Frozen embryo transfer: the present practice and beyond.
With the success of oocyte donation in vitro fertilization (IVF) in postmenopausal women, the importance of endometrial preparation became obvious. This appears also very crucial for achieving pregnancy after frozen embryo transfer (FET) after failed fresh IVF cycles and FET in subsequent natural cycles. Although there are different methods of preparing endometrium, in this study, another method of preparing the implantation bed using letrozole was scrutinized for its usefulness. Two hundred and seventy patients between 28 and 40 years of age undergoing IVF due to bilateral tubal blocks were chosen for FET. They had a previous unsuccessful single IVF attempt or had postponed embryo transfer due to the threat of ovarian hyperstimulation syndrome or poor endometrial development. Informed consents were obtained from the participants. One hundred patients had endometrial preparation by gonadotrophin-releasing hormone agonist down-regulation and with hormone replacement therapy, 55 had natural cycle FET, and the remaining 115 patients had letrozole-induced ovulation induction (OI) for endometrial preparation. The clinical and biochemical pregnancy rate or live birth rate was higher in the letrozole OI group than in the other two groups. OI by letrozole and subsequent endometrial preparation as a result of it may be utilized for FET, and this will be cheap and easy to administer, giving better success rates in FET cycles.


catena-Poly[[zinc-bis-(μ-2-sulfido-1H-benzimidazol-3-ium-5-carboxyl-ato)-κO:S;κS:O] trihydrate].
In the title compound, {[Zn(C(8)H(5)N(2)O(2)S)(2)]·3H(2)O}(n), the Zn(II) atom, lying on a twofold rotation axis, is four-coordinated by two S atoms and two O atoms from four 2-sulfido-1H-benzimidazol-3-ium-5-carboxyl-ate (H(2)mbidc) ligands in a distorted tetra-hedral geometry. Two H(2)mbidc ligands bridge two Zn(II) atoms, generating a double-chain along [[Formula: see text]01]. Adjacent chains are linked by N-H⋯O and O-H⋯O hydrogen bonds, forming a three-dimensional supra-molecular network. One of the two water molecules also lies on a twofold rotation axis.


Application of improved three-dimensional kernel approach to prediction of protein structural class.
Kernel methods, such as kernel PCA, kernel PLS, and support vector machines, are widely known machine learning techniques in biology, medicine, chemistry, and material science. Based on nonlinear mapping and Coulomb function, two 3D kernel approaches were improved and applied to predictions of the four protein tertiary structural classes of domains (all- α , all- β , α / β , and α + β ) and five membrane protein types with satisfactory results. In a benchmark test, the performances of improved 3D kernel approach were compared with those of neural networks, support vector machines, and ensemble algorithm. Demonstration through leave-one-out cross-validation on working datasets constructed by investigators indicated that new kernel approaches outperformed other predictors. It has not escaped our notice that 3D kernel approaches may hold a high potential for improving the quality in predicting the other protein features as well. Or at the very least, it will play a complementary role to many of the existing algorithms in this regard.


Synthesis of 3,3'-spirocyclic oxindoles via phosphine catalyzed [4 + 2] cyclizations.
Triphenylphosphine promoted reactions between 3-arylideneoxindoles and δ-aryl-substituted penta-2,3-dienoates afford an unprecedented access to spirocyclic oxindoles with functionalized six-membered rings. In these new [4 + 2] cyclization processes, the allenoates operate as the four-carbon synthons, thanks to the involvement of the substituted δ-carbons. These reactions give excellent control of the relative stereochemistry of the three stereogenic centers. The stereochemistry of the final product has been ascertained by X-ray diffraction studies.


Exploring the Dunning-Kruger Effect in Health Communication: How Perceived Food and Media Literacy and Actual Knowledge Drift Apart When Evaluating Misleading Food Advertising.
Marketers often advertise products high in sugar, fat or calories as healthy products. With this potentially misleading information, they can influence eating decisions with negative consequences for human health. Consumers need the ability to uncover misleading food advertising. However, individuals' perceived knowledge and their actual objective abilities often drift apart - a phenomenon which has come to be known as the Dunning-Kruger Effect. Thus, this study set out to uncover the phenomenon's potential existence in health communication, more precisely in the area of food and media literacy. In a quantitative survey representative of the Austrian population (n = 1000) the Dunning-Kruger Effect (DKE) could be detected: Individuals who were most knowledgeable underestimated their food and media literacy, but - on the positive side - they acted as opinion leaders. Individuals who were least knowledgeable about advertising strategies used to market an unhealthy product as healthy and about the actual nutrition score of the advertised product were most likely to overestimate their own food and media literacy. Worryingly, further concerning consequences emerged, especially for least knowledgeable individuals. The study's results provide important implications for public health campaigns.


Metabolic syndrome components are associated with future medical costs independent of cardiovascular hospitalization and incident diabetes.
Higher medical care costs have been associated with the number of metabolic syndrome components present, but the association with future medical costs has not been described. Furthermore, the independent cost contribution of each component alone and in combination with other components is unknown. We identified 57,420 nondiabetic adults aged ≥30 with all metabolic syndrome components measured in 2003-2004 and with 5 years of follow-up data available. We calculated and compared total annualized direct medical costs across the number of metabolic syndrome components present and for all possible combinations of metabolic syndrome components. The independent contribution to costs of each component was isolated by adjusting for age, sex, the other metabolic syndrome components, incident diabetes, number of years with diabetes, cardiovascular (CVD) hospitalization, and years after hospitalization. Annualized age- and sex-adjusted medical costs incurred over follow-up increased with each additional metabolic syndrome component present. After full adjustment, hypertension ($550), obesity ($366), low high-density lipoprotein (HDL) ($363), and high triglycerides ($317) were significantly associated with higher annual costs (P < 0.001 for all), but impaired fasting glucose was not. Further analysis indicated that costs were significantly elevated for each of these components only among those who did not develop diabetes or were not hospitalized for CVD. Incident diabetes or CVD hospitalizations accounted for the association between each metabolic syndrome component and future costs when these events occurred, but the elevated costs associated with metabolic syndrome components were observed even when these events did not occur. Further research is needed to understand the underlying morbidity that is driving the increased costs.


Comparison of malocclusions and orthodontic treatment needs of handicapped and normal children in Ibadan using the Dental Aesthetic Index (DAI).
This study compared the prevalences of malocclusion and Orthodontic needs between normal Nigerian children and their handicapped counterparts using the Dental Aesthetic Index. The samples consisted of 1,010 children -614 normal (321 males; 294 females) and 396 handicapped (199 males;197 females) aged 12-18 years with mean ages for normal and handicapped children as 14.8+/-1.9 and 15.0+/- 2.2 respectively. They were drawn randomly from their respective schools in Ibadan, Nigeria. Although some differences were observed in the ten malocclusion traits of DAI between the normal and the handicapped children, none was found statistially significant (P> 0.05). Missing teeth were noted in 1.9% of the normal children as against 4.8% of the handicapped. Crowding of incisal segments was observed in 20.0% of the normal and in 21.7% of the disabled children. Spacing of incisal segments was recorded in 47% and 55.5% of normal and handicapped children respectively. Others in that order were: Disatema-31.7% and 32.3%; Anterior maxillary irregularity - 55.5% and 40.9%; Anterior mandibular irregularity- 50.2% and 34.3%; Overjet - 20.7% and 13.1 %; Reversed overjet - 1.9% and 2.3%; Open bite - 7.5% and 9.8% and total deviations from normal molar relation in 23.8% and 31.3%. Also, although higher proportions of handicapped children than the normal group were noted having DAI scores indicative of treatment needs ranging from elective to mandatory, no significant differences were noted (P>0.05). About 13% of the normal and 16% of the handicapped children in the study sample deserved publicly funded orthodontic care.


Multi-physiopathological consequences of the c.1392G>T CFTR mutation revealed by clinical and cellular investigations.
This study combines a clinical approach and multiple level cellular analyses to determine the physiopathological consequences of the c.1392G>T (p.Lys464Asn) CFTR exon 10 mutation, detected in a CF patient with a frameshift deletion in trans and a TG(11)T(5) in cis. Minigene experiment, with different TG(m)T(n) alleles, and nasal cell mRNA extracts were used to study the impact of c.1392G>T on splicing in both in cellulo and in vivo studies. The processing and localization of p.Lys464Asn protein were evaluated, in cellulo, by western blotting analyses and confocal microscopy. Clinical and channel exploration tests were performed on the patient to determine the exact CF phenotype profile and the CFTR chloride transport activity. c.1392G>T affects exon 10 splicing by inducing its complete deletion and encoding a frameshift transcript. The polymorphism TG(11)T(5) aggravates the effects of this mutation on aberrant splicing. Analysis of mRNA obtained from parental airway epithelial cells confirmed these in cellulo results. At the protein level the p.Lys464Asn protein showed neither maturated form nor membrane localization. Furthermore, the in vivo channel tests confirmed the absence of CFTR activity. Thus, the c.1392G>T mutation alone or in association with the TG repeats and the poly T tract revealed obvious impacts on splicing and CFTR protein processing and functionality. The c.[T(5); 1392G>T] complex allele contributes to the CF phenotype by affecting splicing and inducing a severe misprocessing defect. These results demonstrate that the classical CFTR mutations classification is not sufficient: in vivo and in cellulo studies of a possible complex allele in a patient are required to provide correct CFTR mutation classification, adequate medical counseling, and adapted therapeutic strategies.


Two Web Resources Linking Major Human Embryology Collections Worldwide.
Human embryology is a core subject for medicine and current research. While animal models of development now have significant online resources available, the vast majority of human embryonic material is locked up in historic collections. When accessed today, these collections are still contributing to our understanding of human development. This paper describes two online resources for studying human development that are unlocking these invaluable collections and providing related human developmental resources. The first of these is the online Embryology website (http://tiny.cc/Embryo) that links the human developmental timeline to historic and current research findings. Secondly is the Digital Embryology Consortium (https://human-embryology.org), an international research partnership to digitise, preserve, and make the major embryology histological collections available for researchers. By making this histological material more widely available to researchers with new methods of analysis, a better understanding of human development can be reached. This also opens the opportunity for new 3D reconstruction and virtual reality representation of these embryos.


Breast Cancer Stem Cells and Sex Steroid Hormones.
Breast cancer stem cells (BCSCs) are a small population of tumor-initiating cells that express stem cell-associated markers. In recent years, their properties and mechanisms of regulation have become the focus of intense research due to their intrinsic resistance to conventional cancer therapies. This review describes breast cancer stem cell origin, signaling pathways involved in self-renewal, such as Wnt, Notch and Hedgehog, biomarkers linked to stemness, and the role of sex steroid hormones in BCSC regulation.


Rider-handlebar injury in two-wheel frontal collisions.
This work analyses blunt abdominal trauma produced by driver-handlebar collision, in low speed two-wheel accidents. A simplified dynamic model is introduced, whose parameters have been estimated on the basis of cadaver tests. This model allows calculating the peak impact force and the abdominal penetration depth; therefore the likelihood of occurrence of serious injuries can be estimated for different masses of contacting bodies and different speeds. Results have been checked against literature data and true-accident reports. Numerical simulations demonstrate that serious injuries (AIS>3) can occur even at low speeds (<20km/h), therefore the design of protective clothing is recommendable. The model can allow both the analysis of true accident data and the virtual testing of protective equipment in the conceptual design phase.


Reflections on achieving professional leadership.
This inspirational message was prepared as the capstone speech for the 1999 Helene Fuld Health Trust Fellowship Program for Emerging Nurse Leaders. At the time Dr. Fitzpatrick was President of the American Academy of Nursing. Key to her message is that future leaders should be encouraged to focus on the development of a career perspective as they develop transformational leadership skills.


Resistance to heat stress in the spontaneously hypertensive rat.
Thermal resistance as determined by survival time was examined in different age groups of spontaneously hypertensive (SHR) rats during terminal heating. A comparison with age or weight matched controls indicated that the thermal resistance of SHR animals was markedly inferior to that of normotensive animals as evidenced by 56% and 36% decreases in the total heating time to the lethal temperature, respectively. The decrease in thermal resistance in SHR animals occurred after 8 weeks of age and was coincident with the elevation of mean blood pressure to about 150 mmHg. The observation of significantly decreased total body water and rates of evaporation at critical colonic temperatures (39-40 degrees C) suggested the possibility of a reduced ability for water mobilization for thermoregulatory purposes in hypertensive animals although it appeared that other factors affecting heat gain or loss were involved.


Patients' experience and perceived concerns regarding obtaining and taking prescriptions for head and neck osteoradionecrosis.
The main components of the medical management of osteoradionecrosis (ORN) are combinations of clodronate, pentoxifylline, tocopherol, sometimes with antibiotics or chlorhexidine rinses. Anecdotally in the Cheshire and Merseyside network, patients report having difficulties getting and taking their prescription, hence the aim was to survey patient experience of obtaining prescriptions, administration of the medications, and side effects. Patients prescribed tocopherol and pentoxifylline from the pharmacy department's record database from the period of January 2019 to June 2020 were invited to take part in a semi-structured telephone survey. Sixteen patients out of a total 33 (48%) responded. 11 patients (69%) reported some issue collecting their repeat prescriptions, commonly low stock of medicines in community or unwillingness of GPs to prescribe. One patient permanently stopped treatment owing to difficulties obtaining medication, whilst for three there were temporary gaps in treatment. Difficulty in administration of the medications was reported in 7 patients (44%) patients, most commonly in those with pre-existing dysphagia. Issues related to difficulties in swallowing the large pentoxifylline tablet or with the vitamin E capsules. Patients crushed the medications, but this was associated with gastrointestinal side-effects in one patient who had to stop treatment. One patient stopped chlorhexidine mouthwash due to oral soreness. In conclusion, medical management of ORN is well tolerated by patients. There is difficulty for patients getting prescriptions in primary care. Few patients need to stop taking the medication due to difficulty in administration or side-effects. More patient information would be useful for all concerned.


Tunable resonance-domain diffraction gratings based on electrostrictive polymers.
Critical combination of high diffraction efficiency and large diffraction angles can be delivered by resonance-domain diffractive optics with high aspect ratio and wavelength-scale grating periods. To advance from static to electrically tunable resonance-domain diffraction grating, we resorted to its replication onto 2-5 μm thick P(VDF-TrFE-CFE) electrostrictive ter-polymer membranes. Electromechanical and optical computer simulations provided higher than 90% diffraction efficiency, a large continuous deflection range exceeding 20°, and capabilities for adiabatic spatial modulation of the grating period and slant. A prototype of the tunable resonance-domain diffraction grating was fabricated in a soft-stamp thermal nanoimprinting process, characterized, optically tested, and provided experimental feasibility proof for the tunable sub-micron-period gratings on electrostrictive polymers.


[Arbuscular mycorrhizal fungi enhance cadmium uptake of wetland plants in contaminated water].
Arbuscular mycorrhizal fungi (AMF) play an important role in plant growth enhancement, tolerance to heavy metal toxicity, and rehabilitation of contaminated ecosystems. An experiment was carried out with Phragmites communis and Pennisetum alopecuroides inoculated with or without Funneliformis mosseae (Fm), or Rhizophagus intraradices (Ri) under the simulated wetland system with Cd polluted water (0, 5, 10 or 20 mg·L-1). The results showed that Cd addition significantly decreased mycorrhizal colonization. AMF increased plant height, dry mass, leaf chlorophyll, N and Cd contents in shoot and root of P. communis and P. alopecuroides, enhanced Cd enrichment capability by roots, and decreased Cd transfer coefficient. Under Cd 5 mg·L-1 treatment, all of the indices in Fm + P. communis combination treatment were higher than those of other treatments, with 60.6% of AMF colonization, and the entry points and vesicles per mm root length were 2.3 and 3.7, respectively. Under the inoculation treatment, dry mass of shoot and root was improved by 69.1%, and 75.0%, nitrogen contents in shoot and root were increased by 38.7% and 27.8%, and the chlorophyll content and plant height were increased by 3.8% and 11.1%, respectively. There was a significant positive correlation between Cd concentration in wetland system and Cd content in shoot and root. Under Cd 20 mg·L-1 treatment, Fm + P. communis combination had the maximum Cd contents of 182.4 mg·kg-1 and 663.3 mg·kg-1 in shoot and root, respectively, the lowest Cd transfer coefficient (0.27), and the highest enrichment coefficient (0.55). In conclusion, Fm + P. communis was the best combination for absorbing Cd in polluted water.


The long-distance effects of brain lesions: visualization of myelinated pathways in the human brain using polarizing and fluorescence microscopy.
We describe several new possibilities for the study of degenerated myelinated tracts in the human central nervous system (CNS). The methods are based on the visualization of myelin breakdown products that show birefringence in polarized light and, when stained with Nile blue and benzpyrene-3,4, exhibit fluorescence. Even after lengthy formalin fixation, the methods permit the localization of anterogradely degenerated tracts in a variety of fiber systems in the brains of patients who died between five and 20 months after the onset of neurological symptoms. Particularly the polarizing technique, because of its simplicity, can be added to the usual neuropathological methods for demonstrating the long-distance effects of a brain lesion. As research tools, these methods would also aid in the study of the anatomical substrate of human neurological symptomatology.


Effect of irradiation distance on image contrast in epi-optoacoustic imaging of human volunteers.
In combined clinical optoacoustic (OA) and ultrasound (US) imaging, epi-mode irradiation and detection integrated into one single probe offers flexible imaging of the human body. The imaging depth in epi-illumination is, however, strongly affected by clutter. As shown in previous phantom experiments, the location of irradiation plays an important role in clutter generation. We investigated the influence of the irradiation geometry on the local image contrast of clinical images, by varying the separation distance between the irradiated area and the acoustic imaging plane of a linear ultrasound transducer in an automated scanning setup. The results for different volunteers show that the image contrast can be enhanced on average by 25% and locally by more than a factor of two, when the irradiated area is slightly separated from the probe. Our findings have an important impact on the design of future optoacoustic probes for clinical application.


Zinc-ligand interactions modulate assembly and stability of the insulin hexamer -- a review.
Zinc and calcium ions play important roles in the biosynthesis and storage of insulin. Insulin biosynthesis occurs within the beta-cells of the pancreas via preproinsulin and proinsulin precursors. In the golgi apparatus, proinsulin is sequestered within Zn(2+)- and Ca(2+)-rich storage/secretory vesicles and assembled into a Zn(2+) and Ca(2+) containing hexameric species, (Zn(2+))(2)(Ca(2+))(Proin)(6). In the vesicle, (Zn(2+))(2)(Ca(2+))(Proin)(6) is converted to the insulin hexamer, (Zn(2+))(2)(Ca(2+))(In)(6), by excision of the C-peptide through the action of proteolytic enzymes. The conversion of (Zn(2+))(2)(Ca(2+))(Proin)(6)to (Zn(2+))(2)(Ca(2+))(In)(6) significantly lowers the solubility of the hexamer, causing crystallization within the vesicle. The (Zn(2+))(2)(Ca(2+))(In)(6) hexamer is an allosteric protein that undergoes ligand-mediated interconversion among three global conformation states designated T(6), T(3)R(3) and R(6). Two classes of allosteric sites have been identified; hydrophobic pockets (3 in T(3)R(3) and 6 in R(6)) that bind phenolic ligands, and anion sites (1 in T(3)R(3) and 2 in R(6)) that bind monovalent anions. The allosteric states differ widely with respect to the physical and chemical stability of the insulin subunits. Fusion of the vesicle with the plasma membrane results in the expulsion of the insulin crystals into the intercellular fluid. Dissolution of the crystals, dissociation of the hexamers to monomer and transport of monomers to the liver and other tissues then occurs via the blood stream. Insulin action then follows binding to the insulin receptors. The role of Zn(2+) in the assembly, structure, allosteric properties, and dynamic behavior of the insulin hexamer will be discussed in relation to biological function.


Use of a monoclonal antibody to distinguish between precursor and mature forms of human lysosomal alpha-glucosidase.
The maturation of lysosomal alpha-glucosidase in cultured human skin fibroblasts was studied using a monoclonal antibody that distinguishes between the precursor and mature forms of the enzyme. Monoclonal antibodies against alpha-glucosidase isolated from placenta were produced by the hybridoma technique [Hilkens et al. (1981) Biochim. Biophys. Acta 678, 7-11]. One of these monoclonal antibodies, that synthesized by clone 43G8, reacts with the mature forms, but not with the precursor form of alpha-glucosidase isolated from urine. By means of pulse-labelling studies, it could be shown that monoclonal antibody 43G8 does not react with either the intracellular or the secreted precursor of alpha-glucosidase from cultured human skin fibroblasts. However, the antibody does react with the intermediate and mature forms of alpha-glucosidase. Endocytosis of the precurosor of alpha-glucosidase from urine by fibroblasts is followed by its conversion to a form with lower molecular mass. After endocytosis urinary precursor alpha-glucosidase is converted to a form that binds to monoclonal antibody 43G8. The t 1/2 for this conversion is 2 h. The conversion is inhibited by addition of leupeptin to the culture medium. It is concluded that a thiol proteinase is involved in the maturation of alpha-glucosidase in fibroblasts and the appearance of the antigenic determinant for 43G8.


Neurobehavioral consequences of traumatic brain injury.
At least 1.4 million people die, or receive hospital or emergency care every year in the United States as a result of traumatic brain injury (TBI). Many more are treated in other settings or receive no treatment at all. Thus TBI is often unidentified, with subsequent cognitive, behavioral, emotional and physical sequelae that are not linked to the injury. Yet, over 5.3 million Americans live with TBI-related disabilities that interfere with their overall performance and social roles within the community. The pathophysiology and consequences of TBI are discussed, as are functional changes and psychiatric manifestations after TBI. Finally, implications and recommendations for clinical practice are reviewed, including the importance of screening for TBI.


Influence of pH and Salt Concentration on Pickering Emulsions Stabilized by Colloidal Peanuts.
Solid-stabilized emulsions commonly known as Pickering emulsions offer unique benefits such as superior stability and controlled permeability compared to conventional surfactant stabilized emulsions. In this article, the effect of pH, the electrolyte and particle concentration, homogenization speed, and volume fraction of oil on the formation, stability, and the microstructure of emulsion droplets stabilized by micron-size peanut-shaped hematite particles are investigated. The influence of surface charge of particles on emulsification is studied by varying the pH of the dispersing medium, the addition of an electrolyte or a combination of both. Stable O/W emulsions are formed only when the aqueous dispersions at intermediate pH between 4 and 11, and decane (2:1 volume ratio) are vigorously mixed. However, emulsions are not formed when the particles are highly charged that is, at pH 2 and 12. The presence of monovalent salt or high-speed homogenization assists the emulsion formation at pH 3, whereas their combination helps in emulsification at pH 2. However, neither the addition of an electrolyte nor the high-speed homogenization or their combination facilitates the formation of emulsions at pH 12. We show that the image-charge repulsion and the surface charge induced wettability change can explain the influence of both pH and salt concentrations on the formation of Pickering emulsions. Although oil-in-water emulsions typically cream because of the density difference, microscopy observations revealed the presence of a large number of small particle-covered oil droplets in the sediments of the emulsified samples. These drops are observed to be entrapped in dense-particle networks. This leads to a considerable reduction in the number of particles available for the stabilization of floating emulsion droplets and thus influences their size and surface coverage. The possibility of tailoring the stability, droplet size and, the surface coverage discussed in this article can play a crucial role in situations that demand controlled release of active components.


Class of small multicopy plasmids originating from the mutant antibiotic resistance factor R1 drd-19B2.
The large mutant R-factor R1drd-19B2 gives rise to several classes of small, covalently closed circular deoxyribonucleic acids (DNAs), designated as Rsc DNAs, when harbored by the K-12 strain CRT46 which carries a dnaA mutation. The molecular weights of these DNA molecules range from 3 X 106 to 8.4 X 106. Cells arising from single colonies of CRT46-R1drd-19B2 harbor only one to two copies of the large mutant R-factor and in addition 10 to 20 copies of Rsc plasmid of a discrete size class per chromosome. The larger Rsc DNAs carry the ampicillin resistance gene. After transformation the small circular DNAs are present in Escherichia coli C in a large number of copies, up to 100 copies per chromosome. Hybridization studies between Rsc plasmids indicate that they possess common DNA sequences.


New insights into trophic aerenchyma formation strategy in maize (Zea mays L.) organs during sulfate deprivation.
Aerenchyma attributes plant tissues that contain enlarged spaces exceeding those commonly found as intracellular spaces. It is known that sulfur (S) deficiency leads to formation of aerenchyma in maize adventitious roots by lysis of cortical cells. Seven-day-old maize plants were grown in a hydroponics setup for 19 days under S deprivation against full nutrition. At day 17 and 26 from sowing (d10 and d19 of the deprivation, respectively), a detailed analysis of the total sulfur and sulfate allocation among organs as well as a morphometric characterization were performed. Apart from roots, in S-deprived plants aerenchyma formation was additionally found in the second leaf and in the mesocotyl, too. The lamina (LA) of this leaf showed enlarged gas spaces between the intermediate and small vascular bundles by lysis of mesophyll cells and to a greater extent on the d10 compared to d19. Aerenchymatous spaces were mainly distributed along the middle region of leaf axis. At d10, -S leaves invested less dry mass with more surface area, whilst lesser dry mass was invested per unit surface area in -S LAs. In the mesocotyl, aerenchyma was located near the scutelar node, where mesocotyl roots were developing. In -S roots, more dry mass was invested per unit length. Our data suggest that trying to utilize the available scarce sulfur in an optimal way, the S-deprived plant fine tunes the existing roots with the same length or leaves with more surface area per unit of dry mass. Aerenchyma was not found in the scutelar node and the bases of the attached roots. The sheaths, the LAs' bases and the crown did not form aerenchyma. This trophic aerenchyma is a localized one, presumably to support new developing tissues nearby, by induced cell death and recycling of the released material. Reduced sulfur allocation among organs followed that of dry mass in a proportional fashion.


[Subperiosteal orbital hemorrhage after heart surgery].
We report on a patient who suffered sudden diplopia after heart surgery. Computed tomography of the orbita revealed a subperiosteal hemorrhage as the underlying cause. We discuss possible mechanisms that may have led to the bleeding as well as therapeutic options.


High density lipoprotein apolipoprotein AI kinetics in NIDDM: a stable isotope study.
High density lipoprotein (HDL) kinetics were studied by infusing [5,5,5-2H3]-leucine in five subjects with normal glucose tolerance and eight patients with non-insulin-dependent diabetes mellitus (NIDDM) with poor metabolic control (HbA1c = 8.16 +/- 1.93%) (mean +/- SD). HDL were modelled as a single compartment since no kinetic differences were observed between HDL2 and HDL3 subclasses. Plasma apolipoprotein AI (apo AI) concentration was significantly lower in NIDDM patients (96.1 +/- 12.1 vs 124.4 +/- 13.1 mg.dl-1, p < 0.01). HDL composition was altered in NIDDM, as an increase in HDL-triglyceride and a decrease in HDL-cholesterol, negatively correlated (r = 0.780, p < 0.01). The mean fractional catabolic rate (FCR) of apo AI-HDL was significantly higher (0.39 +/- 0.16 vs 0.21 +/- 0.06 d-1, p < 0.05) while the apo AI-HDL absolute production rate was not significantly greater (13.6 +/- 5.1 vs 12.0 +/- 4.2 mg.kg-1.d-1) in diabetic patients compared to normal subjects. There were significant correlations between apo AI-HDL FCR and plasma apo AI concentration (r = -0.580, p < 0.05), plasma triglycerides (r = 0.839, p < 0.0001) or HDL-triglyceride levels (r = 0.597, p < 0.05). No correlation was observed between apo AI-HDL FCR and HbA1c or HDL-cholesterol level. These data support the view that the decrease in plasma apo AI level in patients with NIDDM is due to an increase of apo AI-HDL FCR, which may itself be related to changes in HDL composition.


Chronic Kidney Disease-Associated Pruritus and Quality of Life: Learning from Our Patients.
Chronic kidney disease-associated pruritus is itching directly related to kidney disease that cannot be explained by any other condition. Despite technological advances in the different aspects of dialysis sessions and the best treatment for chronic kidney disease patients, it is still a common problem in our patients. The many complex physiological mechanisms involved, the different hypotheses made over the years on the aetiology of the condition, and the great clinical variability may partially explain the limited knowledge about this problem and the difficulties in treating it. The presence of all these factors leads to the persistence of unpleasant symptoms, which must affect the disease burden and quality of life of kidney patients. Through the presentation of an illustrative clinical case, the aim of this review article is to highlight the need for adequate diagnosis and an improved approach to all aspects of chronic kidney disease-associated pruritus, in view of the heavy burden of the disease and the huge impact on the patient's quality of life.


Self-reported work-related accumulative fatigue of nurses: A cross-sectional study in public hospitals in China.
Work-related fatigue is a serious safety risk to nurses and their patients. This study aimed to assess self-reported work-related accumulative fatigue of nurses and its associated factors. A questionnaire survey of 2,918 clinical nurses conveniently sampled from 48 public hospitals across six provinces in China was conducted. The "Self-diagnosis Checklist for Assessment of Workers' Accumulated Fatigue" was adopted to assess the level of work-related accumulative fatigue of the study participants. Chi-square tests and ordinal regression analyses were performed to determine the sociodemographic characteristics associated with work-related accumulative fatigue. About one third of respondents reported low work-related accumulative fatigue, compared with 23.1% reporting high and 24.6% reporting very high levels of work-related accumulative fatigue. Higher levels of work-related accumulative fatigue were associated with female gender (AOR = 0.614 for male relative to female, p = 0.005), age between 30 and 40 years (AOR = 1.346 relative to >40 years, p = 0.034), 5-10 years of work experience (AOR = 1.277 relative to >10 years, p = 0.034), and bachelor or above degree qualifications (AOR = 0.806 for associate degree relative to bachelor or above degree, p = 0.007). Those who worked in rural county hospitals (AOR = 0.816 for metropolitan relative to rural county hospitals, p = 0.006) and resided in central China (AOR = 1.276 relative to western China, p = 0.004) had higher odds of reporting higher levels of work-related accumulative fatigue. High levels of work-related accumulative fatigue are evident in nurses of public hospitals in China. The problem is more serious in the female nurses in their mid-career and those who worked in the central region and rural setting.


Clinical evaluation, ultrasound, cholescintigraphy, and endoscopic retrograde cholangiography in cholestasis. A prospective comparative clinical study.
The accuracy of clinical evaluation (CE), ultrasonography (US), and cholescintigraphy (CS) was prospectively compared in a group of 72 cholestatic patients, using the results of endoscopic retrograde cholangiography (ERC) as the true standard. Forty-six cases (63.9%) had a final diagnosis of extrahepatic biliary obstruction. Clinical evaluation had a sensitivity of 82.6% and a specificity of 46.2% for the identification of mechanical obstruction. Ultrasonography was the single most powerful noninvasive diagnostic procedure, with a sensitivity of 65.2%, a specificity of 92.3%, a positive likelihood ratio of 8.5, and a positive predictive value (PVpos) of 93.8%, which was superior to the diagnostic power of CS (0.05 less than p less than 0.1). Inconclusive results or technical failures were counted as diagnostic errors. Contingency table analyses in an extended group of 112 patients, complete for CE, US, and CS, revealed that concordant results of CE and US had a high probability of correctness (combined PVpos 92.6%, PVneg 98.0%). Contradictory ratings of these two tests were unlikely to be clarified reliably by additional CS. We conclude that the combined evaluation of CE and US allows an accurate differentiation between intrahepatic cholestasis and extrahepatic biliary obstruction. When both give contradictory results, direct cholangiography, rather than further noninvasive procedures, appears to be the diagnostic strategy of choice.


Can but don't: olfactory discrimination between own and alien offspring in the domestic cat.
Mammalian maternal care usually comes at a large energetic cost. To maximize their fitness, mothers should preferentially care for their own offspring. However, the majority of studies of mother-offspring recognition have focused on herd- or colony-living species and there is little information on maternal discrimination in more solitary-living species. Olfaction has been found to play a major role in mother-offspring recognition across various taxa. Therefore, our aim was to study this in a species evolved from a solitary-living ancestor, the domestic cat. We asked whether cat mothers distinguish between their own and alien offspring when providing maternal care, and whether cat mothers use olfactory cues in the offspring discrimination process. Results of Experiment 1 showed that cat mothers do not discriminate between own and alien young when retrieving them to the nest. They treated own and alien young similarly with respect to latency and order of retrieval. However, the results of Experiments 2 and 3, where we used an olfactory habituation-discrimination technique, showed that mothers were able to distinguish between the odours of their own and alien kittens. We discuss what ecological and/or behavioural factors might influence a mother's decision when faced with discriminating between own and alien young, and why mothers might not discriminate between them when they are able to do so. Our findings support the view that maternal care alone should not be used as a measure of offspring recognition, and equal maternal care of own and alien young should not be immediately interpreted as an inability to discriminate between them.


The influence of BMI on perioperative morbidity following abdominal hysterectomy.
The objective of the study was to assess the impact of body mass index (BMI) on 30 day perioperative morbidity following abdominal hysterectomy. The 2006-2010 National Surgical Quality Improvement Program data registry was retrospectively reviewed for patients undergoing abdominal hysterectomy. Logistic regression was used to investigate the relationship between BMI and postoperative complications. A total of 9917 patients were captured, of which, 2219 were of an ideal BMI, 2765 were overweight, and 4933 were obese. Complications occurred in 11.3% of the procedures, with obese patients experiencing significantly higher rates of morbidity compared with overweight and nonobese patients (13.2%, 9.7%, and 9.0%, respectively; P < .001). Surgical complications were rare; however, a significant step-wise progression was observed with increasing BMI (P < .001). The rate of reoperations and overall medical complication did not differ among cohorts, although the incidence of deep vein thromboses (DVTs) was notably elevated in obese and overweight patients (P = .032). Adjusted odds ratios (ORs) found both overweight and obese patients to be at a significantly higher risk of surgical complications (OR, 1.6 and 3.0, respectively) and wound infections (OR, 1.7 and 3.0, respectively). Overweight patients were also at higher risk for DVTs (OR, 4.6) and obese patients for overall morbidity (OR, 1.4) and wound disruption (OR, 3.6). Obese and overweight patients demonstrated an increased risk for periorperative morbidity following abdominal hysterectomies.


Optically programmable encoder based on light propagation in two-dimensional regular nanoplates.
We design an efficient optically controlled microdevice based on CdSe nanoplates. Two-dimensional CdSe nanoplates exhibit lighting patterns around the edges and can be realized as a new type of optically controlled programmable encoder. The light source is used to excite the nanoplates and control the logical position under vertical pumping mode by the objective lens. At each excitation point in the nanoplates, the preferred light-propagation routes are along the normal direction and perpendicular to the edges, which then emit out from the edges to form a localized lighting section. The intensity distribution around the edges of different nanoplates demonstrates that the lighting part with a small scale is much stronger, defined as '1', than the dark section, defined as '0', along the edge. These '0' and '1' are the basic logic elements needed to compose logically functional devices. The observed propagation rules are consistent with theoretical simulations, meaning that the guided-light route in two-dimensional semiconductor nanoplates is regular and predictable. The same situation was also observed in regular CdS nanoplates. Basic theoretical analysis and experiments prove that the guided light and exit position follow rules mainly originating from the shape rather than material itself.


Neural mechanisms underlying neurooptometric rehabilitation following traumatic brain injury.
Mild to severe traumatic brain injuries have lasting effects on everyday functioning. Issues relating to sensory problems are often overlooked or not addressed until well after the onset of the injury. In particular, vision problems related to ambient vision and the magnocellular pathway often result in posttrauma vision syndrome or visual midline shift syndrome. Symptoms from these syndromes are not restricted to the visual domain. Patients commonly experience proprioceptive, kinesthetic, vestibular, cognitive, and language problems. Neurooptometric rehabilitation often entails the use of corrective lenses, prisms, and binasal occlusion to accommodate the unstable magnocellular system. However, little is known regarding the neural mechanisms engaged during neurooptometric rehabilitation, nor how these mechanisms impact other domains. Event-related potentials from noninvasive electrophysiological recordings can be used to assess rehabilitation progress in patients. In this case report, high-density visual event-related potentials were recorded from one patient with posttrauma vision syndrome and secondary visual midline shift syndrome during a pattern reversal task, both with and without prisms. Results indicate that two factors occurring during the end portion of the P148 component (168-256 milliseconds poststimulus onset) map onto two separate neural systems that were engaged with and without neurooptometric rehabilitation. Without prisms, neural sources within somatosensory, language, and executive brain regions engage inefficient magnocellular system processing. However, when corrective prisms were worn, primary visual areas were appropriately engaged. The impact of using early neurooptometric rehabilitation for posttrauma vision syndrome, visual midline shift syndrome, and other similar subtle vision disorders to support neural reorganization is discussed.


Endoscopic retrograde biliary drainage.
Endoscopic retrograde biliary drainage (ERBD) was completed in 30 of 34 attempts (88.2%). Sixteen patients are alive with functioning stents one to 14 months following insertion of the catheters. Eight patients died with functioning stents two weeks to four months following placement. Six stents were replaced due to sepsis or rising bilirubin one to eight months following initial insertion. The only immediate complication was sepsis, which developed in one patient. Since ERBD circumvents many of the complications associated with percutaneous transhepatic drainage, it has replaced this technique in our institution as the primary non-operative modality for biliary decompression. Percutaneous transhepatic drainage is now reserved for ERBD failures.


Uniformly minimum variance unbiased estimation of gene diversity.
Gene diversity is an important measure of genetic variability in inbred populations. The survival of species in changing environments depends on, among other factors, the genetic variability of the population. In this communication, I have derived the uniformly minimum variance unbiased estimator of gene diversity. The proposed estimator of gene diversity does not assume that the inbreeding coefficient is known. I have also provided the approximate variance of this estimator according to Fisher's method. In addition, I have developed a numerical resampling-based method for obtaining variances and confidence intervals based on the maximum likelihood estimator and the uniformly minimum variance unbiased estimator. Efficiency in estimation of the gene diversity based on these two estimators is discussed. In accordance with the simulation results, I found that the uniformly minimum variance estimator developed in this report is more accurate for estimation of gene diversity than the maximum likelihood estimator.


Comparison of virulence of different Sporothrix schenckii clinical isolates using experimental murine model.
The virulence of two strains of Sporothrix schenckii isolated from patients with lymphocutaneous or disseminated sporotrichosis were examined in BALB/c mice (Group 1 and 2, respectively). The mice were inoculated subcutaneously into the left hind footpad with 4 x 10(6) S. schenckii yeast cells in order to evaluate (i) the development of cutaneous lesions, (ii) signs of inactivity, (iii) weight loss, (iv) survival rates, (v) number of viable yeast cells in the lungs and spleen, (vi) splenic index, (vii) extent of organ lesions, and (viii) immunological responses. Comparison of the two groups showed more severe disease in Group 2 mice that developed significant weight and hair loss associated with inactivity and left hind footpad lesions that extended close to the testicular area. The histopathology and large number of viable microorganisms isolated from the spleen confirmed the higher invasive ability of this strain. Moreover, a decrease of an in vitro specific lymphoproliferative response and IFN-gamma production were observed over time in Group 2 mice. As a result, at the end of the experiment, the S. schenckii-antigen (Ss-Ag) response was considered negative with a stimulation index (SI) = 2. In contrast, Group 1 mice presented a positive response to Ss-Ag (SI = 14.1). These results confirm the existence of different virulence profiles in S. schenckii strains. In addition, the use of subcutaneous inoculation as a suitable route for verification of the pathogenicity of this fungus in the murine model was confirmed.


Antioxidant properties of natural compounds used in popular medicine for gastric ulcers.
There is evidence concerning the participation of reactive oxygen species in the etiology and physiopathology of human diseases, such as neurodegenerative disorders, inflammation, viral infections, autoimmune pathologies, and digestive system disorders such as gastrointestinal inflammation and gastric ulcer. The role of these reactive oxygen species in several diseases and the potential antioxidant protective effect of natural compounds on affected tissues are topics of high current interest. To consider a natural compound or a drug as an antioxidant substance it is necessary to investigate its antioxidant properties in vitro and then to evaluate its antioxidant functions in biological systems. In this review article, we shall consider the role of natural antioxidants derived from popular plants to reduce or prevent the oxidative stress in gastric ulcer induced by ethanol.


Relationship of progression of visual field damage to postural changes in intraocular pressure in patients with normal-tension glaucoma.
To evaluate whether postural changes of intraocular pressure (IOP) are associated with progression of visual field damage in patients with normal-tension glaucoma (NTG). Prospective, noncomparative, nonrandomized study. Sixty eyes of 33 patients with NTG. Intraocular pressure, blood pressure (BP), and pulse rate (PR) were measured in both sitting and supine positions. Visual fields were examined using Humphrey Field Analyzer (HFA; Zeiss-Humphrey Instruments, Inc., San Leandro, CA). Changes in mean deviation (MD) per year (dB/year), that is, MD slope, were calculated by linear regression analysis of the HFA Statpac 2 program. The relationship between postural changes of IOP and MD slope was analyzed. The correlation between postural changes of IOP and cardiovascular parameters such as BP and PR also was analyzed. The IOP in the supine position was significantly higher than that in the sitting position (P<0.001, paired t test). There was no significant correlation between MD slope and sitting IOP (Pearson r = 0.172; P = 0.188), but a significant correlation was found between MD slope and supine IOP (r = -0.261; P = 0.043). The MD slope significantly correlated with IOP elevation caused by the postural change (r = -0.682; P<0.001). The systolic BP in the supine position correlated with postural changes of IOP (r = 0.364; P = 0.004), but other cardiovascular parameters did not correlate with IOP parameters. The progression of visual field damage in NTG is associated with IOP in the supine position and the magnitude of IOP elevation accompanying postural changes. These results suggest that deterioration in NTG may occur when patients are lying flat during sleep.


Disk-shaped Bose-Einstein condensates in the presence of an harmonic trap and an optical lattice.
We study the existence and stability of solutions of the two-dimensional nonlinear Schrodinger equation in the combined presence of a parabolic and a periodic potential. The motivating physical example consists of Bose-Einstein condensates confined in an harmonic (e.g., magnetic) trap and an optical lattice. By connecting the nonlinear problem with the underlying linear spectrum, we examine the bifurcation of nonlinear modes out of the linear ones for both focusing and defocusing nonlinearities. In particular, we find real-valued solutions (such as multipoles) and complex-valued ones (such as vortices). A primary motivation of the present work is to develop "rules of thumb" about what waveforms to expect emerging in the nonlinear problem and about the stability of those modes. As a case example of the latter, we find that among the real-valued solutions, the one with larger norm for a fixed value of the chemical potential is expected to be unstable.


Neuroplasticity mechanisms in the pathophysiology of chronic pain.
Chronic pain is a widespread healthcare problem with great impact on mental health, professional and family life of the patient. It can be a consequence of many disorders; however, its pathogenesis has not yet been fully understood. Neuroplasticity is the ability of the nervous system to adapt to different changes and it is present throughout life, not only in prenatal period, infancy and childhood. However, in the pathophysiology of chronic pain, neuroplasticity shows its "dark side". Due to the central sensitization process, noxious stimuli can produce chronic pain or misinterpretation of non-noxious stimuli (secondary hyperalgesia and allodynia). These changes occur at the level of brain cortex as well at peripheral nerves and receptors. This review summarizes a significant portion of literature dealing with neuroplasticity processes in well known chronic pain conditions such as migraine, chronic posttraumatic headache, low back pain, fibromyalgia, and others. The relevance of this topic lies in providing a new insight in the pathophysiology of chronic pain, while also offering a possibility of new therapeutic approaches including not only pharmacological agents.


Collagen degradation in tuberculosis pathogenesis: the biochemical consequences of hosting an undesired guest.
The scenario of chemical reactions prompted by the infection by Mycobacterium tuberculosis is huge. The infection generates a localized inflammatory response, with the recruitment of neutrophils, monocytes, and T-lymphocytes. Consequences of this immune reaction can be the eradication or containment of the infection, but these events can be deleterious to the host inasmuch as lung tissue can be destroyed. Indeed, a hallmark of tuberculosis (TB) is the formation of lung cavities, which increase disease development and transmission, as they are sites of high mycobacterial burden. Pulmonary cavitation is associated with antibiotic failure and the emergence of antibiotic resistance. For cavities to form, M. tuberculosis induces the overexpression of host proteases, like matrix metalloproteinases and cathepsin, which are secreted from monocyte-derived cells, neutrophils, and stromal cells. These proteases destroy the lung parenchyma, in particular the collagen constituent of the extracellular matrix (ECM). Namely, in an attempt to destroy infected cells, the immune reactions prompted by mycobacterial infections induce the destruction of vital regions of the lung, in a process that can become fatal. Here, we review structure and function of the main molecular actors of ECM degradation due to M. tuberculosis infection and the proposed mechanisms of tissue destruction, mainly attacking fibrillar collagen. Importantly, enzymes responsible for collagen destruction are emerging as key targets for adjunctive therapies to limit immunopathology in TB.


Preferential staining of granulocytic cells by sulphonaphthyl red.
Using sulphonaphythyl red (Michrome #947), granules in mature and immature granulocytic cells stained bright red. Granules were not visualized in other types of normal or leukemic blood cells. As such, sulphonaphthyl red may be useful in distinguishing normal and abnormal granulocytic cells from other types of blood and bone marrow cells.


Gender differences of brain activity in the conflicts based on implicit self-esteem.
There are gender differences in global and domain-specific self-esteem and the incidence of some psychiatric disorders related to self-esteem, suggesting that there are gender differences in the neural basis underlying one's own self-esteem. We investigated gender differences in the brain activity while subjects (14 males and 12 females) performed an implicit self-esteem task, using fMRI. While ventromedial prefrontal cortex (vmPFC) was significantly activated in females, medial and dorsomedial PFC (dmPFC) were activated in males in the incongruent condition (self = negative) compared with the congruent condition (self = positive). Additionally, scores on the explicit self-esteem test were negatively correlated with vmPFC activity in females and positively correlated with dmPFC activity in males. Furthermore, the functional relationships among the regions found by direct gender comparisons were discussed based on the somatic-marker model. These showed that, compared to males, females more firmly store even the incongruent associations as part of their schematic self-knowledge, and such associations automatically activate the neural networks for emotional response and control, in which vmPFC plays a central role. This may explain female cognitive/behavioral traits; females have more tendency to ruminate more often than males, which sometimes results in a prolonged negative affect.


Safety and efficacy of nitrous oxide for endoscopic ultrasound procedures that need irrigation.
Echo-endoscopes are much stiffer and thicker than regular endoscopes. During the procedure of endoscopic ultrasound (EUS) procedure, water irrigation is a very useful for imaging but very dangerous if the patient receive the procedure under anesthesia without intubation. In this study, we evaluated the safety and effectiveness of nitrous oxide (N2O) (≤70%) for EUS. Among 4230 patients who underwent EUS from December 2012 to December 2013, 347 out patients who need irrigation during the procedure were enrolled and divided into Group A. Group A (N2O sedation group, n = 162) and Group B (no sedative group, n = 185). For Group A, patients received N2O by inhalation during the procedure. The mixture rate of N2O and O2 was 45-65% and controlled by nurses according to individual effect. The cardiorespiratory functions, procedure duration, complications, and visual analog scale (VAS) of the patient and examiner satisfaction were compared. Both group had comparable diagnostic accuracy, but VAS of the patients who received N2O sedation was higher than that in Group B (7.5 vs. 4.5, P < 0.05) and the examiner procedural satisfaction ratings of Group A was also better than that of Group B (8.1 vs. 5.1, P < 0.05); Most patients in Group A reported willingness to reconsider N2O for a future EUS. No pulmonary aspiration occurred in this study. N2O for EUS is comfortable, safe and feasible, especially for the procedures that need irrigation.


Ferritin: A Multifunctional Nanoplatform for Biological Detection, Imaging Diagnosis, and Drug Delivery.
Ferritins are spherical iron storage proteins within cells that are composed of a combination of 24 subunits of two types, heavy-chain ferritin (HFn) and light-chain ferritin (LFn). They autoassemble naturally into a spherical hollow nanocage with an outer diameter of 12 nm and an interior cavity that is 8 nm in diameter. In recent years, with the constantly emerging safety issues and the concerns about unfavorable uniformity and indefinite in vivo behavior of traditional nanomedicines, the characteristics of native ferritin nanocages, such as the unique nanocage structure, excellent safety profile, and definite in vivo behavior, make ferritin-based formulations uniquely attractive for nanomedicine development. To date, a variety of cargo molecules, including therapeutic drugs (e.g., cisplatin, carboplatin, paclitaxel, curcumin, atropine, quercetin, gefitinib, daunomycin, epirubicin, doxorubicin, etc.), imaging agents (e.g., fluorescence dyes, radioisotopes, and MRI contrast agents), nucleic acids (e.g., siRNA and miRNA), and metal nanoparticles (e.g., Fe3O4, CeO2, AuPd, CuS, CoPt, FeCo, Ag, etc.) have been loaded into the interior cavity of ferritin nanocages for a broad range of biomedical applications from in vitro biosensing to targeted delivery of cargo molecules in living systems with the aid of modified targeting ligands either genetically or chemically. We reported that human HFn could selectively deliver a large amount of cargo into tumors in vivo via transferrin receptor 1 (TfR1)-mediated tumor-cell-specific targeting followed by rapid internalization. By the use of the intrinsic tumor-targeting property and unique nanocage structure of human HFn, a broad variety of cargo-loaded HFn formulations have been developed for biological analysis, imaging diagnosis, and medicine development. In view of the intrinsic tumor-targeting property, unique nanocage structure, lack of immunogenicity, and definite in vivo behavior, human HFn holds promise to promote therapeutic drugs, diagnostic imaging agents, and targeting moieties into multifunctional nanomedicines.Since the report of the intrinsic tumor-targeting property of human HFn, we have extensively explored human HFn as an ideal nanocarrier for tumor-targeted delivery of anticancer drugs, MRI contrast agents, inorganic nanoparticles, and radioisotopes. In particular, by the use of genetic tools, we also have genetically engineered human HFn nanocages to recognize a broader range of disease biomarkers. In this Account, we systematically review human ferritins from characterizing their tumor-binding property and understanding their mechanism and kinetics for cargo loading to exploring their biomedical applications. We finally discuss the prospect of ferritin-based formulations to become next-generation nanomedicines. We expect that ferritin formulations with unique physicochemical characteristics and intrinsic tumor-targeting property will attract broad interest in fundamental drug research and offer new opportunities for nanomedicine development.


Use of Naloxone in 9-1-1 Patients without Respiratory Depression in Los Angeles County, California (USA).
Along with an increase in opioid deaths, there has been a desire to increase the accessibility of naloxone. However, in the absence of respiratory depression, naloxone is unlikely to be beneficial and may be deleterious if it precipitates withdrawal in individuals with central nervous system (CNS) depression due to non-opioid etiologies. The aim of this study was to evaluate how effective prehospital providers were in administering naloxone. This is a retrospective study of naloxone administration in two large urban Emergency Medical Service (EMS) systems. The proportion of patients who had a respiratory rate of at least 12 breaths per minute at the time of naloxone administration by prehospital providers was determined. During the two-year study period, 2,580 patients who received naloxone by prehospital providers were identified. The median (interquartile range) respiratory rate prior to naloxone administration was 12 (6-16) breaths per minute. Using an a priori respiratory rate of under 12 breaths per minute to define respiratory depression, only 1,232 (47.8%; 95% CI, 50.3%-54.2%) subjects who received naloxone by prehospital providers had respiratory depression. This study showed that EMS providers in Los Angeles County, California (USA) frequently administered naloxone to individuals without respiratory depression.


AllerCatPro-prediction of protein allergenicity potential from the protein sequence.
Due to the risk of inducing an immediate Type I (IgE-mediated) allergic response, proteins intended for use in consumer products must be investigated for their allergenic potential before introduction into the marketplace. The FAO/WHO guidelines for computational assessment of allergenic potential of proteins based on short peptide hits and linear sequence window identity thresholds misclassify many proteins as allergens. We developed AllerCatPro which predicts the allergenic potential of proteins based on similarity of their 3D protein structure as well as their amino acid sequence compared with a data set of known protein allergens comprising of 4180 unique allergenic protein sequences derived from the union of the major databases Food Allergy Research and Resource Program, Comprehensive Protein Allergen Resource, WHO/International Union of Immunological Societies, UniProtKB and Allergome. We extended the hexamer hit rule by removing peptides with high probability of random occurrence measured by sequence entropy as well as requiring 3 or more hexamer hits consistent with natural linear epitope patterns in known allergens. This is complemented with a Gluten-like repeat pattern detection. We also switched from a linear sequence window similarity to a B-cell epitope-like 3D surface similarity window which became possible through extensive 3D structure modeling covering the majority (74%) of allergens. In case no structure similarity is found, the decision workflow reverts to the old linear sequence window rule. The overall accuracy of AllerCatPro is 84% compared with other current methods which range from 51 to 73%. Both the FAO/WHO rules and AllerCatPro achieve highest sensitivity but AllerCatPro provides a 37-fold increase in specificity. https://allercatpro.bii.a-star.edu.sg/. Supplementary data are available at Bioinformatics online.


Delayed brain atrophy after electrical injury.
We report a case of delayed brain atrophy after electrical injury. A 12-year-old boy sustained extensive burns by touching a high-voltage power line. The burn area comprised more than 60% TBSA, and he subsequently underwent several surgical procedures. Two months later, he suddenly developed seizures. Initial findings on magnetic resonance imaging showed diffuse cortical damage in the left brain. Two months later, motor aphasia appeared, and a second magnetic resonance imaging scan showed atrophy in the left temporal and frontal lobes. Owing to speech rehabilitation, the patient gradually recovered his capacity for speech. Eight months later, his speech was almost perfect. We believe that because the patient was young, early speech rehabilitation was effective.


[Beginnings of nursing education and nurses' contribution to nursing professional development in Serbia].
The oldest records of developmental beginnings of patients' healthcare relate to the first hospital founded by St. Sava at the monastery Studenica in 1199. The profile of the Kosovian girl became the hallmark of nursing profession in Serbia. The first school for midwives was founded in 1899 at the Department of Gynecology and Obstetrics of the General State Hospital in Belgrade. However, there were no other schools for nurses in Serbia until the foundation of the School for Midwives of the Red Cross Society in 1021. Until then the healthcare of patients and the injured was carried out by self-taught volunteer nurses with completed short courses of patients' healthcare. The first course for male and female nurses was organized by the Serbian Red Cross at the beginning of the First Serbian-Turkish War in 1876. During wars with Serbian participation in 19th and 20th centuries with Serbian participation, nurses gave a remarkable contribution being exposed to extreme efforts and often sacrificing their own lives. In war times great merit belongs to the members of the humanitarian society the Circle of Serbian Sisters founded in Belgrade in 1903, which was the resource of a great number of nurses who became the pride of nursing profession. Generations of nurses were educated on their example. In 2004 the annual award "Dušica Spasić" was established which is awarded to the best medical nurse is Serbia. Dušica Spasić was a medical nurse that died at her workplace, when aged 23 years, nursing the sick from variola.


MeCP2 attenuates cardiomyocyte hypoxia/reperfusion-induced injury via regulation of the SFRP4/Wnt/β-catenin axis.
Objective: Methylated CpG binding protein 2 (MeCP2) is closely associated with heart failure, but its role in I/R injury remains unclear. The purpose of this study was to explore the role and underling mechanism of MeCP2 in myocardial I/R injury.Methods: Hypoxia/reperfusion (H/R)-induced H9c2 cardiomyocytes was used to establish an in vitro I/R injury model. Oxidative stress was assessed by measuring reactive oxygen species (ROS) generation, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity. Cell viability and cell cycle arrest were evaluated by the Cell Counting Kit-8 assay and cell cycle assay, respectively. Apoptosis was determined using flow cytometry analysis.Results: The expression of MeCP2 in H9c2 cells was decreased after H/R treatment. The overexpression of MeCP2 inhibited H/R-induced oxidative stress, cell cycle arrest and apoptosis of H9c2 cells. Moreover, MeCP2 inhibited the activation of secreted frizzled related protein 4 (SFRP4)/Wnt/β-catenin axis, and SFRP4 relieved the effect of MeCP2 on oxidative stress, cell cycle arrest and apoptosis in H/R-induced H9c2 cells.Conclusions: MeCP2 attenuated H/R-induced injury in H9c2 cardiomyocytes by modulating the SFRP4/Wnt/β-catenin axis, which suggested that MeCP2 might serve as a therapeutic target of patients with AMI after reperfusion.


Using Similarity Metrics on Real World Data and Patient Treatment Pathways to Recommend the Next Treatment.
Non-small-cell lung cancer (NSCLC) is one of the most prevalent types of lung cancer and continues to have an ominous five year survival rate. Considerable work has been accomplished in analyzing the viability of the treatments offered to NSCLC patients; however, while many of these treatments have performed better over populations of diagnosed NSCLC patients, a specific treatment may not be the most effective therapy for a given patient. Coupling both patient similarity metrics using the Gower similarity metric and prior treatment knowledge, we were able to demonstrate how patient analytics can complement clinical efforts in recommending the next best treatment. Our retrospective and exploratory results indicate that a majority of patients are not recommended the best surviving therapy once they require a new therapy. This investigation lays the groundwork for treatment recommendation using analytics, but more investigation is required to analyze patient outcomes beyond survival.


Pitch encoding in speech and nonspeech contexts in the human auditory brainstem.
Frequency-following responses were recorded from Chinese and English participants at the level of the brainstem in response to four Mandarin tonal contours presented in a speech and nonspeech context. Pitch strength analysis of these preattentive brainstem responses showed that the Chinese group exhibited stronger pitch representation than the English group regardless of context. Moreover, the Chinese group exhibited relatively more robust pitch representation of rapidly changing pitch segments. These findings support the view that at early preattentive stages of subcortical processing, neural mechanisms underlying pitch representation are shaped by particular features of the auditory stream rather than speech per se. These findings have implications for optimizing signal-processing strategies for cochlear implant design for speakers of tonal languages.


Catalytic activity of human carbonic anhydrase isoform IX is displayed both extra- and intracellularly.
Most carbonic anhydrases catalyse the reversible conversion of carbon dioxide to protons and bicarbonate, either as soluble cytosolic enzymes, in or at intracellular organelles, or at the extracellular face of the cell membrane as membrane-anchored proteins. Carbonic anhydrase isoform IX (CA IX), a membrane-bound enzyme with catalytic activity at the extracellular membrane surface, has come to prominence in recent years because of its association with hypoxic tissue, particularly tumours, often indicating poor prognosis. We have evaluated the catalytic activity of CA IX heterologously expressed in Xenopus laevis oocytes by measuring the amplitude and rate of cytosolic pH changes as well as pH changes at the outer membrane surface (pHs ) during addition and removal of 5% CO2 /25 mm HCO3-, and by mass spectrometry. Our results indicate both extracellular and intracellular catalytic activity of CA IX. Reduced rates of CO2 -dependent intracellular pH changes after knockdown of CA IX confirmed these findings in two breast cancer cell lines: MCF-7 and MDA-MB-231. Our results demonstrate a new function of CA IX that may be important in the search for therapeutic cancer drugs targeting CA IX.


MRI of suspected lower extremity musculoskeletal infection in the pediatric patient: how useful is bilateral imaging?
The purpose of this study was to determine the frequency of bilateral abnormalities in children with suspected lower extremity musculoskeletal infection and the impact of detection of contralateral abnormalities by MRI on patient management. A retrospective review of 165 consecutive bilateral lower extremity MRI examinations performed for suspected musculoskeletal infection in pediatric patients (64% boys and 36% girls; mean age, 7.5 years; age range, 0-18 years) in 2010 at a children's hospital was performed. Imaging findings were compared with the final clinical diagnosis and management. The MRI examination was normal in 2% (4/165). Osteomyelitis was diagnosed in 33% (54/165) of the MRI examinations; among these examinations 20% (11/54) had both ipsilateral septic arthritis and osteomyelitis, 2% (1/54) had bilateral osteomyelitis, and 67% (111/165) of the examinations were negative for osteomyelitis. Bilateral abnormalities were detected in 20% (22/111) of patients without osteomyelitis, with 18% (4/22) presenting with bilateral signs or symptoms. Abnormalities in the contralateral extremity included myositis (18%, 4/22), stress reaction (18%, 4/22), subcutaneous edema (18%, 4/22), leukemia (14%, 3/22), reactive joint effusion (14%, 3/22), Baker cyst (5%, 1/22), and osteonecrosis (5%, 1/22). Identification of clinically unsuspected abnormalities of the contralateral extremity by MRI was not associated with alterations in medical or surgical management in children with or without osteomyelitis. Clinically unsuspected abnormalities of the asymptomatic contralateral lower extremity are common in children referred for MRI of suspected musculoskeletal infection. However, detection of these abnormalities is not associated with alterations in patient management.


Outcome of pregnancy in women diagnosed with idiopathic polyhydramnios.
Polyhydramnios is present in approximately 2% of pregnancies and it has been associated with a variety of adverse pregnancy outcomes. The aim of our study was to evaluate the association between polyhydramnios and adverse pregnancy outcomes. This was a retrospective case control study of 288 singleton pregnancies delivered in the Rotunda Hospital, Dublin, between 2013 and 2014. Polyhydramnios was defined as: (i) amniotic fluid index (AFI) ≥ 25 cm; (ii) maximal vertical pocket (MVP) of ≥8 cm; and (iii) a gestational age-specific threshold for AFI. Demographic information, obstetric and neonatal outcomes were obtained by review of hospital databases. Exclusion criteria included gestational or pre-existing diabetes, multiple pregnancy, carrying a fetus with structural or chromosomal abnormalities, Rhesus factor isoimmunisation, and TORCH screen positive. Outcomes were compared with outcomes of those without polyhydramnios. A total of 8798 deliveries occurred during the study period. The frequency of polyhydramnios was 1.6%. One hundred and forty-four women were selected in each group. There was no significant difference in preterm deliveries, low birth weight, low Apgar score at one minute and five minutes and perinatal mortality. However, increase in caesarean delivery rate (43.1% vs 21.5%), number of fetal distresses (17.4% vs 6.9%) and number of neonatal intensive care unit (NICU) admissions (17.4% vs 4.9%) were observed in our study. In conclusion, idiopathic polyhydramnios is associated with specific adverse outcomes, such as higher rate of caesarean delivery, fetal distress and NICU admissions. Therefore, close surveillance of these pregnancies is required, especially near term.


Effects of histamine H1-receptor blockade on respiratory and cardiac manifestation of systemic anaphylaxis.
In vivo anaphylaxis is associated with respiratory distress and cardiovascular failure. The present investigation was designed to further characterize respiratory and cardiac anaphylactic events. In guinea pigs, sensitization was produced by subcutaneous application of ovalbumin together with Freund's adjuvant. Fourteen days after sensitization, the effects of an intravenous infusion of ovalbumin were tested in the anesthetized artificially ventilated guinea pigs. The renewed application of the antigen induced an initial increase of left ventricular pressure which was followed by a rapid decrease 5 min after antigenic challenge. Enddiastolic left ventricular pressure increased within 3 min, thus indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, heart rate steadily decreased. All animals died within 15 min. Simultaneously with cardiac anaphylactic malfunction, severe arterial hypoxia and carbon dioxide retention occurred, revealing respiratory distress. Histamine is known as a potent bronchoconstrictor via histamine H1-receptor stimulation. Administration of H1-receptor antagonists to improve respiration may therefore provide further information on the contribution of pulmonary malfunction to anaphylactic cardiovascular shock. Therefore, additional experiments were performed with sensitized guinea pigs pretreated with the histamine H1-receptor blocker mepyramine. In these experiments the antigenic challenge induced a dissociation of cardiac and respiratory manifestation of anaphylaxis. Despite inhibition of hypoxia and carbon dioxide retention, left ventricular pump failure and occurrence of myocardial ischemia were delayed but not suppressed. It is concluded that histamine is an important mediator of anaphylactic respiratory distress. However, vasoactive anaphylactic mediators other than histamine are primarily involved in anaphylactic cardiac malfunction occurring during the later phase of systemic anaphylaxis.


Predicting drinking outcomes: Evidence from the United Kingdom Alcohol Treatment Trial (UKATT).
To explore client characteristics that predict drinking outcomes using data from the UK Alcohol Treatment Trial (UKATT). Multiple linear regression was used to determine if there were any characteristics, measured before the start of treatment, that could predict drinking outcomes at three and 12months, as measured by percent day abstinent (PDA) and drinks per drinking day (DDD) over the preceding 90days. Lower baseline DDD score and greater confidence to resist drinking predicted lower DDD at both three and twelve months following entry to treatment. In addition to baseline PDA and having greater confidence to resist heavy drinking, female gender, aiming for abstinence, more satisfaction with family life and a social network that included less support for drinking were predictors of percent days abstinent. Overall the strongest and most consistent predictors of outcome were confidence to avoid heavy drinking and social support for drinking. More predictors were identified for percent of days abstinent than for drinks per drinking day. For percent of days abstinent, a number of client characteristics at baseline consistently predicted outcome at both month three and month twelve.


Differential gene expression in uterine endometrium during implantation in pigs.
Embryonic mortality during the implantation period strongly affects litter size in pigs. To analyze the differentially expressed genes (DEGs) in the endometrium during implantation and further to identify candidate genes for litter size, tissues of endometrial attachment sites and intersites were collected from nine pregnant sows on Days 13, 18, and 24 of pregnancy. Endometrium tissue was also collected from another three nonpregnant sows. Samples were hybridized to the porcine Agilent GeneChip microarray. The analysis of gene expression patterns over the implantation period revealed 858 DEGs at endometrial attachment sites. Comparisons of the gene files of attachment sites and intersites revealed 12, 51, and 89 DEGs on Days 13, 18, and 24 of pregnancy, respectively. Annotated function was used to identify overrepresented genetic processes, and several biological processes were considered as the most enriched. Genes related to vascular development, proteolysis, RNA metabolism and translation, protein modification, immune response, and hormone-related are discussed in detail. Then we combined microarray technology and linkage analysis to select powerful candidate genes for quantitative trait loci affecting pig litter size. Eighty-seven DEGs were located in quantitative trait loci related to litter size, that is, total number born and number born alive. Those candidate genes were thought to affect litter size by influencing embryonic implantation. Furthermore, single nucleotide polymorphism of VEGFA was shown to be associated with litter size in pigs. This study identified candidate genes for litter size that were related to embryonic implantation and could be a resource for target studies of genetic markers for litter size in pigs.


Transarterial chemoembolization vs bland embolization in hepatocellular carcinoma: A meta-analysis of randomized trials.
Although transarterial chemoembolization is considered the standard of care for intermediate hepatocellular carcinoma patients, robust data in favor of a clear superiority of chemoembolization (with chemotherapy injection) over bland embolization are lacking. The objective of this article is to systematically analyze the results provided by randomized controlled trials comparing these two treatments in hepatocarcinoma patients. A computerized bibliographic search on the main databases was performed. Survival rates assessed at one, two, and three years, objective response, one-year progression-free survival, and severe adverse event rate were analyzed. Comparisons were performed by using the Mantel-Haenszel test in cases of low heterogeneity or DerSimonian and Laird test in cases of high heterogeneity. Six trials with 676 patients were included. No difference in one-year (risk ratio: 0.93, 0.85-1.03, p = 0.16), two-year (risk ratio: 0.88, 0.74-1.06, p = 0.18) and three-year survival (risk ratio: 0.97, 0.74-1.27, p = 0.81) was observed. Objective response and one-year progression-free survival showed no significant difference between the two treatments (p = 0.36 and p = 0.40, respectively). A statistically significant increase in severe toxicity after chemoembolization was found (risk ratio: 1.44, 1.08-1.92, p = 0.01), although this result could be affected by the heterogeneity of techniques adopted. Our meta-analysis demonstrates a non-superiority of transarterial chemoembolization with respect to bland embolization in hepatocarcinoma patients.


Spatial-mode demultiplexing for enhanced intensity and distance measurement.
Spatial-mode demultiplexing (SPADE) has recently been adopted to measure the separation in the transverse plane between two incoherent point-like sources with sub-wavelength separation. It has been argued that this approach may yield extraordinary performances in the photon-counting regime. Here, we explore SPADE as a tool for precision measurements in the regime of bright, incoherent sources. First we analyze the general problem of estimating the second moments of the source's intensity distribution, for an extended incoherent source of any shape. Our theory predicts a substantial improvement in signal-to-noise ratio (SNR) of SPADE over direct imaging in the sub-wavelength regime. Second, we present an experimental application of SPADE to the case of two point-like, bright sources. We demonstrate the use of this setup for the estimation of the transverse separation and for the estimation of the relative intensity, confirming the expected improvement in SNR.


Identification and verification of a glycolysis-related gene signature for gastric cancer.
Glycolysis is a central metabolic pathway for tumor cells. However, the relationship between glycolysis and the prognosis of gastric cancer (GC) patients is not well established. In this study, we sought to construct a glycolysis-related gene signature for GC. The messenger ribonucleic acid (mRNA) expression profiles were analyzed using data from The Cancer Genome Atlas (TCGA) database. Glycolysis-related gene sets and pathways were obtained from the Molecular Signatures Database (MSigDB). Subsequently, a prognosis prediction model of the glycolysis-related genes was constructed using Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. An external validation was conducted using data from the Gene Expression Omnibus (GEO) database. Risk scores were also calculated based on the signature. Finally, the correlations between the risk score and overall survival (OS), mutation, immune cell infiltration, immune score, and stromal score were examined in 22 types of infiltrating immune cells. Fifty-five glycolysis-related genes were identified from TCGA database and MSigDB. Using the LASSO and Cox models, 4 novel genes (i.e., VCAN, EFNA3, ADH4, and CLDN9) were identified to construct a gene signature for GC prognosis prediction. The GC patients with low-risk scores had significantly better OS than those with high-risk scores in the training set. Similar results were also found in the independent GEO GSE84437 testing set. Additionally, the degree of cell infiltration in the low-risk group was significantly higher than that in the high-risk group in terms of naive B cells, plasma cells, and T follicular helper cells. In monocytes, M2 macrophages, resting dendritic cells, and resting Mast cells, the degree of infiltration in the high-risk group was significantly higher than that in the low-risk group. The immune score and stromal score of the high-risk group were also significantly higher than those of the low-risk group. Finally, the univariate and multivariate Cox regression analyses showed that 4 glycolysis-related genes were independent prognostic factors for GC. The established 4 glycolysis-related gene signature may serve as a reliable tool for the prognosis of GC patients and provide a potential glycolysis therapeutic target for GC.


Morphological analysis using geometric parameters for splenic aneurysms.
Background Considering the unique characteristics of splenic artery aneurysms, we hypothesized that hemodynamic forces could play an important role in splenic artery aneurysm formation and that splenic artery geometry should be correlated with aneurysm development. Methods Tortuosity of the splenic artery was evaluated three-dimensionally by calculating the curvature using software and the original modeling system. We selected 54 splenic artery aneurysm patients who had undergone thin-slice computed tomography imaging with contrast. We compared the splenic artery aneurysm group to non-vascular patients via propensity-score matching (35 patients in each group). The splenic artery length index, average curvature, and maximum curvature were analyzed. Results Splenic artery aneurysm patients tended to have a longer splenic artery and the curvature was more severe compared to the non-vascular control patients. The average curvature of splenic artery aneurysm patients was associated with the dilatation rate in female patients. Conclusion Females with a tortuous splenic artery may have an increased risk of aneurysm formation.


Synergistic Effects of Continuous Low Level Heat Wraps and Vitamins in Improving Balance and Gait in Adults.
Ageing is associated with a loss of balance and mobility. This study was conducted to determine if the use of heat, vitamins alone or heat with vitamins could increase mobility and balance in adults with mobility impairments. Eighty adults in the age range between 55 and 64 were randomly divided into 4 different groups; low level continues heat (LLCH), vitamins (VT) alone, vitamins combined with heat (VT + H), and control group. Subjects were sedentary individuals that were not participating in any balance or walking exercises regularly and were not taking vitamins for at least 1 year. 4000 units vitamin D, 1000 units vitamin E, 300mg CoQ10, 600 mg Calcium, 1 tablet multivitamin were taken each day in the VT and VT + H groups. LLCH was applied with a dry chemical heat wrap, average temperature 42°C for 4 hours per day over the upper leg. The outcome was assessed through postural sway and tremor during standing, tremor, gait speed, symmetry, ground reaction force, and muscle activity during gait. All experimental groups showed significant improvement in balance and walking ability after 4 months of interventions (p < 0.05) but no significant changes were found in the control group. The difference between the control group and all other groups was significant (p < 0.05). The greatest improvements were found in VT + H group after 4 months. This is evidenced by better balance, less muscle tremor and faster and more stable gait, especially with the heat and vitamins used together. Heat and vitamins used together were synergistic.


Cholesterol metabolism and violence: a study of individuals convicted of violent crimes.
To examine the relationship between plasma lipoproteins and apolipoproteins in men with convictions for violent offences, blood was obtained from 15 men with a history of violence who were serving prison sentences for violent offences, and 25 age-matched male controls from the staff of the Argyll and Bute Psychiatric Hospital, who had no criminal records. The two groups did not differ in plasma total cholesterol concentrations, HDL-C, LDL-C, VLDL-C or in HDL subfractions. The most significant differences in the offenders were higher apoprotein AIV (3.62 vs 0.85: p = < 0.000001) and higher apoprotein E (7.70 vs 5.19: p = < 0.0002).


Leukocytes of patients with Schistosoma mansoni respond with a Th2 pattern of cytokine production to mitogen or egg antigens but with a Th0 pattern to worm antigens.
Cytokine responses of peripheral blood mononuclear cells from humans infected with Schistosoma mansoni were assessed. By ELISA and ELISPOT, persons with acute and hepatosplenic infections produced higher levels of interleukin (IL)-4 and IL-5 and higher frequencies of IL-4-producing cells in response to mitogen than did uninfected persons. In contrast, mitogen-induced production of the Th1 cytokine interferon-gamma (IFN-gamma) did not differ from that of uninfected controls. Upon stimulation with egg antigens, many patients responded with elevated IL-4 mRNA levels but displayed no appreciable increases in Th1 (i.e., IFN-gamma and IL-2) cytokine transcripts. Nevertheless, in cells stimulated with adult worm antigen, a more mixed Th0-type response was observed with production of both Th1 and Th2 cytokines. These results support previous findings in laboratory mice that schistosome infection results in increased production of Th2 cytokines. Unlike mice, infected humans do not display a generalized down-modulation in Th1 responses but instead show a selective deficiency in IFN-gamma and usually IL-2 responses to egg antigens.


Engaging family members in maternal, infant and young child nutrition activities in low- and middle-income countries: A systematic scoping review.
The influence of fathers, grandmothers and other family members on maternal, infant and young child nutrition practices has been well documented for decades, yet many social and behavioural interventions continue to reach only mothers. While recent guidelines recommend involving fathers, grandmothers and other family members in maternal and child nutrition, we lack a comprehensive review of interventions that have engaged them. This scoping review aimed to address this gap by describing social and behavioural interventions to engage family members in maternal and child nutrition in low- and middle-income countries. We systematically searched PubMed, Scopus, Web of Science, Global Health and CINAHL for peer-reviewed studies meeting inclusion criteria. We screened 6,570 abstracts, evaluated 179 full-text articles, and included 87 articles from 63 studies. Studies reported a broad range of approaches to engage fathers, grandmothers and other family members to support maternal nutrition (n = 6); breastfeeding (n = 32); complementary feeding (n = 6) and multiple maternal and child nutrition practices (n = 19). Interventions were facility and community based; included individual and group-based interpersonal communication, community mobilization, mass media and mHealth; and reached mothers and family members together or separately. Most interventions were located within the health sector; rare exceptions included nutrition-sensitive agriculture, social protection, early child development and community development interventions. Few interventions addressed gender norms, decision-making, and family dynamics or described formative research or theories informing intervention design. These diverse studies can shed light on innovative programme approaches to increase family support for maternal and child nutrition.


Ultrathin Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK) versus Descemet Membrane Endothelial Keratoplasty (DMEK)-a systematic review and meta-analysis.
Endothelial keratoplasty (EK) is a commonly performed transplant procedure used in the treatment of corneal endothelial dysfunction. The aim of this systematic review and meta-analysis is to evaluate the differences in visual acuity outcomes, endothelial cell density (ECD) and complications between two forms of EK, ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) and Descemet membrane endothelial keratoplasty (DMEK). A literature search of MEDLINE, Embase and Cochrane Library was conducted to identify studies reporting comparative results of UT-DSAEK versus DMEK. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used for search strategy. Of 141 titles, 7 studies met the inclusion criteria; best corrected visual acuity (BCVA) (LogMAR), ECD (cells/mm2), and complications were compared, with all statistical analysis performed using Review Manager. A total of 362 eyes were included for analysis. DMEK resulted in significantly better BCVA at 3 months (0.14 vs 0.22, p = 0.003), 6 months (0.08 vs 0.18, p = 0.005) and 1 year post-op (0.07 vs 0.14, p = 0.0005). UT-DSAEK resulted in significantly lower total complications (25.2% vs 57.3%, p = 0.0001) and rates of re-bubbling (11.0% vs 33.7%, p = 0.004). No differences were found in ECD between the two procedures (1541 vs 1605, p = 0.77). DMEK results in superior visual acuity rates with quicker recovery. However, UT-DSAEK has a more favourable complication profile, particularly regarding lower rates of re-bubbling. Both are valuable options in the treatment of corneal endothelial disease and choice of procedure may depend on surgical expertise.


Human Monocyte Subsets Are Transcriptionally and Functionally Altered in Aging in Response to Pattern Recognition Receptor Agonists.
Age-related alterations in immunity have been linked to increased incidence of infections and decreased responses to vaccines in the aging population. Human peripheral blood monocytes are known to promote Ag presentation and antiviral activities; however, the impact of aging on monocyte functions remains an open question. We present an in-depth global analysis examining the impact of aging on classical (CD14+CD16-), intermediate (CD14+CD16+), and nonclassical (CD14dimCD16+) monocytes. Monocytes sorted from nonfrail healthy adults (21-40 y) and old (≥65 y) individuals were analyzed after stimulation with TLR4, TLR7/8, and retinoic acid-inducible gene I agonists. Our data showed that under nonstimulated conditions, monocyte subsets did not reveal significant age-related alternations; however, agonist stimulated-monocytes from adults and old subjects did show differences at the transcriptional and functional levels. These alternations in many immune-related transcripts and biological processes resulted in reduced production of IFN-α, IFN-γ, IL-1β, CCL20, and CCL8, and higher expression of CX3CR1 in monocytes from old subjects. Our findings represent a comprehensive analysis of the influence of human aging on pattern recognition receptors signaling and monocyte functions, and have implications for strategies to enhance the immune response in the context of infection and immunization.


Immunofluorescence studies on complement components in the hair follicles of normal scalp and of scalp affected by alopecia areata.
The deposition of complement components (Clq, C4 C3, C5 and C9) and properdin in scalp hair follicles was examined by the immunofluorescence method in patients with alopecia areata and in normal subjects. C3, C5 and C9 were found deposited there. The complement deposition was most frequent in the case of C3 and less frequent in C9 and C5. There was no difference regarding deposition between normal subjects and patients with alopecia areata. No deposition of Clq, C4 or properdin was observed in the hair follicles of the scalp. These findings suggest a relationship between the hair cycle and the activity of C3 and its late complement components in the scalp.


Provider Specialty, Anticoagulation, and Stroke Risk in Patients With Atrial Fibrillation and Cancer.
It is unknown whether early cardiology involvement shortly after atrial fibrillation (AF) diagnosis is associated with favorable outcomes in AF patients who have cancer. The purpose of this study was to examine the relationship between early cardiology involvement after AF diagnosis in patients with history of cancer. This study examined associations of early cardiology involvement with oral anticoagulation use, stroke, and bleeding among nonvalvular AF patients (n = 388,045; mean age 68 ± 15 years; 59% male) with a history of cancer (past or active) from the MarketScan database (2009 to 2014). International Classification of Disease-9th Revision-Clinical Modification codes in any position were used to identify cancer diagnosis prior to AF diagnosis. Provider specialty and filled anticoagulant prescriptions 3 months prior to and 6 months after AF diagnosis were obtained. Poisson regression models were used to compute the probability of an oral anticoagulant prescription fill, and Cox regression was used to estimate the risks of stroke and major bleeding. A total of 64,016 (17%) AF patients had a history of cancer. Cardiology involvement was less likely to occur among patients with a history of cancer than those without (relative risk [RR]: 0.92 [95% confidence interval (CI): 0.91 to 0.93]). Patients with history of cancer were less likely to fill prescriptions for anticoagulants (RR: 0.89 [95% CI: 0.88 to 0.90]) than those without cancer, and similar results were observed across cancer types. Patients with cancer were more likely to fill prescriptions for anticoagulants (RR: 1.48 [95% CI: 1.45 to 1.52]) if seen by a cardiologist. A reduced risk of stroke (hazard ratio: 0.89 [95% CI: 0.81 to 0.99]) was observed among all cancer patients who were seen by a cardiology provider, without an increased risk of bleeding (hazard ratio: 1.04 [95% CI: 0.95 to 1.13]). Similar results were observed when the analysis was stratified by active versus remote history of cancer. Although AF patients with cancer were less likely to see a cardiologist, or fill anticoagulant prescriptions, cardiology involvement was associated with increased anticoagulant prescription fills and favorable AF-related outcomes in AF patients with cancer.