Guar gum reduces serum cholesterol in sea quail fed a cholesterol diet.
Guar gum at 6% and 12% in the diet reduces total serum cholesterol by 31% and 51%, respectively, in male SEA quail fed a diet containing 0.5% cholesterol for a period of one week. Although the potency of hypocholesterolemic action of guar gum in cholesterol fed SEA quail is much less than that in cholesterol fed chickens, SEA quail are a reasonable alternative to chickens for evaluation of guar and similar products, based on other considerations such as smaller size and compound requirements and shorter duration of testing.


[The analysis of intervention studies for patients with metabolic syndrome].
This study was to analyze the trend of research on intervention for patients with metabolic syndrome. Using Pubmed, Medline, and CINAHL search engines, a randomized controlled trial(RCT) researching titles such as "metabolic syndrome", "intervention", "lifestyle modification", or "community-based" were collected. A total of 16 researches were analyzed based on the guidelines of the National Cholesterol Education Program-Adult Treatment Panel(NCEP-ATP III). 1) The total period of the intervention was from 12 to 24 weeks, the frequency was 3 to 5 times per week, and the duration of each session was from 45 to 60 minutes. The types of intervention included exercise, diet, and medication. Among these types, diet was performed most frequently. 2) The outcomes of the intervention was measured with physical aspects such as anthropometric measures, body composition, or biological markers. No studies have evaluated psychosocial outcomes such as quality of life. 3) In terms of effectiveness of the intervention, anthropometric indicators, body composition, or serological markers showed positive effects, whereas results on endothelial or urine indicators were inconsistent. Methodological research developing comprehensive therapeutic lifestyle modification programs and intervention studies are needed for patients with metabolic syndrome. In addition, effects should be evaluated with multidimensional perspectives.


Enhanced Surface Activity of MWW Zeolite Nanosheets Prepared via a One-Step Synthesis.
The synthesis of two-dimensional (2D) zeolites has garnered attention due to their superior properties for applications that span catalysis to selective separations. Prior studies of 2D zeolite catalysts demonstrated enhanced mass transport for improved catalyst lifetime and selectivity. Moreover, the significantly higher external surface area of 2D materials allows for reactions of bulky molecules too large to access interior pores. There are relatively few protocols for preparing 2D materials, owing to the difficultly of capping growth in one direction to only a few unit cells. To accomplish this, it is often necessary to employ complex, commercially unavailable organic structure-directing agents (OSDAs) prepared via multistep synthesis. However, a small subset of zeolite structures exist as naturally layered materials where postsynthesis steps can be used to exfoliate samples and produce ultrathin 2D nanosheets. In this study, we selected a common layered zeolite, the MWW framework, to explore methods of preparing 2D nanosheets via one-pot synthesis in the absence of complex organic templates. Using a combination of high-resolution microscopy and spectroscopy, we show that 2D MMW-type layers with an average thickness of 3.5 nm (ca. 1.5 unit cells) can be generated using the surfactant cetyltrimethylammonium (CTA), which operates as a dual OSDA and exfoliating agent to affect Al siting and to eliminate the need for postsynthesis exfoliation, respectively. We tested these 2D catalysts using a model reaction that assesses external (surface) Brønsted acid sites and observed a marked increase in the conversion relative to three-dimensional MWW (MCM-22) and 2D layers prepared from postsynthesis exfoliation (ITQ-2). Collectively, our findings identify a facile and effective route to directly synthesize 2D MWW-type materials, which may prove to be more broadly applicable to other layered zeolites.


Two-dimensional MgX2Se4 (X = Al, Ga) monolayers with tunable electronic properties for optoelectronic and photocatalytic applications.
Two new two-dimensional (2D) layered materials, namely, MgX2Se4 (X = Al, Ga) monolayers, are predicted to possess novel electronic properties. Ab initio electronic structure calculations show that both MgAl2Se4 and MgGa2Se4 monolayers are direct-gap semiconductors with bandgaps of 3.14 eV and 2.34 eV, respectively. The bandgap of both 2D materials is very sensitive to the in-plane biaxial strain, while the strain induced bandgap changes allow the tuning of optical absorption from the violet to green-light region. Also importantly, the in-plane electron mobility of both 2D materials is predicted to be as high as ∼0.7-1.0 × 103 cm2 V-1 s-1, notably higher than that of the MoS2 sheet (∼200 cm2 V-1 s-1), while it is comparable to that of black phosphorene (∼1000 cm2 V-1 s-1), suggesting their potential application in n-type field-effect transistors. Moreover, suitable bandgap and band-edge alignment make the monolayer MgX2Se4 a potential photocatalyst for water splitting. Lastly, we show that MgX2Se4 possesses a lower monolayer cleavage energy than that of graphite, indicating easy exfoliation of MgX2Se4 layers from their bulk.


[Hepatitis E virus antibodies in the macaques and in the personnel serving the macaques of the Adler apery].
There is evidence for the rather high detection rate of antibodies against hepatic E virus (HEV) was rather high in the macaques from the Adler apery in 1999-2005. Anti-HEV was detected in 232 (57.3%) out of 405 examined rhesus macaques (Macaca mulata) and in 16 (16%) out of 100 Java ones (M. fascicularis). The detection rate of anti-HEV ranged from 12.5 to 89.5%% among the rhesus macaques and from 5.9 to 37.5% among the Java ones. Class M anti-HEV was found only in 3 (4.3%) out of 69 Java macaques and in none of the rhesus ones. Of importance are the data of detection of anti-HEV in 3 (7.5%) out of 40 examined employees of the Research Institute of Medical Primatology, all 3 (18.8%) out of 10 employees looking after the monkeys that belonged to the highest-risk group. The epidemiological and epizootological aspects of this infection require further studies.


Aortic atheroma burden predicts acute cerebrovascular events after transcatheter aortic valve implantation: insights from volumetric multislice computed tomography analysis.
Embolisation of atheromatous debris during catheter manipulation is considered to underlie acute cerebrovascular events (CVE) after transcatheter aortic valve implantation (TAVI). However, the relationship between aorta atheroma burden and acute CVE after TAVI has not been established. We investigated the impact of aorta atheroma burden on acute CVE. Preoperative multislice computed tomographic (MSCT) images in 278 patients receiving TAVI were analysed. Total atheroma volume (TAV) was calculated by measuring aorta vessel and lumen areas in every 1 mm cross-sectional image. Acute CVE was observed in 16 patients. Patients having acute CVE were more likely to have a prior CVE (p=0.002), and to exhibit greater TAV in the ascending aorta (12.8±3.5 vs. 7.0±2.1 cm3, p<0.001) and the aortic arch (3.1±1.6 vs. 1.2±0.2 cm3, p<0.001). TAV in the ascending aorta >10.3 cm3 and in the aortic arch >2.9 cm3 predicted acute CVE. The incidence of acute CVE was highest (36.4%) if patients had a prior CVE and TAV in the ascending aorta and the aortic arch above cut-offs. Patients with acute CVE after TAVI had greater aorta atheroma burden. Our findings might underscore preoperative MSCT analysis of aorta atherosclerosis to identify high-risk patients for acute CVE, who might require an embolic protection device during TAVI.


Pharmacokinetic Comparison of Soy Isoflavone Extracts in Human Plasma.
The soy isoflavones daidzein and genistein produce several biological activities related to health benefits. A number of isoflavone extracts are commercially available, but there is little information concerning the specific isoflavone content of these products or differences in their bioavailability and pharmacokinetics. This study describes the development and validation of an analytical method to detect and quantify daidzein, genistein, and equol in human plasma using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The method was applied in a crossover, randomized, bioavailability study. Twelve healthy volunteers were administered the same total isoflavones dose from two isoflavone supplement preparations (Super-Absorbable Soy Isoflavones (Life Extension, USA) and Fitoladius (Merck, Spain)). The pharmacokinetic parameters (AUC0-24/dose and Cmax/dose) of the isoflavones from the two preparations differed significantly. Such differences in bioavailability and kinetics may have relevant effects on the health benefits derived from their intake.


Phase retrieval from images in the presence of first-order vortices.
We discuss retrieval of the phase of quantum-mechanical and classical wave fields in the presence of first-order vortices. A practical method of phase retrieval is demonstrated which is robust in the presence of noise. Conditions for the uniqueness of the retrieved phase are discussed and we show that determination of the phase in a given plane requires a series of at least three two-dimensional intensity images at different propagation distances. The method is applicable to a wide range of scenarios such as the imaging of imperfect crystals, quantitative determination of the strength of vortex filaments in high-temperature superconductors, and x-ray and electron holography.


Self-driven perfusion culture system using a paper-based double-layered scaffold.
Shear stress caused by fluid flow is known to promote tissue development from cells in vivo. Therefore, perfusion cultures have been studied to investigate the mechanisms involved and to fabricate engineered tissues in vitro, particularly those that include blood vessels. Microfluidic devices, which function with fine machinery of chambers and microsyringes for fluid flow and have small culture areas, are conventionally used for perfusion culture. In contrast, we have developed a self-driven perfusion culture system by using a paper-based double-layered scaffold as the fundamental component. Gelatin microfibers were electrospun onto a paper material to prepare the scaffold system, in which the constant perfusion of the medium and the scaffold for cell adhesion/proliferation were functionally divided into a paper and a gelatin microfiber layer, respectively. By applying both the capillary action and siphon phenomenon of the paper-based scaffold, which bridged two medium chambers at different height levels, a self-driven medium flow was achieved and the flow rate was also stable, constant, and quantitatively controllable. Moreover, the culture area was enlargeable to the cm(2) scale. The endothelial cells cultivated on this system oriented along the medium-flow direction, suggesting that the shear stress caused by medium flow was effectively applied. This perfusion culture system is expected to be useful for fabricating three-dimensional and large engineered tissues in the future.


Ceftazidime-avibactam use for the treatment of OXA-48- and/or New Delhi metallo-β-lactamase-producing Enterobacterales in cancer patients: a retrospective observational study.
Infection is the second-leading cause of death among cancer patients, but there have been few studies on the effectiveness of novel antimicrobial agents to treat carbapenem-resistant Enterobacterales in cancer patients. Evaluate the mortality and clinical outcomes of ceftazi-dime-avibactam for OXA-48- and/or New Delhi metallo-β-lactamase (NDM)-producing Enterobacterales infection in cancer patients. Retrospective observational cohort study. Tertiary academic medical center in Riyadh, Saudi Arabia. This study included patients who had cancer and received ceftazidime-avibactam for at least 72 hours for infections caused by OXA-48- and/or NDM-producing Enterobacterales. We excluded patients who died within 72 hours of treatment, patients with polymicrobial infections, and patients who did not receive appropriate antimicrobial therapy. Primary outcomes were 30-day mortality and hospital mortality. Secondary outcomes included clinical cure, relapse, and reinfection. 32 cancer patients. The 30-day mortality among all patients was 15/32 (47%), clinical cure was achieved in 19/32 (59%) of the patients, and the relapse and reinfection rates were 2/19 (10.5%) and 4/17 (23.5%), respectively. This is the largest study to evaluate clinical outcomes associated with infections caused by OXA-48- and/or NDM-producing Enterobacterales in cancer patients. The mortality rate remains high; however, ceftazidime-avibactam is an encouraging alternative for treating severe infections in cancer patients. Small sample size and single center.


Retinal structure and visual acuity in a polyprotodont marsupial, the fat-tailed dunnart (Sminthopsis crassicaudata).
The visual system of the fat-tailed dunnart (Sminthopsis crassicaudata), a small polyprotodont marsupial, has been examined both anatomically and behaviourally. The ganglion cell layer was examined in cresyl-violet stained wholemounts and found to contain a mean of 81,400 ganglion cells (SD +/- 3,360); the identification of ganglion cells was supported by a correspondence to optic axon counts. Ganglion cells were distributed as a mid-temporally situated area centralis, embedded in a pronounced visual streak. Localised implants of horseradish peroxidase into retinal wholemounts revealed both A-type and B-type horizontal cells. Sections of the outer retina showed it to be rod-dominated, with a rod-to-cone ratio of 40:1 at the area centralis; cones were found to contain oil droplets but double cones were not a prominent feature. The retinal pigment epithelium consisted of squamous cells. Visual acuity, estimated from counts of peak ganglion cell density (8,300/mm2, SD +/- 1,180) and measurements of posterior nodal distance (2.9 mm), was found to be 2.30 cycles per degree. The value was close to that of 2.36 cycles per degree estimated by behavioural tests using a Mitchell jumping stand; values were similar at low, intermediate and high light levels. Our findings are discussed in relation to the lifestyle of the dunnart.


The kissing balloons technique. Simultaneous dilatation of stenoses of branch arteries at the bifurcation of the renal artery.
Whereas dilatation of a single stenosis of the main renal artery is a routine intervention, a narrowing of the renal artery at its bifurcation extending into the branch arteries poses a more complex problem. The procedural risks of renal artery dilatation are compounded by the danger of occlusion of one of the branch arteries during maneuvers to dilate the other. Long-term results of surgical vascular reconstruction at a renal artery bifurcation are not satisfactory. Untreated, these stenoses lead to intractable hypertension and impairment or loss of renal function. We present a patient with hypertension and impaired function of the right kidney on account of a renal arterial bifurcation stenosis. Using a bilateral transfemoral arterial approach 2 balloon catheters were simultaneously placed into the origins of the renal artery branches and both arteries were successfully dilated by the kissing balloons technique. This method provides an elegant alternative to difficult surgery to save an endangered kidney.


European consensus table on the use of botulinum toxin type A in adult spasticity.
A group of clinicians from across Europe experienced in the use of botulinum toxin type A for the treatment of spasticity following acquired brain injury gathered to develop a consensus statement on best practice in managing adults with spasticity. This consensus table summarizes the current published data, which was collated following extensive literature searches, their assessment for level of evidence and discussion among the whole group. Published information is supplemented by expert opinion based on clinical experience from 16 European countries, involving 28 clinicians, who treat an average of approximately 200 patients annually, representing many thousand spasticity treatments with botulinum toxin per year.


rac regulates its effector phospholipase Cgamma2 through interaction with a split pleckstrin homology domain.
Several isoforms of phospholipase C (PLC) are regulated through interactions with Ras superfamily GTPases, including Rac proteins. Interestingly, of two closely related PLCgamma isoforms, only PLCgamma(2) has previously been shown to be activated by Rac. Here, we explore the molecular basis of this interaction as well as the structural properties of PLCgamma(2) required for activation. Based on reconstitution experiments with isolated PLCgamma variants and Rac2, we show that an unusual pleckstrin homology (PH) domain, designated as the split PH domain (spPH), is both necessary and sufficient to effect activation of PLCgamma(2) by Rac2. We also demonstrate that Rac2 directly binds to PLCgamma(2) as well as to the isolated spPH of this isoform. Furthermore, through the use of NMR spectroscopy and mutational analysis, we determine the structure of spPH, define the structural features of spPH required for Rac interaction, and identify critical amino acid residues at the interaction interface. We further discuss parallels and differences between PLCgamma(1) and PLCgamma(2) and the implications of our findings for their respective signaling roles.


Host and Water Microbiota Are Differentially Linked to Potential Human Pathogen Accumulation in Oysters.
Oysters play an important role in coastal ecology and are a globally popular seafood source. However, their filter-feeding lifestyle enables coastal pathogens, toxins, and pollutants to accumulate in their tissues, potentially endangering human health. While pathogen concentrations in coastal waters are often linked to environmental conditions and runoff events, these do not always correlate with pathogen concentrations in oysters. Additional factors related to the microbial ecology of pathogenic bacteria and their relationship with oyster hosts likely play a role in accumulation but are poorly understood. In this study, we investigated whether microbial communities in water and oysters were linked to accumulation of Vibrio parahaemolyticus, Vibrio vulnificus, or fecal indicator bacteria. Site-specific environmental conditions significantly influenced microbial communities and potential pathogen concentrations in water. Oyster microbial communities, however, exhibited less variability in microbial community diversity and accumulation of target bacteria overall and were less impacted by environmental differences between sites. Instead, changes in specific microbial taxa in oyster and water samples, particularly in oyster digestive glands, were linked to elevated levels of potential pathogens. For example, increased levels of V. parahaemolyticus were associated with higher relative abundances of cyanobacteria, which could represent an environmental vector for Vibrio spp. transport, and with decreased relative abundance of Mycoplasma and other key members of the oyster digestive gland microbiota. These findings suggest that host and microbial factors, in addition to environmental variables, may influence pathogen accumulation in oysters. IMPORTANCE Bacteria in the marine environment cause thousands of human illnesses annually. Bivalves are a popular seafood source and are important in coastal ecology, but their ability to concentrate pathogens from the water can cause human illness, threatening seafood safety and security. To predict and prevent disease, it is critical to understand what causes pathogenic bacteria to accumulate in bivalves. In this study, we examined how environmental factors and host and water microbial communities were linked to potential human pathogen accumulation in oysters. Oyster microbial communities were more stable than water communities, and both contained the highest concentrations of Vibrio parahaemolyticus at sites with warmer temperatures and lower salinities. High oyster V. parahaemolyticus concentrations corresponded with abundant cyanobacteria, a potential vector for transmission, and a decrease in potentially beneficial oyster microbes. Our study suggests that poorly understood factors, including host and water microbiota, likely play a role in pathogen distribution and pathogen transmission.


Managing the tension between caring and charting: Labor and delivery nurses' experiences of the electronic health record.
Over a decade following the nationwide push to implement electronic health records (EHRs), the focus has shifted to addressing the cognitive burden associated with their use. Most research and discourse about the EHR's impact on clinicians' cognitive work has focused on physicians rather than on nursing-specific issues. Labor and delivery nurses may encounter unique challenges when using EHRs because they also interact with an electronic fetal monitoring system, continuously managing and synthesizing both maternal and fetal data. This grounded theory study explored labor and delivery nurses' perceptions of the EHR's impact on their cognitive work. Data were individual interviews and participant observations with twenty-one nurses from two labor and delivery units in the western U.S. and were analyzed using dimensional analysis. Nurses managed the tension between caring and charting using various strategies to integrate the EHR into their dynamic, high-acuity, specialty practice environment while using EHRs that were not designed for perinatal patients. Use of the EHR and associated technologies disrupted nurses' ability to locate and synthesize information, maintain an overview of the patient's status, and connect with patients and families. Individual-, group-, and environmental-level factors facilitated or constrained nurses' integration of the EHR. These findings represent critical safety failures requiring comprehensive changes to EHR designs and better processes for responding to end-user experiences. More research is needed to develop EHRs that support the dynamic and relationship-based nature of nurses' work and to align with specialty practice environments.


Movement Improves the Quality of Temporal Perception and Decision-Making.
A critical aspect of behavior is that mobile organisms must be able to precisely determine where and when to move. A better understanding of the mechanisms underlying precise movement timing and action planning is therefore crucial to understanding how we interact with the world around us. Recent evidence suggests that our experience of time is directly and intrinsically computed within the motor system, consistent with the theory of embodied cognition. To investigate the role of the motor system, we tested human subjects (n = 40) on a novel task combining reaching and time estimation. In this task, subjects were required to move a robotic manipulandum to one of two physical locations to categorize a concurrently timed suprasecond. Critically, subjects were divided into two groups: one in which movement during the interval was unrestricted and one in which they were restricted from moving until the stimulus interval had elapsed. Our results revealed a higher degree of precision for subjects in the free-moving group. A further experiment (n = 14) verified that these findings were not due to proximity to the target, counting strategies, bias, or movement length. A final experiment (n = 10) replicated these findings using a within-subjects design, performing a time reproduction task, in which movement during encoding of the interval led to more precise performance. Our findings suggest that time estimation may be instantiated within the motor system as an ongoing readout of timing judgment and confidence.


Carbendazim-induced haematological, biochemical and histopathological changes to the liver and kidney of male rats.
Carbendazim is a systemic broad-spectrum fungicide controlling a wide range of pathogens. It is also used as a preservative in paint, textile, papermaking and leather industry, as well as a preservative of fruits. In the present study, carbendazim was administered at 0, 150, 300 and 600 mg/kg per day doses orally to male rats (Rattus rattus) for 15 weeks. At the end of the experiment, blood samples, liver and kidney tissues of each animal were taken. Serum enzyme activities, and haematological and biochemical parameters were analysed. In toxicological tests, 600 mg/kg per day doses of carbendazim caused an increase of albumin, glucose, creatinine and cholesterol levels. Also, at the same doses, white blood cell and lymphocyte counts decreased. However, mean cell hemoglobin and mean cell hemoglobin concentrations increased. Histopathological examinations revealed congestion, an enlargement of the sinusoids, an increase in the number of Kupffer cells, mononuclear cell infiltration and hydropic degeneration in the liver. At the highest doses, congestion, mononuclear cell infiltration, tubular degeneration and fibrosis were observed in the kidney tissue. These results indicate that 300 and 600 mg/kg per day carbendazim affected the liver and kidney tissue and caused some changes on haematological and biochemical parameters of rats.


Preliminary Experience with Stent-Assisted Coiling of Aneurysms Arising from Small (<2.5 mm) Cerebral Vessels Using The Low-Profile Visualized Intraluminal Support Device.
The Low-Profile Visualized Intraluminal Support (LVIS) stent is a new device recently introduced for the treatment of wide-neck intracranial aneurysms. This single-center study presents the authors' preliminary experience using the LVIS stent to treat saccular aneurysms with parent arteries smaller than 2.5 mm. Aneurysms with a LVIS stent used in a small parent vessel (<2.5 mm in diameter) between October 2014 and April 2016 were included. Procedure-related complications, angiographic results, clinical outcomes, and midterm follow-up data were analyzed retrospectively. A total of 22 patients was studied, including 5 ruptured and 17 unruptured aneurysms. Most of the aneurysms were located in the anterior circulation (90.9%). Stent placement in the parent arteries measuring 1.7-2.4 mm in diameter (mean, 2.1 mm) was successful in 100% of cases. Procedure-related complication developed in 1 patient (4.5%) who presented with aneurysm rupture. No permanent morbidity and mortality occurred. Immediate angiographic outcome showed complete occlusion in 8 aneurysms (36.4%), neck residual in 8 (36.4%), and residual aneurysm in 6 (27.3%). All patients underwent angiographic follow-up at a mean of 8.3 months, which revealed complete occlusion in 18 (81.8%) patients, neck remnant in 3 (13.6%), and residual sac in 1 (4.5%). No recanalization of the target aneurysm was observed. There was 1 case with asymptomatic in-stent stenosis. Our preliminary results show that the deployment of LVIS stents in small vessels is feasible, safe, and effective in the midterm. Larger studies with long-term follow-up are needed to validate our promising results.


[Cytologic diagnosis of rectal melanoma].
The cytologic characteristics of malignant melanoma of the rectum are discussed in the paper. The study was based on the data of examination of 13 cases (pigment-free tumor--6 cases). The basic cytologic features of malignant melanoma were diverse cellularity, presence of binuclear cells, and granules or diffuse inclusion of melanin. Three histologic patterns of tumor were identified: epithelioid, spindle-cell and polymorphous cell. Two cases of pigment-free malignant melanoma of the anorectal area were misdiagnosed as squamous cell carcinoma which was due to reactive changes developing in the cells of the stratified squamous epithelium.


Greater response to cardiac resynchronization therapy in patients with true complete left bundle branch block: a PREDICT substudy.
Cardiac resynchronization therapy (CRT) benefits patients with heart failure and a wide QRS complex. Still, one-third derive no clinical benefit and a majority of patients demonstrate no objective improvement of left ventricular (LV) function. Left bundle branch block (LBBB) is a strong predictor of response to CRT. We evaluated whether absence of electrocardiogram (ECG) markers of residual left bundle (LB) conduction in guideline-defined LBBB predicted a greater response to CRT. An r wave ≥1 mm in lead V1 (r-V1) and/or a q wave ≥1 mm in lead aVL (q-aVL) was used to identify patients with residual LB conduction. Forty patients with a wide QRS were prospectively enrolled and subdivided into three groups: complete LBBB (cLBBB), LBBB without r-V1 or q-aVL (n = 12); LBBB with residual LB conduction (rLBBB), LBBB with r-V1 and/or q-aVL (n = 15); and non-specific intraventricular conduction delay (IVCD), (n = 13). Following CRT: mean change in left ventricular ejection fraction was 11.9 ± 11.9% in cLBBB, 3.8 ± 5.4% in rLBBB (P= 0.045), and 2.5 ± 4.4% in IVCD (P= 0.02 cLBBB vs. IVCD); mean reduction in left ventricular end-systolic volume was 26.4 ± 39.2% in cLBBB, 14.3 ± 22.9% in rLBBB (P= 0.35), and 5.6 ± 17.3% in IVCD (P= 0.11 cLBBB vs. IVCD); mean change in native QRS duration was -8.0 ± 11.0 ms in cLBBB, -0.8 ± 8.24 ms in rLBBB (P= 0.07), and 0.15 ± 8.0 ms in IVCD (P= 0.048 cLBBB vs. IVCD). In patients with guideline-defined LBBB, the absence of ECG markers of residual LB conduction was predictive of a greater improvement in LV function with CRT.


[Importance of early diagnosis of phenylketonuria in women and control of phenylalanine levels during pregnancy].
The phenylalanine hydroxylase (PAH) in the liver hydroxylates phenylalanine from the diet. Fetuses depend for the hydroxylation of phenylalanine the maternal metabolism , fetal maturity does not come until week 26. Though the women with PAH deficiency (phenylketonuria, PKU) not adequately hydroxylate phenylalanine diet so their blood levels are high. Fenilalaninemia levels are considered neurotoxic teratogenic and above 360 umol/L (N < 120). Pregnant women should strictly follow PKU dietary treatment and/or drug to maintain levels of fenilalaninemia < 180 umol/L and avoid the teratogenic complications in the fetus (Hyperphenylalaninaemias Maternal Fetal Syndrome), as the case presented. We recommend discarding Phenylketonuria in women who have not been done a neonatal screening and/or have abortions, children with microcephaly, cardiac or renal malformations.


Virus neutralizing and enhancing epitopes characterized by synthetic oligopeptides derived from the feline leukaemia virus glycoprotein sequence.
Synthetic peptides that mimic antigenic determinants of viral proteins were used in vaccine studies of feline leukaemia virus (FeLV) infection. Immunoreactive epitopes on FeLV gp70 and p15E were predicted according to the criteria of their terminal position, hydrophilicity and the probability of them constituting helical structures. Nineteen peptides, consisting of seven to 19 amino acid residues, were synthesized, of which two peptides were derived from the FeLV subtype A, 16 from subtype B and one from subtype C. Rabbits were immunized with individual peptides coupled to keyhole limpet haemocyanin and the specificity and biological activities of these hyperimmune sera were determined by ELISA, Western blotting, virus neutralization and cytotoxicity assays. All sera reacted specifically with the immunizing peptide. Twelve of the 19 peptides induced antibodies against purified gp85 and antibodies to 11 peptides reacted with the whole virus. One peptide representing the carboxy terminus of the transmembrane protein p15E, and two peptides derived from the external glycoprotein gp70 elicited neutralizing antibodies, whereas antisera against four peptides enhanced virus infection in vitro. None of the peptide antisera mediated complement lysis of FeLV-infected cells.


Longitudinal analysis of metalloproteinases, tissue inhibitors of metalloproteinases and clinical parameters in gingival crevicular fluid from periodontitis-affected patients.
The aim of this work was to improve the assessment of the periodontal disease status through measurements of extracellular matrix metalloproteinases (MMPs) and their tissular inhibitors (TIMPs) in the gingival crevicular fluid from patients diagnosed with chronic periodontitis. Gingival crevicular fluid samples from patients (n = 13) were taken from 60 sites initially, and from 51 and 41 sites, respectively, 3 and 6 months after scaling and root planing. Gingival crevicular fluid samples were also taken from healthy subjects (n = 11, 24 sites). The presence of MMP-9 and MMP-8 was assessed by zymography and immunowestern blotting, respectively. The actual MMP activity (gelatinase and collagenase) was measured using the fluorogenic substrate assay. TIMP-1 and -2 levels were measured by immunodot blot. The fluorogenic substrate assay determinations showed higher MMP activity in sites with probing depth > or = 4 mm, with significant reduction post-treatment. Gelatinase activity followed by zymography consisted mainly of MMP-9. A different pattern of MMP-8 in control and patient sites was found. Controls only showed species of a partially active form (69 kDa), whereas patient sites showed a high frequency of the active form (56 kDa), and in some cases the latent form (85 kDa) was also observed. The active form reduced its frequency in sites with probing depth > or = 4 mm. TIMP-1 and -2 levels in patients were significantly lower than in controls, and after treatment the recovery of TIMP-1 level similar to control was observed. Significant correlations between the severity of the periodontal disease and the actual MMP activity, the active form of MMP-8 and the low level of both TIMP-1 and TIMP-2 were found.


Gaps in Medical Students' Competencies to Deal With Intimate Partner Violence in Key Mozambican Medical Schools.
Purpose: The researchers aimed to identify the gaps in competencies designed to help medical students to deal with Intimate Partner Violence (IPV) in key Mozambican medical schools curricula. Method: A survey was administered to 3rd and 6th-year medical students (N387), enrolled in five medical schools in Mozambique. The instrument focused on mapping students' perceived mastery of their knowledge, skills, and attitudes related to IPV. Results: In total, 387 medical students (RR 66%) participated in the survey. The overall mean perceived mastery of IPV competence was 36.18 (SD = 24.52) for knowledge, 32.01 (SD = 27.37) for skills, and 43.47 (SD = 27.58) for attitudes. Though 6th-year students reported a significantly higher mastery level, it is still below a mastery-learning benchmark of 80%. Conclusions: Medical students report critically low levels in their mastery of IPV- related competencies. This implies a need for a more comprehensive approach to developing knowledge, skills, and attitudes to deal with the victims of IPV.


The effects of acute hyperglycaemia on the in-hospital and long-term prognosis in patients with an acute coronary syndrome--a pilot study.
Acute hyperglycaemia is an adverse prognostic factor in patients with acute coronary syndrome (ACS). It is unclear whether these negative effects apply equally to patients with diabetes mellitus (DM) and non-DM patients. To evaluate the short-term (in-hospital) and long-term (four-year) prognostic value of acute hyperglycaemia in ACS patients with or without DM. The study involved 116 ACS patients admitted between 2004 and 2006 to our department, who were selected for invasive treatment and who had both admission and first fasting glucose levels measured. Patients were classified as DM (n = 23), on the basis of a known history of diabetes or newly detected diabetes, or non-DM (n = 93). Acute hyperglycaemia was defined as an admission glycaemia ≥ 10.0 mmol/L (180 mg/dL) for non-DM patients, or ≥ 7.8 mmol/L (140 mg/dL) for DM patients, or a first fasting glucose level ≥ 5.6 mmol/L (100 mg/dL) for both DM and non-DM patients. The primary end-point was defined as mortality during follow-up. The secondary end-points were death, cardiac arrest or repeated ACS occurrence, stroke or transient ischaemic attack, and the need for repeat percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) procedure during the in-hospital and four-year post-hospital periods. During follow-up, patients were assessed for a composite end-point defined as all-cause death, repeated ACS occurrence, repeat PCI or CABG procedure, and stroke. Acute hyperglycaemia was present in 28 non-DM and 14 DM patients. The mean follow-up time was 4 ± 0.6 years. For DM patients, there was no significant difference in four-year mortality between hyperglycaemic and normoglycaemic patients (14.3% vs 11.1%, respectively; NS). The occurrence of secondary end-points and composite end-point frequency was also similar for these subgroups, both for in-hospital and four-year observations. For non-DM patients, the four-year mortality was similar for hyperglycaemic and normoglycaemic subjects (17.9% vs 10.8%, respectively; NS), whereas cardiac arrest during the in-hospital period was more common for hyperglycaemic than normoglycaemic patients (3.6% vs 0.0%, respectively; n = 1 vs 0; p = 0.01). The composite end-point for the in-hospital period was reached by 17.6% of hyperglycaemic and 13.8% of normoglycaemic non-DM patients (NS). The composite end-point during the four-year observation period was more frequently reached in hyperglycaemic than in normoglycaemic non-DM patients (78.6% vs 56.9%, respectively; p = 0.04). Acute hyperglycaemia in non-DM patients hospitalised due to ACS was found to be an unfavourable long-term (four-year) risk factor, and may also be an unfavourable in-hospital risk factor. In contrast, acute hyperglycaemia did not affect cardiovascular outcomes in DM patients.


Evaluation of clinical frailty screening in geriatric acute care.
While frailty status is an attractive risk stratification tool, the evaluation of frailty in acute care can be challenging as some inpatients are unable to complete performance-based tests as part of frailty assessment and some tools may lack discriminative ability and categorize majority of cohorts as "frail". In this study, we evaluated the feasibility of frailty screening with the simple clinical frailty scale (CFS) by different clinicians, and its association with mortality and rehospitalization in a geriatric acute care setting. This study took place in Geriatric Medicine Department of a General Hospital in Singapore. We analysed records of 314 inpatients aged 70 years and older. At baseline, premorbid frailty was assessed using the CFS of the Canadian Study on Health and Aging. Demographic characteristics and other variables were retrieved from their medical records. Primary outcomes were mortality and rehospitalization during the 6-month follow-up. Survival analysis was used to compare the time to death and rehospitalization among CFS categories (1-4: nonfrail, 5-6: mild-moderate frail, and 7-8: severe frail). CFS showed a high inter-rater reliability when used by different clinicians. In the Cox proportional hazard model controlling for age, gender, Charlson comorbidity index, modified severity of illness index, and discharge placements, severe frailty determined by CFS (HR = 2.09, 95% CI = 1.01-4.33, P = 0.047) and CFS scores (HR = 1.27, 95% CI = 1.05-1.53, P = 0.012) were significantly associated with higher mortality until 6-month postdischarge, but not rehospitalization. Frailty status determined by CFS adds to disease severity and comorbidity in predicting short-term mortality but not rehospitalization in older inpatients who received geriatric acute care in our setting. CFS is reliable and has the potential to be incorporated into routine screening to better identify, communicate, and address frailty in the acute settings.


Forebrain astroglial plasticity is induced following withdrawal from repeated cocaine administration.
Astrocytes actively participate in synaptic plasticity and respond to insult or metabotropic glutamate receptor activation with increased expression of the intermediate filament glial fibrillary acidic protein (GFAP). Extended withdrawal from repeated cocaine administration induces many forms of neuroplasticity. The present study with rats utilized a 3-week withdrawal period from daily cocaine administration (i.p.; 7 days) to investigate whether astrocytes participate in cocaine-mediated plasticity observed in brain nuclei associated with addiction. Following the 3-week withdrawal period, immunoblotting revealed increased GFAP expression in the prefrontal cortex (PFC) and in the shell and core compartments of the nucleus accumbens (NAshell and NAcore). Upregulation of GFAP did not occur in the striatum or in any brain region tested following shorter withdrawal times from repeated cocaine (24 h or 1 week) or following 2-h withdrawal from an acute cocaine injection (30 mg/kg i.p.). However, GFAP expression increased following a 3-week withdrawal from a single cocaine injection selectively in the NAshell. Cell counts revealed that astrocyte cell number increased only in the NAcore while immunoblots of a marker for immature or reactive astrocytes, vimentin, showed an increase only in the PFC following the 3-week withdrawal. Taken together, these results suggest that altered intermediate filament expression within forebrain astrocytes may be a significant part of the plasticity occurring during withdrawal from repeated cocaine. Furthermore, the increase in GFAP may arise from regionally distinct mechanisms, with the NAcore relying more on cell proliferation while the PFC relies on a larger reactive astrocyte population.


Stability of protein-decorated mixed lipid membranes: The interplay of lipid-lipid, lipid-protein, and protein-protein interactions.
Membrane-associated proteins are likely to contribute to the regulation of the phase behavior of mixed lipid membranes. To gain insight into the underlying mechanism, we study a thermodynamic model for the stability of a protein-decorated binary lipid layer. Here, proteins interact preferentially with one lipid species and thus locally sequester that species. We aim to specify conditions that lead to an additional macroscopic phase separation of the protein-decorated lipid membrane. Our model is based on a standard mean-field lattice-gas description for both the lipid mixture and the adsorbed protein layer. Besides accounting for the lipid-protein binding strength, we also include attractive lipid-lipid and protein-protein interactions. Our analysis characterizes the decrease in the membrane's critical interaction parameter as a function of the lipid-protein binding strength. For small and large binding strengths we provide analytical expressions; numerical results cover the intermediate range. Our results reiterate the crucial importance of the line tension associated with protein-induced compositional gradients and the presence of attractive lipid-lipid interactions within the membrane. Direct protein-protein attraction effectively increases the line tension and thus tends to further destabilize the membrane.


A lipopolysaccharide adsorber in adult cardiopulmonary bypass: a single centre randomised controlled pilot trial.
The aim of this study was to describe the biochemical effects and safety of selective removal of endotoxin from whole blood using a lipopolysaccharide adsorber during complex cardiac surgery. We carried out a single centre prospective randomised controlled pilot trial in patients undergoing elective cardiac surgery using cardiopulmonary bypass (CPB) at a large UK cardiothoracic institution. Seventeen patients were randomly allocated to one of two groups: with or without an adsorber included in the CPB circuit. Fourteen patients were included in a complete case analysis. Blood samples were taken at the time of consent, immediately following anaesthesia, at 60, 180 and 360 min after the institution of CPB, and the morning following surgery. Primary outcomes were plasma levels of endotoxin, IL-6, IL-8 and TNF-alpha. Secondary outcomes were measures of patient safety including blood chemistry and coagulation parameters, length of stay, and adverse events. No differences were seen in endotoxin or cytokine levels between adsorber and control groups at any of the measured time-points. No difference between groups was detected in measures of patient safety following the intervention. Haemoglobin and haematocrit were significantly lower in the intervention group pre-bypass, P=0.02 in both instances. There was no effect of the adsorber on endotoxin levels or inflammatory response in this study, we have demonstrated the device to be safe in a complex cardiac surgery setting.


How individual Montagu's Harriers cope with Moreau's Paradox during the Sahelian winter.
Hundreds of millions of Afro-Palaearctic migrants winter in the Sahel, a semi-arid belt south of the Sahara desert, where they experience deteriorating ecological conditions during their overwintering stay and have to prepare for spring migration when conditions are worst. This well-known phenomenon was first described by R.E. Moreau and is known ever since as Moreau's Paradox. However, empirical evidence of the deteriorating seasonal ecological conditions is limited and little is known on how birds respond. Montagu's Harriers Circus pygargus spend 6 months of the year in their wintering areas in the Sahel. Within the wintering season, birds move gradually to the south, visiting several distinct sites to which they are site-faithful in consecutive years. At the last wintering site, birds find themselves at the southern edge of the Sahelian zone and have no other options than facing deteriorating conditions. We tracked 36 Montagu's Harriers with GPS trackers to study their habitat use and behaviour during winter and collected data on the abundance of their main prey, grasshoppers, in Senegal. Since grasshopper abundance was positively related to vegetation greenness (measured as normalized difference vegetation index, NDVI), we used NDVI values as a proxy for prey abundance in areas where no field data were collected. Prey abundance (grasshopper counts and vegetation greenness) at wintering sites of Montagu's Harriers decreased during the wintering period. Montagu's Harriers responded to decreasing food availability by increasing their flight time during the second half of the winter. Individuals increased flight time more in areas with stronger declines in NDVI values, suggesting that lower food abundance required more intense foraging to achieve energy requirements. The apparent consequence was that Montagu's Harriers departed later in spring when their final wintering site had lower NDVI values and presumably lower food abundance and consequently arrived later at their breeding site. Our results confirmed the suggestions Moreau made 40 years ago: the late wintering period might be a bottleneck during the annual cycle with possible carry-over effects to the breeding season. Ongoing climate change with less rainfall in the Sahel region paired with increased human pressure on natural and agricultural habitats resulting in degradation and desertification is likely to make this period more demanding, which may negatively impact populations of migratory birds using the Sahel.


Smoking and bladder symptoms in women.
To estimate the relation of smoking status and smoking intensity with bladder symptoms. Questionnaires were mailed to 3,000 women (aged 18-79 years) randomly identified from the Finnish Population Register. Case definitions for stress urinary incontinence (SUI), urgency, and urgency urinary incontinence (UUI) were "often" or "always" based on reported occurrence (never, rarely, often, always). Case definitions for urinary frequency were based on reporting of longest voiding interval as less than 2 hours and for nocturia reporting of at least two voids per night. Potential confounders included comorbidities, medications, sociodemographic, lifestyle, and reproductive factors. Responses totaled 2,002 (67.0%). Frequency was reported by 7.1%, nocturia 12.6%, SUI 11.2%, urgency 9.7%, and UUI 3.1%. In the multivariable analyses, smoking was associated with urgency (odds ratio [OR] 2.7, 95% confidence interval [CI] 1.7-4.2 for current and OR 1.8, CI 1.2-2.9 for former compared with never smokers) and frequency (OR 3.0, CI 1.8-5.0 for current and OR 1.7, CI 1.0-3.1 for former smokers) but not with nocturia and SUI. Adjusted prevalence differences between never and current smokers were 6.0% (3.0-9.1%) for urgency and 6.0% (3.3-8.7%) for frequency. Similarly, current heavy (compared with light) smoking was associated with additional risk of urgency (OR 2.1, CI 1.1-3.9) and frequency (OR 2.2, CI 1.2-4.3). Urgency and frequency are approximately three times more common among current than never smokers. Parallel associations for urgency and frequency with smoking intensity suggest a dose-response relationship. Nocturia and SUI are not associated with smoking. These results suggest an additional rationale for smoking cessation in women seeking medical attention for bladder symptoms and highlight the diversity between such symptoms. II.


PKC and ERK mediate GH-stimulated lipolysis.
GH regulates several physiological processes in vertebrates, including the promotion of growth, an anabolic process, and the mobilization of stored lipids, a catabolic process. In this study, we used hepatocytes isolated from rainbow trout (Oncorhynchus mykiss) as a model to examine the mechanism of GH action on lipolysis. GH stimulated lipolysis as measured by increased glycerol release in both a time- and a concentration-related manner. The promotion of lipolysis was accompanied by GH-stimulated phosphorylation of the lipolytic enzyme hormone-sensitive lipase (HSL). GH-stimulated lipolysis was also manifested by an increased expression of the two HSL-encoding mRNAs, HSL1 and HSL2. The signaling pathways that underlie GH-stimulated lipolysis were also studied. GH resulted in the activation of phospholipase C (PLC)/protein kinase C (PKC) and the MEK/ERK pathway, whereas JAK-STAT and the PI3K-Akt pathway were deactivated. The blockade of PLC/PKC and the MEK/ERK pathway inhibited GH-stimulated lipolysis and GH-stimulated phosphorylation of HSL as well as GH-stimulated HSL mRNA expression, whereas the blockade of JAK-STAT or the PI3K-Akt pathway had no effect on the activation of lipolysis or the expression of HSL stimulated by GH. These results indicate that GH promotes lipolysis by activating HSL and by enhancing the de novo expression of HSL mRNAs via the activation of PKC and ERK. These findings also suggest molecular mechanisms for activating the lipid catabolic actions of GH while simultaneously deactivating anabolic processes such as antilipolysis and the growth-promoting actions of GH.


Measuring health care performance now, not tomorrow: essential steps to support effective health reform.
Better data on the quality of health care being delivered in the United States are urgently needed if efforts to reform the nation's health care system are to succeed. This paper describes a "distributed data approach" to computing performance results while protecting patients' privacy. The strategy builds on the efforts of the Quality Alliance Steering Committee, a multistakeholder coalition focused on the implementation of performance measures. Instead of waiting for the government or the private sector to build large data warehouses, existing data from administrative sources, laboratories, clinical registries, and electronic health records could be put to greater use now, resulting in improved patient care and spurring further advances in performance measurement. In this article we introduce an overall framework for achieving these goals, and we describe a set of steps to accelerate and expand the availability of performance measures to improve care now.


Candida albicans exhibits heterogeneous and adaptive cytoprotective responses to antifungal compounds.
Candida albicans, an opportunistic human pathogen, poses a significant threat to human health and is associated with significant socio-economic burden. Current antifungal treatments fail, at least in part, because C. albicans can initiate a strong drug tolerance response that allows some cells to grow at drug concentrations above their minimal inhibitory concentration. To better characterize this cytoprotective tolerance program at the molecular single-cell level, we used a nanoliter droplet-based transcriptomics platform to profile thousands of individual fungal cells and establish their subpopulation characteristics in the absence and presence of antifungal drugs. Profiles of untreated cells exhibit heterogeneous expression that correlates with cell cycle stage with distinct metabolic and stress responses. At 2 days post-fluconazole exposure (a time when tolerance is measurable), surviving cells bifurcate into two major subpopulations: one characterized by the upregulation of genes encoding ribosomal proteins, rRNA processing machinery, and mitochondrial cellular respiration capacity, termed the Ribo-dominant (Rd) state; and the other enriched for genes encoding stress responses and related processes, termed the Stress-dominant (Sd) state. This bifurcation persists at 3 and 6 days post-treatment. We provide evidence that the ribosome assembly stress response (RASTR) is activated in these subpopulations and may facilitate cell survival.


Perioperative interventions for prevention of postoperative pulmonary complications: systematic review and meta-analysis.
To identify, appraise, and synthesise the best available evidence on the efficacy of perioperative interventions to reduce postoperative pulmonary complications (PPCs) in adult patients undergoing non-cardiac surgery. Systematic review and meta-analysis of randomised controlled trials. Medline, Embase, CINHAL, and CENTRAL from January 1990 to December 2017. Randomised controlled trials investigating short term, protocolised medical interventions conducted before, during, or after non-cardiac surgery were included. Trials with clinical diagnostic criteria for PPC outcomes were included. Studies of surgical technique or physiological or biochemical outcomes were excluded. Reviewers independently identified studies, extracted data, and assessed the quality of evidence. Meta-analyses were conducted to calculate risk ratios with 95% confidence intervals. Quality of evidence was summarised in accordance with GRADE methods. The primary outcome was the incidence of PPCs. Secondary outcomes were respiratory infection, atelectasis, length of hospital stay, and mortality. Trial sequential analysis was used to investigate the reliability and conclusiveness of available evidence. Adverse effects of interventions were not measured or compared. 117 trials enrolled 21 940 participants, investigating 11 categories of intervention. 95 randomised controlled trials enrolling 18 062 participants were included in meta-analysis; 22 trials were excluded from meta-analysis because the interventions were not sufficiently similar to be pooled. No high quality evidence was found for interventions to reduce the primary outcome (incidence of PPCs). Seven interventions had low or moderate quality evidence with confidence intervals indicating a probable reduction in PPCs: enhanced recovery pathways (risk ratio 0.35, 95% confidence interval 0.21 to 0.58), prophylactic mucolytics (0.40, 0.23 to 0.67), postoperative continuous positive airway pressure ventilation (0.49, 0.24 to 0.99), lung protective intraoperative ventilation (0.52, 0.30 to 0.88), prophylactic respiratory physiotherapy (0.55, 0.32 to 0.93), epidural analgesia (0.77, 0.65 to 0.92), and goal directed haemodynamic therapy (0.87, 0.77 to 0.98). Moderate quality evidence showed no benefit for incentive spirometry in preventing PPCs. Trial sequential analysis adjustment confidently supported a relative risk reduction of 25% in PPCs for prophylactic respiratory physiotherapy, epidural analgesia, enhanced recovery pathways, and goal directed haemodynamic therapies. Insufficient data were available to support or refute equivalent relative risk reductions for other interventions. Predominantly low quality evidence favours multiple perioperative PPC reduction strategies. Clinicians may choose to reassess their perioperative care pathways, but the results indicate that new trials with a low risk of bias are needed to obtain conclusive evidence of efficacy for many of these interventions. Prospero CRD42016035662.


Parametric analysis of thermal preference following sleep deprivation in the rat.
A thermal preference task was used to assess the effects of sleep deprivation on nociceptive behavior using hot and cool stimuli. The thermal preference apparatus allowed male rats to move freely from a hot thermal plate (44.7°C) to an adjacent plate at neutral (33.5°C) or cold temperatures (1.3-11°C). Investigators recorded occupancy on the colder side, frequency of movements between the 2 compartments, and first escape latency from the cold side. Parametric analysis of thermal preference indicated that behavioral allocation was related to temperature ranges previously associated with activation of thermal nociceptors. A 50% occupancy rate was determined from a stimulus-response function identifying 1.3°C vs. 44.7°C as optimal temperatures. This temperature combination was then used to test the effects of sleep deprivation for 48h using the pedestal-over-water method on response allocation to the 2 temperature zones. Sleep deprivation decreased time spent on the cooled plate. Cumulative occupancy indicated differential effects for sleep deprivation with the rats preferring to remain on the hot side vs. the cold side, suggesting that sleep deprivation increased the nociceptive properties of the cold stimulus.


Synchronization of a Removable Optical Element with an Eye Tracker: Test Case for Heterophoria Measurement.
Heterophoria describes the deviation of the optical axes in the absence of binocular fusion. Eye trackers (ET) can provide an objective assessment but are not broadly used clinically. We examined the feasibility of combining an infrared (IR) pass-filter, IR detector, and an off-the-shelf ET. The proposed setup was validated against the broadly used cover test (CT). Furthermore, the setup was used to examine whether testing conditions can affect the measurements. An IR detector was attached to a handheld IR-pass filter that blocks visible light to provide occlusion while passing IR light for eye tracking. The detector senses the IR illumination of the eye tracker, creating a recordable signal of the occluder position synchronized with eye positions acquired by the SMI Red250 tracker. The mean of three measurements of each condition, three versus ten seconds occlusion, the occluded eye, and ET versus CT results were compared using the Wilcoxon test, correlation and Bland and Altman plots. Differences between measurements that were within 2Δ were considered clinically insignificant. Thirty normally-sighted subjects (mean age 24.50 ± 2.20, range 20-28) with heterophoria ranging between 14Δ exophoria and 4Δ esophoria were recruited. There was no significant difference between the occluded eyes. However, there was a difference between 3 and 10 seconds' cover duration. The CT data were more similar to the 10 seconds cover duration, although differences were less than the clinical resolution of 2Δ. An inexpensive off-the-shelf ET can be used to measure heterophoria with controlled testing parameters. Our study demonstrated a robust technique for synchronization of an optical element such as an IR cover, with an off-the-shelf commercial eye tracker. The synchronization of optical elements with eye tracking, which has been described here for heterophoria, can be adapted for other clinical measurements.


Insulin-induced ectodomain shedding of heparin-binding epidermal growth factor-like growth factor in adipocytes in vitro.
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is synthesized as a type I transmembrane protein, which is proteolytically cleaved to release a soluble form via members of the a disintegrin and metalloproteinase (ADAM) family of proteolytic enzymes. This study was designed to elucidate the molecular mechanism underlying insulin-induced HB-EGF shedding in adipocytes in vitro. The 3T3-L1 adipocytes with stable expression of alkaline phosphatase (AP)-tagged proHB-EGF (3T3-L1/HB-EGF-AP adipocytes) were developed and AP activities of conditioned media were determined. Using 3T3-L1/HB-EGF-AP adipocytes, we demonstrated that insulin induces HB-EGF shedding in differentiated 3T3-L1 adipocytes in a dose- and time-dependent manner. There is no significant increase in insulin-induced HB-EGF shedding in undifferentiated 3T3-L1 preadipocytes. Studies with metalloprotease inhibitors suggested that insulin-induced HB-EGF shedding in adipocytes is mediated at least in part via ADAM17. Treatment with recombinant HB-EGF results in a dose- and time-dependent increase in HB-EGF shedding in adipocytes, which is significantly suppressed by pharmacologic blockade of ADAM17 (P < 0.01). Moreover, insulin-induced HB-EGF shedding in adipocytes is significantly inhibited by AG1478, an EGF receptor antagonist (P < 0.01). This study provides in vitro evidence that insulin induces HB-EGF shedding in 3T3-L1 adipocytes. Our data also suggest the role of ADAM17 in insulin-induced HB-EGF shedding in adipocytes.


On the evolution of altruism by kin selection.
A general model for the evolution of altruism is formulated. Central to the model is a pair of local fitness functions, which prescribe the fitness of the altruist and selfish phenotypes as functions of the composition of local groups into which prereproductives are subdivided. When the local groups are sibships or other kin groups, the model is one for kin selection. Functions for cost and benefit of altruism are derived from the fitness functions. Conditions for evolution of altruism are then determined in terms of cost and benefit. It is shown that the Hamilton rule has quantitative validity only in the special case of linear fitness functions. Sufficient conditions are found for qualitative validity of the Hamilton rule. Qualitative violation of the rule is also possible.


Pairing state with a time-reversal symmetry breaking in FeAs-based superconductors.
We investigate the competition between the extended s+/--wave and dx2-y2-wave pairing order parameters in the iron-based superconductors. Because of the frustrating pairing interactions among the electron and the hole Fermi pockets, a time-reversal symmetry breaking s+id pairing state could be favored. We analyze this pairing state within the Ginzburg-Landau theory and explore the experimental consequences. In such a state, spatial inhomogeneity induces a supercurrent near a nonmagnetic impurity and the corners of a square sample. The resonance mode between the s+/-- and dx2-y2-wave order parameters can be detected through the B1g Raman spectroscopy.


Resting energy expenditure; assessment methods and applications.
The energetic expense daily total of an individual (EEDT) represents the energy that the organism consumes. It is constituted by the sum of: metabolic basal rate (MBR), termogenesis endogenous (TE) and energetic expense linked to the physical activity (EEPA). The determination of the EEDT considering the physical activity and the state of health of a person, it is very important to fit the calculation of the nutritional need for every individual. The MBR is the minimal quantity of energy that an organism needs to be alive. It constitutes a from 60 to 70 % of the EEPA in the majority of the sedentary adults, while, in the physically very active individuals it is of approximately 50 %. It changes depending on the corporal composition, specially on the corporal lean mass. The basal metabolism expressed as MRB, it is different from the metabolic rate in rest (MRR) or Resting energy expenditure (REE); the latter is obtained when the determination is done in rest and in the conditions described for the MRB but not in fasting, including therefore the energy used for the biological utilization of the food. Habitually, the REE decides by means of different technologies as the indirect calorimetry, the electrical bioimpedancy, the doubly marked water, the predictive equations, between others. These methods are used in the clinical practice and in scientific studies. Nevertheless, due to the inconsistency of the results of these researches, still there is no a consensus with regard to his applicability though the evidence indicates that the measurement of the consumption of oxygen, it is the method of major precision. This review has as aim expose the components of the energetic expense in rest, as well as the technologies for its determination and estimation, indicating its advantages, limitations and practical applications. Part of the technologies of evaluation of the energetic expense described in this review, they remain relegated, for its complexity and cost to the area of the investigation. For a long time the indirect calorimetry, she remained also restricted to this field. Nevertheless, the technological advances have allowed the development of precise light and attainable equipments that allow that at present it should be a very useful method in the clinical space of the determination of the REE.


The effect of excess fluid balance on the mortality rate of surgical patients: a multicenter prospective study.
In some studies including small populations of patients undergoing specific surgery, an intraoperative liberal infusion of fluids was associated with increasing morbidity when compared to restrictive strategies. Therefore, to evaluate the role of excessive fluid infusion in a general population with high-risk surgery is very important. The aim of this study was to evaluate the impact of intraoperative fluid balance on the postoperative organ dysfunction, infection and mortality rate. We conducted a prospective cohort study during one year in four ICUs from three tertiary hospitals, which included patients aged 18 years or more who required postoperative ICU after undergoing major surgery. Patients who underwent palliative surgery and whose fluid balance could change in outcome were excluded. The calculation of fluid balance was based on preoperative fasting, insensible losses from surgeries and urine output minus fluid replacement intraoperatively. The study included 479 patients. Mean age was 61.2 ± 17.0 years and 8.8% of patients died at the hospital during the study. The median duration of surgery was 4.0 (3.2 to 5.5) h and the value of the Simplified Acute Physiology Score (SAPS) 3 score was 41.8 ± 14.5. Comparing survivors and non-survivors, the intraoperative fluid balance from non-survivors was higher (1,950 (1,400 to 3,400) mL vs. 1,400 (1,000 to 1,600) mL, P <0.001). Patients with fluid balance above 2,000 mL intraoperatively had a longer ICU stay (4.0 (3.0 to 8.0) vs. 3.0 (2.0 to 6.0), P <0.001) and higher incidence of infectious (41.9% vs. 25.9%, P = 0.001), neurological (46.2% vs. 13.2%, P <0.001), cardiovascular (63.2% vs. 39.6%, P <0.001) and respiratory complications (34.3% vs. 11.6%, P <0.001). In multivariate analysis, the fluid balance was an independent factor for death (OR per 100 mL = 1.024; P = 0.006; 95% CI 1.007 to 1.041). Patients with excessive intraoperative fluid balance have more ICU complications and higher hospital mortality.


Effects of atmospheric turbulence on photodetector arrays.
In this paper we study quantitatively the effects of atmospheric turbulence on the measurement sensitivity of a quadrant detecting array, along with the measurement variance induced by atmospheric turbulence. Our results show that the stronger the turbulence strength, the lower the measurement sensitivity, and the larger the measurement variance. This agrees with the experimental phenomena we have observed up to now. In addition, the measurement sensitivity in the X direction could be affected by the deviation of light spots in the Y direction due to the existence of gaps between the quadrant elements. Such effects still exist for the measurement variance even when there are no gaps at all. This effect is analyzed quantitatively.


Prosecutorial Discretion for Self-Managed Abortion Helpers.
Elected prosecutors have pledged not to enforce abortion laws, in response to state-level abortion bans. For their pledges to be meaningful, prosecutors must exercise their discretion in cases of individuals who face legal risk, including people who help others self-manage their abortions. With a harm-reduction approach to improving abortion access, prosecutors should aim to reduce abortion helpers' involvement with the criminal justice system.


[Morpho-functional condition of heart in patients with lymphogranulomatosis late after chemoradiotherapy].
The study of clinical and echocardiographic status of the heart in patients with lymphogranulomatosis (LGM) late after chemoradiotherapy. 44 patients with IIA-IV stage of LGM exposed to irradiation of lymph nodes and polychemotherapy according to the schemes ACOP, ABVD, COPP, CHOP, CVPP were examined. Echocardiography was carried out on the unit Sigma-44 and Toshiba. Some changes in the heart by type of myocardiodystrophy or endomyocardial fibrosis were found. The latter are characterized by diminution of the left and (or) right ventricles due to apex obliteration, hardening and thickening of the endocardium and subvalvular structures, diastolic dysfunction and pulmonary hypertension. The main and additional signs are distinguished. The reasons of endomyocardial fibrosis are discussed: severity of the disease, frequent exacerbations and, consequently, higher doses of specific chemoradiotherapy. It is necessary to employ sparing policy in planning radiotherapy after high loading antracycline antibiotics.


Biochemical response of late rickets and osteomalacia to a chupatty-free diet.
Eight Pakistani children with late rickets and two Pakistani women with osteomalacia were given a chupatty-free diet for seven weeks, substituting leavened bread of lower extraction. On this diet serum calcium levels rose to normal or near normal, levels of serum inorganic phosphorus rose slightly but significantly, and serum alkaline phosphatase levels showed a definite rise indicative of healing bone disease. It is concluded that the high phytate content of unleavened bread is the major cause of late rickets and osteomalacia in Pakistani and Indian communities in the United Kingdom. The simplest prophylactic measure seems to be the additional fortification with calcium carbonate of the high extraction flour used in preparing unleavened bread.


How MCM loading and spreading specify eukaryotic DNA replication initiation sites.
DNA replication origins strikingly differ between eukaryotic species and cell types. Origins are localized and can be highly efficient in budding yeast, are randomly located in early fly and frog embryos, which do not transcribe their genomes, and are clustered in broad (10-100 kb) non-transcribed zones, frequently abutting transcribed genes, in mammalian cells. Nonetheless, in all cases, origins are established during the G1-phase of the cell cycle by the loading of double hexamers of the Mcm 2-7 proteins (MCM DHs), the core of the replicative helicase. MCM DH activation in S-phase leads to origin unwinding, polymerase recruitment, and initiation of bidirectional DNA synthesis. Although MCM DHs are initially loaded at sites defined by the binding of the origin recognition complex (ORC), they ultimately bind chromatin in much greater numbers than ORC and only a fraction are activated in any one S-phase. Data suggest that the multiplicity and functional redundancy of MCM DHs provide robustness to the replication process and affect replication time and that MCM DHs can slide along the DNA and spread over large distances around the ORC. Recent studies further show that MCM DHs are displaced along the DNA by collision with transcription complexes but remain functional for initiation after displacement. Therefore, eukaryotic DNA replication relies on intrinsically mobile and flexible origins, a strategy fundamentally different from bacteria but conserved from yeast to human. These properties of MCM DHs likely contribute to the establishment of broad, intergenic replication initiation zones in higher eukaryotes.


"I have the strength to get through this using my past experiences with HIV": findings from a mixed-method survey of health outcomes, service accessibility, and psychosocial wellbeing among people living with HIV during the Covid-19 pandemic.
We examined the impact of Covid-19 restrictions on the wellbeing and access to care among people living with HIV (PLWH) in the UK. A cross-sectional anonymous online survey was circulated to PLWH attending care at three HIV services in Sussex. The questionnaire covered key themes: socio-demographic characteristics; changes in physical and mental health; accessibility of essential health services and information; and socio-economic concerns. Free-text qualitative responses were examined through framework analysis. Quantitative data from 653 respondents were available, with a subset of 385 free-text qualitative responses. In terms of mental health, 501 (77.6%) respondents reported feeling more anxious; 464 (71.8%) reported feeling more depressed than usual; and 128 (19.8%) reported having suicidal thoughts since the start of the pandemic. Respondents worried about running out of HIV medicine (n = 264, 40.7%); accessing HIV services (n = 246, 38.0%) as well as other health services (n = 408, 63.0%). Widespread resilience was also noted: 537 (83.3%) of respondents felt that living with HIV had equipped them with the strength to adapt to the Covid-19 pandemic. Findings highlight important gaps between the multifaceted needs of PLWH. Multisectoral collaborations and investments are needed to adequately support PLWH and to build resilience to future shocks within HIV services.


Multiple Myeloma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.
The treatment of relapsed/refractory multiple myeloma (MM) has evolved to include several new options. These include new combinations with second generation proteasome inhibitors (PI); second generation immunomodulators, monoclonal antibodies, CAR T cells, bispecific antibodies, selinexor, venetoclax, and many others. Most patients with MM undergo several cycles of remissions and relapse, and therefore need multiple lines of combination therapies. Selecting treatment options for relapsed/refractory MM requires consideration of resistance status to specific classes, and patient-specific factors such as age and other comorbidities should be considered. The NCCN Guidelines for MM provide a framework on which to base decisions regarding workup, treatment, and follow-up of newly diagnosed and previously treated MM. This manuscript outlines the recommendations from NCCN Guidelines for MM specific to relapsed/refractory disease.


Phenotypic Environmental Sensitivity and Mental Health During Pregnancy and Post Partum: Protocol for the Experiences of Pregnancy Longitudinal Cohort Study.
Mental health problems during pregnancy and post partum are common and associated with negative short- and long-term impacts on pregnant individuals, obstetric outcomes, and child socioemotional development. Socio-environmental factors are important predictors of perinatal mental health, but the effects of the environment on mental health are heterogeneous. The differential susceptibility theory and the environmental sensitivity framework suggest that individuals differ in their degree of sensitivity to positive and negative environments, which can be captured by individual phenotypes such as temperament and personality. While there is strong evidence for these models in childhood, few studies examined them in adults, and they were not examined in pregnancy. The primary objective of the Experiences of Pregnancy study is to explore whether childhood and current environments are associated with mental health and well-being in pregnancy and whether these effects depend on individual sensitivity phenotypes (personality). This study also aims to gather important psychosocial and health data for potential secondary data analyses and integrative data analyses. We will conduct a longitudinal cohort study. The study was not registered elsewhere, other than this protocol. Participants will be recruited through social media advertisements linking to the study website, followed by an eligibility call on Zoom (Zoom Video Communications). Participants must be aged 18 years or older, currently residing in the United States as citizens or permanent residents, and currently planning to continue the pregnancy. A minimum of 512 participants will be recruited based on power analyses for the main objectives. Since the data will also be a resource for secondary analyses, up to 1000 participants will be recruited based on the available budget. Participants will be in their first trimester of pregnancy, and they will be followed at each trimester and once post partum. Data will be obtained through self-reported questionnaires assessing demographic factors; pregnancy-related factors; delivery, labor, and birth outcomes; early infant feeding; individual personality factors; childhood and current environments; mental health and well-being; attachment; and infant temperament. A series of measures were taken to safeguard the study from web robots and fraudulent participants, as well as to reduce legal and social risks for participants following Dobbs v. Jackson. The study received ethics approval in April 2023 from the University of Oklahoma-Norman Campus Institutional Review Board. Recruitment occurred from May to August 2023, with 3 follow-ups occurring over 10 months. The Experiences of Pregnancy study will extend theories of environmental sensitivity, mainly applied in children to the perinatal period. This will help better understand individual sensitivity factors associated with risk, resilience, plasticity, and receptivity to negative and positive environmental influences during pregnancy for pregnant individuals. PRR1-10.2196/49243.


Can single knockouts accurately single out gene functions?
When analyzing complex biological systems, a major objective is localization of function - assessing how much each element contributes to the execution of specific tasks. To establish causal relationships, knockout and perturbation studies are commonly executed. The vast majority of studies perturb a single element at a time, yet one may hypothesize that in non-trivial biological systems single-perturbations will fail to reveal the functional organization of the system, owing to interactions and redundancies. We address this fundamental gap between theory and practice by quantifying how misleading the picture arising from classical single-perturbation analysis is, compared with the full multiple-perturbations picture. To this end we use a combination of a novel approach for quantitative, rigorous multiple-knockouts analysis based on the Shapley value from game theory, with an established in-silico model of Saccharomyces cerevisiae metabolism. We find that single-perturbations analysis misses at least 33% of the genes that contribute significantly to the growth potential of this organism, though the essential genes it does find are responsible for most of the growth potential. But when assigning gene contributions for individual metabolic functions, the picture arising from single-perturbations is severely lacking and a multiple-perturbations approach turns out to be essential. The multiple-perturbations investigation yields a significantly richer and more biologically plausible functional annotation of the genes comprising the metabolic network of the yeast.


Ruptured cervical intervertebral discs.
Intractable pain in the neck and upper extremity is frequently radicular in character and mechanical in origin. Rupture of a cervical intervertebral disc is the most common cause. Diagnosis and localization are more difficult in the cervical than in the lumbar region. Pantopaque myelogram should be considered only as a mean of localization. Operation should be preceded by a thorough trial of conservative treatment.


[Participation of iron ions in antioxidant action of urea].
The in vitro and in vivo experiments show that urea inhibits the bivalent iron oxidation and as a result inhibits the lipids peroxide oxidation in homogenates of the brain and liver tissues and in suspension of rat erythrocytes.


How Patient Centered Are Addiction Treatment Intake Processes?
The substance use disorder (SUD) treatment field has conducted significant research on creating intake tools and processes that best match patients to the most appropriate treatment setting, but less research has been conducted on how those tools impact the patient experience. The study took advantage of a natural experiment in California to evaluate whether the implementation of American Society of Addiction Medicine (ASAM) assessment criteria and a computer-facilitated intake assessment based on the ASAM criteria affects patient experiences and patient-centeredness during intake relative to patients receiving intake assessments not based on ASAM criteria. We analyzed surveys completed by 851 patients covered by Medi-Cal who were receiving specialty SUD treatment at 33 providers across 10 California counties about their experiences and perceptions of the intake assessment process. To account for differences in patient mix, we used inverse-probability weighting and computed differences in the weighted means for patients across non-ASAM, ASAM, and computerized-ASAM patients. We have found that patients who underwent intake based on ASAM assessment criteria or computerized ASAM assessment experienced a more patient-centered intake. We also found that patients who received ASAM-based assessments were more satisfied with their choice of treatment setting. This evidence is encouraging for the SUD treatment field, especially considering that many Medicaid programs are adopting ASAM or similar patient placement criteria and multidimensional assessments. Future research should consider whether increases in the patient-centeredness of assessments are associated with increased retention in SUD treatment and other positive treatment outcomes.


Federated and distributed learning applications for electronic health records and structured medical data: a scoping review.
Federated learning (FL) has gained popularity in clinical research in recent years to facilitate privacy-preserving collaboration. Structured data, one of the most prevalent forms of clinical data, has experienced significant growth in volume concurrently, notably with the widespread adoption of electronic health records in clinical practice. This review examines FL applications on structured medical data, identifies contemporary limitations, and discusses potential innovations. We searched 5 databases, SCOPUS, MEDLINE, Web of Science, Embase, and CINAHL, to identify articles that applied FL to structured medical data and reported results following the PRISMA guidelines. Each selected publication was evaluated from 3 primary perspectives, including data quality, modeling strategies, and FL frameworks. Out of the 1193 papers screened, 34 met the inclusion criteria, with each article consisting of one or more studies that used FL to handle structured clinical/medical data. Of these, 24 utilized data acquired from electronic health records, with clinical predictions and association studies being the most common clinical research tasks that FL was applied to. Only one article exclusively explored the vertical FL setting, while the remaining 33 explored the horizontal FL setting, with only 14 discussing comparisons between single-site (local) and FL (global) analysis. The existing FL applications on structured medical data lack sufficient evaluations of clinically meaningful benefits, particularly when compared to single-site analyses. Therefore, it is crucial for future FL applications to prioritize clinical motivations and develop designs and methodologies that can effectively support and aid clinical practice and research.


Trehalose dimycolate interferes with FcγR-mediated phagosome maturation through Mincle, SHP-1 and FcγRIIB signalling.
The causative agent of tuberculosis, Mycobacterium tuberculosis (M. tuberculosis), contains an abundant cell wall glycolipid and a crucial virulence factor, trehalose-6,6'-dimycolate (TDM). TDM causes delay of phagosome maturation and thus promotes survival of mycobacteria inside host macrophages by a not fully understood mechanism. TDM signals through the Monocyte-INducible C-type LEctin (Mincle), a recently identified pattern recognition receptor. Here we show that recruitment of Mincle by TDM coupled to immunoglobulin (Ig)G-opsonised beads during Fcγ receptor (FcγR)-mediated phagocytosis interferes with phagosome maturation. In addition, modulation of phagosome maturation by TDM requires SH2-domain-containing inositol polyphosphate 5' phosphatase (SHP-1) and the FcγRIIB, which strongly suggests inhibitory downstream signalling of Mincle during phagosome formation. Overall, our study reveals important mechanisms contributing to the virulence of TDM.


Rhodovulum bhavnagarense sp. nov., a phototrophic alphaproteobacterium isolated from a pink pond.
An oval to rod-shaped, Gram-stain-negative, phototrophic bacterium, strain JA738(T), was isolated from a sediment sample collected from a pink pond. Strain JA738(T) was non-motile and had vesicular-type intracellular photosynthetic membranes. Bacteriochlorophyll a and carotenoids of the spheroidene series were present as the major photosynthetic pigments. Strain JA738(T) required thiamine and pantothenate for growth. The major cellular fatty acids were C(18 : 1)ω7c, C(18 : 1)ω5c, C(18 : 0) and C(18 : 1)ω7c11-methyl; minor amounts of C(10 : 0) 3-OH and C(16 : 0) were also present. The major quinone was Q-10 and major polar lipids were phosphatidylglycerol, phosphatidylethanolamine and two unidentified sulfolipids (SL1-2). Phylogenetic analysis on the basis of 16S rRNA gene sequences showed that strain JA738(T) clustered with species of the genus Rhodovulum in the class Alphaproteobacteria. Strain JA738(T) was most closely related to Rhodovulum adriaticum DSM 2781(T) (96.4 % 16S rRNA gene sequence similarity) and other members of the genus Rhodovulum (<96.1 %). On the basis of phenotypic and molecular genetic evidence, it is proposed that strain JA738(T) should be classified as a novel species of the genus Rhodovulum for which the name Rhodovulum bhavnagarense sp. nov. is proposed. The type strain is JA738(T) ( = DSM 24766(T) = KCTC 15110(T)).


Identification and analysis of type II TGF-β receptors in BMP-9-induced osteogenic differentiation of C3H10T1/2 mesenchymal stem cells.
Our previous studies have demonstrated that bone morphogenetic protein 9 (BMP-9) is one of the most efficacious BMPs to induce osteoblast differentiation of mesenchymal stem cells (MSCs). However, the molecular mechanism underlying the BMP-9-induced osteogenic differentiation of MSCs remains to be fully elucidated. In this study, dominant negative (DN) type II TGF-β receptors were constructed and introduced into C3H10T1/2 stem cells, then in vitro and in vivo assays were carried out to analyze and identify the type II TGF-β receptors required for BMP-9-induced osteogenesis. We found that three DN type II TGF-β receptors, DN-BMPRII, DN-ActRII, and DN-ActRIIB, diminished BMP-9-induced alkaline phosphatase (ALP) activity, led to a decrease in BMP-9-induced Smad binding element (SBE)-controled reporter activity, reduced BMP-9-induced expressions of Smad6 and Smad7, and decreased BMP-9-induced mineralization in vitro and ectopic bone formation in vivo, finally resulted in decreased bone masses and immature osteogenesis. These findings strongly suggested that three wild-type II TGF-β receptors, BMPRII, ActRII and ActRIIB, may play a functional role in BMP-9-induced osteogenic differentiation of C3H10T1/2 cells. However, C3H10T1/2 stem cells can express BMPRII and ActRII, but not ActRIIB. Using RNA interference (RNAi), we found that luciferase reporter activity and ALP activity induced by BMP-9 were accordingly inhibited along with the knockdown of BMPRII and ActRII. Taken together, our results demonstrated that BMPRII and ActRII are the functional type II TGF-β receptors in BMP-9-induced osteogenic differentiation of C3H10T1/2 cells.


Tissue distribution and toxicokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats after intravenous injection.
Male Sprague-Dawley rats (240-290 g) received intravenously a nonlethal (9.25 micrograms/kg) or a lethal (72.7 micrograms/kg) dose of 14C-labeled 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) administered as an emulsion. Animals were euthanized between 5 min and 16 days (lethal dose) or 32 days (nonlethal dose) after treatment. Tissue distribution was considered complete after 24 hr, as by this time radioactivity levels in white adipose tissue had reached a maximum. The highest levels of radioactivity were found in liver (5% of dose/g tissue), followed by white fat (1% of dose/g tissue); serum was lowest at 0.01% of dose/ml serum. Relatively high levels of radioactivity were also detected in most known target organs of TCDD toxicity, e.g., brown fat, adrenals, and thyroid. The pattern of organ distribution of TCDD was essentially the same after the lethal and the nonlethal dose, but did not follow a simple lipophilicity relationship, as levels in liver were higher than those in white fat, and those in brain were extremely low. A pool of TCDD in liposomes initially trapped in lung and spleen was redistributed within 24 hr mainly to liver and adipose tissue. Affinity of TCDD to storage fat seemed to play a more important role as a driving force for redistribution than did induction of cytochrome P450 1A2. The terminal slope of elimination of TCDD from tissues indicated a half-life of 16 days after the nonlethal dose. After the lethal dose radioactivity declined in all tissues for 2 to 8 days and then increased again, reflecting shrinking tissue volumes as well as remobilization of TCDD caused by the process of body mass wasting. Distribution data for 17 tissues and serum were subjected to regression analysis and resulted in up to two uptake phases and up to three elimination phases for a given tissue. After the nonlethal dose TCDD was mainly excreted via feces; combined urinary and fecal excretions occurred with a biological half-life of 16.3 +/- 3.0 days. Much longer half-lives were detected in white fat and skin. After the lethal dose, the fecal excretion of TCDD-derived radioactivity decreased after 8 days, and urinary excretion increased starting 12 days after dosing. Radioactivity in liver and white fat and the extractable portion in feces was mainly unchanged TCDD, as determined by thin-layer chromatography. Radioactivity in urine indicated the presence of a metabolite(s) of TCDD only.


Skin manifestations in children with MIS-C and COVID-19: a narrative review.
This review aims to highlight the diverse skin manifestations in children and adolescents with COVID induced multisystem inflammatory syndrome in children (MIS-C). The symptoms of COVID-19 can vary greatly in severity between different age groups. Although most children infected with SARS-CoV-2 experience either no symptoms or only mild symptoms, some reported cases of severely affected children with a clinical presentation similar to incomplete Kawasaki disease have led to the definition of a new condition called MIS-C. MIS-C can involve multiple organs, including the skin, and may pose a life-threatening risk to affected children. Such cases highlight the need for continuous research into the possible skin manifestations associated with COVID-19 in pediatric populations to aid in early diagnosis and prompt treatment. We conducted a search of PubMed, Scopus, and ScienceDirect databases for studies published up until October 1, 2022. Three reviewers independently examined each study, and a fourth reviewer resolved any disagreements. A narrative review of all relevant papers was conducted. We present an overview of the clinical presentation, pathophysiology, diagnosis, and treatment of the various skin manifestations in children and adolescents with COVID-19 or MIS-C. The skin manifestations of COVID-19 and MIS-C can be diverse and are frequently overlooked. It is important to conduct further research to better understand the impact of this disease on children to provide appropriate care for these at-risk populations.


A visible allele of the muscle gene sup-10X of C. elegans.
In this paper, we extend our previous analyses of a set of genes in Caenorhabditis elegans that are involved in muscle structure and function: unc-93 III, sup-9 II, sup-10 X and sup-11 I. We describe an unusual, visible allele of sup-10, examine how this allele interacts genetically with mutations in other genes of this set and propose that the wild-type products of the unc-93 and sup-10 loci may be components of a protein complex. We also describe a new gene of this set, sup-18 III, and the interaction of sup-18 alleles with mutations in the other genes.


Comparative immunogenicity in mice of rotavirus VP6 tubular structures and virus-like particles.
Rotavirus (RV) is the most important cause of severe gastroenteritis in children worldwide. Current live RV vaccines are efficacious but show lower efficacy in developing countries, as well as a low risk of intussusception. This has led to the development of parenteral non-live candidate vaccines against RV. RV capsid VP6 protein is highly conserved and the most abundant RV protein forming highly immunogenic oligomeric structures with multivalent antigen expression. Both recombinant VP6 (rVP6) or double-layered (dl) 2/6-virus-like particles (VLPs), might be considered as the simplest RV subunit vaccine candidates. Human rVP6 protein and dl2/6-VLPs were produced in Sf9 insect cells by baculovirus expression system. Formation of rVP6 tubules and VLPs were confirmed by electron microscopy. BALB/c mice were immunized intramuscularly, and immune responses were analyzed. Both rVP6 and dl2/6-VLPs induced a balanced Th1-type and Th2-type response and high levels of serum IgG antibodies with cross-reactivity against different RV strains (Wa, SC2, BrB, 69M, L26, WC3, and RRV). In addition, mucosal VP6-specific IgG and IgA antibodies were detected in feces and vaginal washes (VW) of immunized animals. Importantly, VWs of immunized mice inhibited RV Wa and RRV infection in vitro. Immunization with either protein preparation induced a similar level of VP6-specific, interferon-γ secreting CD4(+) T cells in response to different RVs or the 18-mer peptide (AA 242-259), a VP6-specific CD4(+) T cell epitope. RV rVP6 and dl2/6-VLPs induced equally strong humoral and cellular responses against RV in mice and therefore, may be considered as non-live vaccine candidates against RV.


Immediate Dental Implant Placements Using Osteotome Technique: A Case Report and Literature Review.
This clinical case describes the effect of the osteotome technique on the osseointegration of a mandibular dental implant in a 42-year-old female patient with dento-alveolar bony defects and to review the literature regarding immediate implant placement using osteotome technique. The amount of bone expansion at the alveolar ridge and the marginal bone resorption from the time of implant placement to one year after the implant's functional loading were recorded clinically. The esthetic outcome for the restored implant (the gingival margin) was achieved one years after the implant's functional loading. The surgical and prosthetic sites for the implant showed no postoperative complications, and no infection or wound dehiscence was recorded during the follow-up period. The osteotome technique is good for the purpose for which it was introduced, and its advantages with immediate implant placement include reduced surgical trauma and a shorter treatment time.


Genetic characterization of specific pathogen-free rhesus macaque (Macaca mulatta) populations at the California National Primate Research Center (CNPRC).
A study based on 14 STRs was conducted to understand intergenerational genetic changes that have occurred within the California National Primate Research Center's (CNPRC) regular specific pathogen-free (SPF) and super-SPF captive rhesus macaque populations relative to their conventional founders. Intergenerational genetic drift has caused age cohorts of each study population, especially within the conventional population, to become increasingly differentiated from each other and from their founders. Although there is still only minimal stratification between the conventional population and either of the two SPF populations, separate derivation of the regular and super-SPF animals from their conventional founders has caused the two SPF populations to remain marginally different from each other. The regular SPF and, especially, the super-SPF populations have been influenced by the effects of differential ancestry, sampling, and lost rare alleles, causing a substantial degree of genetic divergence between these subpopulations. The country of origin of founders is the principal determinant of the MHC haplotype composition of the SPF stocks at the CNPRC. Selection of SPF colony breeders bearing desired genotypes of Mamu-A*01 or -B*01 has not affected the overall genetic heterogeneity of the conventional and the SPF research stocks.Because misclassifying the ancestry of research stocks can undermine experimental outcomes by excluding animals with regional-specific genotypes or phenotypes of importance, understanding founder/descendent genetic relationships is crucial for investigating candidate genes with distinct geographic origins. Together with demographic management, population genetic assessments of SPF colonies can curtail excessive phenotypic variation among the study stocks and facilitate successful production goals.