Differential cardiopulmonary monitoring system for artifact-canceled physiological tracking of athletes, workers, and COVID-19 patients.
Soft, skin-integrated electronic sensors can provide continuous measurements of diverse physiological parameters, with broad relevance to the future of human health care. Motion artifacts can, however, corrupt the recorded signals, particularly those associated with mechanical signatures of cardiopulmonary processes. Design strategies introduced here address this limitation through differential operation of a matched, time-synchronized pair of high-bandwidth accelerometers located on parts of the anatomy that exhibit strong spatial gradients in motion characteristics. When mounted at a location that spans the suprasternal notch and the sternal manubrium, these dual-sensing devices allow measurements of heart rate and sounds, respiratory activities, body temperature, body orientation, and activity level, along with swallowing, coughing, talking, and related processes, without sensitivity to ambient conditions during routine daily activities, vigorous exercises, intense manual labor, and even swimming. Deployments on patients with COVID-19 allow clinical-grade ambulatory monitoring of the key symptoms of the disease even during rehabilitation protocols.


Bone marrow edema syndrome associated with uterine myoma: a case report.
A patient with bone marrow edema syndrome of the hip associated with a uterine myoma is presented. A 51-year-old woman could not walk because of severe pain in both hips and had been referred to the authors' institute. Magnetic resonance imaging scans showed abnormal intensity on T1- and T2-weighted images in both femoral heads and a large mass arising from the uterus which was diagnosed as a uterine myoma. A 99mTc-methylene diphosphonate scintigraph showed diffuse uptake in both femoral heads. The pain in both hips decreased shortly after a hysterectomy and the patient could walk without crutches within 2 weeks after the gynecologic surgery. Magnetic resonance imaging scans taken 8 months after surgery showed high signal intensity on T1- and T2-weighted images, indicating normal bone marrow in the femoral heads. To the authors' knowledge, this is the first case report showing a bone marrow edema syndrome of the hip associated with uterine myoma. The pathophysiologic mechanisms for bone marrow edema syndrome of the hip in the current patient and in pregnancy may be identical. More specifically, a large intrapelvic mass may cause an increase of intrapelvic pressure and subsequent blood stasis in both conditions. The current case suggests the possible factors of bone marrow edema syndrome of the hip which need to be investigated.


Influence of exercise adherence level on modifiable coronary heart disease risk factors and functional-fitness levels in middle-aged men.
The study investigated the potential health benefits of two levels of short-term exercise intervention, compared with non-intervention, on selected modifiable coronary heart disease (CHD) risk factors and functional fitness states in middle-aged men. All subjects underwent medical screening and signed informed consent before carrying out a standardized graded treadmill walk which required exercise up to 85% of age-predicted maximal heart rate. The results of the test were used together with musculoskeletal fitness assessments, for the prescription of a personalized exercise programme lasting 14 weeks. In all, 55 subjects were classified by adherence into high (HA, n = 20), low (LA, n = 19), or non-adherence (NA, n = 16) groups according to the degree of documented participation in the programme based on standard criteria (American College of Sports Medicine 1978, 1990). In addition, the respective groups of subjects were classified according to other modifiable and non-modifiable CHD risk factors and compared by self-reported levels of activity and sport involvement as well as perceived body weight classification. The results indicated that there were more comprehensive improvements in functional fitness including significant gains in aerobic endurance capacity, muscular endurance and flexibility in the HA group compared with the LA and NA groups. However, there was little or no change in the modifiable CHD risk factors in any of the respective groups, although anthropometric indices of weight, body mass index (BMI), skinfolds and waist:hips ratio tended to decrease in the HA and LA groups but increased marginally in the NA group.(ABSTRACT TRUNCATED AT 250 WORDS)


ISG15: a ubiquitin-like enigma.
ISG15 is a 17 kDa protein encoded by an interferon stimulated gene. Described in 1979, it was the first ubiquitin-like modifier to be identified, and its discovery followed the first reports of ubiquitin by only four years. While many important functions for ubiquitin have been reported, the functions for ISG15 and its conjugation are still largely unknown. Evidence suggests that ISG15 and its modification system play important roles in the innate immune response, regulation of interferon signaling, pregnancy, and several cancers. Modification of proteins by ISG15 occurs in a manner similar to that of ubiquitin and other ubiquitin-like modifiers. The enzymes which help perform the activation and conjugation of ISG15 have recently been identified. The conjugation enzyme identified for ISG15 was revealed to be an enzyme that was also involved in ubiquitin conjugation. Identification of an ISG15 specific protease has also been reported. Knockout of this protease in mice decreases the lifespan of these mice and makes them hypersensitive to treatment with interferon or lipopolysaccharide. The study of ISG15 and its modification system may yield a set of potentially useful therapeutic targets and thus, there is an increasing awareness and interest in this protein modifier. This review will highlight the history of its discovery, describe more recent observations about the enzymes involved in ISG15 modification, and summarize new findings which have important implications for the ISG15 system in signal transduction and immunology. This review will also point out important questions that remain to be answered and identify the major roadblocks which currently obstruct the understanding of ISG15 biologic functions.


Age-dependent responses of the mesenteric vasculature to ischemia-reperfusion.
The age-dependent responses of the mesenteric vasculature to ischemia-reperfusion (I/R) were compared in 2-mo-old and 2-yr-old rats. Measurements were made of leukocyte adherence, albumin leakage, and oxidative stress in postcapillary venules. In young rats I/R induced an increase in leukocyte adherence and albumin leakage, but in aged rats I/R induced an increase in albumin leakage without an increase in leukocyte adherence. Furthermore, I/R-induced oxidative stress was higher in the aged rats than in the young rats. To investigate whether the age-associated oxidative stress is related to a decrease in the role of nitric oxide, NG-nitro-L-arginine methyl ester (L-NAME) was superfused onto the mesentery of young and aged rats. L-NAME induced an increase in postcapillary protein leakage only in young rats; however, arteriolar constriction induced by L-NAME occurred in both age groups. These results suggest that different mechanisms contribute to the inflammatory responses and microvascular dysfunction elicited by I/R in young and aged rats.


The Dietary Approaches to Stop Hypertension eating plan affects C-reactive protein, coagulation abnormalities, and hepatic function tests among type 2 diabetic patients.
Few studies exist regarding the effects of the Dietary Approaches to Stop Hypertension (DASH) diet on novel cardiovascular risk factors among type 2 diabetic patients. We evaluated the effects of the DASH eating pattern on C-reactive protein (CRP) level, coagulation abnormalities, and hepatic function tests in type 2 diabetic patients. In this randomized, crossover clinical trial, 31 type 2 diabetic patients consumed a control diet or the DASH diet for 8 wk. The DASH diet was rich in fruits, vegetables, whole grains, and low-fat dairy products and low in saturated fat, total fat, cholesterol, refined grains, and sweets, with a total of 2400 mg/d sodium. The control diet was a standard diet for diabetic patients. There was a 4-wk washout between the 2 trial phases. The main outcome measures were CRP level, coagulation indices, and hepatic function tests. The mean percent change for plasma CRP level was -26.9 ± 3.5% after the DASH diet period and -5.1 ± 3.8% after the control diet period (P = 0.02). Decreases in both alanine aminotransferase and aspartate aminotransferase levels were greater after consuming the DASH diet compared with the control diet (-14.8 ± 3.0% vs -6.6 ± 3.4%; P = 0.001; -29.4 ± 3.7% vs -5.9 ± 1.4%; P = 0.001, respectively). The decrease in the plasma fibrinogen level during the DASH diet period (-11.4 ± 3.6%) was greater than that during the control diet (0.5 ± 3.4%) (P = 0.03). Among diabetic patients, the DASH diet can play an important role in reducing inflammation, plasma levels of fibrinogen, and liver aminotransferases. Future longer term studies are recommended.


LINC00520 is induced by Src, STAT3, and PI3K and plays a functional role in breast cancer.
Long non-coding RNAs (lncRNAs) have been implicated in normal cellular homeostasis as well as pathophysiological conditions, including cancer. Here we performed global gene expression profiling of mammary epithelial cells transformed by oncogenic v-Src, and identified a large subset of uncharacterized lncRNAs potentially involved in breast cancer development. Specifically, our analysis revealed a novel lncRNA, LINC00520 that is upregulated upon ectopic expression of oncogenic v-Src, in a manner that is dependent on the transcription factor STAT3. Similarly, LINC00520 is also increased in mammary epithelial cells transformed by oncogenic PI3K and its expression is decreased upon knockdown of mutant PIK3CA. Additional expression profiling highlight that LINC00520 is elevated in a subset of human breast carcinomas, with preferential enrichment in the basal-like molecular subtype. ShRNA-mediated depletion of LINC00520 results in decreased cell migration and loss of invasive structures in 3D. RNA sequencing analysis uncovers several genes that are differentially expressed upon ectopic expression of LINC00520, a significant subset of which are also induced in v-Src-transformed MCF10A cells. Together, these findings characterize LINC00520 as a lncRNA that is regulated by oncogenic Src, PIK3CA and STAT3, and which may contribute to the molecular etiology of breast cancer.


A reassessment of the genetic determinants, the effect of growth conditions and the availability of an electron donor on the nitrosating activity of Escherichia coli K-12.
Anaerobic, but not aerobic, cultures of Escherichia coli K-12 catalysed the rapid nitrosation of the model substrate 2,3-diaminonaphthalene when incubated with nitrite. Formate and lactate were effective electron donors for the nitrosation reaction, which was inhibited by nitrate. Optimal growth conditions for the expression of nitrosation activity by various strains and mutants were determined. Highest activities were found with bacteria that had been grown anaerobically in a minimal medium rather than in Lennox broth, with glycerol and fumarate rather than glucose as the main carbon and energy source, and in the presence of a low concentration of nitrate. Bacteria harvested in the early exponential phase were more active than those harvested in later stages of growth. Well-characterized mutants defective in the synthesis of one or more anaerobically induced electron transfer chains were screened for nitrosation activity under these optimal growth conditions: only the respiratory nitrate reductase encoded by the narGHJI operon was implicated as a major contributor to nitrosation activity. Due to the limited sensitivity of the assays currently available, a minor contribution from the two alternative nitrate reductases or even other molybdoproteins could not be excluded. The role of formate in nitrosation was complex and was clearly not limited simply to that of an electron donor in the bacterial reduction of nitrite to nitric oxide: at least two further, chemical roles were inferred. This extensive study of more than 400 independent cultures of E. coli K-12 and its derivatives resolved some, but not all, of the apparently conflicting data in the literature concerning nitrosation catalysed by enteric bacteria.


Should we recommend oral anticoagulation therapy in patients with atrial fibrillation undergoing coronary artery stenting with a high HAS-BLED bleeding risk score?
Recent European guidelines for the management of atrial fibrillation recommend oral anticoagulation (OAC) in patients with CHA(2)DS(2)-VASc score (congestive heart failure, hypertension, age ≥75 years, diabetes, history of previous stroke, vascular disease, age 65-74 years, and sex category [female]) ≥1. The HAS-BLED score (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly [>65 years], Drugs/alcohol concomitantly) has been suggested to assess bleeding risk in patients with atrial fibrillation (score ≥3 indicates high risk of bleeding). Despite the guidelines, this approach has never been tested in a cohort of patients with atrial fibrillation undergoing percutaneous coronary intervention with stent implantation. We studied 590 consecutive patients with atrial fibrillation undergoing percutaneous coronary intervention/stenting and CHA(2)DS(2)-VASC score >1 (ie, OAC recommended). We compared patients with low-intermediate bleeding risk (HAS-BLED 0-2) and high risk (HAS-BLED ≥3), the relation between CHA(2)DS(2)-VASC and HAS-BLED, and the benefit and risks of the use of OAC in patients with high bleeding risk. The development of any bleeding episode, thromboembolism, mortality, cardiac events, and the composite major adverse cardiac events (ie, death, acute myocardial infarction, and/or target lesion revascularization) end point was recorded as well as the composite major adverse events (ie, major adverse cardiac events, major bleeding, or thromboembolism) end point at 1-year follow-up. Of the study cohort, 420 (71%) had a HAS-BLED score ≥3, and patients who were on OAC at discharge had lower mortality rate (9.3% versus 20.1%; P<0.01) and major adverse cardiac events (13.0% versus 26.4%; P<0.01) but with a similar major adverse event (20.5% versus 27.6%; P=0.11) and higher major bleeding rate (11.8% versus 4.0%; P<0.01). In a Cox multivariable analysis in patients with HAS-BLED ≥3, predictors of increased death were chronic renal failure and heart failure (both P<0.05), whereas OAC at discharge was associated with a reduced death rate (P<0.01). Predictors of major bleeding were chronic renal failure and the use of drug-eluting stents (both P<0.05). Most patients with atrial fibrillation undergoing percutaneous coronary intervention/stenting have a high risk for major bleeding (HAS-BLED score ≥3). Even in these patients, OAC improves prognosis in these patients (reduced mortality and major adverse cardiac events) with an increase in major bleeding.


Cyclins that don't cycle--cyclin T/cyclin-dependent kinase-9 determines cardiac muscle cell size.
A subset of cyclin-dependent protein kinases--Cdk7, Cdk8, and Cdk9--participates directly, in complex ways, with the fundamental machinery for gene transcription, as elements of general transcription factors whose substrate is the C-terminal domain (CTD) of RNA polymerase II. Here, we review recent data implicating the CTD kinase Cdk9 as a critical determinant of cardiac hypertrophy, in vitro and in vivo. Diverse trophic signals that increase cardiac mass all activated Cdk9 (work load, the small G-protein Gaq, and the calcium-dependent phosphatase calcineurin in mouse myocardium; endothelin-1, a hypertrophic agonist, in cultured cardiomyocytes). Little or no change occurred in levels of the kinase or its activator, cyclin T. Instead, in all four hypertrophic models, Cdk9 activation involves the dissociation of 7SK small nuclear RNA (snRNA), an endogenous inhibitor. In culture, dominant-negative Cdk9 blocked ET-1-induced hypertrophy, whereas an anti-sense "knockdown" of 7SK snRNA provoked spontaneous cell growth. In trans-genie mice, concordant with these results, activation of Cdk9 activity via cardiac-specific overexpression of cyclin Tl suffices to provoke hypertrophy. Together, these findings implicate Cdk9 activity as a pivotal regulator of pathophysiological heart growth. Because hypertrophy, in turn, is a cardinal risk factor for developing cardiac pump failure, these results support the logic of examining Cdk9 as a potential drug target in heart disease.


Raman scattering and in-water ocean optical properties.
Inelastic (transpectral) scattering may contribute significantly to the in-waterlightfield. Major mechanisms for inelastic scattering include Raman scattering, which we show is important in clear ocean waters, and fluorescence from a variety of sources, which may be important in more turbid waters. We have determined the Raman cross section for liquid water, 8.2 x 10(-30) (cm(2) sr(-1) molecule(-1)), which is in agreement with the lower range of published values. The influence of Raman scattering, based on predictions of a modified two-stream model, is in agreement with measured values of spectral reflectance R(lambda,z) and the spectral diffuse attenuation coefficient for irradiance K(lambda,z). Inelastic scattering has important ramifications for several aspects of marine biooptics including the determination of in-water spectral absorption, the estimation of clear water ocean optical properties, and possibly various aspects of algal photobiology.


Advances in peptide-based human papillomavirus therapeutic vaccines.
Cervical cancer is the second leading cause of cancer in women worldwide. Human papillomavirus (HPV) is responsible for all cases of cervical cancer. Commercial prophylactic HPV vaccines are now available, but unfortunately these vaccines have no therapeutic effect against established HPV infections. In order to accelerate the control of cervical cancer and treat established HPV infections, it is necessary to develop therapeutic vaccines to eradicate HPV by generating cell-mediated immunity against HPV infected cells. Two HPV-encoded early proteins, the E6 and E7 oncoproteins, are the preferred targets because they are consistently expressed in virtually all cervical cancer cells and are necessary for the induction and maintenance of HPV-associated disease. A variety of vaccine strategies have been employed targeting immune responses to these proteins. Peptide-based vaccines are a promising strategy for the development of therapeutic HPV vaccines because of their safety, stability, and ease of production. This review summarizes the prospects of peptide-based vaccines for the treatment of established HPV infections. We address the challenges that scientists currently face for developing peptide-based vaccines and explore feasible strategies for improving the potency of the induced immune response with the aim of treating established HPV infections.


A method for the reconstruction of four-dimensional synchronized CT scans acquired during free breathing.
Breathing motion is a significant source of error in radiotherapy treatment planning for the thorax and upper abdomen. Accounting for breathing motion has a profound effect on the size of conformal radiation portals employed in these sites. Breathing motion also causes artifacts and distortions in treatment planning computed tomography (CT) scans acquired during free breathing and also causes a breakdown of the assumption of the superposition of radiation portals in intensity-modulated radiation therapy, possibly leading to significant dose delivery errors. Proposed voluntary and involuntary breath-hold techniques have the potential for reducing or eliminating the effects of breathing motion, however, they are limited in practice, by the fact that many lung cancer patients cannot tolerate holding their breath. We present an alternative solution to accounting for breathing motion in radiotherapy treatment planning, where multislice CT scans are collected simultaneously with digital spirometry over many free breathing cycles to create a four-dimensional (4-D) image set, where tidal lung volume is the additional dimension. An analysis of this 4-D data leads to methods for digital-spirometry, based elimination or accounting of breathing motion artifacts in radiotherapy treatment planning for free breathing patients. The 4-D image set is generated by sorting free-breathing multislice CT scans according to user-defined tidal-volume bins. A multislice CT scanner is operated in the ciné mode, acquiring 15 scans per couch position, while the patient undergoes simultaneous digital-spirometry measurements. The spirometry is used to retrospectively sort the CT scans by their correlated tidal lung volume within the patient's normal breathing cycle. This method has been prototyped using data from three lung cancer patients. The actual tidal lung volumes agreed with the specified bin volumes within standard deviations ranging between 22 and 33 cm3. An analysis of sagittal and coronal images demonstrated relatively small (<1 cm) motion artifacts along the diaphragm, even for tidal volumes where the rate of breathing motion is greatest. While still under development, this technology has the potential for revolutionizing the radiotherapy treatment planning for the thorax and upper abdomen.


A Hough transform global probabilistic approach to multiple-subject diffusion MRI tractography.
A global probabilistic fiber tracking approach based on the voting process provided by the Hough transform is introduced in this work. The proposed framework tests candidate 3D curves in the volume, assigning to each one a score computed from the diffusion images, and then selects the curves with the highest scores as the potential anatomical connections. The algorithm avoids local minima by performing an exhaustive search at the desired resolution. The technique is easily extended to multiple subjects, considering a single representative volume where the registered high-angular resolution diffusion images (HARDI) from all the subjects are non-linearly combined, thereby obtaining population-representative tracts. The tractography algorithm is run only once for the multiple subjects, and no tract alignment is necessary. We present experimental results on HARDI volumes, ranging from simulated and 1.5T physical phantoms to 7T and 4T human brain and 7T monkey brain datasets.


Does local adaptation to resources explain genetic differentiation among Daphnia populations?
Substantial genetic differentiation is frequently observed among populations of cyclically parthenogenetic zooplankton despite their high dispersal capabilities and potential for gene flow. Local adaptation has been invoked to explain population genetic differentiation despite high dispersal, but several neutral models that account for basic life history features also predict high genetic differentiation. Here, we study genetic differentiation among four populations of Daphnia pulex in east central Illinois. As with other studies of Daphnia, we demonstrate substantial population genetic differentiation despite close geographic proximity (<50 km; mean theta = 0.22). However, we explicitly tested and failed to find evidence for, the hypothesis that local adaptation to food resources occurs in these populations. Recognizing that local adaptation can occur in traits unrelated to resources, we estimated contemporary migration rates (m) and tested for admixture to evaluate the hypothesis that observed genetic differentiation is consistent with local adaptation to other untested ecological factors. Using Bayesian assignment methods, we detected migrants in three of the four study populations including substantial evidence for successful reproduction by immigrants in one pond, allowing us to reject the hypothesis that local adaptation limits gene flow for at least this population. Thus, we suggest that local adaptation does not explain genetic differentiation among these Daphnia populations and that other factors related to extinction/colonization dynamics, a long approach to equilibrium F(ST) or substantial genetic drift due to a low number of individuals hatching from the egg bank each season may explain genetic differentiation.


Potential impact of evidence-based medicine in acute coronary syndromes: insights from GUSTO-IIb. Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes trial.
The purpose of this study to determine whether use of cardiac medications reflects evidence-based recommendations for patients with non-ST elevation acute coronary syndromes. Agency for Health Care Policy and Research practice guidelines for unstable angina recommend the use of cardiac medications based on evidence from randomized trials. It is unknown whether practitioners in the U.S., Canada and Europe follow these recommendations in patients with non-ST elevation acute coronary syndromes. We studied 7,743 patients with non-ST elevation acute coronary syndromes enrolled in the international Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes trial. The use of aspirin, beta-adrenergic blocking agents, angiotensin-converting enzyme inhibitors and calcium channel blocking agents was determined at discharge for all patients and "ideal" patients (those with indications and no contraindications). Using published estimates of relative mortality reductions with these drugs, we calculated the lives that could have been saved at 1 year if discharge medication use had better matched guideline recommendations. Overall, guideline adherence at discharge in "ideal" patients was 85.6% for aspirin, 59.1% for beta-blockers and 51.7% for angiotensin-converting enzyme inhibitors. Calcium channel blockers were given to 26.7% of patients with a contraindication to these drugs. These rates were similar across locations of enrollment. Women and older patients less often received aspirin when "ideal," and younger patients more often received calcium channel blockers when they were contraindicated. If medication use had been more evidence-based, 1-year mortality might have been reduced by a relative 22%. There is significant room for improvement in the use of recommended drugs in patients with non-ST elevation acute coronary syndromes. Medication use that more closely follows recommendations could reduce mortality in this population.


Waist-to-Height Ratio in Indian Women: Comparison With Traditional Indices of Obesity, Association With Inflammatory Biomarkers and Lipid Profile.
We compared waist-to-height ratio (WHtR) with traditional anthropometric indices in healthy women aged 21 to 45 years from urban slums of Mumbai city, India. Lipid profile and inflammatory markers were measured in a subsample of 200 women, and their relationship with WHtR was examined. Mean WHtR was 0.50 ± 0.1, but a little more than half (51.9%) of the women had WHtR ≥0.50. WHtR could correctly identify centrally obese adult women, even when they were categorized as healthy or normal according to body mass index, waist circumference, waist to hip ratio, and percentage body fat. Also, in centrally obese women, inflammatory markers-namely, high-sensitivity C-reactive protein, interleukin-6, and interleukin-10-were significantly and positively correlated with WHtR. Thus, results of this study indicate that WHtR is a simple and effective anthropometric variable that has the potential to identify central obesity and the associated inflammation even in women with normal BMI.


Integrative structural modeling with small angle X-ray scattering profiles.
Recent technological advances enabled high-throughput collection of Small Angle X-ray Scattering (SAXS) profiles of biological macromolecules. Thus, computational methods for integrating SAXS profiles into structural modeling are needed more than ever. Here, we review specifically the use of SAXS profiles for the structural modeling of proteins, nucleic acids, and their complexes. First, the approaches for computing theoretical SAXS profiles from structures are presented. Second, computational methods for predicting protein structures, dynamics of proteins in solution, and assembly structures are covered. Third, we discuss the use of SAXS profiles in integrative structure modeling approaches that depend simultaneously on several data types.


Normalization of Congenital Venous Stasis Retinopathy Following Sclerotherapy of a Macrocystic Lymphatic Malformation.
The authors describe, for the first time to their knowledge, a case of a congenital macrocystic lymphatic malformation of the orbit with associated venous stasis retinopathy that acutely normalized after drainage and sclerotherapy of the lesion. Prenatal ultrasound revealed prominence of the left orbital soft tissue, and at birth, the patient was noted to have unilateral proptosis, tortuous retinal vessels, and intraretinal hemorrhages in all 4 quadrants in the left eye. MRI demonstrated a primarily intraconal, multiloculated, T2-hyperintense mass consistent with a lymphatic malformation. Ultrasound-guided cyst aspiration and sclerotherapy was performed, with subsequent improvement of the proptosis and resolution of the vessel tortuosity and intraretinal hemorrhages. Although venous stasis retinopathy is usually related to central retinal vein occlusion or carotid artery occlusive disease, any entity that increases orbital venous resistance can generate retinal venous dilation and intraretinal hemorrhages, including an orbital lymphatic malformation.


Risk Stratification for Diabetic Retinopathy Screening Order Using Deep Learning: A Multicenter Prospective Study.
Real-world evaluation of a deep learning model that prioritizes patients based on risk of progression to moderate or worse (MOD+) diabetic retinopathy (DR). This nonrandomized, single-arm, prospective, interventional study included patients attending DR screening at four centers across Thailand from September 2019 to January 2020, with mild or no DR. Fundus photographs were input into the model, and patients were scheduled for their subsequent screening from September 2020 to January 2021 in order of predicted risk. Evaluation focused on model sensitivity, defined as correctly ranking patients that developed MOD+ within the first 50% of subsequent screens. We analyzed 1,757 patients, of which 52 (3.0%) developed MOD+. Using the model-proposed order, the model's sensitivity was 90.4%. Both the model-proposed order and mild/no DR plus HbA1c had significantly higher sensitivity than the random order (P < 0.001). Excluding one major (rural) site that had practical implementation challenges, the remaining sites included 567 patients and 15 (2.6%) developed MOD+. Here, the model-proposed order achieved 86.7% versus 73.3% for the ranking that used DR grade and hemoglobin A1c. The model can help prioritize follow-up visits for the largest subgroups of DR patients (those with no or mild DR). Further research is needed to evaluate the impact on clinical management and outcomes. Deep learning demonstrated potential for risk stratification in DR screening. However, real-world practicalities must be resolved to fully realize the benefit.


Postoperative deep venous thrombosis after renal transplantation. Effects of cyclosporine.
In this prospective study the frequency of deep venous thrombosis during the first three weeks after renal transplantation was determined using a combination of strain gauge plethysmography and thermography for objective diagnosis. Ninety-seven consecutive patients were studied, 30 patients having juvenile diabetes mellitus. As immunosuppression cyclosporine and low-dose steroids were used. The series was compared with a similar group of 83 patients, 33 having juvenile diabetes mellitus treated with azathioprine and high-dose steroids as immunosuppression, in which the diagnosis of deep venous thrombosis was made with an identical technique. The overall frequency of thrombosis was 9.3% in the cyclosporine-treated group, which is a significant reduction in comparison with the azathioprine group (24.1%). It is concluded that the combination of cyclosporine and low-dose steroids does not increase the frequency of deep venous thrombosis in comparison with azathioprine and high-dose steroids in renal transplanted patients.


The current state of medical education in Japan: a system under reform.
Not since just after World War II has there been as dramatic a change in the system of medical education in Japan as in the last several years. Medical school curricula are including more education that mimics clinical practice through problem-based learning, organ-based curricula and implementation of the objective structured clinical examination (OSCE). In response to criticism and concerns, the Japanese government has also implemented 2 major changes in the system of postgraduate medical education. First, a 2-year structured internship has been required of all medical school graduates; the first cohort to undertake this completed it in April 2006. Second, an internship matching system was adopted and first implemented in 2003. These reforms are leading to significant shifts in clinical education in Japan. Increasing numbers of medical graduates are entering residency programmes outside specialised university hospitals and core rotations place an increased emphasis on primary care. These changes in the training of young doctors suggest that the general clinical competency of doctors in Japan will improve in the coming years.


[The contradictions between the universal Unified Health System and the transfer of public funds to private health plans and insurances].
Trailing the whole group of trends and changes in the scenario of relations between the public and the private, this article analyses the effects of the rise in the rates of return of health plan operators and health insurance companies in 2007. Special attention is given to the segmentation of the system, the complaints about the naturalization of inequitable access to health services and to the depreciation of the original concepts of the Unified Health System. The study also gathers information regarding the production of knowledge about supplementary care with the intent to systemize the bases and methodological approaches adopted by a selected sub-group of scientific papers. Finally, the article develops conjectures and hypotheses with regard to possible associations between growth and stability of the health plan and insurance market and as refers to the nature of scientific production about this issue, taking into consideration the contradictions between the political and economical circuit in which the health plan and insurance companies are operating and the universality of the Brazilian Health System.


Polymorphism control of superconductivity and magnetism in Cs(3)C(60) close to the Mott transition.
The crystal structure of a solid controls the interactions between the electronically active units and thus its electronic properties. In the high-temperature superconducting copper oxides, only one spatial arrangement of the electronically active Cu(2+) units-a two-dimensional square lattice-is available to study the competition between the cooperative electronic states of magnetic order and superconductivity. Crystals of the spherical molecular C(60)(3-) anion support both superconductivity and magnetism but can consist of fundamentally distinct three-dimensional arrangements of the anions. Superconductivity in the A(3)C(60) (A = alkali metal) fullerides has been exclusively associated with face-centred cubic (f.c.c.) packing of C(60)(3-) (refs 2, 3), but recently the most expanded (and thus having the highest superconducting transition temperature, T(c); ref. 4) composition Cs(3)C(60) has been isolated as a body-centred cubic (b.c.c.) packing, which supports both superconductivity and magnetic order. Here we isolate the f.c.c. polymorph of Cs(3)C(60) to show how the spatial arrangement of the electronically active units controls the competing superconducting and magnetic electronic ground states. Unlike all the other f.c.c. A(3)C(60) fullerides, f.c.c. Cs(3)C(60) is not a superconductor but a magnetic insulator at ambient pressure, and becomes superconducting under pressure. The magnetic ordering occurs at an order of magnitude lower temperature in the geometrically frustrated f.c.c. polymorph (Néel temperature T(N) = 2.2 K) than in the b.c.c.-based packing (T(N) = 46 K). The different lattice packings of C(60)(3-) change T(c) from 38 K in b.c.c. Cs(3)C(60) to 35 K in f.c.c. Cs(3)C(60) (the highest found in the f.c.c. A(3)C(60) family). The existence of two superconducting packings of the same electronically active unit reveals that T(c) scales universally in a structure-independent dome-like relationship with proximity to the Mott metal-insulator transition, which is governed by the role of electron correlations characteristic of high-temperature superconducting materials other than fullerides.


Comparison of the short-term outcomes between trigger point dry needling and trigger point manual therapy for the management of chronic mechanical neck pain: a randomized clinical trial.
Randomized clinical study. To compare the effects of trigger point (TrP) dry needling (DN) and TrP manual therapy (MT) on pain, function, pressure pain sensitivity, and cervical range of motion in subjects with chronic mechanical neck pain. Recent evidence suggests that TrP DN could be effective in the treatment of neck pain. However, no studies have directly compared the outcomes of TrP DN and TrP MT in this population. Ninety-four patients (mean ± SD age, 31 ± 3 years; 66% female) were randomized into a TrP DN group (n = 47) or a TrP MT group (n = 47). Neck pain intensity (11-point numeric pain rating scale), cervical range of motion, and pressure pain thresholds (PPTs) over the spinous process of C7 were measured at baseline, postintervention, and at follow-ups of 1 week and 2 weeks after treatment. The Spanish version of the Northwick Park Neck Pain Questionnaire was used to measure disability/function at baseline and the 2-week follow-up. Mixed-model, repeated-measures analyses of variance (ANOVAs) were used to determine if a time-by-group interaction existed on the effects of the treatment on each outcome variable, with time as the within-subject variable and group as the between-subject variable. The ANOVA revealed that participants who received TrP DN had outcomes similar to those who received TrP MT in terms of pain, function, and cervical range of motion. The 4-by-2 mixed-model ANOVA also revealed a significant time-by-group interaction (P<.001) for PPT: patients who received TrP DN experienced a greater increase in PPT (decreased pressure sensitivity) than those who received TrP MT at all follow-up periods (between-group differences: posttreatment, 59.0 kPa; 95% confidence interval [CI]: 40.0, 69.2; 1-week follow-up, 69.2 kPa; 95% CI: 49.5, 79.1; 2-week follow-up, 78.9 kPa; 95% CI: 49.5, 89.0). The results of this clinical trial suggest that 2 sessions of TrP DN and TrP MT resulted in similar outcomes in terms of pain, disability, and cervical range of motion. Those in the TrP DN group experienced greater improvements in PPT over the cervical spine. Future trials are needed to examine the effects of TrP DN and TrP MT over long-term follow-up periods. Therapy, level 1b.


Retinal and intraventricular cerebral hemorrhages in the preterm infant born at or before 30 weeks' gestation.
To determine the prevalence of retinal hemorrhages and their association with cerebral intraventricular hemorrhages (IVH) in low-birth-weight preterm neonates born at or before 32 weeks' gestation. We prospectively studied a consecutive series of 22 neonates (24-30 weeks' gestation; mean gestational age, 27 weeks; mean weight, 1065 g) admitted to the neonatal intensive care unit. Anterior segment and indirect ophthalmoscopic examination, as well as cranial ultrasonographic examination, were performed on day 1 and day 10 of life. The prevalence of retinal and intraventricular hemorrhage was tested statistically for association with obstetric and neonatal clinical variables. The prevalence of retinal hemorrhage was 9% (2/22; 95% CI, 3%-21%) on day 1 and 2% (1/22) on day 10. The prevalence of IVH was 27% (6/22; 95% CI, 9%-46%): 14% (3/22) on day 1 and 23% (5/22) on day 10. Retinal hemorrhages occurred with greater frequency in neonates born to women who had intrauterine infection (chorioamnionitis, P =.043) and low umbilical cord pH levels (P =.027). No association was found between the presence of retinal hemorrhage and IVH (P = 1.000), mode of delivery (ie, vaginal vs cesarean section, P = 1.000), birth weight (P =.476), or gestational age (P = 1.000). The presence of subconjunctival hemorrhage was associated with IVH (P =.046). Retinal hemorrhages occur in less than 10% of low-birth-weight neonates, ie, a prevalence one half that observed in term neonates (22%). The hemorrhages tend to resolve without sequelae in the first 10 days of life and occur more commonly in infants born to women with uterine infection. Retinal hemorrhages in very premature neonates are not predictive of IVH-related brain damage.


Patient experiences of a theory-based lifestyle-focused group treatment in the prevention of cardiovascular diseases and type 2 diabetes.
Cardiovascular disease and type 2 diabetes are two of the most common public health diseases, and up to 80 % of the cases may be prevented by lifestyle modification. The physiological effects of lifestyle-focused treatment are relatively well studied, but how patients actually experience such treatments is still rather unclear. The aim of this study was to explore how patients experience lifestyle-focused group treatment in primary and secondary prevention of cardiovascular disease and type 2 diabetes. Qualitative interviews were conducted with 19 patients attending lifestyle-focused group treatment based on social cognitive theory at a behavioral medicine clinic in northern Sweden. The interviews were transcribed verbatim and analyzed according to Malterud's systematic text condensation. The study shows that patients participating in this kind of group-based lifestyle treatment went through a process of self-development which deepened their understanding of own responsibility for health and improved their skills in finding support in others. The process could be tracked through three different themes (the holistic view, personal responsibility, and group treatment) which together reflected the most essential parts of the informants' experience and showed the patient as an active decision maker struggling to adopt the principles of behavioral change. Lifestyle-focused group treatment, based on social cognitive theory, was shown to stimulate different components that strengthen patients' self-efficacy for long-term behavioral change.


[The coagulation link of the hemostatic system in newborn infants from mothers with extragenital pathology].
Overall, fifty newborn infants born to mothers with extragenital pathology (diabetes mellitus) were studied for the coagulative link of the homeostasis system as were 20 babies born to essentially healthy mothers. The studies were made by day 1 to 3 and 5 to 7 the babies' life. The conducted studies revealed signs of hypercoagulation presenting with activation of the external and internal route of hemostasis in those infants born to mothers with diabetes mellitus (DM). Toward the period of early neonatal adaptation shifts are still observable in the coagulating system at the expense of stimulation of the first phase of coagulation. The disclosed abnormalities in the coagulative link of the coagulating system in infants born to DM mothers pose a threat of development of thrombohaemorrhagic complications.


The Phenotypic Approach to Osteoarthritis: A Look at Metabolic Syndrome-Associated Osteoarthritis.
Metabolic syndrome-associated osteoarthritis (Met-OA) is a clinical phenotype defined by the role of obesity and metabolic syndrome as risk factors and by chronic low-grade inflammation. Obesity is an established risk factor for osteoarthritis not only at the knee, but also at the hands. Metabolic syndrome is also a risk factor for osteoarthritis, and a cumulative effect of the various syndrome components combines with an independent effect of each individual component (diabetes, dyslipidemia, and/or hypertension). The higher incidence of osteoarthritis in patients with obesity is related to several factors. One is the larger fat mass, which imposes heavier loads on the joints. Another is endocrine production by the adipose tissue of proinflammatory mediators (cytokines, adipokines, fatty acids, and reactive oxygen species) that adversely affect joint tissues. Obesity-related dysbiosis and sarcopenia were more recently implicated in the association between obesity and osteoarthritis. Finally, patients who have osteoarthritis, with or without metabolic syndrome, are at increased risk for cardiovascular mortality due not only to a sedentary lifestyle, but also to shared risk factors. Among these is the low-grade inflammation seen in patients with metabolic disorders. Thus, primary prevention and appropriate management of obesity and metabolic syndrome may delay the development and slow the progression of osteoarthritis.


Onychocryptosis associated with the treatment of onychomycosis.
With the advent of effective oral therapies for onychomycosis, there have been anecdotal reports of an increased incidence of onychocryptosis associated with the use of these new agents. The authors undertook a chart review of 100 consecutive patients treated for onychomycosis in a private medical practice to determine the incidence of onychocryptosis. A total of 37 of these patients (37%) developed paronychia ranging from simple pain to a severe inflammatory response with redness, drainage, and granuloma formation. Of these, 19 patients (19%) required surgical procedures to control onychocryptotic symptoms. Podiatric physicians should be aware that ingrown toenails may be an adverse consequence of effective treatment for onychomycosis.


Respiratory manifestations and respiratory diseases: prevalence and risk factors among pig farmers in Braço do Norte, Brazil.
To describe the prevalence of signs and symptoms of respiratory disease among pig farmers in Braço do Norte, Santa Catarina, Brazil, evaluating the characteristics of swine confinement buildings and identifying potential risk factors. An exploratory, cross-sectional, observational study involving interviews and pulmonary function tests (spirometry). Aspects related to job history, work conditions, and environment, as well as to respiratory status and smoking, were evaluated. Odds ratios were used to estimate the chances of exposure when comparing pig farmers according to the signs and symptoms of respiratory disease. The prevalence of clinical signs and symptoms of respiratory disease was 84.3%, clinical manifestations of bronchial asthma were detected in 5.6% of the farmers evaluated, and chronic bronchitis was diagnosed in 5.1% of the workers over the age of 40. Only 2.6% used specific individual respiratory protection devices. Respiratory disease was positively associated with low socioeconomic level, low level of education, smoking, the use of wood stoves, and the use of disinfectants. Work load and length of employment were both apparently associated with a lower prevalence of respiratory disease. The association between duration of employment and lower prevalence of respiratory disease can be attributed to the healthy worker effect. However, the evident respiratory impairment among pig farmers and the limited use of personal protective equipment draw attention to the need to implement a program to monitor exposure and regulate environmental factors.


African green monkeys avoid SIV disease progression by preventing intestinal dysfunction and maintaining mucosal barrier integrity.
Unlike HIV infection, SIV infection is generally nonpathogenic in natural hosts, such as African green monkeys (AGMs), despite life-long high viral replication. Lack of disease progression was reportedly based on the ability of SIV-infected AGMs to prevent gut dysfunction, avoiding microbial translocation and the associated systemic immune activation and chronic inflammation. Yet, the maintenance of gut integrity has never been documented, and the mechanism(s) by which gut integrity is preserved are unknown. We sought to investigate the early events of SIV infection in AGMs, specifically examining the impact of SIVsab infection on the gut mucosa. Twenty-nine adult male AGMs were intrarectally infected with SIVsab92018 and serially sacrificed at well-defined stages of SIV infection, preramp-up (1-3 days post-infection (dpi)), ramp-up (4-6 dpi), peak viremia (9-12 dpi), and early chronic SIV infection (46-55 dpi), to assess the levels of immune activation, apoptosis, epithelial damage and microbial translocation in the GI tract and peripheral lymph nodes. Tissue viral loads, plasma cytokines and plasma markers of gut dysfunction were also measured throughout the course of early infection. While a strong, but transient, interferon-based inflammatory response was observed, the levels of plasma markers linked to enteropathy did not increase. Accordingly, no significant increases in apoptosis of either mucosal enterocytes or lymphocytes, and no damage to the mucosal epithelium were documented during early SIVsab infection of AGMs. These findings were supported by RNAseq of the gut tissue, which found no significant alterations in gene expression that would indicate microbial translocation. Thus, for the first time, we confirmed that gut epithelial integrity is preserved, with no evidence of microbial translocation, in AGMs throughout early SIVsab infection. This might protect AGMs from developing intestinal dysfunction and the subsequent chronic inflammation that drives both HIV disease progression and HIV-associated comorbidities.


Differential tonic GABA conductances in striatal medium spiny neurons.
Medium spiny neurons (MSNs) provide the principal output for the dorsal striatum. Those that express dopamine D2 receptors (D2+) project to the globus pallidus external and are thought to inhibit movement, whereas those that express dopamine D1 receptors (D1+) project to the substantia nigra pars reticulata and are thought to facilitate movement. Whole-cell and outside-out patch recordings in slices from bacterial artificial chromosome transgenic mice examined the role of GABA(A) receptor-mediated currents in dopamine receptor D1+ striatonigral and D2+ striatopallidal MSNs. Although inhibitory synaptic currents were similar between the two neuronal populations, D2+ MSNs showed greater GABA(A) receptor-mediated tonic currents. TTX application abolished the tonic current to a similar extent as GABA(A) antagonists, suggesting a synaptic origin of the ambient GABA. Low GABA concentrations produced larger whole-cell responses and longer GABA channel openings in D2+ than in D1+ MSNs. Recordings from MSNs in alpha1-/- mice and pharmacological analysis of tonic currents suggested greater expression of alpha5-containing GABA(A) receptors in D2+ than in D1+ MSNs. As a number of disorders such as Parkinson's disease, Huntington's chorea, and tardive dyskinesia arise from an imbalance between these two pathways, the GABA(A) receptors responsible for tonic currents in D2+ MSNs may be a potential target for therapeutic intervention.


One-step fabrication of bimetallic PtNi mesoporous nanospheres as an efficient catalyst for the oxygen reduction reaction.
The controlled synthesis of Pt-based bimetallic porous nanostructures is highly important for the design of electrocatalysts with high performance. Herein, we report a one-step method for the direct synthesis of well-dispersed bimetallic PtNi mesoporous nanospheres (PtNi MNs) at high yield. Benefitting from the synergistic effect of composition (bimetallic PtNi) and structure (mesoporous and highly open structure), the as-obtained PtNi MNs exhibit superior catalytic activity and stability for the oxygen reduction reaction.


Recent trends in risky alcohol consumption and related harm among young people in Victoria, Australia.
To examine recent trends in the proportion of young people who drink at risky levels and the rate of alcohol-related harms experienced by young people in Victoria, Australia. The study uses published data from a series of surveys that ask questions relating to alcohol consumption to ascertain whether the proportion of young people drinking at risky levels has increased over the time period in which data are available. Alcohol-caused hospital admissions and emergency department presentations for young people are also examined over recent years to assess trends in alcohol-related harms. The survey data shows mixed results, with no clear trend in the rate of risky drinking among young people. The harms data suggests that rates of alcohol-related harm, particularly acute intoxication, have increased dramatically over recent years. The relationship between survey-derived estimates of alcohol consumption and rates of alcohol-related harms is not as clear-cut as expected, and raise concerns about the sensitivity of population surveys in detecting changes in harmful drinking patterns. The current increasing trends in alcohol-related harms for young people in Victoria suggest the need for immediate public health interventions.


Specifying quality in health care.
Quality should be a central issue in the commissioning and provision of health care. This requires a systematic approach to defining and monitoring quality. Such an approach should address: quality characteristics such as efficiency, accessibility, effectiveness (which may conflict with each other); the several levels at which quality may be specified, from general (across all health care) to specific (particular conditions or patient groups); and the methods of quality monitoring which include documented policies, clinical audit, inspection visits/patient surveys, and routine information returns. Shows how a matrix for quality surveillance can be devised which provides a framework for purchasers and providers to work together in developing quality in health care.


Enzyme-assisted aqueous extraction of oleosomes from soybeans (Glycine max).
Oleosomes, with their unique structural proteins, the oleosins, are known to be useful in cosmetics and other emulsion applications. A procedure to fractionate intact oleosomes to produce soybean oil without the use of organic solvents was investigated. Process parameters, enzyme treatment, filtration, cell lysis, and centrifugation, were studied. Successive extractions of the residue, eliminating the filtration step, pressurization, or ultrasonication of soybean flour prior to enzyme treatment and enzyme treatment on the residue, were the key steps. A mixture of Multifect Pectinase FE, Cellulase A, and Multifect CX 13L in equal proportion gave 36.42-63.23% of the total soybean oil from oleosomes, respectively, for 45 and 180 s of blending time, compared to the conventional method with lower yields (34.24 and 28.65%, respectively, for 45 and 180 s of blending time). Three successive extractions of the residue increased the oil yield to a maximum of 84.65% of the total soybean oil recovered in intact oleosomes. The percentage of lipid in the supernatant fraction decreased to a minimum value of 0.33% with the use of the enzymes at a 3% dosage. The results are considered to be useful for developing large-scale and efficient extraction of oleosomes from soybean.


Some adverse cardiodynamic effects of prostaglandin E2 in congestive heart failure.
The cardiodynamic effects of prostaglandin E(2) (PGE(2)) were studied in both healthy sheep and in animals with congestive heart failure (CHF). Merino ewes were equipped surgically with high fidelity micromanometers and left ventricular pressures measured. Heart rate, left ventricular systolic and end-diastolic pressures, +dP/dt and T(ln) were calculated on a computer from the recorded pressure curves. The paired t-test was used to determine the statistical significance of the differences. PGE(2) (25 mu g/kg) significantly improved the cardiac contractility and relaxation rate of healthy sheep and significantly reduced the heart rate, while the loading conditions under which the heart operates were not significantly affected. In contrast to healthy sheep, PGE(2) significantly reduced the contractility and relaxation rate of sheep with congestive heart failure and significantly increased the preload while heart rate and afterload were significantly reduced. The study suggests that despite the promising vasodilatory, positive inotropic and relaxation rate actions of PGE(2) in normal hearts, PGE(2) might not be a suitable therapeutic agent for CHF, because of the worsening effect it has on the cardiodynamics and loading conditions of the failing heart.


Maturation of the liver-specific peroxisome versus laminin, collagen IV and integrin expression.
The interaction of cells with extracellular matrix components contributes to their specific differentiation. We studied hepatic peroxisomes and their changing features during embryonic development, and we immunolocalized in the same tissue the extracellular matrix components laminin and collagen IV as well as the integrin receptor subunits alpha 1, alpha 2, beta 1, and beta 4. Rat and human embryonic liver peroxisome expression were studied at the light- and electron-microscopic level by means of localizing catalase-, D-amino acid oxidase- and polyamine oxidase activities and by means of the immunocytochemistry of six peroxisomal proteins. The successive import of catalase and the peroxisomal beta-oxidation enzymes, the late appearance of the other enzymes, and the gradual increase of peroxisomal size and number to adult values occurred as asynchronous events. Although still immature, peroxisomes were recognized at every stage examined and coexisted with laminin and collagen IV in both species. The beta 1 integrin subunit was immunodetected as early as at 12.5 days in rat. It was concluded that these extracellular matrix factors may be important for the differentiation of liver parenchyma from the liverbud stage onwards. However, the stepwise maturation of the liver-specific peroxisome suggests the involvement of many other regulating factors.


The role of polymorphonuclear leukocytes in the initiation and cessation of the Arthus vasculitis.
The role of polymorphs in the Arthus type hypersensitivity vasculitis has been studied. Polymorphs were found to play an essential role in not only producing the inflammatory vasculitis, but also were instrumental in ridding the damaged vessel of the antigen, probably by means of proteolytic catabolism at the inflammatory site. A temporal relationship between the disappearance of antigen from the damaged vessels and a decrease in inflammatory reaction was found. The earliest localization of antigen and its associated rabbit globulin in the Arthus vasculitis was found to be beneath the endothelium of small vessels. Since submitting this article for publication, Sorkin and Boyden (J. Immunol., 1959, 82, 332) have reported the catabolism of antigen in the presence of antibody by mononuclear cells obtained from the peritoneal cavities of guinea pigs. Evidence was presented indicating that the antigen molecule was actually broken down by the mononuclear cells. Techniques similar to those reported here were used.


Multicenter phase III trial to evaluate CD34(+) selected versus unselected autologous peripheral blood progenitor cell transplantation in multiple myeloma.
High-dose chemotherapy followed by autologous transplantation has been shown to improve response rates and survival in multiple myeloma and other malignancies. However, autografts frequently contain detectable tumor cells. Enrichment for stem cells using anti-CD34 antibodies has been shown to reduce autograft tumor contamination in phase I/II studies. To more definitively assess the safety and efficacy of CD34 selection, a phase III study was completed in 131 multiple myeloma patients randomized to receive an autologous transplant with either CD34-selected or unselected peripheral blood progenitor cells after myeloablative therapy. Tumor contamination in the autografts was assessed by a quantitative polymerase chain reaction detection assay using patient-specific, complementarity-determining region (CDR) Ig gene primers before and after CD34 selection. A median 3.1 log reduction in contaminating tumor cells was achieved in the CD34 selected product using the CEPRATE SC System (CellPro, Inc, Bothell, WA). Successful neutrophil engraftment was achieved in all patients by day 15 and no significant between-arm difference for time to platelet engraftment occurred in patients who received an infused dose of at least 2.0 x 10(6) CD34(+) cells/kg. In conclusion, this phase III trial demonstrates that CD34-selection of peripheral blood progenitor cells significantly reduces tumor cell contamination yet provides safe and rapid hematologic recovery for patients receiving myeloablative therapy.


Chaotic Experiences and Low-Income Children's Social-Emotional Development.
Development in early childhood is increasingly likely to take place in multiple contexts. Continuity and discontinuity in children's experiences across multiple contexts have important implications for their development. This study examines the extent to which children experience chaos in their homes and in their preschool settings is linked with their social-emotional development over the course of the preschool year. Data from a large, representative sample of low-income preschool children attending Head Start was used to test a series of multi-level models. Children whose experiences of their homes were highly chaotic, regardless of the how chaotic their experiences of their classroom were, decreased in their social-emotional skills over the preschool year. Chaotic experiences in the home environment thus appear to have more influence on children's development than do chaotic preschool experiences.


The neurobiology of drug addiction.
Animals models have begun to provide insights into the neurobiological basis of reinforcement in drug addiction. The reinforcing effects of indirect sympathomimetics such as cocaine and amphetamine appear to depend on release of dopamine in the terminal fields of the mesocorticolimbic dopamine system. The acute reinforcing effects of opiates involve not only an activation of dopamine, but also dopamine-independent elements in the terminal regions of the mesocorticolimbic dopamine system. Nicotine's reinforcing effects may involve both dopaminergic and opioid peptidergic systems. Ethanol's reinforcing effects may result from multiple neurotransmitter interactions including gamma-aminobutyric acid, glutamate, dopamine, opioid peptides, and serotonin. Subtle changes in neurochemical function and signal transduction and transcription mechanisms in sensitive neuronal elements in the extended amygdala may be mediators of chronic drug action that lead to vulnerability to relapse and may provide exciting insight into the neuroadaptations associated with drug addiction.


Alternating motion rate as an index of speech motor disorder in traumatic brain injury.
The task of syllable alternating motion rate (AMR) (also called diadochokinesis) is suitable for examining speech disorders of varying degrees of severity and in individuals with varying levels of linguistic and cognitive ability. However, very limited information on this task has been published for subjects with traumatic brain injury (TBI). This study is a quantitative and qualitative acoustic analysis of AMR in seven subjects with TBI. The primary goal was to use acoustic analyses to assess speech motor control disturbances for the group as a whole and for individual patients. Quantitative analyses included measures of syllable rate, syllable and intersyllable gap durations, energy maxima, and voice onset time (VOT). Qualitative analyses included classification of features evident in spectrograms and waveforms to provide a more detailed description. The TBI group had (1) a slowed syllable rate due mostly to lengthened syllables and, to a lesser degree, lengthened intersyllable gaps, (2) highly correlated syllable rates between AMR and conversation, (3) temporal and energy maxima irregularities within repetition sequences, (4) normal median VOT values but with large variation, and (5) a number of speech production abnormalities revealed by qualitative analysis, including explosive speech quality, breathy voice quality, phonatory instability, multiple or missing stop bursts, continuous voicing, and spirantization. The relationships between these findings and TBI speakers' neurological status and dysarthria types are also discussed. It was concluded that acoustic analyses of the AMR task provides specific information on motor speech limitations in individuals with TBI.


An automatic cephalometric landmark detection method based on heatmap regression and Monte Carlo dropout.
Cephalometric analysis plays an important role in orthodontic diagnosis and treatment planning. It depends on the detection of multiple landmarks, while the process is time-consuming and tedious. Although some deep learning-based automatic landmark detection algorithms have achieved excellent performance, most of them adopt multi-stage models increasing the complexity and detection time. Meanwhile, few studies focused on the uncertainty of detection results, thereby ignoring its significant clinical value. In this paper, we propose a novel approach based on heatmap regression for landmark detection, which can achieve competitive accuracy and good robustness with only one step. Furthermore, by applying Monte Carlo dropout to a U-shaped convolutional neural network, we can obtain not only the coordinate of each landmark but also the corresponding simple uncertainty, so that doctors can pay more attention to those landmarks with higher uncertainty. The evaluation results showed the mean radial error is 1.39±1.06mm and the average successful detection rate is 79.65%, 97.22% within 2mm, 4mm for the IEEE ISBI2015 Test Dataset 1, the indicators for the IEEE ISBI2015 Test Dataset 2 are 1.33±0.93mm, 80.05% and 97.53%, respectively. Our method has the potential to become an assistant tool in clinical practice. Automatic and accurate detection with uncertainty analysis is expected to help guide the doctor's judgment.


Aerosol Therapy for Pneumonia in the Intensive Care Unit.
Antibiotic aerosolization in patients with ventilator-associated pneumonia (VAP) allows very high concentrations of antimicrobial agents in the respiratory secretions, far more than those achievable using the intravenous route. However, data in critically ill patients with pneumonia are limited. Administration of aerosolized antibiotics might increase the likelihood of clinical resolution, but no significant improvements in important outcomes have been consistently documented. Thus, aerosolized antibiotics should be restricted to the treatment of extensively resistant gram-negative pneumonia. In these cases, the use of a vibrating-mesh nebulizer seems to be more efficient, but specific settings and conditions are required to improve lung delivery.


[Cytokine imbalance in patients with chronic obstructive bronchitis].
A reactive ability of immunocompetent cells was assessed by the level of cytokines TNF alpha and IL-8 estimated by enzyme immunoassay ("Genzyme diagnostics" kit) in 18 patients with chronic obstructive bronchitis (mean age 58 +/- 4.2 years, mean duration of the disease 11.2 +/- 5.2 years) and 15 control patients matched for age, with normal external respiration function, free of chronic bronchopulmonary pathology and allergic diseases. The greatest differences in cytokine levels were registered between the control group and patients with moderate generalized irreversible obstruction. These patients had similar basal and E. coli LPS induced synthesis of the above cytokines showing the lack of cell reserves, adequate immune response to exogenic antigen.


Chromosome banding in Amphibia. XXVIII. Homomorphic XY sex chromosomes and a derived Y-autosome translocation in Eleutherodactylus riveroi (Anura, Leptodactylidae).
Extensive cytogenetic analyses on a population of the leptodactylid frog Eleutherodactylus riveroi in northern Venezuela revealed the existence of multiple XXAA male/XYAA female/XAA(Y) female sex chromosomes. The XAA(Y) karyotype originated by a centric (Robertsonian) fusion between the original, free Y chromosome and an autosome. 46.2% of the male individuals in this population are carriers of this Y-autosome fusion. In male meiosis the XAA(Y) sex chromosomes pair in the expected trivalent configuration. In the same population 53.8% of the male animals still possess the original, free XY sex chromosomes. E. riveroi is only the second vertebrate species discovered in which a derived Y-autosome fusion coexists with the ancestral free XY sex chromosomes. The free XY sex chromosomes, as well as the multiple XA(Y) sex chromosomes are still in a very primitive (homomorphic) stage of differentiation. With no banding technique applied it is possible to distinguish the Y from the X. Various banding techniques and in situ hybridizations have been carried out to characterize the karyotypes. DNA flow cytometric measurements show that the genome size of E. riveroi resembles that of other Eleutherodactylus species. The cytogenetic data obtained in E. riveroi are compared with those of the sole other vertebrate known to possess the extremely rare, multiple XXAA male/XYAA female/XAA(Y) female sex chromosomes. Surprisingly enough, this vertebrate again is a frog belonging to the genus Eleutherodactylus [E. ((maussi) biporcatus] which lives exactly in the same habitat in northern Venezuela as does E. riveroi.


Adipose tissue as a possible therapeutic target for polyphenols: A case for Cyclopia extracts as anti-obesity nutraceuticals.
Obesity is a significant contributor to increased morbidity and premature mortality due to increasing the risk of many chronic metabolic diseases such as type 2 diabetes, cardiovascular disease and certain types of cancer. Lifestyle modifications such as energy restriction and increased physical activity are highly effective first-line treatment strategies used in the management of obesity. However, adherence to these behavioral changes is poor, with an increased reliance on synthetic drugs, which unfortunately are plagued by adverse effects. The identification of new and safer anti-obesity agents is thus of significant interest. In recent years, plants and their phenolic constituents have attracted increased attention due to their health-promoting properties. Amongst these, Cyclopia, an endemic South African plant commonly consumed as a herbal tea (honeybush), has been shown to possess modulating properties against oxidative stress, hyperglycemia, and obesity. Likewise, several studies have reported that some of the major phenolic compounds present in Cyclopia spp. exhibit anti-obesity effects, particularly by targeting adipose tissue. These phenolic compounds belong to the xanthone, flavonoid and benzophenone classes. The aim of this review is to assess the potential of Cyclopia extracts as an anti-obesity nutraceutical as underpinned by in vitro and in vivo studies and the underlying cellular mechanisms and biological pathways regulated by their phenolic compounds.


Comprehensive analysis of circRNA-miRNA-mRNA networks in the kidney of snakehead (Channa argus) response to Nocardia seriolae challenge.
Non-coding RNAs (ncRNAs) play vital roles in regulating the expression levels of genes that control essential biological functions, including immune response to bacterial infections in teleost. To dissect the roles of ncRNAs in the Channa argus (snakehead), a systematic analysis of the expression profiles of circRNA, miRNA and mRNA, as well as competing endogenous RNAs (ceRNA) regulatory networks in the kidney of snakehead following Nocardia seriolae infection were performed in the present study. A total of 111 differentially expressed circRNAs, 706 differentially expressed miRNAs, and 2548 differentially expressed mRNAs were identified in the N. seriolae infected snakehead. Based on these differently expressed RNAs, we identified 55 circRNA-mRNA pairs, 124 miRNA-mRNA pairs, and 35 circRNA-miRNA-mRNA regulatory networks, including dre-miR-103-CD302, dre-miR-27e-IGSF3, novel_circ_0005462/novel_403-IGKC, novel_circ_0001750/novel_circ_0002162-novel_477-OCLN, and novel_circ_0003847-novel_4-KCNAB3. In addition, luciferase reporter assay was employed to detect the target relationships of several circRNA-miRNA-mRNA pairs. Taken together, this study demonstrates that the genes associated with immunity and structures in the kidney of snakehead can be regulated by circRNAs and miRNAs at post-transcription levels, and provided theoretical guidance for ncRNAs studies for other teleost. However, further studies are still in great need to validate the regulatory mechanisms of ncRNAs in snakehead.


Pituitary homeobox 2 (PITX2) protects renal cancer cell lines against doxorubicin toxicity by transcriptional activation of the multidrug transporter ABCB1.
The multidrug resistance (MDR) P-glycoprotein ABCB1 plays a major role in MDR of malignant cells and is regulated by various transcription factors, including Wnt/β-catenin/TCF4. The transcription factor PITX2 (Pituitary homeobox-2) is essential for embryonic development. PITX2 operates by recruiting and interacting with β-catenin to increase the expression of growth-regulating genes, such as cyclin D1/2 and c-Myc. The importance of PITX2 in malignancy is not yet known. Here we demonstrate that in the renal cancer cell lines ACHN and A498, the level of ABCB1 expression and function correlate with nuclear PITX2 localization and PITX2-luciferase reporter gene activity (A498 > ACHN). In A498 cells, doxorubicin toxicity is augmented by the ABCB1 inhibitor, PSC833. PITX2 overexpression increases ABCB1 expression and cell survival in ACHN cells. Silencing of PITX2 by siRNA downregulates ABCB1 and induces a greater chemotherapeutic response to doxorubicin in A498 cells, as determined by MTT cell viability and clonogenic survival assays. Two PITX2 binding sequences were identified in the ABCB1 promoter sequence. PITX2 binding was confirmed by chromatin immunoprecipitation. β-Catenin is not required for PITX2 upregulation of ABCB1 because ABCB1 mRNA increased and doxorubicin toxicity decreased upon PITX2 overexpression in β-catenin(-/-) cells. The data show for the first time that ABCB1 is a target gene of PITX2 transcriptional activity, promoting MDR and cell survival of cancer cells.


Intergroup Relations During the Refugee Crisis: Individual and Cultural Stereotypes and Prejudices and Their Relationship With Behavior Toward Asylum Seekers.
In this paper, I investigate intergroup relations between natives and asylum seekers during the European refugee crisis, and contribute to the reemerging methodological debate on the measurement of stereotypes and prejudices as individual and collective constructs. Drawing on data from the Norwegian Citizen Panel (NCP; N = 1,062), I examined how Norwegians stereotyped asylum seekers at the height of the refugee crisis and the emotional prejudices asylum seekers as a group elicited. By experimentally manipulating the survey question format, I examined whether and how stereotypes and emotional prejudices toward asylum-seekers differed depending on their measurement as individual or collective constructs. A subset of respondents (n = 228) had reception centers for asylum-seekers established in their local community during the crisis. These participants reported their behaviors toward the asylum seekers in their neighborhood. In this subsample, I investigated how individual facilitating and harming intergroup behavior was related to individual and collective conceptualizations of stereotypes and prejudices. The results showed that both low warmth and low competence stereotypes, as well as negative emotions toward asylum seekers, were rated as stronger when measured as collective as compared to individual-level constructs. In the individual condition, respondents reported feeling more admiration and sympathy than respondents in the collective condition attributed to others. Individual stereotypes and prejudices correlated systematically with individual facilitating and harming intergroup behaviors. The perception that others hold more negative stereotypes of asylum seekers, and the perceived anger and fear of others, did correlated with individual harming behaviors. Perceptions of others' anxiety correlated negatively with facilitating behaviors. Implications and future directions for the conceptualization and measurement of stereotypes and emotional prejudices are discussed.


[Effect of melatonin on the functional properties of transformed cells].
In vitro, we studied the effect of melatonin (1mkM) on the sensitivity of murine transformed fibroblasts 3T3-SV40 and murine hepatoma cells MN22a to the lysis by natural killer cells. In vivo, we examined changes in tumorigenic properties of MN22a cells treated with melatonin. It was shown that the sensitivities of both cell types to lysis by killer cells fell sharply fourfold after 24-hour treatment with melatonin; their cytotoxic index value approximated to that of intact cells, insensitive to natural killer cells. After MN22a cells were pre-treated with melatonin for 24 h before injection into syngenic mice, tumorigenesis and development slowed down and mortality rates decreased. Both effects were reversible. All cellular parameters were similar to control ones 24 hrs after evacuation of melatonin. Thus melatonin failed to change cell cycle progression which pointed to an unaltered rate of cell proliferation. Different hypotheses are discussed on the mechanisms of melatonin action which result in transient reversion of transformed phenotype.


Detection of human papillomavirus DNA in squamous cell carcinoma of the nail bed and finger determined by polymerase chain reaction.
Increasing evidence supports the association of squamous cell carcinoma of the finger and nail bed with human papillomavirus infection. We treated 12 patients with squamous cell carcinoma of the finger and nail bed, none of whom was originally diagnosed as having a malignant lesion. Half of the patients were referred for carbon dioxide laser ablation of what was believed to be a recalcitrant verruca vulgaris. Our objective was to evaluate these lesions for the presence of human papillomavirus by in situ hybridization techniques and the polymerase chain reaction. This is the first report of use of the polymerase chain reaction to detect human papillomavirus in formalin-fixed, paraffin-embedded specimens of periungual squamous cell carcinoma. Seven of the 12 lesions were evaluated for the presence of human papillomavirus by both in situ hybridization and the polymerase chain reaction. Five of the seven periungual lesions were found to contain human papillomavirus type 16 but not type 18 DNA with use of the polymerase chain reaction technique. In situ hybridization failed to identify human papillomavirus in any of these patients' tumors. Our data confirm the association between human papillomavirus and squamous cell carcinoma of the periungual region and suggest that biopsies should be performed on chronic, isolated lesions of the finger in adults before therapy is initiated.


Understanding Behavioural Development of Calves in Natural Settings to Inform Calf Management.
One important type of animal welfare concern is "natural living" (i.e., that animals are able to express natural behaviours that are important to them, and to engage with aspects of the natural world that they find important). The aims of this narrative review were to describe the behavioural development of calves (Bos taurus) in natural settings and use this to identify characteristics of natural systems that may be important to consider relative to this natural living conception of animal welfare. At birth, calves are licked by their mothers and soon stand to suckle for colostrum, and during the milk-feeding period, calves spend much of their time lying down. In natural systems, calves perform a variety of social behaviours with herd-mates, and slowly transition from their mother's milk to eating solid food, by gradually increasing time spent grazing and ruminating. In contrast, on most commercial dairy systems, dairy calves are removed from their mothers at birth, housed individually, fed restricted amounts of milk and weaned abruptly at a young age. The results of this review suggest that accommodating key natural behaviours, for example through the use of teat feeding of milk, social housing, and gradual weaning, can help address welfare concerns.


Advanced Methodologies for Trace Elements in Edible Oil Samples: A Review.
Advanced methodologies were applied for the detection of some elements at trace levels in edible oils. Trace elements play a role in oil stability, quality of edible oils and fats. In the present study, problems were addressed related to simple, cheap, less time consuming and suitable pretreatment advanced methods for suitable sample introduction and calibrations as well as the strategies and techniques are discussed. The present review is aimed to discuss the significance of simplifying sample treatments are offered for trace elements in oils. The period covered by this review is last twenty years. However, the various applications of advanced methodologies including extraction and microextraction. The scope of spectrometric techniques used for the analysis of trace elements in edible oils was discussed by new instrumental development trends.


Expected population impacts of discontinued prostate-specific antigen screening.
Prostate-specific antigen (PSA) screening for prostate cancer has high risks of overdiagnosis, particularly among older men, and reports from screening trials indicate that it saves few lives after 11 to 13 years of follow-up. New clinical guidelines recommend against PSA screening for all men or for men aged >70 years, but, to the authors' knowledge, the expected population effects of these guidelines have not been studied to date. Two models of prostate cancer natural history and diagnosis were previously developed using reconstructed PSA screening patterns and prostate cancer incidence in the United States. Assuming a survival benefit of PSA screening consistent with the screening trials, the authors used the models to predict incidence and mortality rates for the period from 2013 through 2025 under continued PSA screening and under discontinued PSA screening for all men or for men aged >70 years. The models predicted that continuation of recent screening rates will overdiagnose 710,000 to 1,120,000 men (range between models) but will avoid 36,000 to 57,000 cancer deaths over the period 2013 through 2025. Discontinued screening for all men eliminated 100% of overdiagnoses but failed to prevent 100% of avoidable cancer deaths. Continued screening for men aged <70 years eliminated 64% to 66% of overdiagnoses but failed to prevent 36% to 39% of avoidable cancer deaths. Discontinuing PSA screening for all men may generate many avoidable cancer deaths. Continuing PSA screening for men aged <70 years could prevent greater than one-half of these avoidable cancer deaths while dramatically reducing overdiagnoses compared with continued PSA screening for all ages.


[Combined therapy of intracranial germ cell tumors in children].
A retrospective analysis of treatment of 8 children aged 5 to 13 years with intracranial germ cell tumors (3 germinomas, 5 nongerminomatous cell tumors) is reported. All patients were initially operated. Five of them underwent total or incomplete removal of the tumor. After surgery 2 children received radiotherapy alone (1 germinome, 1 nongerminomatous germ cell tumors) and 5 (2 germinomas, 3 nongerminomatous germ cell tumors) combined radio- and chemotherapy. One patient (choriocarcinoma) didn't receive any adjuvant treatment after total tumor removal. All 3 children with germinomas show complete remission for 29, 40 and 93 months. Of 5 patients with nongerminomatous germ cell tumors in 2 the duration of remission was 22 and 53 months and 3 relapsed 4, 12 and 24 months after treatment. The data presented demonstrate that the treatment results of intracranial germ cell tumors in children depend on histologic type of the tumor. Thus, precise tumor type determination is most important for choosing optimally adequate treatment approach.


A link between thrifty phenotype and maternal care across two generations of intercrossed mice.
Maternal effects are causal influences from mother to offspring beyond genetic information, and have lifelong consequences for multiple traits. Previously, we reported that mice whose mothers did not nurse properly had low birth weight followed by rapid fat accumulation and disturbed development of some organs. That pattern resembles metabolic syndromes known collectively as the thrifty phenotype, which is believed to be an adaptation to a stressful environment which prepares offspring for reduced nutrient supply. The potential link between maternal care, stress reactivity, and the thrifty phenotype, however, has been poorly explored in the human and animal literature: only a couple of studies even mention (much less, test) these concepts under a cohesive framework. Here, we explored this link using mice of the parental inbred strains SM/J and LG/J-who differ dramatically in their maternal care-and the intercrossed generations F1 and F2. We measured individual differences in 15 phenotypes and used structural equation modeling to test our hypotheses. We found a remarkable relationship between thrifty phenotype and lower quality of maternal behaviors, including nest building, pup retrieval, grooming/licking, and nursing. To our knowledge, this is the first study to show, in any mammal, a clear connection between the natural variation in thrifty phenotype and maternal care. Both traits in the mother also had a substantial effect on survival rate in the F3 offspring. To our surprise, however, stress reactivity seemed to play no role in our models. Furthermore, the strain of maternal grandmother, but not of paternal grandmother, affected the variation of maternal care in F2 mice, and this effect was mediated by thrifty phenotype in F2. Since F1 animals were all genetically identical, this finding suggests that maternal effects pass down both maternal care and thrifty phenotype in these mice across generations via epigenetic transmission.


Trap-door optical buffering using a flat-top coupled microring filter: the superluminal cavity approach.
We propose and analyze theoretically a trap-door optical buffer based on a coupled microrings flat-top add/drop filter (ADF). By tuning one of the microrings into and out of resonance we can effectively open and close the buffer trap door and, consequently, trap and release optical pulses. To attain a maximally flat filter we present a new design approach utilizing the concept of a white light cavity to attain an ADF that resonates over a wide spectral band. We show that the resulting ADF exhibits superior performance in terms of bandwidth and flatness compared to previous design approaches. We also present a realistic silicon-on-insulator-based design and a performance analysis, taking into consideration the realistic properties and limitations of the materials and the fabrication process, leading to delays exceeding 5 ns for an 80 GHz bandwidth and a corresponding delay-bandwidth product of approximately 400.


The regional distribution of emotional sweating in man.
1. Emotional sweating was induced in normal subjects by mental arithmetic at environmental temperatures of 29 and 26 degrees C and estimated from continuous records of body weight loss.2. The sweat output from four independent regions of the body - (a) the head and neck, (b) the arms and legs, (c) the trunk, and (d) the hands and feet - was studied separately, the remainder of the body being covered in each case by plastic bags. The evaporative water loss from each skin region increased markedly during mental arithmetic.3. The sweat contribution from each region was a substantial fraction of the total body sweat response and appeared to be roughly proportional to the calculated number of sweat glands in each region.4. There is no evidence from these experiments to indicate that the sweat glands of the skin of the hands and feet behave differently to those of the skin of the rest of the body in response to emotional stress.


Combination of Face Regions in Forensic Scenarios.
This article presents an experimental analysis of the combination of different regions of the human face on various forensic scenarios to generate scientific knowledge useful for the forensic experts. Three scenarios of interest at different distances are considered comparing mugshot and CCTV face images using MORPH and SC face databases. One of the main findings is that inner facial regions combine better in mugshot and close CCTV scenarios and outer facial regions combine better in far CCTV scenarios. This means, that depending of the acquisition distance, the discriminative power of the facial regions change, having in some cases better performance than the full face. This effect can be exploited by considering the fusion of facial regions which results in a very significant improvement of the discriminative performance compared to just using the full face.


Preliminary validation of the Child Abuse Potential Inventory in Turkey.
This study aims to provide preliminary findings on the validity of Child Abuse Potential Inventory (CAP Inventory) on Turkish sample of 23 abuser and 47 nonabuser parents. To investigate validity in two groups, Minnesota Multiphasic Personality Inventory (MMPI) Psychopathic Deviate (MMPI-PD) scale is also used along with CAP. The results show that, with the 200.5 cutoff point, which is the average score of the whole Turkish sample, Abuse Scale correctly classified 83% of the participants in the abuse group and 78.8% of the participants in the control group, which gives 21.2% false-positive result. MMPI-PD to all group and Pearson correlation coefficient analysis is found to be significant for both groups. These results show us high reliability and validity of the abuse scale for Turkey.


A sibling-comparison study of smoking during pregnancy and childhood psychological traits.
Prenatal exposure to substances of abuse is associated with numerous psychological problems in offspring, but quasi-experimental studies controlling for co-occurring risk factors suggest that familial factors (e.g., genetic and environmental effects shared among siblings) confound many associations with maternal smoking during pregnancy (SDP). Few of the quasi-experimental studies in this area have explored normative psychological traits in early childhood or developmental changes across the lifespan, however. The current study used multilevel growth curve models with a large, nationally-representative sample in the United States to investigate for potential effects of SDP on the developmental trajectories of cognitive functioning, temperament/personality, and disruptive behavior across childhood, while accounting for shared familial confounds by comparing differentially exposed siblings and statistically controlling for offspring-specific covariates. Maternal SDP predicted the intercept (but not change over time) for all cognitive and externalizing outcomes. Accounting for familial confounds, however, attenuated the association between SDP exposure and all outcomes, except the intercept (age 5) for reading recognition. These findings, which are commensurate with previous quasi-experimental research on more severe indices of adolescent and adult problems, suggest that the associations between SDP and developmental traits in childhood are due primarily to confounding factors and not a causal association.


Vitamin D replacement in children, adolescents and pregnant women in the Middle East and North Africa: A systematic review and meta-analysis of randomized controlled trials.
Hypovitaminosis D affects one-third to two-thirds of children and pregnant women from the Middle East and North Africa (MENA) region. To evaluate in infants, children, adolescents and pregnant women, from the MENA region, the effect of supplementation with different vitamin D doses on the change in 25-hydroxyvitamin D [25(OH)D] level reached, and other skeletal and non-skeletal outcomes. This is a systematic review of randomized controlled trials of vitamin D supplementation conducted in the MENA region. We conducted a comprehensive literature search in 7 databases, without language or time restriction, until November 2016. Two reviewers abstracted data from the included studies, independently and in duplicate. We calculated the mean difference (MD) and 95% CI of 25(OH)D level reached when at least 2 studies were eligible in each comparison (low (<800IU), intermediate (800-2000IU) or high (>2000IU) daily dose of vitamin D, or placebo). We pooled data using RevMan version 5.3. We identified a total of 15 eligible trials: one in infants, 4 in children and adolescents and 10 in pregnant women. In children and adolescents, an intermediate vitamin D dose (1901IU/d), resulted in a mean difference in 25(OH)D level of 13.5 (95% confidence interval (CI) 8.1-18.8) ng/ml, compared to placebo, favoring the intermediate dose (p<0.001). The proportion of children and adolescents reaching a 25(OH)D level≥ 20ng/ml was 74% in the intermediate dose group. In pregnant women, four trials started supplementation at 12-16weeks of gestation and continued until delivery, and six trials started supplementation at 20-28weeks' gestation and stopped it at delivery. The MD in 25(OH)D level reached was 8.6 (95% CI 5.3-11.9) ng/ml (p<0.001) comparing the high dose (3662IU/d) to the intermediate dose (1836IU/d), and 12.3 (95% CI 6.4-18.2) ng/ml (p<0.001), comparing the high dose (3399IU/d) to the low dose (375IU/d). Comparing the intermediate (1832IU/d) to the low dose (301IU/d), the MD in 25(OH)D level achieved was 7.8 (95% CI 4.5-10.8) ng/ml (p<0.001). The proportion of pregnant women reaching a 25(OH)D level≥20ng/ml was 80%-90%, 73% and 27%-43% in the high, intermediate, and low dose groups, respectively. The risk of bias in the included studies, for children, adolescents and pregnant women, ranged from low to high across all doamins. In children, adolescents and pregnant women from the MENA, an intermediate vitamin D dose of 1000-2000IU daily may be necessary to allow for the majority of the population to reach a desirable 25(OH)D level of 20ng/ml. Further high quality RCTs are required to confirm/refute the beneficial impact of vitamin D supplementation on various clinically important outcomes.


Tanshinone IIA Attenuates H₂O₂ -induced injury in human umbilical vein endothelial cells.
The injury of endothelial cell is the critical event of vascular disease. In endothelial cell, oxidative stress is regarded as critical to pathogenic factors in endothelial cell injury and apoptosis. Tanshinone IIA is the main effective component of Salvia miltiorrhiza known as "Danshen" in traditional Chinese medicine for treating cardiovascular disorders, but the mechanism by which it exerts the protective effect is not well established. The present study was designed to test the hypothesis that tanshinone IIA can inhibit hydrogen peroxide ( H(2)O(2) )-induced injury and unravel its intracellular mechanism in human umbilical vein endothelial cells (HUVECs). In this study, HUVECs were treated with tanshinone IIA in the presence/absence of H(2)O(2) . The protective effects of tanshinone IIA against H(2)O(2) were evaluated. Our results show that HUVECs incubated with 200 μM H(2)O(2) had significantly decreased the viability of endothelial cells, which was accompanied with apparent cell apoptosis, the activation of caspase-3 and the upregulation of p53 expression, which was known to play a key role in H(2)O(2) -induced cell apoptosis. However, pretreatment with tanshinone IIA (3-10 μM) resulted in a significant resistance to H(2)O(2) -induced apoptosis. In addition, pretreatment with tanshinone IIA decreased the activity of caspase-3 and p53 expression. Tanshinone IIA also induced activating transcription factor (ATF) 3 expression; while knockdown of ATF-3 with ATF-3 siRNAsignificantly reduced tanshinone IIA's protective effect. In conclusion, the present study shows that tanshinone IIA can protect endothelial cells against oxidative injury induced by H(2)O(2) , suggesting that this compound may constitute a promising intervention against cardiovascular disorders and ATF-3 may play an important role in this process.


Evaluation of fire-safety programs that use 10-year smoke alarms.
The Centers for Disease Control and Prevention began funding a Smoke Alarm Installation and Fire Safety Education (SAIFE) program in 1998. This program involves the installation of lithium-powered "10-year" smoke alarms in homes at high risk for fires and injuries. This study aimed to (1) determine among original SAIFE homes if the lithium-powered alarms were still present and functional 8-10 years after installation and (2) understand factors related to smoke alarm presence and functionality. Data on a total of 384 homes and 601 smoke alarms in five states were collected and analyzed. Only one-third of alarms were still functional; 37% of installed alarms were missing; and 30% of alarms were present, but not functioning. Alarms were less likely to be functioning if they were installed in the kitchen and if homes had a different resident at follow-up. Of the 351 alarms that were present and had a battery at the time of the evaluation, only 21% contained lithium-powered batteries. Of these, 78% were still functioning. Programs that install lithium-powered alarms should use units that have sealed-in batteries and "hush" buttons. Additionally, education should be given on smoke alarm maintenance that includes a message that batteries in these alarms should not be replaced. Lithium-powered smoke alarms should last up to 10 years if maintained properly.