Morphological changes following ESWL in the rat kidney.
Fifty four Wistar rats were treated with 500, 1,000 or 2,000 shock waves, using the modified DORNIER HM 3 system with the new SG40 shock wave generator. The animals were sacrificed after a period of 24 hours, 7 days or 35 days. Histological examination, scanning electron microscopy (SEM) and magnetic resonance imaging (MRI) were used to evaluate acute and long term effects after extracorporeal shock-wave lithotripsy (ESWL). Acute morphological changes such as glomerular bleeding, tubular dilatation, atrophy and partial necrosis occurred immediately after ESWL throughout the kidney. SEM revealed a tubular loss of microvilli and cilia. There was restitutio ad integrum of these diffuse lesions. The extent of the long term lesions was determined by the following mechanism: venous rupture occurred during ESWL, especially in thin arcuatae veins which are, tortuous their and run between two different tissue densities. This resulted in interstitial haematoma, demonstrable by MRI; in the long term groups, the haematomas progressed to interstitial fibrosis with segmental retraction of renal convexity. The blood supply in these areas was reduced and secondary changes such as glomerular-tubular atrophy and sclerosis followed. The degree to which long-term renal lesions resulted was determined by the extent of these changes, which were shock-wave dose dependent up to a dose of 2,000 shock waves.


[Foreign body in paranasal sinuses].
All cases of the last 5 years requiring foreign bodies to be removed from the paranasal sinuses were investigated as to causes, special aspects in diagnostics and therapy, occurrence of pathologic germs and possible sequels. 68 cases were evaluated: 43 patients were male, 25 female. Average age was 29 years in males and 37 years in females. In our patients foreign bodies in the paranasal sinuses were in more than 60% the result of medical or dental procedures followed by industrial accidents (25%). The maxillary sinus was affected in 75%, the frontal sinus in about 18%. Involvement of the ethmoid or sphenoid sinus was rare. The spectrum of pathologic microbes was dominated by mixed infections, the share of actinomyces and aspergillus was unexpected high. Most important acute complications were bleeding, compression of the optic nerve and liquorrhoe. Late complications consisted mainly of pain--often associated with disturbances of sensibility- and infections. A smear should be taken whenever the foreign body remained in the sinus for more than 4 days. Foreign bodies jammed in the posterior wall of the sinus require a sufficiently open view since the risk of heavy bleeding is especially high.


Demographic predictors of objectification theory and tripartite influence model constructs: The U.S. Body Project I.
We examined how demographic factors (gender, sexual orientation, racial group, age, body mass) were linked to measures of sociocultural appearance concerns derived from objectification theory and the tripartite influence model (McKinley & Hyde, 1996; Schaefer et al., 2015) among 11,620 adults. Men were less likely than women to report high body surveillance, thin-ideal internalization, appearance-related media pressures, and family pressures; did not differ in peer pressures; and reported greater muscle/athletic internalization. Both men and women expressed greater desire for their bodies to look "very lean" than to look "very thin". Compared to gay men, heterosexual men reported lower body surveillance, thin-ideal internalization, peer pressures, and media pressures. Black women reported lower thin-ideal internalization than White, Hispanic, and Asian women, whereas Asian women reported greater family pressures. Being younger and having higher BMIs were associated with greater sociocultural appearance concerns across most measures. The variation in prevalence of sociocultural appearance concerns across these demographic groups highlights the need for interventions.


Efficient removal of toxic phosphate anions from aqueous environment using pectin based quaternary amino anion exchanger.
Pectin based quaternary amino anion exchanger (Pc-QAE) was prepared using simple crosslinking polymerization method. This anion exchanger was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Pc-QAE was applied for the removal of phosphate anion from the aqueous solution. The adsorption process which was pH dependent showed maximum adsorption of phosphate anions at pH 7. Pc-QAE showed good monolayer adsorption capacity for phosphate anions which demonstrated its good capability towards Langmuir isotherm model. Moreover, the adsorption was evaluated thermodynamically and the negative value of Gibbs free energy (-1.791KJ/mol) revealed the spontaneity of adsorption process. The value of ΔH° and ΔS° were found to be 15.28 and 49.48KJ/mol, respectively representing the endothermic nature and enhancement in degree of freedom due to the adsorption process.


Comparative computational study to augment UbiA prenyltransferases inherent in purple photosynthetic bacteria cultured from mangrove microbial mats in Qatar for coenzyme Q10 biosynthesis.
Coenzyme Q10 (CoQ10) is a powerful antioxidant with a myriad of applications in healthcare and cosmetic industries. The most effective route of CoQ10 production is microbial biosynthesis. In this study, four CoQ10 biosynthesizing purple photosynthetic bacteria: Rhodobacter blasticus, Rhodovulum adriaticum, Afifella pfennigii and Rhodovulum marinum, were identified using 16S rRNA sequencing of enriched microbial mat samples obtained from Purple Island mangroves (Qatar). The membrane bound enzyme 4-hydroxybenzoate octaprenyltransferase (UbiA) is pivotal for bacterial biosynthesis of CoQ10. The identified bacteria could be inducted as efficient industrial bio-synthesizers of CoQ10 by engineering their UbiA enzymes. Therefore, the mutation sites and substitution residues for potential functional enhancement were determined by comparative computational study. Two mutation sites were identified within the two conserved Asp-rich motifs, and the effect of proposed mutations in substrate binding affinity of the UbiA enzymes was assessed using multiple ligand simultaneous docking (MLSD) studies, as a groundwork for experimental studies.


Can we achieve bone healing using the diamond concept without bone grafting for recalcitrant tibial nonunions?
The purpose of this study was to evaluate the efficacy and safety of a combination of recombinant human bone morphogenetic protein 7 (rhBMP-7) and resorbable calcium phosphate bone substitute (rCPBS) as a salvage solution for recalcitrant tibial fracture nonunions. Twenty consecutive patients, 16 male and four female, with a mean age of 46.8±15.7 years (21-78) and a mean body mass index (BMI) of 24.2±5.3kgm(-2) (21.5-28.5), suffering from 20 recalcitrant tibial fracture nonunions were included. The mean number of operations performed prior to the procedure was 3.3, with homolateral iliac crest bone grafts being used for all of the patients. All patients were treated with a procedure including debridement and decortications of the bone ends, nonunion fixation with a locking plate, and filling of the bony defect with a combined graft of rhBMP-7 (as osteoinductor) with an rCPBS (as scaffold). The mean follow-up was 14±2.7 months. Both clinical and radiological union occurred in 18 cases, within a mean time of 4.7±3.2 months. A recurrence of deep infection was diagnosed for one of the non-consolidated patients. No specific complication of rCPBS or rhBMP-7 was encountered. This study supports the view that the application of rCPBS combined with rhBMP-7, without any bone grafting, is safe and efficient in the treatment of recalcitrant bone union.


Multi-parameter evaluation of the effect of processing conditions on meat protein modification.
Evaluating the interconnecting effects of pH, temperature and time on food proteins is of relevance to food processing, and food functionality. Here we describe a matrix-based approach in which meat proteins were exposed to combinations of these parameters, selected to cover coordinates in a realistic processing space, and analyzed using redox proteomics. Regions within the matrix showing high levels of protein modification were evaluated for oxidative and other modifications. Both pH and temperature, independently, had a significant effect on the oxidative modifications mostly detected in myofibrillar proteins such as myosin and troponin and also collagen. Heat induced pyroglutamic acid formation was exclusively observed in the myofibrillar proteins. Potential interdependencies between pH, temperature and exposure time were evaluated using a 3-way analysis of variance (ANOVA) on protein modification levels to better understand how industry relevant process parameters influence protein quality and function.


Effects of vertical opening on pharyngeal dimensions in patients with obstructive sleep apnoea.
It is still subject to controversy if an increased vertical opening (VO) is beneficial in oral appliance therapy for the treatment of obstructive sleep apnoea. Each oral appliance has a given thickness causing VO. Therefore, evaluation of the effects of the amount of VO on pharyngeal dimensions is mandatory. The effects of VO on the cross-sectional area of the upper airway at the level of the tongue base during sleep endoscopy were scored and categorised. The figures demonstrate the possible effects of VO on pharyngeal collapse relative to the baseline cross-sectional area and the maximal comfortable protrusion of the mandible. Thirty-two patients (80%) showed an adverse effect of VO (Fig. 1), one patient (2.5%) had a positive effect (Fig. 2), and seven patients (17.5%) demonstrated an indifferent effect (Fig. 3). Based on literature, the effect of VO on pharyngeal collapse is unclear and the therapeutic impact of VO is not determined. The results of the present study indicate that the effect of VO on the degree of pharyngeal collapse as assessed during sleep endoscopy tends to be adverse, causing an increase in collapsibility in the majority of patients.


Diagnosis of obstructive sleep apnea in women: Is there any difference?- Experience from a tertiary care hospital of North India.
Obstructive sleep apnea (OSA) considered classically to be a male-dominant disease, may have significant gender-based differences in clinical presentation and diagnosis. To evaluate gender-based differences in the clinical profile and polysomnographic features of Indian patients with OSA. A prospective observational study was conducted over a period of 12 months involving adult ambulatory patients, referred for evaluation of OSA. Enrolled patients underwent detailed clinical evaluation followed by supervised polysomnography. Sleep studies were manually validated and analyzed. Continuous variables were compared using two-tailed independent- sample t-test. For the univariate analysis, the Chi-square test was used. Out of 150 enrolled patients, 94 (62.7%) were males (male-to-female: 1.7:1; age: 51.85 ± 12.60 years; BMI: 32.09 ± 5.53 kg/m2). Most common presenting features were excessive daytime somnolence, snoring, and easy fatiguability. Women with OSA were older than men. Insomnia and anxiety were significantly higher among females. Parameters defining sleep architecture were similar in both groups. Although obstructive apneas and hypopneas were similar, mean apnea hypopnea index was significantly higher (P < 0.05) in males compared to females with higher titratable continuous positive airway pressure. There are gender-specific differences in the clinical presentation of OSA due to various anatomical, physiological, and psychosocial factors. Their potential influence on the clinical features, natural history, and implications on treatment need further evaluation on a larger scale.


MHC class I recognition by Ly49 natural killer cell receptors.
Natural killer (NK) cell function is regulated by NK receptors that bind either classical MHC class I (MHC-I) molecules or their structural relatives (MICA, RAE-1 and H-60). Two distinct families of NK receptors have been identified: the C-type lectin-like family (Ly49, NKG2D and CD94/NKG2) and the immunoglobulin-like family (KIRs and LIRs). Here, we describe the crystal structure of the C-type lectin-like NK receptor (Ly49A), bound to its MHC-I ligand (H-2D(d)). We also discuss results from recent mutagenesis studies of the Ly49A/H-2D(d) interaction in the context of the complex structure.


Plasma radio-metabolite analysis of PET tracers for dynamic PET imaging: TLC and autoradiography.
In molecular imaging with dynamic PET, the binding and dissociation of a targeted tracer is characterized by kinetics modeling which requires the arterial concentration of the tracer to be measured accurately. Once in the body the radiolabeled parent tracer may be subjected to hydrolysis, demethylation/dealkylation and other biochemical processes, resulting in the production and accumulation of different metabolites in blood which can be labeled with the same PET radionuclide as the parent. Since these radio-metabolites cannot be distinguished by PET scanning from the parent tracer, their contribution to the arterial concentration curve has to be removed for the accurate estimation of kinetic parameters from kinetic analysis of dynamic PET. High-performance liquid chromatography has been used to separate and measure radio-metabolites in blood plasma; however, the method is labor intensive and remains a challenge to implement for each individual patient. The purpose of this study is to develop an alternate technique based on thin layer chromatography (TLC) and a sensitive commercial autoradiography system (Beaver, Ai4R, Nantes, France) to measure radio-metabolites in blood plasma of two targeted tracers-[18F]FAZA and [18F]FEPPA, for imaging hypoxia and inflammation, respectively. Radioactivity as low as 17 Bq in 2 µL of pig's plasma can be detected on the TLC plate using autoradiography. Peaks corresponding to the parent tracer and radio-metabolites could be distinguished in the line profile through each sample (n = 8) in the autoradiographic image. Significant intersubject and intra-subject variability in radio-metabolites production could be observed with both tracers. For [18F]FEPPA, 50% of plasma activity was from radio-metabolites as early as 5-min post injection, while for [18F]FAZA, significant metabolites did not appear until 50-min post. Simulation study investigating the effect of radio-metabolite in the estimation of kinetic parameters indicated that 32-400% parameter error can result without radio-metabolites correction. TLC coupled with autoradiography is a good alternative to high-performance liquid chromatography for radio-metabolite correction. The advantages of requiring only small blood samples (~ 100 μL) and of analyzing multiple samples simultaneously, make the method suitable for individual dynamic PET studies.


Chemical function-based pharmacophore development for novel, selective kappa opioid receptor agonists.
In an effort to reduce or eliminate the centrally associated side effects produced by opioid analgesics there has been an interest in the preparation of peripherally acting opioid receptor agonists. These compounds would have very limited or no access to the central nervous system. As a first step towards developing peripheral kappa opioid receptor (KOP) agonists, we have developed a quantitatively predictive chemical function-based pharmacophore model of selective kappa opioid receptor agonists by using the HypoGen algorithm implemented in the Catalyst software. The input for HypoGen was a training set of 26 KOP agonists exhibiting K(i) values ranging between 0.015nM and 2300nM. The best output hypothesis consists of four features: one hydrophobic (HYD), one ring aromatic (RA), one hydrogen bond acceptor (HBA), and one positive ionizable (PI) function. The predictive power of the model could be demonstrated by internal and external validation of the generated hypothesis. The resulting Catalyst pharmacophore can be used concurrently for rapid virtual screening of chemical databases to identify novel, selective KOP agonists that may be easily restricted to target tissues by synthetic modification. It is anticipated that such an approach will lead to the generation of novel selective KOP agonists that are clinically useful for the treatment of pain through peripheral mechanisms.


Prenatal Diagnosis of Nasal Glioma Associated with Metopic Craniosynostosis: Case Report and Review of the Literature.
Nasal gliomas (nasal glial heterotopia) are rare benign congenital frontonasal lesions occurring in approximately 1:20.000-40,000 live births. The diagnosis is rarely reported prenatally. Nasal gliomas are typically isolated lesions, with syndromic association being exceedingly rare. Metopic craniosynostosis can occur as an isolated abnormality or in association with multiple syndromes. This case is the first reported case of nasal glioma in association with craniosynostosis in the published literature.


Enhancement of Pathogen Resistance in Common Bean Plants by Inoculation With Rhizobium etli.
Symbiotic Rhizobium-legume associations are mediated by exchange of chemical signals that eventually result in the development of a nitrogen-fixing nodule. Such signal interactions are thought to be at the center of the plants' capacity either to activate a defense response or to suppress the defense response to allow colonization by symbiotic bacteria. In addition, the colonization of plant roots by rhizobacteria activates an induced condition of improved defensive capacity in plants known as induced systemic resistance, based on "defense priming," which protects unexposed plant tissues from biotic stress.Here, we demonstrate that inoculation of common bean plants with Rhizobium etli resulted in a robust resistance against Pseudomonas syringae pv. phaseolicola. Indeed, inoculation with R. etli was associated with a reduction in the lesion size caused by the pathogen and lower colony forming units compared to mock-inoculated plants. Activation of the induced resistance was associated with an accumulation of the reactive oxygen species superoxide anion (O2 -) and a faster and stronger callose deposition. Transcription of defense related genes in plants treated with R. etli exhibit a pattern that is typical of the priming response. In addition, R. etli-primed plants developed a transgenerational defense memory and could produce offspring that were more resistant to halo blight disease. R. etli is a rhizobacteria that could reduce the proliferation of the virulent strain P. syringae pv. phaseolicola in common bean plants and should be considered as a potentially beneficial and eco-friendly tool in plant disease management.


Highly correlating distance/connectivity-based topological indices 5. Accurate prediction of liquid density of organic molecules using PCR and PC-ANN.
The primary goal of a quantitative structure-property relationship (QSPR) is to identify a set of structurally based numerical descriptors that can be mathematically linked to a property of interest. Recently, we proposed some new topological indices (Sh indices) based on the distance sum and connectivity of a molecular graph that derived directly from two-dimensional molecular topology for use in QSAR/QSPR studies. In this study, the ability of these indices to predict the liquid densities (rho) of a large and diverse set of organic liquid compounds (521 compounds) has been examined. Ten different Sh indices were calculated for each molecule. Both linear and non-linear modeling methods were implemented using principal component regression (PCR) and principal component-artificial neural network (PC-ANN) with back-propagation learning algorithm, respectively. Correlation ranking procedure was used to rank the principal components and entered them into the models. PCR analysis of the data showed that the proposed Sh indices could explain about 91.82% of variations in the density data, while the variations explained by the ANN modeling were more than 97.93%. The predictive ability of the models was evaluated using external test set molecules and root mean square errors of prediction of 0.0308 g ml(-1) and 0.0248 g ml(-1) were obtained for liquid densities of external compounds by linear and non-linear models, respectively.


Selective separation and co-culture of cells by photo-induced enhancement of cell adhesion (PIECA).
Taking advantage of the phenomenon that animal cells adhering to a culture substrate are temporarily immobilized by light irradiation, we established a technique to manipulate the cells adhering to a culture substrate under microscopic observation. Using this technique, we demonstrated a separation of cells adhering to a culture substrate and fabrication of an elaborately patterned co-culture system.


Age-related disruptions of circadian rhythm and memory in the senescence-accelerated mouse (SAMP8).
Common complaints of the elderly involve impaired cognitive abilities, such as loss of memory and inability to attend. Although much research has been devoted to these cognitive impairments, other factors such as disrupted sleep patterns and increased daytime drowsiness may contribute indirectly to impaired cognitive abilities. Disrupted sleep-wake cycles may be the result of age-related changes to the internal (circadian) clock. In this article, we review recent research on aging and circadian rhythms with a focus on the senescence-accelerated mouse (SAM) as a model of aging. We explore some of the neurobiological mechanisms that appear to be responsible for our aging clock, and consider implications of this work for age-related changes in cognition.


Various methods of lymphocyte separation and their relevance with the formation of non-immune rosettes.
Lymphocytes (leukocytes mainly containing mononuclear cells) are separated by six different methods and these lymphocytes are used for non-immune rosette formation. It is found that the percentage of non-immune rosettes varies according to the method of separation of lymphocytes. Buffy coat on Dextran-70 and Gravity Sedimentation method give the best rosette yields as compared with lymphocytes separated by centrifugation of heparinized blood (unsupported centrifugation) P less than 0.001) or on Hypaque-Ficoll or Diaginol-Ficoll gradients (supported centrifugation) P less than 0.05). Furthermore, the buffy coat separated on Dextran-70, layered on Ficoll-gradients (supported centrifugation) yields lower values of rosettes (P less than 0.05). It is possible that in certain methods which yield lower values of rosettes there is loss of selected subpopulations of lymphocytes. This loss of subpopulation appears to be due to the centrifugation of the blood and the loss is appreciably more on 'unsupported' than 'supported' centrifugation.


Field testing the utility of procalcitonin and the acute infantile observation score in febrile infants 6 to 36 months old presenting to the pediatric emergency department with no obvious focus of infection.
Serious bacterial illness (SBI) presents a diagnostic challenge in febrile infants. History, clinical signs, and laboratory information combined with experiential knowledge affects decisions to admit and treat. To assess the utility of serum procalcitonin and the Acute Infantile Observation Score (AIOS) performed at emergency department presentation in predicting (a) confirmed serious bacterial illness and (b) illness severity. Sensitivity, specificity, and likelihood ratios were calculated for C-reactive protein, white cell count, serum procalcitonin, and AIOS. Forty-six infants were recruited. Seven had a diagnosis of SBI, 28 were moderately ill with length of stay >24 hours, and 12 were severely ill with length of stay >96 hours. The positive likelihood ratios for confirmed SBI were C-reactive protein = 5.3, procalcitonin = 0.43, white cell count = 1.9, and AIOS = 1.5. Procalcitonin and the AIOS do not modify the diagnostic uncertainty of the ED physician assessing the febrile infant with respect to admission or antibiotic treatment above standard laboratory investigations.


Redox Potentials of Disulfide Bonds in LOXL2 Studied by Nonequilibrium Alchemical Simulation.
Lysyl oxidase-like 2 (LOXL2) is a metalloenzyme that catalyzes the oxidative deamination ε-amino group of lysine. It is found that LOXL2 is a promotor for the metastasis and invasion of cancer cells. Disulfide bonds are important components in LOXL2, and they play a stabilizing role for protein structure or a functional role for regulating protein bioactivity. The redox potential of disulfide bond is one important property to determine the functional role of disulfide bond. In this study, we have calculated the reduction potential of all the disulfide bonds in LOXL2 by non-equilibrium alchemical simulations. Our results show that seven of seventeen disulfide bonds have high redox potentials between -182 and -298 mV and could have a functional role, viz., Cys573-Cys625, Cys579-Cys695, Cys657-Cys673, and Cys663-Cys685 in the catalytic domain, Cys351-Cys414, Cys464-Cys530, and Cys477-Cys543 in the scavenger receptor cysteine-rich (SRCR) domains. The disulfide bond of Cys351-Cys414 is predicted to play an allosteric function role, which could affect the metastasis and invasion of cancer cells. Other functional bonds have a catalytic role related to enzyme activity. The rest of disulfide bonds are predicted to play a structural role. Our study provides an important insight for the classification of disulfide bonds in LOXL2 and can be utilized for the drug design that targets the cysteine residues in LOXL2.


Localization of protease nexin-1 on the fibroblast extracellular matrix.
Protease nexin-1 (PN-1) is a protease inhibitor that is secreted by fibroblasts and several other cultured cells. PN-1 forms complexes with certain serine proteases in the extracellular environment including thrombin, urokinase, and plasmin. The complexes then bind to the cells and are rapidly internalized and degraded. This report demonstrates that PN-1 is present on the surface of fibroblasts, bound to the extracellular matrix. Immunofluorescent studies showed that PN-1 colocalized with fibronectin on both intact cells and in preparations of extracellular matrix made from these cells. In contrast, PN-1 did not colocalize with the epidermal growth factor receptor, a plasma membrane marker. An enzyme-lined immunosorbent assay was developed which showed that the extracellular matrix contained at least 60-80% of the cellular immunoreactive PN-1. Extraction of the matrix with 2 M NaCl removed PN-1 in a form which reacted with 125I-thrombin to form complexes which were immunoprecipitated by anti-PN-1 IgG and were of identical size as complexes made from soluble PN-1 and 125I-thrombin. These data indicate that in addition to its role as a soluble protease inhibitor, PN-1 is also a component of the extracellular matrix and might control its proteolysis.


Measurement of the thermal diffusivity of dental filling materials using modified Angström's method.
A new measuring technique for the determination of thermal diffusivity is proposed. Using this technique, the thermal properties of a few different dental filling materials were measured. The proposed method for measurement of thermal diffusivity is based on the classical Angström's method. The method exploits the propagation of a plane thermal wave generated by a Peltier's device in a cylindrical sample along its axis. The thermal diffusivity of the sample is calculated from the phase difference between harmonic components of temperatures measured at sample surfaces, perpendicular to the direction of thermal wave propagation. The estimated accuracy of measurement is typically about 10% for samples with low thermal diffusivity. The proposed method was used for the determination of thermal diffusivities of Achatit Bichromatic, Charisma and Dentimet dental filling materials. The measured thermal diffusivities were: 0.295(0.020)x10(-6)m(2)s(-1) for Achatit Bichromatic, 0.321(0.015)x10(-6)m(2)s(-1) for Charisma and 1.70(0.12)x10(-6)m(2)s(-1) for Dentimet. The thermal conductivities of these materials were also estimated. The results were compared with values obtained from independent constant flux measurements with marble as a reference material. There are no standard techniques for the determination of the thermal properties of dental filling materials. Moreover, it is difficult to find the thermal diffusivity and the thermal conductivity of many of them. The method proposed in this paper allows the simple and accurate measurement of thermal diffusivity. Thermal parameters of dental filling materials should be compatible with the parameters of human teeth. Lack of thermal compatibility can cause not only patient discomfort but also mechanical stresses leading to microcracks.


Preventive home visits to elderly people in Denmark.
During the last 20 years several randomised controlled trials have been published about preventive home visits to old people, but the benefit of the visits is still controversial and under debate. Based on a state law from the Ministry of Social Affairs in 1998, the municipalities in Denmark are obliged to offer home visits twice a year to all citizens 75 years and older. After six years with this law, there is still variation of how the law is managed and implemented. About 60% of the elderly people accept and receive the visits. Less than 50% of the municipalities have made specific guidelines and quality assurance indicators. More than the half have systematically used the visits to collect information of community needs and older people' wishes to be used for administrative and political purposes. In a prospective, controlled, feasibility study conducted over a 3-year period we found that a brief, manageable and ongoing educational intervention towards professionals working with preventive home visits is feasible and improves older people's functional mobility.


[Experimental study of the antihypoxic properties of ibuprofen and other nonsteroidal anti-inflammatory preparations].
The antihypoxic properties of ibuprofen, diclofenac sodium, acetylsalicylic acid and phenylbutazone have been studied. Ibuprofen significantly increases survival of mice in the model of hypoxic hypoxia with hypercapnia. In addition, ibuprofen and diclofenac sodium possess antihypoxic protective activity in the models of circulatory and anoxic hypoxia in rats.


Biodegradable nanoparticles for controlled subconjunctival delivery of latanoprost acid: in vitro and in vivo evaluation. Preliminary results.
Purpose of the study was to develop and assess a novel controlled drug delivery system of latanoprost acid (LA). Poly(lactide)/Monomethoxy-poly(ethyleneglycol) (PLA-PEG) nanoparticles (NPs) were prepared using an emulsification-solvent evaporation technique. NPs were characterized in vitro according to their size, ζ-potential, drug entrapment efficiency and LA release. LA-loaded NPs (equivalent to 8.5 μg LA) were administered into the subconjunctival space of normotensive rabbits (group A). A free LA solution of the same drug content was subconjunctivally injected in a second rabbit group (group B), while blank NPs were administered in a third group (group C). A group of untreated animals (group D) served as the control. Intraocular pressure (IOP) was monitored for 8 consecutive days, using the Tono-pen XL. Aqueous humor (AH) levels of LA were evaluated for 6 days post-administration, by means of HPLC. Mean nanoparticle size was 80 nm. The drug entrapment efficiency was 18.3%. NPs sustained the release of LA over several days in vitro. Non-significant differences in baseline IOP were found between groups (p = 0.22). LA-loaded NPs exerted a significant hypotensive effect on group A, while IOP values remained significantly lower compared to the rest groups, throughout the study (p = 0.04). LA AH concentrations in group B continuously decreased with time, while LA levels in group A steadily increased. On day 6, LA levels were higher in group A compared to group B (344 ± 73.5 ng/ml and 228 ± 41.01 ng/ml, respectively). No adverse effects were observed. In conclusion, after subconjunctival administration, the LA-loaded NPs provided sustained LA delivery in vivo. They appear to be a promising system for the controlled subconjunctival delivery of LA.


Recent Advancements of Stimuli-Responsive Targeted Liposomal Formulations for Cancer Drug Delivery.
Liposomes have gained attention as a well-accepted nanocarrier for several chemotherapeutic drugs and are considered a drug delivery system of choice for a wide range of products. These amphipathic spherical vesicles primarily consist of one or more phospholipid bilayers, showing promise for drug delivery of both hydrophilic and hydrophobic components in addition to unique properties, such as biocompatibility, biodegradability, low toxicity, and nonimmunogenicity. Recent advances in liposomes are mainly centered on chemical and structural modification with the multifunctional approach to target the cancer cells activating the offensive mechanisms within the proximity of the tumors. Stimuli-responsive liposomes are a precisive approach to deliver and release chemotherapeutic drugs in the tumor site in a controlled fashion, thus reducing damage to normal tissues and preventing the side effects of the conventional chemotherapy regimen. The unique characteristics of the tumor microenvironment facilitate applying an endogenous stimulus (pH, redox potential, or enzymatic activity) to trigger the release of the drug or the application of an external stimulus (heat or light) to tailor the drug release from liposomes. This review focuses on newer developments in stimuli-sensitive liposomal drug delivery systems designed to implement either exogenous (temperature, light, and magnetic field) or endogenous (pH changes, enzymatic triggers, or redox potential) approaches.


Effect of different aspirin doses on platelet aggregation in patients with stable coronary artery disease.
Aspirin is widely used as an antiplatelet agent in the primary and secondary prevention of cardiovascular disease. In order to spare prostacyclin formation and reduce gastrointestinal side-effects, very low doses of aspirin have been introduced. However, it remains unclear whether these low doses are equally effective with respect to inhibition of platelet aggregation. In a randomized, controlled study in 60 patients with stable coronary artery disease, the effects on platelet aggregation of five doses (50, 80, 100, 162.5 and 325 mg) of aspirin, which are widely used in clinical practice, given for 70 days, were investigated. Two reagents, adenosine diphosphate (ADP) and epinephrine, were used to induce platelet aggregation in platelet-rich plasma. An age- and sex-matched group of people without coronary artery disease served as the control. ADP- and epinephrine-induced platelet aggregation was 78.2 +/- 12.8% and 76.7 +/- 15.5% of maximum aggregation in the control group. Aspirin inhibited platelet aggregation in a dose-dependent manner. Minimum platelet aggregation was observed at a dose of 325 mg aspirin (27.5 +/- 17.4% with ADP). Doses of 50 and 80 mg aspirin were much less effective in inhibiting platelet aggregation (59.1 +/- 11.4% and 50.3 +/- 12.1% with ADP, respectively). Doses of 100 and 162.5 mg aspirin produced significantly greater inhibition of platelet aggregation than lower doses (36.2 +/- 11.7% and 38.5 +/- 19.8% platelet aggregation with ADP, respectively). Our results demonstrate that doses of aspirin less than 100 mg are not as effective at inhibiting platelet aggregation as doses greater than 100 mg.


Ecological risks associated to trace metals of contaminated sediments from a densely urbanized tropical eutrophic estuary.
The sediment contamination by trace metals in coastal aquatic ecosystems is a worldwide environmental problem, since metals can be toxic, persistent, and bioaccumulated. In case of natural events, such as storms, or anthropogenic activities, like dredging, the sediment resuspension to the water column occurs and can solubilize metals, probably increasing their bioavailability and consequently the risk to aquatic life. This study evaluated the bioavailability on reactive trace metals (Cd, Cr, Cu, Fe, Mn, Ni, Pb, and Zn) in estuarine sediments from Iguaçu and Meriti Rivers, both in the drainage basin of Guanabara Bay (Rio de Janeiro, Brazil). Additionally, a discussion about the anthropogenic interference throughout time of six short sediments cores, calculating three different indexes (contamination factors, CF; potential ecological risk index for a single heavy metal, Eif for short; potential ecological risk, PERI) was performed. It was considered as reactive phase, the metal concentrations obtained using a weak acid extraction (in HCl 1 mol L-1 solution). Zn presented high concentrations after resuspension, being above effect range medium (ERM) (52.81 to 1337.4 mg kg-1). The CF indicated very high contamination degree for Cu (14.62 to 17.96) and Zn (27.80 to 35.85) for both rivers. The Eif for short presented higher risk to Cu and Zn for Iguaçu and Meriti rivers. PERI index classified Meriti River samples as severely contaminated (238.10 to 351.62).


Dynamical ansatz for path integrals and nonperturbative trace formulas.
It is shown that a recently discovered representation of the Green's function is equivalent to a certain "dynamical ansatz" for the corresponding path integral, which brings about a convenient method of nonperturbative approximations. Based on this observation, a set of nonperturbative approximations to the trace of the Green's function is established.


Spine immobilization and neurological outcome in vertebral osteomyelitis SPONDIMMO, a prospective multicentric cohort.
The aim of our study was to describe spine immobilization in a multicentric cohort of vertebral osteomyelitis (VO), and evaluate its association with neurological complications during follow-up. We prospectively included patients from 2016 to 2019 in 11 centers. Immobilization, imaging, and neurological findings were specifically analyzed during a 6-month follow-up period. 250 patients were included, mostly men (67.2%, n=168). Mean age was 66.7±15 years. Diagnosis delay was 25 days. The lumbo-sacral spine was most frequently involved (56.4%). At diagnosis, 25.6% patients (n=64) had minor neurological signs and 9.2% (n=23) had major ones. Rigid bracing was prescribed for 63.5% (n=162) of patients, for a median of 6 weeks, with variability between centers (P<0.001). The presence of epidural inflammation and abscess on imaging was associated with higher rates of rigid bracing prescription (OR 2.33, P=0.01). Frailness and endocarditis were negatively associated with rigid bracing prescription (OR 0.65, P<0.01, and OR 0.42, P<0.05, respectively). During follow up, new minor or major neurological complications occurred in respectively 9.2% (n=23) and 6.8% (n=17) of patients, with similar distribution between immobilized and non-immobilized patients. Spine immobilization prescription during VO remains heterogeneous and seems associated inflammatory lesions on imaging but negatively associated with frailness and presence of endocarditis. Neurological complications can occur despite rigid bracing. Our data suggest that in absence of any factor associated with neurological complication spine bracing might not be systematically indicated. We suggest that spine immobilization should be discussed for each patient after carefully evaluating their clinical signs and imaging findings.


Impact of an Okinawa/Nordic based diet on endocrinological and periodontal conditions in individuals with type 2 diabetes. A randomized case-control study.
To assess if the results following intake of a diet using an Okinawan-based Nordic diet (OBND) over one month differs in endocrinological, periodontal clinical outcome, and serum cytokine levels compared to a standard hospital care diet in individuals with diabetes type 2 (T2D) (control group). Scientific evidence suggests that the use of diet for individuals with T2D may be beneficial. Participating individuals with T2D were randomly assigned to a test (OBND) (n = 14), or control group (n = 16). Anthropometric data, blood glucose levels, HbA1c levels, lipids, serum inflammation markers (CRP, and a routine panel of 24 cytokines), blood pressure, gingival bleeding on probing (BOP), probing pocket depths (PPD), and clinical attachment levels (CAL) were studied. Statistical analyses of baseline study data failed to demonstrate study group differences. The mean weight reduction was greater in the OBND group (4.1 kg) versus the control group (1.3 kg) (p < 0.01). The reduction in BMI was 1.4 kg/m2 in OBND (p < 0.001) and 0.5 kg/m2 in the control group, respectively (p < 0.01). Diastolic and systolic blood pressure reductions were greater in the OBND group than in the control group (p < 0.01). Periodontal study parameters (BOP % scores) and (PPD values) decreased (p < 0.001) overall with no between group differences. The OBND resulted in reduction of serum levels of IFNγ, Eotaxin IL-9, IP10,IL17a, MCP-1,m and PDFBB compared to the control diet. A strict T2D- diet provides an association between reduction in serum HbA1c and BOP scores. Serum levels decreases in IFNγ, Eotaxin IL-9, IP-10, IL17a. MCP-1, and PDFBB were only found in the test group.


Cobalt-Porphyrin-Platinum-Functionalized Reduced Graphene Oxide Hybrid Nanostructures: A Novel Peroxidase Mimetic System For Improved Electrochemical Immunoassay.
5,10,15,20-Tetraphenyl-21H,23H-porphine cobalt flat stacking on the reduced graphene oxide with platinum nanoparticles (PtNPs/CoTPP/rGO) were first synthesized and functionalized with monoclonal rabbit anti-aflatoxin B1 antibody (anti-AFB1) for highly efficient electrochemical immunoassay of aflatoxin B1 (AFB1) in this work. Transmission electron microscopy (TEM), atomic force microscope (AFM) and spectral techniques were employed to characterize the PtNPs/CoTPP/rGO hybrids. Using anti-AFB1-conjugated PtNPs/CoTPP/rGO as the signal-transduction tag, a novel non-enzymatic electrochemical immunosensing system was designed for detection of target AFB1 on the AFB1-bovine serum albumin-functionalized sensing interface. Experimental results revealed that the designed immunoassay could exhibit good electrochemical responses for target analyte and allowed the detection of AFB1 at a concentration as low as 5.0 pg mL(-1) (5.0 ppt). Intra- and inter-assay coefficients of variation were below 10%. Importantly, the methodology was further validated for analyzing naturally contaminated or spiked blank peanut samples with consistent results obtained by AFB1 ELISA kit, thus providing a promising approach for quantitative monitoring of organic pollutants.


The utility of two Wechsler Adult Intelligence Scale short forms with prisoners.
Previous research has suggested that the Pauker (1963) and Satz and Mogul (1962) short forms of the WAIS have been efficacious in estimating the standard form. While there is a growing need in correctional settings for quicker evaluation procedures, the lack of WAIS short form research with prisoners prohibits their use with such populations. Hence, this study employed 126 young adult male inmates to test the comparability of the above cited short forms and the standard WAIS across a variety of evaluative criteria. The results generally suggested the superiority of the Pauker (1963) form in estimating the standard WAIS. However, because the current study employed only black and white young male offenders it is suggested that the current findings not be generalized to other age groups, races, or women inmates until these findings are cross-validated on such samples.


The effects of guided imagery on state and trait anxiety and sleep quality among patients receiving hemodialysis: A randomized controlled trial.
This study aimed to investigate the effects ofguided imagery on state and trait anxiety and sleep quality among hemodial ysis patients. This was a randomized controlled trial. A total of seventy hemodialysis patients were assigned through block randomization to either an intervention group to receive guided imagery or a control group to receive routine care services. The study was performed in the hemodialysis unit of Akhavan teaching hospital, Kashan, Iran. In addition to routine care services, patients in the intervention group received guided imagery six times a week for four successive weeks via listening to a guided imagery instructional compact disk and following the instructions. Before and four weeks after the intervention, state and trait anxiety and sleep quality were measured via Spielberger's State-Trait Anxiety Inventory and Pittsburgh Sleep Quality Index. The results of analysis of covariance showed that the intervention and the control groups significantly differed from each other respecting the posttest mean scores of state anxiety (adjusted mean difference: -9.11; 95% CI = -10.26 to_-7.96; P < 0.001), trait anxiety (adjusted mean difference: -8.94; 95% CI = -10.31_to -7.57; P < 0.001), and sleep quality (adjusted mean difference: -0.877; 95% CI = -1.51_to -0.24; P < 0.007). Guided imagery can significantly alleviate anxiety and improve sleep quality among hemodialysis patients. Nurses are recommended to use guided imagery to alleviate hemodialysis patients' anxiety and improve their sleep quality.


Quantification of heart sounds interference with lung sounds.
An index to quantify the contamination of lung sounds by heart sounds is described. Using the index, the efficacy of high pass filtering and adaptive filtering methods for the reduction of heart sounds is evaluated.


Peripheral measurements of venous oxygen saturation and lactate as a less invasive alternative for hemodynamic monitoring.
Peripheral measurement of venous oxygen saturation and lactate is a less invasive alternative to monitor tissue oxygenation as compared to measurements from a central venous catheter. However, there is a lack of evidence to support the use of peripheral measurements. In this study, we investigated the agreement between central and peripheral venous oxygen saturation and lactate. We conducted a prospective observational study including 115 patients who underwent elective cardiac surgery between April and May 2015 at Rigshospitalet, Copenhagen, Denmark. Measurements were obtained simultaneously at induction of anaesthesia, upon arrival in the ICU and 3-4 h postoperatively. Bias and trending ability was identified using Bland-Altman analysis and a four-quadrant plot. Bias was 13.37% for venous oxygen saturation preoperatively (95% CI: 11.52-15.22, LoA: ±19.10, PE: 22.08%), 11.29% at arrival to the ICU (95% CI: 8.81-13.77, LoA: ±25.10, PE: 32.39%) and 16.49% at 3-4 h postoperatively (95% CI: 14.16-18.82, LoA: ±21.20, PE: 26.82%). A four-quadrant plot demonstrated an 89% concordance. Central and peripheral lactate showed a bias of 0.14 mmol/L preoperatively (95% CI: 0.11-0.17, LoA: ±0.30, PE: 32.08%), 0.16 mmol/L at arrival to ICU (95% CI: 0.09-0.23, LoA: ±0.70, PE: 38.88%) and 0.23 mmol/L at 3-4 h postoperatively (95% CI: 0.11-0.35, LoA: ±0.50, 25.18%). Measurements of peripheral oxygen saturation and lactate may be valuable in an emergency setting, avoiding unnecessary and time consuming application of a CVC. We found a high bias but an acceptable trending ability between central and peripheral venous oxygenation. Central and peripheral lactate had excellent agreement. Further studies are necessary to validate the use of peripheral venous samples to identify patients at risk of impaired tissue oxygenation.


Outcomes of esophageal and gastric bone foreign bodies in dogs.
Bone foreign bodies are commonly encountered in small animal practice. Esophageal bone foreign bodies (E-bFBs) warrant removal, whereas gastric bone foreign bodies might not. Describe management and outcomes for dogs with esophageal or gastric bone foreign bodies. One hundred twenty-nine dogs with esophageal (n = 45) or gastric (n = 84) bone foreign bodies. Retrospective review of medical records. Dogs with E-bFBs were younger than dogs with gastric bone foreign bodies (median age esophageal, 4 years [IQR 2-8]; median age gastric, 6 years [IQR 3-10]; P = .03), and had a higher bone cross-sectional area relative to body weight (median esophageal, 98.21 mm2 /kg [IQR 48.25-142.6]; median gastric, 28.6 mm2 /kg [IQR 17.25-64.28]; P < .001). Forty-two of 45 esophageal foreign bodies were resolved non-surgically and 3 by esophagotomy. Esophageal erosions were more likely with distal entrapment (OR 12.88, [95% CI 31.95-129.29], P = .01) and longer duration (OR 18.82 [95% CI 2.22-273.97], P = .01). Sixty-two of 84 bone gastric foreign bodies were left in situ. Endoscopic removal was successful in 20 of 22 (91%; 95% CI 70-99) attempts. While all E-bFBs were dislodged either by advancement into the stomach, endoscopic removal, or esophagotomy, the majority of gastric bone foreign bodies were left in situ for dissolution, with no reported complications. Gastric advancement of E-bFBs should be considered when oral removal is not feasible, and dissolution can be considered even with large bones.


Schizorchis arfaai sp. n. (Cestoda: Anoplocephalidae) from the wood-mouse, Apodemus sylvaticus, in Caspian area of Iran.
Schizorchis arfaai sp. n. is described from the wood-mouse in the Caspian area of Iran and its morphological characteristics compared with those of the five previously known species of Schizorchis Hansen, 1948.


Macrophage migration inhibitory factor is associated with vascular dysfunction in patients with end-stage renal disease.
Patients with end-stage renal disease (ESRD) show a high prevalence of cardiovascular disease with arterial stiffness, atherosclerosis and endothelial dysfunction, leading to increased morbidity and mortality. The cytokine macrophage migration inhibitory factor (MIF) exhibits proinflammatory and proatherogenic functions and has recently emerged as a major regulator of atherogenesis. Studies examining the relationship between circulating MIF levels and vascular dysfunction in this high-risk population do not exist. In patients with ESRD (n = 39) and healthy controls (n = 16) we assessed endothelial function by flow-mediated dilation of the brachial artery and arterial stiffness (augmentation pressure, augmentation index and pulse pressure) using applanation tonometry. High-sensitive Troponin and subendocardial viability ratio were determined to assess myocardial injury. Patients with ESRD had impaired endothelial function and higher plasma MIF levels. MIF levels negatively correlated with endothelial function (r = -0.345, P = 0.031) and positively with arterial stiffness indices in patients with ESRD (pulse pressure r = -0.374, P = 0.019 and augmentation pressure r = -0.423, P = 0.025). In multivariate regression models besides age, gender, weight, and heart rate, MIF was an independent predictor for arterial stiffness. Impact on myocardial end-organ damage was reflected by correlation with high-sensitive Troponin I (r = 0.43, P = 0.009). Our findings show that high MIF plasma levels are associated with diminished endothelial function and arterial stiffness and are correlated with myocardial injury. Further studies are necessary to investigate whether modulation of MIF might have an impact on atherosclerotic disease in this high-risk population.


A sorghum gigantea mutant attenuates florigen gene expression and delays flowering time.
GIGANTEA (GI) is a conserved plant-specific gene that modulates a range of environmental responses in multiple plant species, including playing a key role in photoperiodic regulation of flowering time. The C4 grass Sorghum bicolor is an important grain and subsistence crop, animal forage, and cellulosic biofuel feedstock that is tolerant of abiotic stresses and marginal soils. To understand sorghum flowering time regulatory networks, we characterized the sbgi-ems1 nonsense mutant allele of the sorghum GIGANTEA (SbGI) gene from a sequenced M4 EMS-mutagenized BTx623 population. sbgi-ems1 plants flowered later than wild type siblings under both long-day or short-day photoperiods. Delayed flowering in sbgi-ems1 plants accompanied an increase in node number, indicating an extended vegetative growth phase prior to flowering. sbgi-ems1 plants had reduced expression of floral activator genes SbCO and SbEHD1 and downstream FT-like florigen genes SbFT, SbCN8, and SbCN12. Therefore, SbGI plays a role in regulating SbCO and SbEHD1 expression that serves to accelerate flowering. SbGI protein physically interacts with the sorghum FLAVIN-BINDING, KELCH REPEAT, F-BOX1-like (SbFFL) protein, a conserved flowering-associated blue light photoreceptor, and the SbGI-SbFFL interaction is stimulated by blue light. This work demonstrates that SbGI is an activator of sorghum flowering time upstream of florigen genes under short- and long-day photoperiods, likely in association with the activity of the blue light photoreceptor SbFFL. This study elucidates molecular details of flowering time networks for the adaptable C4 cereal crop Sorghum bicolor, including demonstration of a role for blue light sensing in sorghum GIGANTEA activity. This work validates the utility of a large publicly available sequenced EMS-mutagenized sorghum population to determine gene function.


Pre-surgical management of unilateral cleft lip and palate in a neonate: a clinical report.
Cleft lip and palate deformity is a congenital defect of the middle third of the face, consisting of fissures of the upper lip and/or palate. Naso-alveolar molding provides excellent results when considered and started early in the neonatal. Early treatment is important not only due to esthetic and functional concerns, but also for a positive psychological impact it has on the child. In the pre-surgical management, an interdisciplinary approach is necessary where an Orthodontist and a Prosthodontist play a major role. Also any treatment procedure in an infant becomes difficult due to the lack of co-operation from the child. This clinical report describes the multidisciplinary approach for complete pre-surgical management of a neonate with complete unilateral cleft of soft palate, hard palate, alveolar ridge and lip.


Alien flora causes biotic homogenization in the biodiversity hotspot regions of India.
Biotic homogenization by invasive alien species is one of the dominant drivers of global environmental change. However, little is known about the patterns of biotic homogenization in global biodiversity hotspots. Here, we fill this knowledge gap by studying the patterns of biotic homogenization and associated geographic and climatic correlates in Indian Himalayan Region (IHR). For this, we use a novel biodiversity database comprising 10,685 native and 771 alien plant species across 12 provinces of the IHR. The database was assembled by screening 295 and 141 studies published from 1934 to 2022 for natives and aliens, respectively. Our results revealed that each native species on average was distributed among 2.8 provinces, whereas the alien species in 3.6 provinces, thereby indicating wider distribution range of alien species in the IHR. The Jaccard's similarity index between the provinces was higher for alien species (mean = 0.29) as compared to natives (mean = 0.16). Addition of alien species pool has homogenized most of the provincial pairwise floras (89.4 %) across the IHR, with greater dissimilarity in their native floras. Our results revealed that the alien species have strong homogenization effect on the provincial floras, regardless of their differences in geographic and climatic distances. The biogeographic patterns of alien and native species richness in the IHR were better explained by a different set of climatic variables, the former by precipitation of driest month and the latter by annual mean temperature. Our study contributes to better understanding of the patterns of biotic homogenization in the IHR and its geographic and climatic correlates. Looking ahead, in an era of Anthropocene, we discuss the wide implications of our findings in guiding biodiversity conservation and ecosystem restoration in global hotspot regions.


The treatment of hypertension in care home residents: a systematic review of observational studies.
To describe the prevalence of hypertension in care home residents, its treatment, change in treatment over time, and the achievement of blood pressure (BP) control. The PubMed, Cochrane, Embase, and PsychINFO databases were searched for observational studies involving care home residents with a diagnosis of hypertension. The search was limited to English language articles involving adults and humans published from 1990 onward. Abstracts and titles were reviewed with eligible articles read in full. Bibliographies were examined for further relevant studies. The final selection of studies was then analyzed and appraised. Sixteen articles were identified for analysis, of which half were studies carried out in the United States. The prevalence of hypertension in care home residents was 35% (range 16%-71%); 72% of these were on at least 1 antihypertensive (mean 1.5 antihypertensives per individual), with diuretics being the most common. The prevalence of hypertension in study populations was greater in more recent studies (P = .004). ACEi/ARBs (P = .001) and β-blockers (P = .04) were prescribed more frequently in recent studies, whereas use of calcium-channel blockers and diuretics remained unchanged over time. The number of antihypertensives prescribed per patient was higher (correlation 0.332, P = .009), whereas fewer patients achieved target BP (correlation -0.671, P = .099) in more recent studies. Hypertension is common in care home residents and is commonly treated with antihypertensive drugs, which were prescribed more frequently in more recent studies but with no better BP control. These studies indicate a tendency toward increasing polypharmacy over time, with associated risk of adverse events, without demonstrable benefit in terms of BP control.


Group differences in the structure of illness.
The paper reports an attempt to study in a naturalistic and quantitative fasion the features of illness episodes. Such episodes, as perceived and reported by lay persons, constitute a basic datum in ethnomedicine. Yet, they have rarely been the object of systematic research for theoretical and methodological reasons. The paper discusses ways in which illness episodes have significance in ethnomedicine and in health services research generally, and describes a method which can be used in field situations to study them. The content, internal structure and organization which illness episodes have are given attention by analysing and measuring the components of illness in a panel of adult females who reside in the highland state of Chiapas in Southeastern Mexico. Comparisons are undertaken in the two most dissimilar subgroupings of the region. Some commonalities and group differences in the duration of symptoms and in the way symptoms interrelate are described. An interpretation of these differences is offered, with principal emphasis given to the social circumstances and to the (cultural) meanings of illness in the two groups. The procedure employed, which is consistent with the way in which vital signs are recorded in the hospital, lends itself to field studies of the way symptoms and signs of disease unfold in the individual across time. The idea of a language of illness, which is introduced and developed in the paper, is used to draw emphasis to the communicative and symbolic features of illness.


Hepatitis safety of a new prothrombin complex preparation, sterilized according to the method of LoGrippo. Results of a prospective clinical trial.
In a controlled, prospective clinical trial with almost 300 patients undergoing cardiovascular surgery, the hepatitis risk was examined of a new prothrombin complex (PPSB) preparation produced from pooled plasma, which was cold sterilized according to the method of LoGrippo with beta-propiolactone and UV-light. Of 268 evaluable patients, 102 belonged to a group receiving PPSB and 166 belonged to a control group without PPSB. 25 batches of PPSB in dosages of up to 4,500 units per patient, in total, were used. The mean requirement for transfusion of blood or plasma was 10 units per patient in the group receiving PPSB and slightly more than 2 units per patient in the control group. In both of the groups, 3 hepatitis infections occurred (5 cases of non-A, non-B, 1 case of type B), corresponding to hepatitis incidences of 2.9 and 1.8%, respectively. The difference in hepatitis incidence between both groups was statistically not significant. This demonstrates, on the one hand, the hepatitis safety of the sterilized PPSB and, on the other, that multiple transfusion is no longer associated with a high risk of hepatitis when the guidelines of modern donor screening are followed.


Use of water quality index and multivariate statistical methods for the evaluation of water quality of a stream affected by multiple stressors: A case study.
The Sürgü Stream, located in the Euphrates River basin of Turkey, is used for drinking water source, agricultural irrigation and rainbow trout production. Therefore, water quality of the stream is of great importance. In this study, multivariate statistical techniques (MSTs) and water quality index (WQI) were applied to assess water quality of the stream affected by multiple stressors such as untreated domestic sewage, effluents from fish farms, agricultural runoff and streambank erosion. For this, 16 water quality parameters at five sites along the stream were monitored monthly during one year. Most of parameters showed significant spatial variations, indicating the influence of anthropogenic activities. All parameters except TN (total nitrogen) showed significant seasonal differences due to high seasonality in WT (water temperature) and water flow. The spatial variations in the WQI were significant (p < 0.05) and the mean WQI values ranged from 87.6 to 95.3, indicating "good" to "excellent" water quality in the stream. Cluster analysis classified five sites into three groups, that is, clean region, low polluted region and very clean region. Stepwise temporal discriminant analysis (DA) identified that pH, WT, Cl-, SO42-, COD (chemical oxygen demand), TSS (total suspended solids) and Ca2+ are the parameters responsible for variations between seasons, and stepwise spatial DA identified that DO (dissolved oxygen), EC (electrical conductivity), NH4-N, TN (total nitrogen) and TSS are the parameters responsible for variations between the regions. Principal component analysis/factor analysis revealed that the parameters responsible for water quality variations were mainly associated with suspended solids (both natural and anthropogenic), soluble salts (natural) and nutrients and organic matter (anthropogenic).


Comparison and optimization of in situ hybridization procedures yielding rapid, sensitive mRNA detections.
This paper describes methods that are commonly used for performing mRNA in situ hybridizations. Each stage of the procedure has been analyzed to identify the parameters that most significantly affect the final cell morphology and sensitivity of the system. We have identified key elements of the procedure as the fixation employed, the type of polynucleotide probe and label chosen, and the detection system used. By optimizing these critical components, we have developed a procedure for performing mRNA in situ hybridizations that takes 2-4 hours and has a sensitivity of 1-10 molecules of mRNA per cell. This system has been used to detect levels of oncogene expression in normal bone marrow and peripheral blood. It is possible to detect the expression of three oncogenes (c-myc, c-sis, and c-abl) simultaneously in a small population of cells from the peripheral blood of leukemic patients.


Characterization of a 4 lncRNAs-based prognostic risk scoring system in adults with acute myeloid leukemia.
The study aims to develop a prognostic scoring system based on prognostic lncRNAs for acute myeloid leukemia (AML). Based on lncRNA expression profiles downloaded from The Cancer Genome Atlas (TCGA), differentially expressed long noncoding RNAs (DELs) between good prognosis and bad prognosis samples were screened, from which prognosis-related lncRNAs were selected using uni-variate and multi-variate Cox regression analysis. Based on the expression profiles of these signature prognosis-related lncRNAs, a risk scoring system was developed and applied to a training set and validated on a testing set. With sample-matched mRNAs of the signature lncRNAs, lncRNA-mRNA networks were built, followed by function analysis for the mRNAs in these networks. Total 66 DELs were identified between good prognosis and bad prognosis samples. Among these DELs, LINC01003, CTD-2234N14, RP1-137K24, and RP11-834C111 were found to be independent predictors of prognosis. A risk scoring system based on the expressions of the 4 signature lncRNAs was developed. Kaplan-Meier survival analysis found that the risk score system could classify patients into high-risk and low-risk groups with significantly different survival outcomes. Function analysis showed that the mRNAs in these lncRNA-mRNA networks were significantly linked to mTOR signaling pathway, apoptosis, Fc epsilon RI signaling pathway, B cell receptor signaling pathway, natural killer cell mediated cytotoxicity, and T cell receptor signaling pathway. This study suggested a promising 4 prognostic lncRNAs-based risk scoring system in AML. These 4 lncRNAs may play roles in regulating prognosis partly via mTOR signaling pathway, apoptosis, and some immune-related pathways.


The Role of CD44 and Cancer Stem Cells.
Solid tumors are composed of mutually interacting cancer cells and tumor microenvironment. Many environmental components, such as extracellular matrix (ECM), mesenchymal stem cells, endothelial and immune cells, and various growth factors and cytokines, provide signals, either stimulatory or inhibitory, to cancer cells and determine their fates. Meanwhile, cancer cells can also educate surrounding cells or tissues to undergo changes that are in favorable of tumor progression. CD44, as a transmembrane receptor for hyaluronic acid (HA) and many other ECM components and a coreceptor for growth factors and cytokines, is a critical cell surface molecule that can sense, integrate, and transduce cellular microenvironmental signals to membrane-associated cytoskeletal proteins or to cell nucleus to regulate a variety of gene expressions that govern cell behaviors. Mounting evidence suggests that CD44, particularly CD44v isoforms, are cancer stem cell (CSC) markers and critical regulators of cancer stemness, including self-renewal, tumor initiation, and metastasis. Thus, CD44 is widely used alone or in combination with other cell surface markers to isolate or enrich CSCs through fluorescence-activated cell sorting of dissociated single cells that originate from the patient, xenograft tumor tissues, or tumor cell cultures. Sorted cells are cultured in a specialized culture medium for spheroid formation or inoculated into immunodeficient mice for the analysis of tumorigenic or metastatic potential. In this chapter, detailed experimental methods regarding CD44+ tumor cell isolation, spheroid culture, and characterization will be described.


HMGB1 is involved in viral replication and the inflammatory response in coxsackievirus A16-infected 16HBE cells via proteomic analysis and identification.
Coxsackievirus A16 (CV-A16) is still an important pathogen that causes hand, foot and mouth disease (HFMD) in young children and infants worldwide. Previous studies indicated that CV-A16 infection is usually mild or self-limiting, but it was also found that CV-A16 infection can trigger severe neurological complications and even death. However, there are currently no vaccines or antiviral compounds available to either prevent or treat CV-A16 infection. Therefore, investigation of the virus‒host interaction and identification of host proteins that play a crucial regulatory role in the pathogenesis of CV-A16 infection may provide a novel strategy to develop antiviral drugs. Here, to increase our understanding of the interaction of CV-A16 with the host cell, we analyzed changes in the proteome of 16HBE cells in response to CV-A16 using tandem mass tag (TMT) in combination with LC‒MS/MS. There were 6615 proteins quantified, and 172 proteins showed a significant alteration during CV-A16 infection. These differentially regulated proteins were involved in fundamental biological processes and signaling pathways, including metabolic processes, cytokine‒cytokine receptor interactions, B-cell receptor signaling pathways, and neuroactive ligand‒receptor interactions. Further bioinformatics analysis revealed the characteristics of the protein domains and subcellular localization of these differentially expressed proteins. Then, to validate the proteomics data, 3 randomly selected proteins exhibited consistent changes in protein expression with the TMT results using Western blotting and immunofluorescence methods. Finally, among these differentially regulated proteins, we primarily focused on HMGB1 based on its potential effects on viral replication and virus infection-induced inflammatory responses. It was demonstrated that overexpression of HMGB1 could decrease viral replication and upregulate the release of inflammatory cytokines, but deletion of HMGB1 increased viral replication and downregulated the release of inflammatory cytokines. In conclusion, the results from this study have helped further elucidate the potential molecular pathogenesis of CV-A16 based on numerous protein changes and the functions of HMGB1 Found to be involved in the processes of viral replication and inflammatory response, which may facilitate the development of new antiviral therapies as well as innovative diagnostic methods.


Bioelectrodes based on pseudocapacitive cellulose/polypyrrole composite improve performance of biofuel cell.
Enzymatic electrodes with high internal capacitance, based on cellulose/polypyrrole composite were optimized and utilized to design improved enzymatic fuel cell. Fructose dehydrogenase Gluconobacter sp. specifically adsorbed on the cellulose/polypyrrole matrix and electrophoretically immobilized and electrochemically entrapped Laccase Trametes versicolor, were used as the anode and cathode bioelectrocatalysts, respectively. The cellulose/polypyrrole composite film exhibited pseudocapacitive properties under mild pH conditions. Following modification with carboxylic groups the composite material enabled highly efficient adsorption of enzyme and provided good electrical contact between the enzymatic active sites and the electrode surface. The modified cellulose/polypyrrole composite based electrode was used for the anode leading to mediatorless fructose oxidation giving large catalytic current density, 12.8mAcm(-2). Laccase and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) as the mediator entrapped in the cellulose/polypyrrole composite film generated dioxygen reduction current density of 2mAcm(-2). Application of pseudocapacitive matrix and decreasing the distance between electrodes to 1mm lead to improvement of the biofuel cell power output and its regeneration ability. The power of the cell was found to increase by introduction of a preconditioning step during which the cell was kept at open circuit voltage under fuel flow. After 24h of preconditioning the matrix was recharged and the device output reached the power, 2.1mWcm(-2) and OCV, 0.59V.


[Effect of acetylcholine on incorporation of 14C-precursors into uridylic and cytidylic nucleotides of the RNA of digestive glands].
The incorporation rate of [2-14C]orotic acid and [2-14C]uridine into the cytidylic RNA nucleotides is significantly lower than into the uridylic ones. In the liver it was twice as low as in the stomach mucosa or in pancreas of albino rats. The administration of acetylcholine in combination with proserine has no influence on the RNA content and its nucleotide composition in the tissues. The administered drugs however caused changes in the relation of the incorporation rates of both labels into uridylic and cytidylic RNA nucleotides, which evidences for the uridylic nucleotide synthesis. In the liver such changes are not detected, but utilization of the labeled uridine is shown to be more intensive for the cytidylic RNA nucleotides synthesis.


[Results of a private primary health system based on a family health care model in Chile].
The health care network of a University in Chile started a family based primary health care system using pre paid model as financing. To describe the results of this family Health Care Center. Between 1999 and 2006, the Pontificia Universidad Catolica-Health Network offered a family care plan characterized by a preferential access to a Family Care Center (CSF), that coordinated and solved all health care needs. Several indicators and perception of satisfaction were used to assess the results of this plan, in 2003 and 2004. During the study period, 5,402 people were attended. Seventy three percent of these were aged between 15-44 years. The waiting lapse was less than 48 hours for medical appointments and less than 30 days for programmed surgical procedures. The coverage of preventive actions varied from 26% of mammographies among women between 25 to 69 years old to 100% for healthy child care among newborns. Thirty one percent of diabetics achieved a glycosilated hemoglobin of less than 7% and 19% of hypertensive subjects achieved blood pressure values below 135/85 mmHg. Family physicians had 2.3 appointments per person per year and solved 85% of the medical problems that motivated the consultation. In average, 88% of interviewed subjects evaluated the attention received as very good or excellent. The application of this model in the private sector achieves measurable health care results with a good degree of client satisfaction.


Is HIV/AIDS a primary-care disease? Appropriate levels of outpatient care for patients with HIV/AIDS.
To estimate the proportion of outpatient visits that could be managed at a primary-care level, by World Health Organization (WHO) clinical staging. Prospective, descriptive study. Six medical doctors in a tertiary hospital HIV ambulatory clinic recorded clinical diagnoses, WHO clinical staging and their recommendation regarding the appropriate level of care for each outpatient seen. All HIV-infected patients attending a public-sector, urban, South African, referral and teaching hospital HIV outpatient clinic between September and November 1992. There were 238 visits by 148 patients during the study period. Of 238 visits, 165 (69.3%) were deemed suitable for treatment at the primary-care level. After allowing for contradictory responses, at least 141 visits (59.2%) could be appropriately treated at the primary-care level. Although all six doctors assessed more than half of their visits as suitable for primary care, there were significant differences among them. In total, 83 visits (34.8%) needed a medical specialist, and 45 (18.9%) required tertiary-care facilities. Of all the visits, 58 (24.9%), 51 (21.9%), 60 (25.8%) and 64 (27.4%) were classified as WHO stages 1, 2, 3 and 4, respectively. For these stages, 55 (94.8%), 38 (74.5%), 42 (70.0%) and 26 (40.5%) visits, respectively, were suitable for treatment at a primary-care facility. Many of the outpatient visits to this outpatient specialist clinic could have been safely cared for at a primary-care level. As the severity of the disease increases, there is a decrease in the proportion of patients that can be treated at a primary-care level.


Essential functional molecules associated with SARS-CoV-2 infection: Potential therapeutic targets for COVID-19.
The whole world is still suffering substantially from the coronavirus disease 2019 (COVID-19) outbreak. Several protein-based molecules that are associated with the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which are essential for its functionality, survival, and pathogenesis have been identified and are considered as potential therapeutic targets. These protein-based molecules are either structural/non-structural components of SARS-CoV-2 or host factors, which play a crucial role in this infection. Developing drug molecules against these essential functional molecules to hinder their regular functioning and associated physiological pathways could be promising for successful clinical management of this novel coronavirus infection. The review aims to highlight the functional molecules that play crucial roles in SARS-CoV-2 pathogenesis. We have emphasized how these potential druggable targets could be beneficial in tackling the COVID-19 crisis.


Managing type 2 diabetes mellitus in patients with obesity.
Obesity is the most important modifiable risk factor for type 2 diabetes mellitus and most patients with diabetes are overweight or obese. It is well known that excess bodyweight induces or aggravates insulin resistance, which is a characteristic feature of type 2 diabetes. Thus, bodyweight plays a central role in the prevention and treatment of diabetes. Recent data suggest that lifestyle intervention in patients with impaired glucose tolerance results in an impressive reduction in the conversion to overt diabetes, which is greater than the effect of early intervention with drugs such as metformin or acarbose. The prevention of diabetes has been shown to be associated with the extent of weight loss. In patients with type 2 diabetes, weight loss by any means is followed by an improvement of metabolic control and associated risk factors. The most appropriate recommendation for obese patients with type 2 diabetes is a nutritionally balanced, moderately hypocaloric diet with a reduced intake of saturated fat and an increase in physical activity. If this standard approach is only partly successful or not at all, additional strategies such as weight-lowering drugs, very low-calorie diets for limited periods of up to 12 weeks, and, for severely obese patients, bariatric surgery should be carefully considered. A large body of data suggests that such measures can be very effective in this patient group by improving metabolic disturbances and blood pressure. However, it is extremely important for the long-term outcome that the treatment is tailored to the needs and wishes of the individual patient. There is growing agreement that due to the low success rate of conventional therapies and the overwhelming benefit from weight loss, more determined and aggressive strategies may be appropriate to achieve the central goal of weight reduction in obese patients with type 2 diabetes.


Polysomnographic characteristics in patients with Prader-Willi syndrome.
To evaluate the occurrence of sleep-disordered breathing and to clarify the characteristics of sleep among patients with Prader-Willi syndrome (PWS). Overnight continuous EEG-polysomnographic studies were performed in 30 patients with PWS (16 males and 14 females; mean age, 7.4 +/- 4.1 years; age range, 1-19 years) unselected for sleep disturbance. The baseline arterial oxygen saturation (SpO2) was 96.6 +/- 0.6%, with a nadir of 77.2 +/- 10.2%. The rapid eye movement (REM) latency was 67.4 +/- 30.0 min. The percent of total sleep time spent in sleep stages 1, 2, slow wave, and REM were 13.1 +/- 8.2%, 41.9 +/- 10.5%, 21.5 +/- 9.4%, and 21.1 +/- 5.7%, respectively. The respiratory disturbance index (RDI) was 5.8 +/- 3.7/hr and desaturation index (DI) was 8.1 +/- 7.3/hr, respectively. Age-adjusted BMI was associated with more severe hypoxemia during sleep (baseline SpO2, r = -0.53, P < 0.01; nadir SaO2, r = -0.65, P < 0.01; RDI, r = 0.37, P < 0.05; DI, r = 0.53, P < 0.01) and more sleep disruption (arousal index, r = 0.46, P < 0.01). There were no significant associations between gender or genotype pattern (deletion vs. uniparental disomy) and the results of polysomnography. Sleep hypoxemia and sleep disruption are more prevalent in patients with PWS than in normal children. Obesity in these patients is associated with more severe sleep-disordered breathing.


Microsurgical management of male infertility.
The introduction of microsurgical techniques has revolutionized the treatment of male infertility. As a result of technical advances and innovation over the past 10-15 years, previously infertile couples are now able to conceive naturally or to parent their own biological children with the aid of assisted reproductive technologies. This article reviews the indications, techniques, and outcomes of the various microsurgical procedures currently used to optimize male fertility. The most up-to-date methods of microsurgical vasal and epididymal reconstruction, sperm retrieval, and varicocele repair are discussed.


Structure of diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino)uracil reductase from Acinetobacter baumannii.
The bifunctional diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino)uracil reductase (RibD) represents a potential antibacterial drug target. The structure of recombinant Acinetobacter baumannii RibD is reported in orthorhombic and tetragonal crystal forms at 2.2 and 2.0 Å resolution, respectively. Comparisons with orthologous structures in the Protein Data Bank indicated close similarities. The tetragonal crystal form was obtained in the presence of guanosine monophosphate, which surprisingly was observed to occupy the adenine-binding site of the reductase domain.


Excessive blood loss and its relationship to clotting system changes during and after major surgery.
The massively hemorrhaging patient still remains one of the major problems that can be faced by the general surgeon. This article attempts to summarize the biophysiology of this process in an intuitively understandable manner that has direct clinical applications.


Catel-Manzke Syndrome: Further Delineation of the Phenotype Associated with Pathogenic Variants in TGDS.
Catel-Manzke syndrome is a rare autosomal recessive disorder characterized by Pierre Robin sequence with hyperphalangy and clinodactyly of the index finger. Recently, homozygous or compound heterozygous pathogenic variants in TGDS have been discovered to cause Catel-Manzke syndrome. Here, we describe a 12-month-old male with molecularly confirmed Catel-Manzke syndrome who presented with Pierre Robin sequence (but without cleft palate) and hyperphalangy, and we compare his phenotype with the seven previously described patients with pathogenic variants in TGDS. Our patient is on the severe end of the phenotypic spectrum, presenting with respiratory complications and failure to thrive. Furthermore, our finding of a homozygous p.Ala100Ser pathogenic variant in our patient supports that it is a common mutation in Catel-Manzke syndrome.


Doppler ultrasonographic assessment of uterine arteries during normal canine puerperium.
The aim of this study was to describe Doppler ultrasonographic changes of uterine arteries during normal canine puerperium. Eight healthy, pure-bred bitches, were ultrasonographically assessed during the postpartum period on Days -3, 3, 10, 17, 24, 38, 52 and 80 (Day 0 defined as the day of parturition). Total horn diameters (TD) and endometrium thickness (E) were evaluated. Color Doppler was used to localize uterine arteries at both sides of the body and pulsed-wave Doppler was performed to obtain the waveforms. Peak systolic velocity (PSV) and end diastolic velocity (EDV) were measured. Resistance index [(PSV-EDV)/PSV] was automatically calculated. Values of TD, E, PSV, EDV and RI were analyzed by repeated measures ANOVA followed by LSD test (SPSS 18.0; SPSS, Chicago, IL, USA). A correlation analysis was also carried out between RI and TD. A progressive decrease of TD (P<0.01) and E (P<0.01) was found in the course of the study. A gradual diminution of PSV (P<0.01) and EDV (P<0.01) and an increase of RI (P<0.01) were also found throughout the study period. The resistance index negatively correlated with TD (r=-0.46; P<0.01) and E (r=-0.44; P<0.01) while the ultrasonographic and vascular changes in this period are concurrent with regenerative changes in the glandular and epithelial structures of the uterus. It is concluded that uterine artery RI progressively increased during normal canine puerperium, associated to the two-dimensional ultrasonographic regression of the organ.


Counterregulation in female obese emotional eaters: Schachter, Goldman, and Gordon's (1968) test of psychosomatic theory revisited.
In a sample of 31 obese women, the moderating role of restrained, emotional, and external eating (as was measured by the DEBQ) on the relationship between food deprivation and food intake was studied by examining the prediction of grams of cookies eaten by the preload and degree of restrained, external, and emotional eating interactions. In addition, the main effects of each type of eating behaviour on food intake was studied, and also whether any of the effects were attenuated when variance associated with the other types of eating behaviour was partialled out. Emotional eating was found to moderate the relationship between food intake and food deprivation, and this effect became even more pronounced when the variance associated with external eating was removed. Instead of eating less after a preload, emotional eaters ate more, suggesting a counter regulatory eating pattern of female obese emotional eaters. Further, also the main effect of emotional eating on food intake was significant. Both results suggest support for psychosomatic theory.


Esketamine in treatment-resistant depression patients comorbid with substance-use disorder: A viewpoint on its safety and effectiveness in a subsample of patients from the REAL-ESK study.
Esketamine, the S-enantiomer of ketamine, has recently emerged as a therapy for treatment-resistant depression (TRD), showing both rapid antidepressant action and good efficacy and high safety. It is also indicated for the acute short-term treatment of psychiatric emergency due to major depressive disorder (MDD) and for depressive symptoms in adults with MDD with acute suicidal thoughts/behavior. We here provide preliminary insights on esketamine nasal spray (ESK-NS) effectiveness and safety among patients with a substance use disorder (SUD) within the sample of patients with TRD collected for the observational, retrospective, multicentre REAL-ESK study. Twenty-six subjects were retrospectively selected according to the presence of a SUD in comorbidity. Subjects enrolled completed the three different follow-up phases (T0/baseline, T1/after one month, and T2/after three months) and there were no dropouts. A decrease in Montgomery-Asberg depression rating scale (MADRS) scores was recorded, thus highlighting the antidepressant efficacy of ESK-NS (MADRS decreased from T0 to T1, t = 6.533, df=23, p<0.001, and from T1 to T2, t = 2.029, df=20, p = 0.056). Considering tolerability and safety issues, one or more side effects were reported by 19/26 subjects (73%) after treatment administration. All reported side effects were time-dependent and did not cause significant sequelae; among them, dissociative symptoms (38%) and sedation (26%) were the most frequently reported. Finally, no cases of abuse or misuse of ESK-NS were reported. Despite study limitations related to the inherent nature of the study, a limited number of patients, and a short follow-up period, ESK-NS showed to be effective and safe in patients diagnosed with TRD comorbid with a SUD.


Development of a novel chitosan-based two-photon fluorescent nanoprobe with enhanced stability for the specific detection of endogenous H2O2.
Hydrogen peroxide (H2O2) acts as an important reactive oxygen species (ROS) and maintains the redox equilibrium in organisms. Imbalance of H2O2 concentration is associated with the development of many diseases. Traditional small molecular based fluorescent probes often show drawbacks of cytotoxicity and easily metabolic clearance. Herein, a chitosan-based two-photon fluorescent nanoprobe (DC-BI) was constructed and applied for H2O2 detection in live organisms. DC-BI was composed by chitosan nanoparticles and a two-photon fluorophore of naphthalimide analogues (BI) with H2O2-responsive property. The structure of DC-BI was characterized by NMR, FTIR, XPS, XRD, DLS and MLS analyses. As study shown, the nanoprobe DC-BI exhibited improved distribution stability and smaller cytotoxicity. In the presence of H2O2, both the absorption and emission spectra show dramatic changes, the fluorescence intensity at 580 nm obviously enhanced. Furthermore, fluorescence imaging results indicate that DC-BI is capable of imaging endogenous H2O2 in cells and zebrafish. The design and development of chitosan-based nanoprobe DC-BI has provided a general example of nanoprobe construction with excellent distribution stability, two-photon property, and biocompatibility.


Determination of linear expansion of AlSi10Mg aluminium alloy depending on external conditions during solidification.
The article deals with the possibility of influencing the properties of aluminium alloy castings by changing the external conditions during solidification. Due to the high demands of customers, influencing the resulting microstructure is an important process in the production of castings. When casting an aluminium alloy into a metal mould, the mould must be preheated to a high temperature. For this reason, the key parameter of production is the mastery of the control of the resulting microstructure of castings and the related internal quality and mechanical properties, which are subject to high demands defined by international standards. The aim of the experiment is to evaluate the influence of different preheating of the metal mould on the resulting structure of test castings made of AlSi10Mg material and its subsequent thermal expansion. It is hypothesized that as the temperature of the mould preheating increases, the mechanical properties will deteriorate and the expansion of the alloy will increase. In the case of immediate use of castings after production, this could have a negative impact on the service life and safety of entire assembled components. All measured results will be put into comparison and direct connections between the data will be searched using the microsoft excel program.


Athymic rat model for studying acellular human allograft.
Although human acellular nerve allograft is a promising nerve repair tool, optimizing graft application and understanding effective graft dimensions has been hampered by lack of an appropriate animal model. Rodent nerve acellular allograft can be tested in the utilitarian rodent nerve repair model, but testing different size options is limited by the size of the rodent donor animal. Human acellular nerve allograft offers the variety of sizes desired for more complete study but poses a high risk of rejection as xenograft tissue in the rodent model. Athymic nude rats are less prone to reject xenograft tissue due to their immunocompromised state and may offer an animal model for testing human acellular allograft. Fifteen athymic nude and 15 Sprague-Dawley rats underwent unilateral excision and repair of a 10mm tibial nerve segment using 10mm of human acellular nerve graft. Testing at 3 months consisted of muscle force measurements, wet muscle weight, and histological assessment from the middle of the nerve grafts. Athymic rats repaired with human acellular xenograft demonstrated higher reinnervated muscle weight Gross inspection of the xenograft in euthymic rats revealed a brown and scarred center and histological inspection demonstrated larger axon diameters, and higher midgraft axon counts in the grafts of athymic rats. The athymic rat has been used in many studies that require an immunocompromised host, including implantation of foreign nervous tissue. Previous attempts at implanting acellular nerve xenograft into immunocompetent rats have yielded suboptimal results when compared to allograft. This study is the first to test acellular human nerve allograft in an athymic rat. The nerve regeneration was better in human acellular nerve allograft implanted into immunocompromised athymic rats when compared to euthymic rats supporting a potential role of this model in studying acellular human nerve tissue.


Identification of novel benzimidazole derivatives as highly potent AMPK activators with anti-diabetic profiles.
Diabetes is a global healthcare problem that affects more than 400 million people worldwide. Treatment for type 1 and 2 diabetes is expected by targeting adenosine monophosphate activated protein kinase, AMPK, a well-known master regulator of glucose. Many pharmaceutical companies have tried to identify AMPK activators but few direct AMPK activators with high potency for the β2-AMPK isoform, which is important for glucose homeostasis, have been found. In addition, their chemical structure is limited to benzimidazole or indole derivatives bearing an aromatic substituent at the C5 position of the core structure. We describe herein our efforts to identify novel benzimidazole derivatives that directly activate the β2-AMPK isoform. Our newly designed activator 14d bearing a 1-amino indanyl moiety at the C5 position of the core exhibited high in vitro potency and good pharmacokinetic profiles. A single oral dosing of 14d showed dose-dependent activation of AMPK and blood-glucose-lowering effects was observed in a diabetic animal model. In addition, chronic AMPK activation with 14d led to dose-dependent reduction in HbA1c of the animal model.


Correlation among academic performance, recurrent abdominal pain and other factors in Year-6 urban primary-school children in Malaysia.
The present study aimed to investigate the extent to which recurrent abdominal pain and other factors were associated with academic achievement among Year-6 (12 years of age) schoolchildren. The present study was a cross-sectional survey conducted from September to November 2001. Schoolchildren were recruited from primary schools that were selected randomly from a list of all primary schools in Petaling Jaya, Malaysia, using random sampling numbers. Information concerning recurrent abdominal pain, socio-economic status, life events, demographic and other details was obtained using a combination of questionnaires and interviews. Academic achievement was assessed using a score based on the Malaysian Primary School Achievement Examination. An overall score at or above the mean was taken to indicate high academic achievement while a score below the mean indicated poor academic achievement. A total of 1971 children were studied (958 boys and 1013 girls: 1047 Malays, 513 Chinese and 411 Indians). Of these children, 456 (23.1%) fulfilled the criteria for recurrent abdominal pain. Using the method of binary logistic regression analysis, the following factors were found to be independently associated with poor academic performance: a low socio-economic status (odds ratio (OR) 1.30; 95% confidence interval (CI) 1.25-1.35); male sex (OR 1.61; 95% CI 1.26-2.05); the death of a close relative (OR 2.22; 95% CI 1.73-2.85); the divorce or separation of parents (OR 3.05; 95% CI 1.73-5.40); the commencement of work by the mother (OR 1.34; 95% CI 1.02-1.76); hospitalization of the child in the 12 months prior to the study (OR 1.83; 95% CI 1.12-3.01); lack of health-care consultation (OR 1.80; 95% CI 1.36-2.36); missing breakfast (OR 1.47; 95% CI 1.07-2.02); and lack of kindergarten education (OR 1.35; 95% CI 1.04-1.75). Many factors, such as socio-economic status and recent life events, were associated with poor academic performance. Recurrent abdominal pain did not correlate directly to academic performance. Stress may be a means by which various factors cause children to struggle academically.


Radiochemotherapy in the management of pancreatic cancer--part I: neoadjuvant treatment.
In pancreatic cancer, complete resection offers the only hope of cure, but results of surgery alone are suboptimal. Many studies have been conducted in which the treatment regimen consists of surgery in combination with radiation and chemotherapy to improve local control and outcome. Neoadjuvant chemoradiotherapy is a fairly recent approach that appears to be feasible in resectable and locally advanced pancreatic cancer. In resectable tumors, chemoradiation therapy has been shown to be at least as effective in a neoadjuvant setting as in an adjuvant setting. Neoadjuvant therapy offers a few theoretical advantages: (1) beginning the multimodality treatment with chemoradiation therapy increases the chance that more patients will receive all of its components; (2) preoperative chemoradiation therapy provides an observation period to exclude from surgical resection those patients with rapidly progressive disease; and (3) in locally advanced tumors, it provides the opportunity for downstaging and infrequently allows patients to undergo resection. To evaluate the scope and applicability of neoadjuvant treatment, a number of areas need to be addressed. First, the definition of locally advanced disease needs to be more adequately standardized because the resectability definition sometimes varies among surgeons. In addition, because imaging examinations may underestimate the effectiveness of preoperative chemoradiation therapy, some researchers have tried to evaluate treatment response via a pathological examination of the tumor specimen; however, complete pathological response appears to be rare. Finally, more efficient novel neoadjuvant approaches are required to address the high metastatic potential of pancreatic cancer. These areas are discussed in depth.


[Structural abnormalities of the Y chromosome. Observations in ten cases].
The authors report ten cases of structural anomalies involving the Y chromosome: five cases of a dicentric Y chromosome, one ring Y chromosome, one case of a Y isochromosome containing the long arms, one deletion of the long arms (Yq-), one case of an abnormally long Y chromosome (Yq+) and one Y-autosome translocation. Analysis of clinical and chromosomal correlations, especially with respect to sexual differentiation, led to discussing the role of the Y chromosome.


Three Strategies to Overcome Data-Sharing Challenges to Improve the Social Determinants of Health.
This piece identifies and compares three examples of successful data sharing that sought to improve housing and health outcomes, ultimately improving the lives of vulnerable groups. Data strategists should first consider proving out the benefit in consultation with diverse stakeholders, mitigating legal risks from the beginning, and starting with a minimal data prototype.