[Association between Trichomonas vaginalis and some types of lesions of the uterine neck based on data collected in the quinquennium of 1974--1978].
In our statistic the number of cases of vaginal trichomoniasi in which discariosi, displasie, metaplasie are found are represented in about 40%. While 37,5% of women affected with neoplastic lesions had Trichomonas vaginalis. It is certain that in the presence of flogosi from Trichomonas vaginalis we meet more frequently than normal, atipie cellulars and that often an exact valutation of this lesion is put back to an exam after the recovery of the Trichomonas vaginalis, because fortunately, more than often these disturbances disappear.


Clinical Importance of the LDL-C/Apolipoprotein B Ratio for Neointimal Formation after Everolimus-Eluting Stent Implantations.
Smaller low-density lipoprotein (LDL) particle size has been suggested to result in the development of endothelial dysfunction, atherosclerosis, and in-stent restenosis (ISR); however, little is known regarding the impact of the LDL particle size on the neointima formation leading to ISR after everolimus-eluting stent (EES) implantation. In this study, we have included 100 patients to examine the relationship between an LDL-C/apolipoprotein B (Apo B) ≤ 1.2, reportedly representing the LDL particle size, and the neointimal characteristics using optical coherence tomography (OCT) and coronary angioscopy (CAS) during the follow-up coronary angiography (CAG) period (8.8±2.5 months) after EES implantation. We divided them into two groups: LDL-C/Apo B ≤ 1.2 group (low LDL-C/Apo B group, n=53) and LDL-C/Apo B >1.2 group (high LDL-C/Apo B group, n=47). The low LDL-C/Apo B group had a significantly larger neointimal volume (12.8±5.3 vs. 10.3±4.9 mm3, p=0.021) and lower incidence of a neointimal homogeneous pattern (71 vs. 89 %), higher incidence of a neointimal heterogeneous pattern (25 vs. 9 %) (p=0.006) and higher prevalence of macrophage accumulation (9 vs. 2 %) (p=0.030) as assessed via OCT, and, as per the CAS findings, a higher prevalence of yellow grade ≥ 2 (grade 2; adjusted residual: 2.94, grade 3; adjusted residual: 2.00, p=0.017) than the high LDL-C/Apo B group. A low LDL-C/Apo B ratio was found to be strongly associated with neointimal proliferation and neointimal instability evidenced chronically by OCT and CAS. An LDL-C/Apo B ≤ 1.2 will be of aid in terms of identifying high-risk patients after EES implantation.


What's in a Name? Enhancing Communication in the Operating Room with the Use of Names and Roles on Surgical Caps.
A pilot study was conducted in a tertiary referral center to assess whether wearing caps labeled with providers' names and roles has an impact on communication in the operating room (OR). Two obstetricians observed surgeries for name uses and missed communications. Following each case, all providers were given a short survey that queried their attitude about the use of labeled surgical caps, their ability to know the names and roles of other providers during a case, and the impact of scrub attire on identifying others. They were also asked to rate the ease of communication and their ability to recall name and roles of the personnel specific to the case. Patients were asked how they perceived the use of labeled caps by providers. Twenty scheduled cesarean deliveries were randomized to either labeled (10) or nonlabeled (10) surgical caps. A total of 129 providers participated in the study, with 117 providing responses to the survey. Providers reported knowing the names and roles of colleagues more often with labeled caps vs. nonlabeled caps (names: 77.8% vs. 55.0%, 95% confidence interval [CI] = 64.4%-88.0% vs. 41.6%-67.9%, p = 0.011; roles: 92.5% vs. 78.3%, 95% CI = 81.8%-98.0% vs. 65.8%-88.0%, p = 0.036). Name uses increased (43 vs. 34, p = 0.208), and missed communications decreased (16 vs. 20, p = 0.614) when labeled caps were worn. Providers and patients had an overwhelmingly positive response to labeled caps. This pilot study demonstrated that wearing labeled caps in the OR led to more frequent name uses and less frequent missed communications. Providers and patients embraced the concept of labeled caps and perceived wearing labeled caps as improving communication in the OR.


Beyond the report: Prospects and challenges in forensic anthropological investigations of structural vulnerability.
Forensic anthropologists are increasingly interested in accounting for embodied marginalization in addition to the biological profile. A structural vulnerability framework, which assesses biomarkers of social marginalization in individuals within forensic casework, is worthwhile but its application must be informed by ethical, interdisciplinary perspectives that reject categorizing suffering within the pages of a case report. Drawing from anthropological perspectives, we explore prospects and challenges of evaluating embodied experience in forensic work. Particular attention is paid to how forensic practitioners and stakeholders utilize a structural vulnerability profile within and beyond the written report. We argue that any investigation of forensic vulnerability must: (1) integrate rich contextual data, (2) be evaluated for potential to perpetuate harm, and (3) serve the needs of a diverse array of stakeholders. We call for a community-oriented forensic practice, wherein anthropologists may act as advocates for policy change to disrupt power structures driving vulnerability trends in their region.


Comparing injunctive marijuana use norms of salient reference groups among college student marijuana users and nonusers.
Marijuana is the most commonly used illicit drug among college students and has the potential for various negative outcomes. Perceptions of what constitutes typical approval/acceptability of a reference group (i.e. injunctive social norms) have been shown to have strong utility as predictors of health-risk behaviors in the college context, yet this construct remains significantly understudied for marijuana use despite its potential for use in social norms-based interventions. The current research evaluated individuals' marijuana approval level and their perceptions of others' marijuana approval level (i.e. injunctive norms) for various reference groups (typical student on campus, one's close friends, and one's parents) as a function of individual user status (abstainers, experimenters, occasional users, and regular users). A diverse sample of 3553 college students from two universities completed an online survey. Among all user status groups, individual approval yielded mean scores paralleling that of perceived close friends' approval and all groups were relatively uniform in their perception of typical students' approval. Higher levels of marijuana use tended to produce higher endorsements of individual approval, perceived close friends' approval, and perceived parental approval. Among occasional and regular users, there were no differences between one's own approval level for use and the perceptions of close friends' approval, nor did they think the typical student was more approving than themselves. Abstainers and experimenters, however, perceived typical students and close friends to have more permissive attitudes than themselves. Implications and future directions for research regarding the role of injunctive marijuana use norms in the development of social norms intervention are discussed.


Early Neurological Changes and Interpretation of Clinical Grades in Aneurysmal Subarachnoid Hemorrhage.
Hunt and Hess (HH) and World Federation of Neurological Surgeons (WFNS) grades are commonly used to report clinical severity of aneurysmal subarachnoid hemorrhage (aSAH). We sought to determine the impact of early neurological changes and the timing of clinical grade assignment on the prognostication accuracy. We retrospectively reviewed a cohort of consecutive patients with aSAH who were admitted to an academic center. Patients with confirmed aneurysmal cause were included. Relevant clinical data including daily clinical grades, imaging data and functional outcome were analyzed. Favorable outcome was defined as mRS 0 to 3. Early neurological improvement (ENI) and early neurological deterioration (END) were respectively defined as any improvement or deterioration of HH grades from hospital day 1 to the earliest time from hospital day 2 to 5. Of 310 patients, 24% experienced early neurological changes from hospital day 1 to 3. For each point increase in HH grades from day 1 to day 3, the odds ratio for worse outcome was 2.57 (95% CI [1.74-3.79]) and for each point decrease in HH grades from day 1 to day 3, the odds ratio for worse outcome was 0.28 (95% CI [0.17-0.47]). Receiver Operating Characteristic curve analysis revealed that clinical grades on day 3 had higher accuracy in predicting worse outcome than clinical grades on day 1. Early changes in neurological status can alter trajectory of hospital course and functional outcome. The prognostic accuracy of the clinical grades from hospital day 3 is significantly greater than those on admission.


Salvia miltiorrhiza polysaccharides alleviates florfenicol induced kidney injury in chicks via inhibiting oxidative stress and apoptosis.
Florfenicol (FFC) is a commonly used antibiotic in animal husbandry, which is easy to cause organs damage in a variety of animals. It has been proved to have nephrotoxicity and affect the yield and quality of meat products. Salvia miltiorrhiza polysaccharides (SMPs) have been proved to have the pharmacological effects of regulating immunity and protecting the liver of animals, and its alleviative effect on renal injury is unclear. In order to investigate the alleviating effect of SMPs on drug nephrotoxicity and determine its potential molecular mechanism, we took chicks as the research object, FFC as the induced drug, and established the model by adding SMPs in drinking water. The chicks were randomly divided into control group, FFC model group (0.15 g/L FFC), FFC + low, medium and high dose of SMPs groups (0.15 g/L FFC + 1.25, 2.5, 5 g/L SMPs) and SMPs group (5 g/L SMPs). The results showed that, SMPs increased the average weight gain and renal index of chicks, alleviated the pathological changes of renal structure induced by FFC, decreased the contents of uric acid, blood urea nitrogen and creatinine in serum and malondialdehyde in renal tissue, increased the levels of glutathione, superoxide dismutase and catalase in renal tissue, up-regulated the relative expression levels of nuclear factor erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase-1 (NQO-1) mRNA and protein, and down-regulated the relative expression levels of p53, Caspase-3 and Caspase-6 mRNA and protein and the apoptosis rate of renal histiocytes. It is concluded that SMPs could significantly alleviate the renal injury induced by FFC, and its mechanism may be related to improving renal antioxidant capacity and inhibiting abnormal apoptosis of renal histiocytes.


Evaluation of nine formulas for estimating the body surface area of children with hematological malignancies.
Body surface area (BSA) is an important parameter in clinical practice for children. To find out the most accurate BSA formula for Chinese children, nine formulas were compared. This single-center study comprised children who were diagnosed with acute lymphoblastic leukemia and treated with anticancer agents in a specialized children's hospital in China from January 2017 to December 2020. The BSA values were calculated using the formulas from Boyd, Banerjee and Bhattacharya, Costeff, Fujimoto and Watanabe, Haycock, Gehan and George, Mosteller, Stevenson and a Pediatrics textbook. The arithmetic mean of formulas was calculated as the "gold standard" for comparison. A total of 666 children (389 males and 277 females) were included. All nine formulas showed a strong positive correlation with the "gold standard." Underestimation was observed with the Banerjee and Bhattacharya, Fujimoto and Watanabe formulas. The Gehan and George formula showed overestimation. Values estimated from the Haycock and Mosteller formulas were the closest to the mean BSA. The Haycock and Mosteller formulas are the most recommended formulas for Chinese children with hematological malignancies.


Interplay between the transcription factor Zif and aPKC regulates neuroblast polarity and self-renewal.
How a cell decides to self-renew or differentiate is a critical issue in stem cell and cancer biology. Atypical protein kinase C (aPKC) promotes self-renewal of Drosophila larval brain neural stem cells, neuroblasts. However, it is unclear how aPKC cortical polarity and protein levels are regulated. Here, we have identified a zinc-finger protein, Zif, which is required for the expression and asymmetric localization of aPKC. aPKC displays ectopic cortical localization with upregulated protein levels in dividing zif mutant neuroblasts, leading to neuroblast overproliferation. We show that Zif is a transcription factor that directly represses aPKC transcription. We further show that Zif is phosphorylated by aPKC both in vitro and in vivo. Phosphorylation of Zif by aPKC excludes it from the nucleus, leading to Zif inactivation in neuroblasts. Thus, reciprocal repression between Zif and aPKC act as a critical regulatory mechanism for establishing cell polarity and controlling neuroblast self-renewal.


General dental practitioners' perceptions of shared decision making: a qualitative study.
Introduction As patient-centred care becomes more of the focus in healthcare, informed consent is receiving more attention in dental practice as the pinnacle principle in patient care. Shared decision making or person-centred care appears to be taking a back foot in dentistry.Aim This study aims to gain insight into the current views and perceptions of shared decision making by general dental practitioners and how it can be utilised in daily practice.Method Empirical qualitative data were collected using semi-structured interviews of nine dentists working in general practice, with an average of 30 minutes for each interview. The data were analysed using thematic analysis.Results Overall, there was a misunderstanding of what constitutes shared decision making among dental practitioners, with communication focused more on information provision rather than collaborative discussion. There were barriers which prevented full discussions with patients from occurring, some of which directly conflicted with the focus of shared decision making.Conclusion There is a need to provide more clarity of what shared decision making is and how it can facilitate person-centred care in dental practice. Dental practitioners felt that standards and guidelines were not clear; therefore, they were confused as to what was expected of them with regards to communication. More support, in the form of standardised decision-making aids, is needed to assist dental practitioners to streamline the delivery of shared decision making in primary care.


Weight losses with low-energy formula diets in obese patients with and without type 2 diabetes: systematic review and meta-analysis.
This corrects the article DOI: 10.1038/ijo.2016.175.


An evaluation of the pharmacokinetics of tiotropium following a single-dose inhalation in healthy subjects using an ultra-sensitive bioanalytical method.
Objective and significance: The systemic bioavailability of tiotropium following administration via inhalation is known to be very low. A validated ultra-sensitive bioanalytical method with the lowest lower limit of quantitation (LLOQ) was developed and used to evaluate the complete pharmacokinetic profile of tiotropium.Methods: This was a pharmacokinetic study performed in 18 healthy subjects. Each subject was administered a dose of 18 mcg of tiotropium from a dry powder inhaler (DPI). The subjects' plasma tiotropium concentrations were assayed with LLOQ of 0.1 pg/mL.Results: The results showed a mean Cmax of 4.98 ± 3.55 pg/mL, and a median (tmax) of 3.6 minutes (range: 1.8-12 minutes). The means for area under the concentration-time curve (AUC) from time zero hours to infinity (AUCinf) and AUC from time zero hours to the time of the last measurable tiotropium concentration (AUCt) were 51.11 ± 27.4 pg*h/mL and 37.37 ± 23.38 pg*h/mL, respectively. The mean apparent elimination half-life (t1/2) was 68.02 ± 24.55 hours. This calculated half-life is longer than what others have reported where a less sensitive LLOQ was used.Conclusion: The lower LLOQ enabled further insight into the pharmacokinetics of tiotropium that was not possible with other analytical methods. With this method, we were able to quantify tiotropium concentrations as early as one minute following drug administration and up to 144 hours after dosing. The application of this method will allow for studies to be designed properly and enable further investigations into the pharmacokinetics of tiotropium.


Exploring item and higher order factor structure with the Schmid-Leiman solution: syntax codes for SPSS and SAS.
To ease the interpretation of higher order factor analysis, the direct relationships between variables and higher order factors may be calculated by the Schmid-Leiman solution (SLS; Schmid & Leiman, 1957). This simple transformation of higher order factor analysis orthogonalizes first-order and higher order factors and thereby allows the interpretation of the relative impact of factor levels on variables. The Schmid-Leiman solution may also be used to facilitate theorizing and scale development. The rationale for the procedure is presented, supplemented by syntax codes for SPSS and SAS, since the transformation is not part of most statistical programs. Syntax codes may also be downloaded from www.psychonomic.org/archive/.


Robotics is useful for less-experienced surgeons in spinal deformity surgery.
To verify whether robotics was useful for surgeons who had less experience with spinal deformity surgery. A retrospective review was conducted of 70 consecutive patients who underwent robotic-assisted pedicle screw placements with open procedures using a spine robotic system (Mazor X Stealth Edition) at a single institution from April 2021 to April 2022. Gertzbein-Robbins grades were used to assess the deviation of the 599 pedicle screws in the postoperative CT images. The rate of Grade A was considered the perfect accuracy rate, and the rate of Grades C, D, and E was calculated as the deviation rate. The perfect accuracy rate and deviation rate were compared between the spinal deformity and the non-deformity groups. The perfect accuracy rate, deviation rate, and screw insertion time were compared in the spinal deformity cases between the expert surgeon group and the less-experienced surgeon group. The deviation rate of the spinal deformity group was higher than that of the non-deformity group even though there was no statistically significant difference (spinal deformity group: 2.3%, non-deformity group: 1.2%, p = 0.350). In the spinal deformity cases, there was no significant difference in the perfect accuracy rate between the expert surgeon group and the less-experienced surgeon group, but the deviation rate was significantly lower in the less-experienced surgeon group (expert surgeon group: 5.0%, less-experienced surgeon group: 0%, p = 0.008). The screw insertion time was significantly shorter in the less-experienced surgeon group. Robotics is particularly useful for surgeons with less experience in spinal deformity surgery.


Respiratory monitoring during postoperative analgesia.
Respiratory monitoring, using a novel flow sensor based on an acoustic principle, has been investigated in 30 patients during postoperative analgesia. Each patient was subjected to monitoring and human observation for 8 hr. The study was performed by independent observers at three clinics. Significant correlation was noted between respiratory rate (RR) determined by the sensor and the observers. Recordings of respiratory duration index (RDI), breathing time intervals (BTIs) indicated high sensitivity of the instrument to respiratory depression and perturbations in the breathing rhythm. More than 800 apnea alarms were noted, using an alarm setting of 30 sec; 61% of the categorized alarms were noted by the observers as true apneas. From the recordings it was shown that the number of alarms can be reduced by a factor of four if the alarm setting is changed to 45 sec. We conclude that the suggested technique, with slight modifications, provides adequate respiratory monitoring of patients during postoperative analgesia.


Insecurity of the ECG interpretation data as a health mass screening--the serial reliability evaluation study.
To evaluate the reliability of the interpretations of ECG data which have been stored yearly as health mass screening data between 1982 and 1991 in an industry, we recently analyzed the data variation of 10,546 samples. So as not to ignore the longitudinal health management, we are going to reevaluate the clinical significance of the ECG interpretation data, which were stored as an item of health mass screening.


[Platelet adhesion mediated by von Willebrand factor in patients with premature coronary artery disease].
Aim To study platelet adhesion mediated by von Willebrand factor (VWF) in patients with premature ischemic heart disease (IHD).Material and methods This study enrolled 58 patients with stable IHD, including 45 men younger than 55 years with the first manifestation of IHD at the age of <50 years and 13 women younger than 65 years with the first manifestation of IHD at the age of <60 years. The control group consisted of 33 patients, 13 men younger than 55 years and 20 women younger than 65 years without IHD. Platelet adhesion to the collagen surface at the shear rate of 1300 s-1 was studied by evaluating the intensity of scattered laser light from the collagen-coated optical substrate in a flow chamber of a microfluidic device after 15-min circulation of whole blood in the chamber. Decreases in platelet adhesion after addition to the blood of monoclonal antibodies (mAb) to platelet receptors glycoproteins Ib (GPIb) to inhibit the receptor interaction with VWF were compared for patients of both groups. Results In patients with premature IHD, the decrease in platelet adhesion following the platelet GPIb receptor inhibition was significantly less than in patients of the control group (74.8 % (55.6; 82.7) vs. 28.9 % (-9.8; 50,5), p <0.001). For the entire sample, the median decrease in platelet adhesion following the GPIb receptor inhibition was 62.8 % (52.2; 71.2). With an adjustment for traditional risk factors of IHD, a decrease in platelet adhesion of >62.8% after blocking GPIb receptors increased the likelihood of premature IHD (OR=9.84, 95 % CI: 2.80-34.59; p <0.001).Conclusion Blocking the interaction of GPIb receptors with VWF in patients with premature IHD and increased shear rate induced a greater decrease in platelet adhesion than in patients without this disease. This suggested that an excessive interaction of VWF with platelets might contribute to the pathogenesis of premature IHD.


The vacuole shapes the nucleus and the ribosomal DNA loop during mitotic delays.
The ribosomal DNA (rDNA) array of Saccharomyces cerevisiae has served as a model to address chromosome organization. In cells arrested before anaphase (mid-M), the rDNA acquires a highly structured chromosomal organization referred to as the rDNA loop, whose length can double the cell diameter. Previous works established that complexes such as condensin and cohesin are essential to attain this structure. Here, we report that the rDNA loop adopts distinct presentations that arise as spatial adaptations to changes in the nuclear morphology triggered during mid-M arrests. Interestingly, the formation of the rDNA loop results in the appearance of a space under the loop (SUL) which is devoid of nuclear components yet colocalizes with the vacuole. We show that the rDNA-associated nuclear envelope (NE) often reshapes into a ladle to accommodate the vacuole in the SUL, with the nucleus becoming bilobed and doughnut-shaped. Finally, we demonstrate that the formation of the rDNA loop and the SUL require TORC1, membrane synthesis and functional vacuoles, yet is independent of nucleus-vacuole junctions and rDNA-NE tethering.


Coexistence of Hodgkin and Non-Hodgkin Lymphoma; Composite Lymphoma [CL] in a Patient Presenting with Waxing and Waning Lymphadenopathy.
The coexistence of two or more types of lymphoma within the same organ at the same time of diagnosis is defined as composite lymphoma, a rare disease that has recently been identified in the literature. Pointedly, the concurrence may be Hodgkin lymphoma with a Non-Hodgkin lymphoma [NHL], either B or T cells, or two different entities of NHLs. Furthermore, this condition has been described concurrently or sequentially. In order for the diagnosis to be established, two or more distinct clones should be proven by morphological and laboratory tests. Herein, we cite a seventy-three-year old female patient with low-grade fever, waxing and waning cervical lymphadenopathy, whose biopsy of an axillary lymph node demonstrated the rare coexistence of Hodgkin and NHL, known as composite lymphoma. Composite lymphomas pose a particular diagnostic challenge, and currently, there are no agreed standards for treatment.


Phloridzin: biosynthesis, distribution and physiological relevance in plants.
The phenolic compound phloridzin (phloretin 2'-O-glucoside, phlorizin, phlorrhizin, phlorhizin or phlorizoside) is a prominent member of the chemical class of dihydrochalcones, which are phenylpropanoids. The apple tree (Malus sp.) accumulates high amounts of phloridzin, whereas few other species contain this compound only in low amounts. Additionally, Malus sp. show a species- and tissue-specific distribution of phloridzin and its derivatives. Whereas the physiological role of phloridzin in planta is not fully understood, the effect on human health - especially diabetes - and membrane permeability is well documented. The biosynthesis of phloridzin was investigated only recently with recombinant enzymes and plant protein extracts and involved a NADPH-dependent dehydrogenase, chalcone synthase and UDP-glucose:phloretin 2'-O-glycosyltransferase.


Sports injuries: an ounce of prevention and a pound of cure.
To evaluate and review the literature regarding sports-related eye injuries and prevention through appropriate protective eyewear. The literature was reviewed regarding sports-related eye injuries and prevention of these injuries. The review of the literature suggests that ocular sports injuries can occur with all sports and affects all ages. These injuries may affect professional athletes and amateur athletes around the world. There are between 40,000 and 600,000 documented sports-related ocular injuries in the United States every year. More than 90% of these ocular injuries from sports are preventable. Most of sports-related eye injuries are preventable. Increased recognition of the risks of eye injury playing sports may lead to improved protection and a decreased morbidity from eye injuries. To help prevent sports-related eye injuries, education of athletes, parents, coaches, trainers, referees, and health care practitioners is critical.


Gel properties and interactions of Mesona blumes polysaccharide-soy protein isolates mixed gel: The effect of salt addition.
Effect of different salt ions on the gel properties and microstructure of Mesona blumes polysaccharide (MBP)-soy protein isolates (SPI) mixed gels were investigated. Sodium and calcium ions were chosen to explore their effects on the rheological behavior and gel properties of MBP-SPI mixed gels were evaluated by using rheological, X-ray diffraction, protein solubility determination, and microstructure analysis. Results showed that the addition of salt ions change the crystalline state of gels system, the crystal of gel was enhanced at low ion concentrations (0.005-0.01 M). The two peaks of gel characteristic at 8.9° and 19.9° almost disappeared at high salt ions concentrations (0.015-0.02 M), and new crystallization peaks appeared at around 30° and 45°. The elasticity, viscosity, gel strength, water holding capacity, and thermal stability of gel were increased at low ion concentration. Results showed that the main interactions which promoted gel formation and maintain the three-dimensional structure of the gel were electrostatic interactions, hydrophobic interactions, and disulfide interactions.


The interleukin-6 -174 G>C promoter polymorphism is associated with a higher risk of death after an acute coronary syndrome in male elderly patients.
Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are key mediators of inflammation and their increased plasma levels are associated with acute coronary syndrome (ACS). Polymorphisms in the promoter region of IL-6 (-174 G>C) and TNF-alpha (-308 G>A) demonstrated to affect gene expression were analyzed to test their predictive power for cardiovascular death over one year follow-up in elderly male ACS patients. We assessed the IL-6 -174 G>C polymorphism and TNF-alpha -308 G>A polymorphism in 139 consecutive elderly male patients affected by an ACS, such as ST-Elevation (STEMI), No ST-Elevation (NSTEMI) Myocardial Infarction and Unstable Angina. The presence of well known risk factors for Coronary Heart Diseases (CHD) were also assessed in all ACS patients. Survival rate was assessed after one year follow-up. We found that IL-6 -174 G>C polymorphism is an independent predictor of cardiovascular death after an ACS in male patients. In particular ACS patients carrying the IL-6 -174 C- (GG) genotypes showed a marked increase in one year follow-up mortality rate (HR=3.89, 95% CI 1.71-8.86, p=0.001). Moreover CRP serum levels > or = 5.5 mg/dl (HR= 3.79, 95% CI 1.71-8.42, p=0.001), a history of CHD (HR=2.96, 95% CI 1.22-7.20, p=0.016) and the absence of statins treatment (HR=3.27, 95% CI 1.17-9.18, p=0.021), significantly increased one year risk of death in male ACS patients. These data suggest that IL-6 -174 G>C polymorphism can be added to other clinical markers in order to identify a subgroup of elderly ACS male patients at higher risk of death.


Reelin protects from colon pathology by maintaining the intestinal barrier integrity and repressing tumorigenic genes.
We previously reported that reelin, an extracellular matrix protein first known for its key role in neuronal migration, reduces the susceptibility to dextran sulphate sodium (DSS)-colitis. The aim of the current study was to determine whether reelin protects from colorectal cancer and how reelin defends from colon pathology. In the colon of wild-type and of mice lacking reelin (reeler mice) we have analysed the: i) epithelium cell renewal processes, ii) morphology, iii) Sox9, Cdx2, Smad5, Cyclin D1, IL-6 and IFNγ mRNA abundance in DSS-treated and untreated mice, and iv) development of azoxymethane/DSS-induced colorectal cancer, using histological and real time-PCR methodologies. The reeler mutation increases colitis-associated tumorigenesis, with increased tumours number and size. It also impairs the intestinal barrier because it reduces cell proliferation, migration, differentiation and apoptosis; decreases the number and maturation of goblet cells, and expands the intercellular space of the desmosomes. The intestinal barrier impairment might explain the increased susceptibility to colon pathology exhibited by the reeler mice and is at least mediated by the down-regulation of Sox9 and Cdx2. In response to DSS-colitis, the reeler colon increases the mRNA abundance of IL-6, Smad5 and Cyclin D1 and decreases that of IFNγ, conditions that might result in the increased colitis-associated tumorigenesis found in the reeler mice. In conclusion, the results highlight a role for reelin in maintaining intestinal epithelial cell homeostasis and providing resistance against colon pathology.


Multiconstrained gene clustering based on generalized projections.
Gene clustering for annotating gene functions is one of the fundamental issues in bioinformatics. The best clustering solution is often regularized by multiple constraints such as gene expressions, Gene Ontology (GO) annotations and gene network structures. How to integrate multiple pieces of constraints for an optimal clustering solution still remains an unsolved problem. We propose a novel multiconstrained gene clustering (MGC) method within the generalized projection onto convex sets (POCS) framework used widely in image reconstruction. Each constraint is formulated as a corresponding set. The generalized projector iteratively projects the clustering solution onto these sets in order to find a consistent solution included in the intersection set that satisfies all constraints. Compared with previous MGC methods, POCS can integrate multiple constraints from different nature without distorting the original constraints. To evaluate the clustering solution, we also propose a new performance measure referred to as Gene Log Likelihood (GLL) that considers genes having more than one function and hence in more than one cluster. Comparative experimental results show that our POCS-based gene clustering method outperforms current state-of-the-art MGC methods. The POCS-based MGC method can successfully combine multiple constraints from different nature for gene clustering. Also, the proposed GLL is an effective performance measure for the soft clustering solutions.


An experimental study of vertical deviations induced by different interocclusal recording materials.
This study was designed to determine vertical deviations in mounting casts on an articulator as affected by the recording material. Five different recording materials were tested after storage of the records for 30 minutes, 6 hours, and 24 hours. Two measuring systems were used to register simultaneously the vertical errors at the occlusal plane and at the condyle of an articulator. The results indicated that the measurements made at the condyle cannot detect the vertical deviations induced at the occlusal surfaces. None of the materials tested gave reliable results. Advantages, disadvantages, and indications of the different materials were discussed.


Emerging problems in gram-positive infections in the postoperative patient.
Gram-positive bacteria are increasingly prevalent in the postoperative patient population and are important as pathogens. As increasingly ill and elderly patients undergo surgical treatment and as increased use is made of invasive or immunosuppressive treatment modalities, this trend is likely to accelerate. The increasing use of broad-spectrum antibiotics results in the emergence of resistant pathogens or superinfections that are increasingly difficult to treat. Examples of such pathogens include methicillin-resistant Staphylococcus epidermidis, vancomycin-resistant enterococci and Clostridium difficile. No acute care setting, from large urban teaching hospital to small rural community hospital, is immune to the trend. The clinical challenge posed by these organisms is compounded by the fact that serious gram-positive infections can be impossible to distinguish on clinical grounds from their gram-negative counterparts. The host inflammatory response to gram-positive infection is quite similar to that caused by gram-negative infection, including elaboration of cytokine mediators and progression to visceral organ dysfunction. The clinician must be cognizant that serious infections, especially of nosocomial origin, may be caused by gram-positive bacteria.


Glycosaminoglycans and the control of cell surface proteinase activity.
It is postulated that the metabolically variable fine structure of pericellular heparan glycosaminoglycans affects the ability of these molecules to influence cell proliferation-associated proteinase-catalysed reactions occurring at cell surfaces. Evidence suggesting the possibility of a wide repertoire of glycosaminoglycan-mediated positive and negative effects on such reactions is reviewed. It is suggested that clinical administration of compounds related chemically to heparins might usefully modulate cell proliferation-associated proteinase activity.


Impact of knowledge, attitude, and practice on iodized salt consumption at the household level in selected coastal regions of Bangladesh.
Iodine deficiency disorder is one of the major hidden hunger for poverty-stricken coastal rural areas of Bangladesh. Despite various programs, including universal salt iodization, IDD is significantly persistent due to poverty, inadequate knowledge, poor attitude, and practice of iodized salt consumption. The present study aimed to determine iodine concentration in salt at the household level as well as the magnitude of knowledge, attitude, and practice related to iodized salt utilization and iodine deficiency disorders (IDDs). A population-based cross-sectional study was carried out using multistage sampling among 400 households in four coastal districts in Bangladesh. A standard pretested questionnaire was used to determine the knowledge, attitude, and practice towards iodized salt consumption. The iodine level was measured using the gold standard iodometric titration technique in the collected salt samples from the selected households. The study results revealed that almost half of the participants had good knowledge regarding a balanced diet, whereas the positive attitude and practice of balanced diet consumption was relatively low (only 16.2% and 11.3%, respectively). The respondents' education profile and age were strongly correlated with knowledge and attitude; however, the practice was not significantly correlated with age and education. The concentration of iodine in salt at household levels was strongly associated with the practice of using iodized salt. Use of adequate iodized salt was 2.838 times (OR: 2.838, 95% CI: 1.7-4.735) and 3.884 times (OR: 3.884, 95%CI: 2.029-7.433) more likely to have a positive attitude and good practice towards iodized salt and IDDs respectively. Proper knowledge about iodized salt and IDDs should be introduced to all public education premises levels. Interventions and programs can be formulated to enhance knowledge, attitude, and practice at the household level so that the consumption of adequate iodized salt can be ensured to reduce iodine deficiency problems.


Targeting discriminatory SNPs in Salmonella enterica serovar Heidelberg genomes using RNase H2-dependent PCR.
We report a novel RNase H2-dependent PCR (rhPCR) genotyping assay for a small number of discriminatory single-nucleotide polymorphisms (SNPs) that identify lineages and sub-lineages of the highly clonal pathogen Salmonella Heidelberg (SH). Standard PCR primers targeting numerous SNP locations were initially designed in silico, modified to be RNase H2-compatible, and then optimized by laboratory testing. Optimization often required repeated cycling through variations in primer design, assay conditions, reagent concentrations and selection of alternative SNP targets. The final rhPCR assay uses 28 independent rhPCR reactions to target 14 DNA bases that can distinguish 15 possible lineages and sub-lineages of SH. On evaluation, the assay correctly identified the 12 lineages and sub-lineages represented in a panel of 75 diverse SH strains. Non-specific amplicons were observed in 160 (15.2%) of the 1050 reactions, but due to their low intensity did not compromise assay performance. Furthermore, in silico analysis of 500 closed genomes from 103 Salmonella serovars and laboratory rhPCR testing of five prevalent Salmonella serovars including SH indicated the assay can identify Salmonella isolates as SH, since only SH isolates generated amplicons from all 14 target SNPs. The genotyping results can be fully correlated with whole genome sequencing (WGS) data in silico. This fast and economical assay, which can identify SH isolates and classify them into related or unrelated lineages and sub-lineages, has potential applications in outbreak identification, source attribution and microbial source tracking.


Automated beam angle and weight selection in radiotherapy treatment planning applied to pancreas tumors.
To extend and investigate the clinical value of a recently developed algorithm for automatic beam angle and beam weight selection, for irradiation of pancreas tumors. The algorithm aims at generation of acceptable treatment plans, i.e., delivering the prescribed tumor dose while strictly obeying the imposed hard constraints for organs at risk and target. Extensions were made to minimize the beam number and/or to escalate the tumor dose. For 5 pancreas patients, the clinical value and the potential for beam number reduction and dose escalation were investigated. Comparisons were made with clinical plans and equiangular plans. Compared to clinical plans, the generated plans with the same number of beams yielded a substantial reduction in the dose to critical tissues. Using the algorithm, an escalated tumor dose of 58 Gy could be achieved for two cases. Maximum dose escalations required a minimum of 3 to 4 beam orientations. For 13 CT slices and an in-slice resolution of 0.5 cm, the total calculation times were 23-55 min, including precalculation of 180 input dose distributions (15 min). The algorithm yielded acceptable treatment plans with clinically feasible numbers of beams, even for escalated tumor doses. Generated plans were superior to the clinically applied plans and to equiangular setups. Calculation times were clinically acceptable. The algorithm is now increasingly used in clinical routine.


Sonographic findings of fetuses with an empty renal fossa and normal amniotic fluid volume.
To review the antenatal sonographic findings and postnatal follow-up of fetuses with empty renal fossa (ERF) and normal amniotic fluid volume. Sonographic examinations of 13,705 fetuses were retrospectively analyzed and all fetuses with at least one ERF and normal antenatal amniotic fluid volume were included in this study. Forty cases with antenatal ERF were diagnosed. Prenatal diagnosis consisted of pelvic kidney (n = 24), unilateral renal agenesis (n = 13), horseshoe kidney (n = 2) and crossed fused renal ectopia (n = 1). The prevalence of ERF in the low-risk population approximated 3.2 per thousand. There was no serious renal complication during a mean follow-up period of 30 months except one case of crossed fused renal ectopia requiring hemodialysis. The underlying cause of ERF in the majority of cases with normal amniotic fluid volume is renal ectopia. Prenatal ultrasonography seems to be highly reliable in diagnosing these anomalies. Prognosis is favorable in the absence of additional extraurinary malformations.


Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases.
Botulinum toxin type A (BTA) (Botox) received Food and Drug Administration (FDA) approval for therapeutic treatment of strabismus and blepharospasm in 1989, cervical dystonia in 2000, and cosmetic treatment of glabellar wrinkles (Botox Cosmetic) in 2002. In 2002 alone there were approximately 1.1 to 1.6 million patients using cosmetic BTA. Our objective was to review adverse event (AE) reporting to the FDA after BTA administration. We reviewed all (therapeutic and cosmetic use) serious (per FDA regulations) AEs reported to the FDA for the 13.5 years since licensure of the product (December 1989-May 2003) and nonserious AEs reported from December 2001 to November 2002. AEs are reported to the FDA through the MedWatch system. We reviewed 1437 AE reports; 406 followed therapeutic use of BTA (217 serious and 189 nonserious) and 1031 followed cosmetic use (36 serious and 995 nonserious). Reported AEs occurred predominantly in female patients, with a median age of 50 years. In the year December 2001 to November 2002, when both serious and nonserious reports were evaluated, the proportion of reports classified as serious was 33-fold higher for therapeutic than for cosmetic cases. The 217 serious AEs reported in therapeutic cases involved a wide spectrum of events and included all 28 reported deaths. Among cosmetic users, no deaths were reported and, of the 36 serious AEs, 30 were included as possible complications in the FDA-approved label. The remaining 6 serious AEs did not display a pattern suggesting a common causal relationship to BTA. Among the 995 cosmetic cases reported to have nonserious AEs, most commonly noted were lack of effect (623, 63%), injection site reaction (190, 19%), and ptosis (111, 11%). Serious AEs were more likely to be reported for therapeutic than for cosmetic use, which may be related to higher doses, complicated underlying diseases, or both. Among cosmetic cases, few serious AEs were reported, and these were predominantly events that were previously recognized in clinical trials of BTA for the labeled use. This study is limited primarily by the incomplete nature of AE reporting by clinicians. Numerous departures from FDA-approved recommendations for drug dose, dilution, handling, site of injection, and storage were noted in these AE reports.


Immunomodulatory Effects of Perioperative Dexmedetomidine in Ovarian Cancer: An In Vitro and Xenograft Mouse Model Study.
The surgical stress response (SSR) causes immunosuppression which may cause residual tumor growth and micrometastasis after cancer surgery. We investigated whether dexmedetomidine affects cancer cell behavior and immune function in an ovarian cancer xenograft mouse model. The effect of dexmedetomidine on cell viability and cell cycle was assessed using SK-OV-3 cells at drug concentrations of 0.5, 0.1, 5, and 10 µg mL-1. BALB/c nude mice were used for the ovarian cancer model with the Dexmedetomidine group (n=6) undergoing surgery with dexmedetomidine infusion and the Control group (n=6) with saline infusion for 4 weeks. Natural killer (NK) cell activity, serum proinflammatory cytokines, and cortisol were measured at predetermined time points and tumor burden was assessed 4 weeks after surgery. Dexmedetomidine had no effect on cell viability or cell cycle. Following a sharp decrease on postoperative day (POD) 1, NK cell activity recovered faster in the Dexmedetomidine group with significant difference vs. the Control group on POD 3 (P=0.028). In the Dexmedetomidine group, cortisol levels were lower on POD 3 (P=0.004) and TNF-α levels were lower at 4 weeks after surgery (P<0.001) compared to the Control group. The Dexmedetomidine group showed lower tumor burden at 4 weeks vs. the Control group as observed by both tumor weight (P<0.001) and the in vivo imaging system (P=0.03). Dexmedetomidine infusion may improve ovarian cancer surgery outcome by suppressing the SSR and stress mediator release. Further studies are needed to elucidate the mechanisms by which dexmedetomidine acts on cancer and immune cells.


Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide.
The prognosis of patients with severe pulmonary hypertension (PHT) is poor. To determine prognosis and guide therapy, an acute hemodynamic trial of selective pulmonary vasodilators, usually inhaled nitric oxide (iNO), was performed. We hypothesized that oral sildenafil, a phosphodiesterase-5 inhibitor, is a safe and effective alternative to iNO. We studied 13 consecutive patients (mean+/-SEM, 44+/-2 years of age; 9 women) referred for consideration of heart-lung transplantation or as a guide to medical therapy. All but one were functional class III or IV. Patients had primary PHT (n=9), pulmonary arterial hypertension (n=2), or secondary PHT (n=2). Hemodynamics and serum cyclic guanosine-monophosphate levels (cGMP) were measured at baseline and at peak effects of iNO (80 ppm), sildenafil (75 mg), and their combination. The decrease in pulmonary vascular resistance was similar with iNO (-19+/-5%) and sildenafil (-27+/-3%), whereas sildenafil+iNO was more effective than iNO alone (-32+/-5%, P<0.003). Sildenafil and sildenafil+iNO increased cardiac index (17+/-5% and 17+/-4%, respectively), whereas iNO did not (-0.2+/-2.0%, P<0.003). iNO increased, whereas sildenafil tended to decrease, pulmonary capillary wedge pressure (+15+/-6 versus -9+/-7%, P<0.0007). Systemic arterial pressure was similar among groups and did not decrease with treatment. cGMP levels increased similarly with iNO and sildenafil, and their combination synergistically elevated cGMP (P<0.0001). A single oral dose of sildenafil is as effective and selective a pulmonary vasodilator as iNO. Sildenafil may be superior to iNO in that it increases cardiac output and does not increase wedge pressure. Future studies are indicated to establish whether sildenafil could be effective over a longer duration.


Functional Redundancy in Bat Microbial Assemblage in the Presence of the White Nose Pathogen.
Understanding how host-associated microbial assemblages respond to pathogen invasion has implications for host health. Until recently, most investigations have focused on understanding the taxonomic composition of these assemblages. However, recent studies have suggested that microbial assemblage taxonomic composition is decoupled from its function, with assemblages being taxonomically varied but functionally constrained. The objective of this investigation was to understand how the Tri-colored bat, Perimyotis subflavus cutaneous microbial assemblage responds to fungal pathogen invasion within a functional context. We hypothesized that at a broad scale (e.g., KEGG pathways), there will be no difference in the functional assemblages between the white nose pathogen, Pseudogymnoascus destructans, positive and negative bats; and this pattern will be driven by the functional redundancy of bacterial taxa. At finer scales (e.g., gene models), we postulate differences in function attributed to interactions between bacteria and P. destructans, resulting in the production of antifungal metabolites. To test this, we used a combination of shotgun metagenomic and amplicon sequencing to characterize the bat cutaneous microbial assemblage in the presence/absence of P. destructans. Results showed that while there was a shift in taxonomic assemblage composition between P. destructans positive and negative bats, there was little overall difference in microbial function. Functional redundancy across bacterial taxa was clear at a broad-scale; however, both redundancy and variation in bacterial capability related to defense against pathogens was evident at finer scales. While functionality of the microbial assemblage was largely conserved in relation to P. destructans, the roles of particular functional pathways in resistance to fungal pathogens require further attention.


Interleukin 32 participates in cardiomyocyte-induced oxidative stress, inflammation and apoptosis during hypoxia/reoxygenation via the NOD2/NOX2/MAPK signaling pathway.
Although reperfusion of the ischemic myocardium has been used as a vital treatment of various patients with cardiovascular disease, the accompanying myocardial ischemia-reperfusion injury (MIRI) can cause further damage, resulting in a poor prognosis. The present study aimed to explore the roles and regulatory mechanisms of interleukin (IL)-32, a pro-inflammatory cytokine, in MIRI. Cardiomyocytes were subjected to hypoxia and reoxygenation (H/R) to mimic MIRI. The effects of IL-32 on oxidative stress, inflammation and apoptosis of H/R-treated cells were assessed. Given that the nucleotide-binding oligomerization domain 2 (NOD2) and NADPH oxidase 2 (NOX2) play roles in the inflammatory response and myocardial ischemia, the role of this regulatory axis in the function of IL-32 was evaluated. The results indicated that IL-32 levels were elevated following H/R treatment. Downregulation of IL-32 expression attenuated H/R-induced reduction in cell viability, LDH release, oxidative stress, inflammation and apoptosis. Moreover, downregulation of IL-32 expression reversed the activation of the NOD2/NOX2/MAPK signaling pathway caused by H/R treatment. NOD2 overexpression altered the effects of the downregulation of IL-32 expression on the cells, indicating that this regulatory axis mediated the function of IL-32. Collectively, the data indicated that IL-32 participated in the induction of oxidative stress, inflammation, and apoptosis in cardiomyocytes during H/R treatment via the NOD2/NOX2/MAPK signaling pathway.


Vitamin D supplementation reduces serum lipids of children with hypertriacylglycerolemia: A randomized, triple-masked, placebo-controlled crossover trial.
This study aimed to evaluate the effect of cholecalciferol supplementation on the body composition and metabolic profile of children with hypertriacylglycerolemia. This is a randomized, triple-masked, placebo-controlled, crossover trial of 44 Brazilian children with hypertriacylglycerolemia, age 4 to 11 y. The sample included eutrophic and overweight/obese children according to body mass index for age, with sufficient and insufficient vitamin D basal levels. The intervention lasted 34 wk, with two periods of 12 wk each separated by a 10-wk washout. The two groups, supplemented and placebo, received five drops of cholecalciferol (equivalent to 1000 international unit/d) and five drops of sunflower oil, respectively, daily for 12 wk. Sociodemographic, economic, sunscreen use, percentage of body surface area daily exposed to sun, physical activity, anthropometry (body mass and height), body composition (waist circumference, body fat percentage, fat-free mass, triceps, and subscapular skinfolds), biochemical profile (25-hydroxyvitamin D, fasting glucose, and lipid fractions), blood pressure, and food intake data were collected. Of the 44 children who concluded the study, 56.80% were female, 54.50% were of brown race, 81.82% had sufficient serum 25-hydroxyvitamin D (≥75 nmol/L), and 50.00% were overweight/obese according to body mass index for age. There was a reduction in serum total cholesterol (P < 0.001), low-density lipoprotein cholesterol (P < 0.001), nonhigh-density lipoprotein cholesterol (P < 0.001), total cholesterol/high-density lipoprotein cholesterol (P = 0.001), and low/high-density lipoprotein cholesterol ratios (P < 0.001) in the supplemented group compared with the placebo group. Cholecalciferol supplementation improved the lipid profile of children with hypertriacylglycerolemia without altering body composition.


Sonographic evaluation of atherosclerosis burden in carotid arteries of ischemic stroke patients and its relation to paraoxonase 1 and 2, MTHFR and AT1R genetic variants.
Common variants of the Paraoxonase (PON), 5-Methyl-Tetrahydrofolate-Reductase (MTHFR) and Angiotensin-II receptor 1 (AT1R) genes have been associated with ischemic stroke (IS) risk. Moreover, carotid atherosclerosis is a common cause of IS. The aim of this study is to explore whether variants in these genes associate with the severity of ultrasonographic determined atherosclerosis assessed in carotid arteries. Etiologic subtype of cerebral ischemia was determined according to the TOAST classification. Genotypes were detected by PCR and restriction analysis. An ultrasonographic supra-aortic trunks study was performed to all patients to assess their atherosclerotic involvement based on predefined criteria. In IS patients, none of the analyzed gene distributions differed concerning the stenosis degree. Nevertheless, a trend was observed for the rs662 and rs7493 variants of the PON1 and PON2 genes respectively. When evaluated the results based on different inheritance models, a significant contribution of rs7493 variant according to a dominant (OR=2.397, 95% CI (1.001-5.376); p=0.045) and log-additive inheritance forms (OR=1.85, 95% CI (1.07-3.2); p=0.03) was observed. Only rs7493 reached statistical significance (p=0.013), when genotype distribution was analyzed according to carotid intima-media thickness (cIMT) and remain significant in multivariate logistic regression analysis (OR=2.66, 95% CI (1.1 to 6.4); p=0.03). In IS patients of the north area of the Gran Canaria island the PON2 (rs7493) gene variant associates with a worse ultrasonographic profile. Conversely, the Cys311Cys homozygosis of the rs7493 variant was also related to a better ultrasonographic profile in our study.


Inside the 'Hurt Locker': The Combined Effects of Explosive Ordnance Disposal and Chemical Protective Clothing on Physiological Tolerance Time in Extreme Environments.
Explosive ordnance disposal (EOD) technicians are often required to wear specialized clothing combinations that not only protect against the risk of explosion but also potential chemical contamination. This heavy (>35kg) and encapsulating ensemble is likely to increase physiological strain by increasing metabolic heat production and impairing heat dissipation. This study investigated the physiological tolerance times of two different chemical protective undergarments, commonly worn with EOD personal protective clothing, in a range of simulated environmental extremes and work intensities Seven males performed 18 trials wearing 2 ensembles. The trials involved walking on a treadmill at 2.5, 4, and 5.5 km h(-1) at each of the following environmental conditions, 21, 30, and 37°C wet bulb globe temperature. The trials were ceased if the participants' core temperature reached 39°C, if heart rate exceeded 90% of maximum, if walking time reached 60min or due to volitional fatigue. Physiological tolerance times ranged from 8 to 60min and the duration (mean difference: 2.78min, P > 0.05) were similar in both ensembles. A significant effect for environment (21 > 30 > 37°C wet bulb globe temperature, P < 0.05) and work intensity (2.5 > 4 > 5.5 km h(-1), P < 0.05) was observed in tolerance time. The majority of trials across both ensembles (101/126; 80.1%) were terminated due to participants achieving a heart rate equivalent to greater than 90% of their maximum. Physiological tolerance times wearing these two chemical protective undergarments, worn underneath EOD personal protective clothing, were similar and predominantly limited by cardiovascular strain.


Can nonproliferative breast disease and proliferative breast disease without atypia be distinguished by fine-needle aspiration cytology?
Cytologic criteria reported to be helpful in the distinction of proliferative breast disease without atypia (PBD) from nonproliferative breast disease (NPBD) have not been rigorously tested. Fifty-one air-dried, Diff-Quik-stained fine-needle aspirates (FNA) of palpable breast lesions with biopsy-proven diagnoses of NPBD (34 cases) or PBD (17 cases) were reviewed. The smears were evaluated for the cellularity, size, and architectural arrangement of the epithelial groups; the presence of single epithelial cells and myoepithelial cells; and nuclear characteristics. The only cytologic feature found to be significantly different between PBD and NPBD was a swirling pattern of epithelial cells. A swirling pattern was noted in 13 of 17 PBD cases (76%) and 12 of 34 NPBD cases (35%) (P = 0.008). Because there is significant overlap in cytologic features between NPBD and PBD, the distinction between the two entities is difficult in cytologic sampling.


Putrescine transformation to other forms of polyamines in filling grain embryos functioned in enhancing the resistance of maize plants to drought stress.
Polyamines (PAs), one of plant growth regulators, play an important role in the plant resistance to drought stress. However, the precise function of putrescine (Put) transformation to other forms of PAs is not clear in filling maize grain embryos. In this study, two maize (Zea mays L.) cultivars, Yedan No. 13 (drought-resistant) and Xundan No. 22 (drought-sensitive), were used as experimental materials. Maize was planted in big plastic basins during whole growth period, and from the 25th day after fertilization, the plants were treated with drought (-1.0 MPa), PAs and inhibitors for 12 d. The experiments were performed during three consecutive years. The changes in the levels of three main free PAs, Put, spermidine (Spd) and spermine (Spm), covalently conjugated PAs (perchloric acid-soluble), covalently bound PAs (perchloric acid-insoluble), the activities of arginine decarboxylase, S-adenosylmethionine decarboxylase, and transglutaminase were investigated in embryos of filling grains. During drought stress, free Put increased from 109 to 367 nmol g-1 FW and from 107 to 142 nmol g-1 FW in Xundan 22 and in Yedan 13, respectively. Meanwhile, free Spd, free Spm and bound Put increased 2.7, 3.0 and 4.2 times in Yedan 13, respectively, and they merely increased about 1.5 times in Xundan 22. These results suggested that free Spd/Spm and bound Put, which were transformed from free Put, were possibly involved in drought resistance. Exogenous Spd treatment enhanced the drought-induced increase in endogenous free Spd/Spm content in drought-sensitive Xundan 22, coupled with the increase in drought resistance, as judged by the decrease in ear leaf relative plasma membrane permeability and increases in ear leaf relative water content, 1000-grain weight and grain number per ear. The suggestion was further testified with methylglyoxal-bis guanylhydrazone and o-phenanthrolin treatments. Collectively, it could be inferred that transformation of free Put to free Spd/Spm and bound Put in filling grain embryos functioned in enhancing the resistance of maize plants to soil drought.


Migraine in metabolic syndrome.
Recent studies suggest that insulin resistance is more common in patients with migraine. Insulin resistance underlies the pathogenesis of obesity, diabetes, and hypertension that are components of metabolic syndrome. As migraine is associated with an increased risk of vascular disorders, such as stroke, and migraine patients have higher diastolic blood pressure than healthy individuals, we aimed to investigate the 1-year prevalence of migraine in metabolic syndrome. Two hundred ten patients with metabolic syndrome were enrolled in the study. Migraine was diagnosed according to International Classification of Headache Disorders-II criteria. Migraine prevalence was estimated as 11.9% in men and 22.5% in women with metabolic syndrome. Of the metabolic syndrome components, diabetes, increased waist circumference, and body mass index were significantly more frequent in patients with migraine in contrast to those without migraine (P<0.05). Hypertension and dyslipidemia frequencies showed no difference between 2 groups. Our results demonstrate that migraine prevalence in metabolic syndrome was higher than in the general population.


Correlation between manganese dissolution and dynamic phase stability in spinel-based lithium-ion battery.
Historically long accepted to be the singular root cause of capacity fading, transition metal dissolution has been reported to severely degrade the anode. However, its impact on the cathode behavior remains poorly understood. Here we show the correlation between capacity fading and phase/surface stability of an LiMn2O4 cathode. It is revealed that a combination of structural transformation and transition metal dissolution dominates the cathode capacity fading. LiMn2O4 exhibits irreversible phase transitions driven by manganese(III) disproportionation and Jahn-Teller distortion, which in conjunction with particle cracks results in serious manganese dissolution. Meanwhile, fast manganese dissolution in turn triggers irreversible structural evolution, and as such, forms a detrimental cycle constantly consuming active cathode components. Furthermore, lithium-rich LiMn2O4 with lithium/manganese disorder and surface reconstruction could effectively suppress the irreversible phase transition and manganese dissolution. These findings close the loop of understanding capacity fading mechanisms and allow for development of longer life batteries.


Effective treatment of hospital wastewater with high-concentration diclofenac and ibuprofen using a promising technology based on degradation reaction catalyzed by Fe0 under microwave irradiation.
Real hospital wastewater was effectively treated by a promising technology based on degradation reaction catalyzed by Fe0 under microwave irradiation in this work. Fe0 powders were synthesized and characterized by different techniques, resulting in a single-phase sample with spherical particles. Optimum experimental conditions were determined by a central composite rotatable design combined with a response surface methodology, resulting in 96.8% of chemical oxygen demand reduction and 100% organic carbon removal, after applying MW power of 780 W and Fe0 dosage of 0.36 g L-1 for 60 min. Amongst the several organic compounds identified in the wastewater sample, diclofenac and ibuprofen were present in higher concentrations; therefore, they were set as target pollutants. Both compounds were completely degraded in 35 min of reaction time. Their plausible degradation pathways were investigated and proposed. Overall, the method developed in this work effectively removed high concentrations of pharmaceuticals in hospital wastewater.


The Association between TNF-α, IL-6, and Vitamin D Levels and COVID-19 Severity and Mortality: A Systematic Review and Meta-Analysis.
An increasing number of scientific journals have proposed a connection between tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the severity of COVID-19. Vitamin D has been discussed as a potential therapy for COVID-19 due to its immunomodulatory effects. This meta-analysis aims to determine the relationship, if any, between TNF-α, IL-6, vitamin D, and COVID-19 severity and mortality. The design of the study is a systematic review and meta-analysis. A literature search is performed using PubMed, Cochrane, ProQuest, and Google Scholar. TNF-α insignificantly increases the risk of COVID-19 severity (adjusted odds ratio (aOR) = 1.0304; 95% CI 0.8178-1.2983; p = 0.80) but significantly increases the risk of COVID-19 mortality (crude hazard ratio (HR) = 1.0640; 95% CI 1.0259-1.1036; p = 0.0009). IL-6 significantly increases the risk of COVID-19 severity (aOR = 1.0284; 95% CI 1.0130-1.0441; p = 0.0003) and mortality (aOR = 1.0076; 95% CI 1.0004-1.0148; p = 0.04; adjusted hazard ratio (aHR) = 1.0036; 95% CI 1.0010-1.0061; p = 0.006). There is a statistically insignificant difference of the mean vitamin D levels between patients with severe COVID-19 and non-severe COVID-19 (mean difference (MD) = -5.0232; 95% CI 11.6832-1.6368; p = 0.14). A vitamin D deficiency insignificantly increases the risk of mortality of COVID-19 patients (aOR = 1.3827; 95% CI 0.7103-2.6916; p = 0.34). IL-6 is an independent prognostic factor towards COVID-19 severity and mortality.


IS900-PCR-based detection and characterization of Mycobacterium avium subsp. paratuberculosis from buffy coat of cattle and sheep.
Johne's disease is one of the main causes of economic losses in ruminants and a major health hazard in the developing and developed world. Up till now, many microbiological, serological and molecular methods have been tried for the detection of Mycobacterium avium subsp. paratuberculosis (MAP). In this study, we attempt a PCR-based detection of IS900, distinct insertion sequences of MAP from the buffy coat of cattle (n=262) and sheep (n=78), and direct genotyping by single strand conformational polymorphism (SSCP). A total of 30 (11.45%) cattle and one sheep (1.28%) were positive for MAP-IS900. This IS900-based PCR detection proved highly specific, particularly when tested on other non-MAP strains. SSCP analysis grouped the MAP-IS900 into four distinct clusters based on different band patterns. Nucleotide sequence variability between MAPs detected from sheep (GenBank accession ) and cattle (GenBank accession -) was noticed in the study. Although, in recent years IS900-PCR-based detection of MAP from WBCs is being used in human, its use in animals is still limited. Our work not only supports its use in animals but also suggests further IS900-SSCP-based MAP-genotyping, coupled with DNA sequencing, as a promising tool for rapid and effective Johne's disease surveillance.


Crosslinked sulfonated polyacrylamide (Cross-PAA-SO3H) tethered to nano-Fe3O4 as a superior catalyst for the synthesis of 1,3-thiazoles.
Crosslinked sulfonated polyacrylamide (Cross-PAA-SO3H) attached to nano-Fe3O4 as a superior catalyst has been used for the synthesis of 3-alkyl-4-phenyl-1,3-thiazole-2(3H)-thione derivatives through a three-component reactions of phenacyl bromide or 4-methoxyphenacyl bromide, carbon disulfide and primary amine under reflux condition in ethanol. A proper, atom-economical, straightforward one-pot multicomponent synthetic route for the synthesis of 1,3-thiazoles in good yields has been devised using crosslinked sulfonated polyacrylamide (Cross-PAA-SO3H) tethered to nano-Fe3O4. The catalyst has been characterized by Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), dynamic light scattering (DLS), X-ray powder diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA) and vibrating-sample magnetometer (VSM).


Time-varying data processing with nonvolatile memristor-based temporal kernel.
Recent advances in physical reservoir computing, which is a type of temporal kernel, have made it possible to perform complicated timing-related tasks using a linear classifier. However, the fixed reservoir dynamics in previous studies have limited application fields. In this study, temporal kernel computing was implemented with a physical kernel that consisted of a W/HfO2/TiN memristor, a capacitor, and a resistor, in which the kernel dynamics could be arbitrarily controlled by changing the circuit parameters. After the capability of the temporal kernel to identify the static MNIST data was proven, the system was adopted to recognize the sequential data, ultrasound (malignancy of lesions) and electrocardiogram (arrhythmia), that had a significantly different time constant (10-7 vs. 1 s). The suggested system feasibly performed the tasks by simply varying the capacitance and resistance. These functionalities demonstrate the high adaptability of the present temporal kernel compared to the previous ones.


Gonadotropin stimulated protein phosphorylation in porcine granulosa cells.
Treatment of granulosa cells with luteinizing hormone (LH) or follicle-stimulating hormone (FSH) stimulated the phosphorylation of a 58,000 molecular weight protein found in the 900 x g pellet. The phosphorylation of this protein was rapid, being significant at 1 min. LH treatment for 30 min induced greater phosphorylation of this protein than did FSH. LH and FSH also appeared to stimulate the phosphorylation of different 900 x g pellet proteins. Since both are known to utilize cAMP as a second messenger, the finding of these unique gonadotropin-induced phosphorylations may point to an additional regulatory mechanism.


Aureobasidium pullulans metabolism of prostaglandins of the A-type.
Aureobasidium pullulans, originally introduced as an inadvertent contaminant in solutions used for evaluating the stability of prostaglandins, proved to lead to the rapid disappearance of the cyclopentenone unit of PGA2 (as monitored by circular dichroic spectroscopy). The cyclopentenone unit is converted, in various metabolites, to a 9-keto, 9 alpha or 9 beta-hydroxy group lacking the ring unsaturation. The major EtoAc-soluble 9-hydroxy metabolite (Compound-I) was shown to be 9 alpha, 15 alpha-dihydroxy-2, 3, 4, 5-tetranor-13-trans-prostenoic acid. Similar tetranor 9-hydroxy metabolites with one additional degree of unsaturation, and with a 9 beta-hydroxy group, also occur but these have not been fully characterized. Only two of the wide range of 9-keto metabolites are fully characterized by mass spectral (MS) data: 9, 15-oxo-2, 3, 4, 5-tetranorprostanoic acid and 9, 15-oxo-2, 3, 4, 5-tetranor-13-trans-prostenoic acid. The water soluble metabolites have not been characterized further. The fully characterized metabolites together with MS data from mixtures of minor metabolites indicate that A. pullulans can perform the following transformation: beta-oxidation, dehydrogenation at C-15, reduction of the enone carbon-carbon double bonds (both delta 10,11 and delta 13,14), reduction of the 9-ketone, and possibly migration of the cyclopentyl double bond (delta 10, 11 leads to delta 11, 12). A. pullulans metabolizes 15-epimeric PGA2 equally readily with the production of similar products. PGA1 affords less 9-keto metabolites with compound I constituting 33% of the product by HPLC analysis. A. pullulans displays some enantioselectivity, PGA2 and 15-epi-PGA2 are each metabolized more rapidly than their enantiomers. Other prostaglandins appear to be less readily metabolized.


Mapping the Phospho-dependent ALK Interactome to Identify Novel Components in ALK Signaling.
Protein-protein interactions (PPIs) play essential roles in Anaplastic Lymphoma Kinase (ALK) signaling. Systematic characterization of ALK interactors helps elucidate novel ALK signaling mechanisms and may aid in the identification of novel therapeutics targeting related diseases. In this study, we used the Mammalian Membrane Two-Hybrid (MaMTH) system to map the phospho-dependent ALK interactome. By screening a library of 86 SH2 domain-containing full length proteins, 30 novel ALK interactors were identified. Many of their interactions are correlated to ALK phosphorylation activity: oncogenic ALK mutations potentiate the interactions and ALK inhibitors attenuate the interactions. Among the novel interactors, NCK2 was further verified in neuroblastoma cells using co-immunoprecipitation. Modulation of ALK activity by addition of inhibitors lead to concomitant changes in the tyrosine phosphorylation status of NCK2 in neuroblastoma cells, strongly supporting the functionality of the ALK/NCK2 interaction. Our study provides a resource list of potential novel ALK signaling components for further study.


Foot Rotation Gait Modifications Affect Hip and Ankle, But Not Knee, Stance Phase Joint Reaction Forces During Running.
Alterations of foot rotation angles have successfully reduced external knee adduction moments during walking and running. However, reductions in knee adduction moments may not result in reductions in knee joint reaction forces. The purpose of this study was to examine the effects of internal and external foot rotation on knee, hip, and ankle joint reaction forces during running. Motion capture and force data were recorded of 19 healthy adults running at 3.35 m/s during three conditions: (1) preferred (normal) and with (2) internal and (3) external foot rotation. Musculoskeletal simulations were performed using opensim and the Rajagopal 2015 model, modified to a two degree-of-freedom knee joint. Muscle excitations were derived using static optimization, including muscle physiology parameters. Joint reaction forces (i.e., the total force acting on the joints) were computed and compared between conditions using one-way analyses of variance (ANOVAs) via statistical parametric mapping (SPM). Internal foot rotation reduced resultant hip forces (from 18% to 23% stride), while external rotation reduced resultant ankle forces (peak force at 20% stride) during the stance phase. Three-dimensional and resultant knee joint reaction forces only differed at very early and very late stance phase. The results of this study indicate, similar to previous findings, that reductions in external knee adduction moments do not mirror reductions in knee joint reaction forces.


Erucic acid from Isatis indigotica Fort. suppresses influenza A virus replication and inflammation in vitro and in vivo through modulation of NF-κB and p38 MAPK pathway.
Isatis indigotica Fort. (Ban-Lan-Gen) is an herbal medicine prescribed for influenza treatment. However, its active components and mode of action remain mostly unknown. In the present study, erucic acid was isolated from Isatis indigotica Fort., and subsequently its underlying mechanism against influenza A virus (IAV) infection was investigated in vitro and in vivo. Our results demonstrated that erucic acid exhibited broad-spectrum antiviral activity against IAV resulting from reduction of viral polymerase transcription activity. Erucic acid was found to exert inhibitory effects on IAV or viral (v) RNA-induced pro-inflammatory mediators as well as interferons (IFNs). The molecular mechanism by which erucic acid with antiviral and anti-inflammatory properties was attributed to inactivation of NF-κB and p38 MAPK signaling. Furthermore, the NF-κB and p38 MAPK inhibitory effect of erucic acid led to diminishing the transcriptional activity of interferon-stimulated gene factor 3 (ISGF-3), and thereby reducing IAV-triggered pro-inflammatory response amplification in IFN-β-sensitized cells. Additionally, IAV- or vRNA-triggered apoptosis of alveolar epithelial A549 cells was prevented by erucic acid. In vivo, erucic acid administration consistently displayed decreased lung viral load and viral antigens expression. Meanwhile, erucic acid markedly reduced CD8+ cytotoxic T lymphocyte (CTL) recruitment, pro-apoptotic signaling, hyperactivity of multiple signaling pathways, and exacerbated immune inflammation in the lung, which resulted in decreased lung injury and mortality in mice with a mouse-adapted A/FM/1/47-MA(H1N1) strain infection. Our findings provided a mechanistic basis for the action of erucic acid against IAV-mediated inflammation and injury, suggesting that erucic acid may have a therapeutic potential in the treatment of influenza.


SmI2 -mediated C-alkylation of Ketones with Alcohols under Microwave Conditions: A Novel Route to Alkylated Ketones.
A novel protocol is developed towards the preparation of alkylated ketones from alcohols in presence of catalytic amount of SmI2 and base with the elimination of water as a single by-product under microwave irradiation conditions. Furthermore, applicability of this methodology to the synthesis of Donepezil and late-stage functionalization in Pregnenolone is also reported. Successful application of this methodology in Friedländer quinolone synthesis using 2-aminobenzyl alcohol and various acetophenones expand the synthetic utility of this protocol.


CDP840. A prototype of a novel class of orally active anti-inflammatory phosphodiesterase 4 inhibitors.
The discovery, synthesis and biological activity of a series of triarylethane phosphodiesterase 4 inhibitors is described. Structure-activity relationship studies are presented for CDP840 (29), a potent, chiral, selective inhibitor of PDE 4 (IC(50) 4nM). CDP840 is non-emetic in the ferret at 30mgkg(-1) (po), active in models of inflammation and reverses ozone-induced bronchial hyperreactivity in the guinea pig.


Stimulation of the glucose transport system in isolated mouse pancreatic acini by cholecystokinin and analogues.
Cholecystokinin and analogues increased the uptake of 2-deoxy-D-glucose and 3-O-methylglucose into isolated mouse pancreatic acini. This uptake was mediated by a facilitated glucose transport system that was saturable, stereospecific, and was inhibited by both phloretin and cytochalasin B. In agreement with previous studies of acinar function, caerulein was more potent and pentagastrin less potent than cholecystokinin in increasing sugar transport. The cholinergic analogue carbachol mimicked the effect of caerulein; atropine completely abolished the effects of carbachol but was without influence on the effects of the polypeptide hormones. In contrast, secretion, as well as dibutyryl cyclic AMP and dibutyryl cyclic GMP, had no effect on 2-deoxy-D-glucose uptake. Two lines of evidence suggested that hormonal stimulation of this sugar transport system was related to mobilization of cellular Ca2+. First, depletion of cellular Ca2+ by incubation of acini with ethylene glycol bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) reduced the effect of caerulein. Second, the Ca2+ ionophore A23187 mimicked the effects of caerulein on 2-deoxy-D-glucose uptake when Ca2+ was present in the medium.


Activity of some enzymes in the cortex of the cat with pretrigeminal brainstem transection.
The visual and somatic sensory cortex were investigated. The activity of acetylcholinesterase and lactate dehydrogenase was similar in the pretrigeminal and non-operated cats. The activity of these two enzymes, as well as that of choline acetyltransferase, butyrylcholinesterase and acid phosphatase was similar 3 and 8 h after the pretrigeminal transection. Results support the possibility of utilizing the pretrigeminal cat for investigations of biochemical correlates of learning.


Kinetic modeling of Maillard and caramelization reactions in sucrose-rich and low moisture foods applied for roasted nuts and seeds.
A kinetic model was proposed by using a multiresponse kinetic modeling approach for Maillard and caramelization reactions in low moisture foods at neutral pH containing a moderate amount of amino acid and sucrose but a restricted amount reducing sugar. The change in the amount of sucrose, protein-bound lysine, free amino acids, and certain products of Maillard reaction was monitored during roasting of sunflower seed, pumpkin seed, flaxseed, peanut, and almond at 160 and 180 °C. A slightly different model was proposed for pumpkin seed due to its difference in compositional and physicochemical characteristics as expressed by principal component analysis. Accordingly, 3-deoxyglucosone formation via sugar degradation; 5-hydroxymethylfurfural formation from 3-deoxyglucosone and only in pumpkin seeds the conversion of N-ε-fructoselysine to glyoxal and Heyns product to 1-deoxyglucosone were found to be quantitatively important. N-ε-carboxymethyllysine and N-ε-carboxyethyllysine mainly originated through oxidation of N-ε-fructoselysine and the reaction of methylglyoxal with lysine residue, respectively.


Psoriasin (S100A7) and calgranulin-B (S100A9) induction is dependent on reactive oxygen species and is downregulated by Bcl-2 and antioxidants.
S-100 proteins are calcium-binding proteins with important growth regulatory functions. Of these proteins, psoriasin and calgranulin-B have been shown to be highly upregulated in ductal carcinoma in situ (DCIS) of the breast and in psoriasis. The purpose of this study was to further elucidate the functional relevance of the overexpression of these two S-100 proteins in psoriasis and DCIS. We report the induction of both proteins by reactive oxygen species, phorbol ester TPA, and the induction of psoriasin in response to the PI3K inhibitor wortmannin. We also demonstrate that Bcl-2 overexpression represses the induction of psoriasin and calgranulin-B under these different conditions. The same effect was obtained with the antioxidant NAC, which indicates that the suppression of psoriasin and calgranulin-B induction is mediated by the antioxidant function of Bcl-2. Furthermore, we demonstrate that overexpression of a dominant negative IKKbeta also inhibits the induction of psoriasin suggesting that the NFkappaB pathway is involved in the induction of this protein. Also, we found NFkappaB responsive DNA elements in the upstream promoter region of psoriasin. MCF10A cells with a stable retroviral overexpression of psoriasin were significantly more resistant to H2O2-induced cell death than control cells further supporting the hypothesis that these S-100 proteins may play a role in oxidative stress response.


A propensity score-weighted comparison between adalimumab originator and its biosimilars, ABP501 and SB5, in inflammatory bowel disease: a multicenter Italian study.
Adalimumab is an effective and safe biological drug for the treatment of inflammatory bowel disease (IBD). Nowadays, several biosimilar agents are available, but data regarding their efficacy and safety in patients with IBD are still lacking. We aimed to compare the effectiveness and tolerability between adalimumab originator, ABP501 and SB5 biosimilars in patients with IBD in the short term (after induction and after 6 months of treatment) through a propensity score-weighted multicenter cohort study. We included 156 patients with IBD, 69 patients with ulcerative colitis and 87 patients with Crohn's disease (CD) receiving ABP501 or SB5 biosimilars from January 2019 to April 2020 for moderate-to-severe disease. For comparison, a group of age- and sex-matched patients treated with adalimumab originator was used. We collected clinical and biochemical data after induction and at 6 months of treatment. Endoscopic data were recorded only at baseline. Overall, clinical benefit was achieved by 86.4% and 85.3% after induction and at 6 months, respectively, without a statistically significant difference between the three treatment groups (p = 0.68 and p = 0.46). However, after induction, we found significant differences between the two types of the disease (ulcerative colitis or CD, p = 0.004), with a greater clinical benefit achieved by patients with CD. Also, the therapeutic optimization rate between the three drugs was not statistically significant different (p = 0.30). All treatments showed a good safety profile, with only 10 patients who needed to stop therapy because of adverse events. Adalimumab biosimilars seem to be as effective and safe as the originator in patients with IBD. Surely, they represent a great opportunity to reduce the costs of biological therapies, however larger and longer real-life studies are necessary.


[A Prognostic Nomogram Based on Response to Bortezomib and BTK Expression for Treatment-Experienced Multiple Myeloma Patients].
To establish a prognostic nomogram based on response to bortezomib and BTK expression for treatment-experienced multiple myeloma patients. The Oncomine database was utilized to determine BTK expression, sex, age, albumin, Mayo index, response to bortezomib treatment, follow-up time and survival status in multiple myeloma(MM) patients. Cut-off point for BTK expression was calculated using R software. Univariate and multivariate analyses by Cox proportional hazards regression were then performed. Significant prognostic factors were combined to build a nomogram. The discrimination ability and predictive accuracy of the nomogram were evaluated using the index of concordance (C-index) and calibration curves. Multivariate analysis showed that response to bortezomib, BTK expression and sex were independent risk factors for prognosis. The C-index value of the nomogram made according to the independent risk factors was 0.729 (95%CI, 0.642-0.8164). The calibration curves showed good consistency between predicted and actual survivals for 1-year and 2-year overall survival. The proposed nomogram is accurate in predicting the prognosis of patients with MM.


Family structure and the intergenerational transmission of educational advantage.
I examine whether the effect of parents' education on children's educational achievement and attainment varies by family structure and, if so, whether this can be explained by differential parenting practices. Using data from the National Education Longitudinal Study of 1988, I find that as parents' education increases, children in single mother families experience a lower boost in their achievement test scores, likelihood of attending any post-secondary schooling, likelihood of completing a 4-year college degree, and years of completed schooling relative to children living with both biological parents. Differences in parents' educational expectations, intergenerational closure, and children's involvement in structured leisure activities partially explain these status transmission differences by family structure. The findings imply that, among children with highly educated parents, children of single mothers are less likely to be highly educated themselves relative to children who grow up with both biological parents.


Population pharmacokinetics and standard uptake value ratio of aducanumab, an amyloid plaque-removing agent, in patients with Alzheimer's disease.
Aducanumab is a human immunoglobulin G1 anti-amyloid beta (Aβ) antibody currently being evaluated for potential treatment of patients with early Alzheimer's disease. This paper describes the relationship between the population pharmacokinetics (PopPKs) and pharmacokinetics-pharmacodynamics (PKs-PDs) of aducanumab using data from phase I to III clinical studies, with standard uptake value ratio (SUVR) used as a PD marker. Across clinical studies, aducanumab was administered intravenously either as a single dose ranging from 0.3 to 60 mg/kg or as multiple doses of 1, 3, 6, or 10 mg/kg every 4 weeks. A titration regimen with maintenance doses of 3, 6, or 10 mg/kg was also evaluated. Aducanumab PK was characterized with a two-compartment model with first-order elimination. No nonlinearities in PKs were observed. The PopPK-PD model was developed using a sequential estimation approach. The time course of amyloid plaques, as expressed by composite SUVR measured using positron emission tomography, was described using an indirect response model with drug effect stimulating the elimination of SUVR. None of the identified covariates on PK and the PopPK-PD model were clinically relevant. The PopPK-PD model showed that magnitude, duration, and consistency of dosing are important factors determining the degree of Aβ removal. The intrinsic pharmacology of aducanumab remained consistent across studies.


The effect of maternal viral load on the risk of perinatal transmission of HIV-1. New York City Perinatal HIV Transmission Collaborative Study Group.
To determine the effect of maternal viral load at delivery on the risk of perinatal transmission of HIV-1. A nested case-control study within a prospectively followed cohort of HIV-1-infected pregnant women and their infants. The multicenter New York City Perinatal HIV Transmission Collaborative Study. Fifty-one women who gave birth to HIV-1 infected infants were frequency-matched within CD4+ cell count quintiles with 54 non-transmitting mothers. Maternal quantity of HIV-1 viral RNA was assayed in plasma obtained near delivery using the nucleic acid sequence-based amplification assay system. Viral RNA was detected in 73 (70%) out of 105 women and the median viral load was 16,000 RNA copies/ml in transmitters and 6,600 in non-transmitters (P < 0.01). When adjusted for maternal CD4+ count near delivery, women with measurable viral load were nearly sixfold more likely to transmit HIV-1 than women with viral load below detection [adjusted odds ratio (AOR), 5.8; 95% confidence interval (CI), 2.2 15.5]. The odds ratio for perinatal transmission of log10 viral load, adjusted for CD4 count was 2.7 (95% CI, 1.5-5.1). When stratified by the stage of HIV-1 disease, the only group with significant association between log10 viral load and transmission were AIDS-free women with CD4+ count > 500 x 10(6)/l (AOR, 9.1; 95% CI, 2.6-31.5). High maternal viral load increases the likelihood of perinatal transmission of HIV-1 in women without AIDS and advanced immunosuppression. HIV-1 infected pregnant women without advanced disease, shown by others to have the lowest risk of perinatal transmission, may benefit the most from efforts to identify and decrease viral load at delivery.


Parents' Attitudes Toward School Students' Overuse of Smartphones and Its Detrimental Health Impacts: Qualitative Study.
Parents' awareness of the risks of the overuse of smartphones (SPs) among their children and parents' attitudes toward this societal phenomenon are crucial factors to consider when investigating the causes and effects of, as well as interventions to control, this public health issue. This study aimed to explore the awareness and attitudes of parents regarding SP overuse among their children and the detrimental impacts associated with it. The qualitative method of semistructured face-to-face interviews was used to collect data from fathers and mothers of children aged 6-18 years from all 6 educational/governorate regions in the governmental sector in Kuwait. A total of 120 parents agreed to participate in the study; there were more female (75/120, 62.5%) than male (45/120, 37.5%) respondents. Almost all of the participants (118/120, 98.3%) were aware that the overuse of SPs could lead to their children becoming addicted to the devices; they were also aware that there could be side effects on their children's health (117/120, 97.5%). Although the participants, mostly the mothers, supervised their children's use of SPs closely (106/120, 88.3%), the majority could not control their children's length of time using SPs, as the children considered this a deprivation of their rights. Eye-related problems, headaches, and anger were the most common side effects experienced by the children. Although the parents were aware of the detrimental impacts of SP overuse, the majority could not control the length of time their children spent using the devices. It was found that strong social bonds among family members play a large role in controlling the use of SPs. A number of solutions for families and the government to combat the overuse of SPs are suggested.


Impaired sustained attention in euthymic bipolar disorder patients and non-affected relatives: an fMRI study.
Behavioral deficits in sustained attention have been reported during both acute and euthymic phases of type I bipolar disorder (BD-I) and also in non-affected relatives of bipolar disorder (BD) patients. In particular, selective failure in target recognition was proposed as a potential trait marker for BD, but there are few studies exploring the neural correlates. The aim of the present study was to analyze the behavioral and functional magnetic resonance imaging (fMRI) response of euthymic BD-I patients and non-affected relatives during a sustained attention task. Twenty-four euthymic BD-I patients, 22 non-affected first-degree relatives of BD-I subjects, and 24 matched controls underwent a continuous performance test (CPT) with two levels of difficulty during event-related fMRI scanning. Both patients and relatives showed a lower accuracy in target detection when compared to controls. The fMRI data analysis revealed between-group differences in several brain regions involved in sustained attention. During error in target recognition, both patients and relatives showed a larger activation in the bilateral insula and the posterior part of the middle cingulate cortex. By contrast, during correct target response, only patients failed to activate the right insula, whereas relatives showed an increased activation of the left insula and bilateral inferior parietal lobule - limited to the higher attention load - and an augmented deactivation of the posterior cingulate/retrosplenial cortex. A selective impairment in target recognition during a CPT was behaviorally and functionally detectable in both euthymic BD-I patients and non-affected first-degree relatives, suggesting that specific sustained attention deficits may be a potential trait marker for BD-I.


The effects of solvents on embryonic stem cell differentiation.
Dimethyl sulfoxide (DMSO) and ethanol are common organic solvents used for dissolving lipophilic substances for in vitro testing. However, DMSO is known to induce differentiation in embryonic stem (ES) and embryonic teratocarcinoma (EC) cells. In order to clarify if solvents like DMSO and ethanol have an influence on in vitro developmental toxicity test systems, the presented study has evaluated their effects on differentiation by using different test systems. ES and EC cells were transfected with a construct containing the mTert promoter combined with the green fluorescent protein gene (GFP). A down-regulation of mTert, a marker for undifferentiated cells, results in a lower expression of GFP, which could be measured by flow cytometry. Taking the specific characteristics of ES and EC cells into account this effect could be a hint for the interaction of DMSO with embryonic development. Additionally, the effects of the solvents ethanol and DMSO on Oct-4 expression, another marker for undifferentiated cells, were measured in wild-type ES cells. Both selected molecular markers demonstrated an induction of differentiation after exposure to DMSO; in wild-type ES cells at a concentration of 0.125% and in transgenic EC cells at a concentration of 0.25% DMSO. All other differences from controls, including those which attained a level of statistical significance, were minor or not dosage related in degree, or were not consistent over time and are, therefore, considered to be of little toxicological importance. In addition, a cytotoxicity test demonstrated that the solvents affected the employed molecular markers in non-cytotoxic concentrations. The ES cells were the most sensitive towards the cytotoxic effects of the solvent DMSO while the EC cells were more sensitive when treated with the solvent ethanol.


Fast and reliable detection of carbapenemase genes in various Gram negatives using a new commercially available fluorescence-based real-time polymerase chain reaction platform.
The Revogene® Carba C assay is a real-time polymerase chain reaction-based assay that runs on the microfluidic Revogene platform. It was recently designed for the detection of genes encoding the 5 major carbapenemases (NDM, VIM, IMP, KPC, and OXA-48) from various Gram-negatives. A total of 145 clinical Gram-negative strains (96 carbapenemase producers and 49 non-carbapenemase producers) were tested. The overall sensitivity and specificity were 100%. All strains co-producing double carbapenemases have been correctly detected. All non-carbapenemase producers and nontargeted carbapenemase producers gave a negative result. The sample preparation was easy to handle, taking around 5 to 10 min per isolate, with a run time of approximately 70 min. This assay is a rapid, easy-to-perform, reliable tool to detect the most common carbapenemases, with excellent sensitivity and specificity regardless of the host bacteria. Given its user friendliness, simplicity, and short time to result, the Revogene® Carba C assay is suitable for microbiology laboratories.