impact of gender on expression of COPD has received even less attention. Apart from tobacco smoke, indoor air pollution, especially from biomass fuel may play an important role in development of COPD in women. Seven hundred and two patients of COPD were studied regarding the etiological and risk factors leading to COPD, gender-related differences in clinical presentation, radiological expression of COPD and the co-morbidities in COPD. Tobacco smoke in the form of beedi smoking was the predominant smoke exposure in males, whereas smoke from biofuel burning was the predominant exposure in females. As compared to males, females were younger, reported more dyspnea, more severe bronchial obstruction, more exacerbations, and exhibited higher prevalence of systemic features. Also, females smoked less and had lesser incidence of productive cough, lower body mass index, lesser co-morbidities and less number of hospital admissions as compared to males. Males were more likely than females to have an emphysema-predominant phenotype, while airway-predominant disease was more common among females. The current study shows that gender-related differences do exist in COPD patients. Understanding these differences in etiological agent and clinical picture will help early diagnosis of COPD in females.


[Infections, pandemics and sleep disorders].
The study of neurological symptoms and signs connected with acute and long-term periods of infectious diseases is relevant during pandemics. The COVID-19 pandemic has increased the number of patients suffering from insomnia. Sleep disturbance is an unfavorable prognostic factor for infections. Risk factors and mechanisms of sleep disturbance, their relationship with inflammation and dysfunction of the immune system in infectious diseases are presented. In particular, dysfunction of the melatonergic system as the cause of insomnia during pandemics is considered. The authors highlight the relevance of measures aimed at the rehabilitation of patients, in particular, the use of sonnovan to restore normal sleep, which is important for a person's mental and physical health.