Familial renal glycosuria: a genetic reappraisal of hexose transport by kidney and intestine.
Renal glucose titration studies were carried out in 10 members of two pedigrees with familial renal glycosuria to test the accepted hypothesis of autosomal dominant inheritance and to investigate the genetic significance of "type A" and "type B" renal glycosuria. In one family, a brother and sister each had a moderately reduced threshold and tubular maximum for glucose (type A), but both of their parents reabsorbed glucose normally. In the second family, two brothers had severe type A renal glycosuria, their mother and one brother had a mild type A defect, and another brother demonstrated a reduced threshold, an exaggerated splay, and a normal tubular maximum, indicative of type B glycosuria.Hexose transport by intestinal mucosa was also investigated in controls and in the three brothers with the most severe renal glycosuria. D-glucose-(14)C and 3-O-methylglucose-(14)C were accumulated by jejunal mucosa from controls by processes which were saturable and concentrative. No differences in hexose transport were observed in the patients with renal glycosuria. We conclude that familial renal glycosuria can be inherited as an autosomal recessive trait; that mild and severe type A renal glycosuria and type B renal glycosuria can occur in the same pedigree; and that defective reabsorption of glucose by the kidney need not be accompanied by abnormalities in intestinal glucose transport. These findings indicate that glucose transport in the gut and kidney are not mediated by identical mechanisms, and that several different mutations are responsible for the phenotypic variability in familial renal glycosuria.


Spontaneous Pneumomediastinum in a Healthy Young Male: A Case Report from Riyadh, Saudi Arabia.
Pneumomediastinum is defined as the presence of air in the mediastinum. Trauma to the nearby organs can cause air to escape into surrounding tissues that may manifest clinically as severe chest pain, voice change, or shortness of breath. However, pneumomediastinum can present spontaneously in healthy individuals with no inciting factors in which case the condition is termed spontaneous pneumomediastinum (SPM). Pneumomediastinum can be challenging to manage due to the absence of clear guidelines for the diagnosis and management. We present the case of a 21-year-old with no previous medical history who presented with chest pain that was aggravated by speech and breath. The pain was of sudden onset preceded by smoking at 2:00 am. The patient was tachycardic, tachypnoeic with crepitation on palpation and a crunch sound (Hamman's sign) on auscultation. The patient rated the pain as 5/10 on a 11-point numerical pain rating scale, which then evolved to 10/10. The patient did not have fever, loss of consciousness (LOC), diaphoresis, history of trauma, or previous similar presentation. There were no other associated symptoms. A chest X-ray (posteroanterior (PA) and lateral view) showed pneumomediastinum, but laboratory tests results were otherwise normal. The patient was observed in the emergency room overnight. He remained stable, his tachycardia settled, and there was no leukocytosis or desaturation; however, tachypnea was observed. His pain symptoms were treated with analgesia as needed and the patient was discharged home in a stable condition, to be followed on an outpatient basis. Spontaneous pneumomediastinum can be challenging to manage due to the lack of reliable incidence data as well as the absence of clear management guidelines. Further research will aid in understanding the true incidence of SPM in Saudi Arabia and help in establishing a consensual approach and treatment guidelines to deal with SPM in otherwise healthy individuals. To the best of our knowledge, this is the first case of SPM in a young male reported from a tertiary hospital in Riyadh, Saudi Arabia.


Differential effects of omega-conotoxin GVIA and MVIIC on nerve stimulation induced contractions of guinea-pig ileum and rat vas deferens.
omega-Conotoxin GVIA and omega-conotoxin MVIIC caused similar concentration-dependent reductions of the electrically induced twitch responses of guinea-pig ileum. The inhibitory effects of omega-conotoxin GVIA were long-lasting whereas those to omega-conotoxin MVIIC were readily reversed. Preincubation with omega-conotoxin MVIIC prevented the irreversible inhibition of omega-conotoxin GVIA suggesting a common site of interaction. However, unlike omega-conotoxin GVIA which caused inhibition, omega-conotoxin MVIIC did not affect the electrically induced twitch responses of the rat vas deferens nor did it prevent the irreversible inhibition with omega-conotoxin GVIA. This study indicates the possible existence of different subtypes of the N-type voltage-dependent calcium channel.


A comprehensive evaluation of polygenic score and genotype imputation performances of human SNP arrays in diverse populations.
Regardless of the overwhelming use of next-generation sequencing technologies, microarray-based genotyping combined with the imputation of untyped variants remains a cost-effective means to interrogate genetic variations across the human genome. This technology is widely used in genome-wide association studies (GWAS) at bio-bank scales, and more recently, in polygenic score (PGS) analysis to predict and stratify disease risk. Over the last decade, human genotyping arrays have undergone a tremendous growth in both number and content making a comprehensive evaluation of their performances became more important. Here, we performed a comprehensive performance assessment for 23 available human genotyping arrays in 6 ancestry groups using diverse public and in-house datasets. The analyses focus on performance estimation of derived imputation (in terms of accuracy and coverage) and PGS (in terms of concordance to PGS estimated from whole-genome sequencing data) in three different traits and diseases. We found that the arrays with a higher number of SNPs are not necessarily the ones with higher imputation performance, but the arrays that are well-optimized for the targeted population could provide very good imputation performance. In addition, PGS estimated by imputed SNP array data is highly correlated to PGS estimated by whole-genome sequencing data in most cases. When optimal arrays are used, the correlations of PGS between two types of data are higher than 0.97, but interestingly, arrays with high density can result in lower PGS performance. Our results suggest the importance of properly selecting a suitable genotyping array for PGS applications. Finally, we developed a web tool that provides interactive analyses of tag SNP contents and imputation performance based on population and genomic regions of interest. This study would act as a practical guide for researchers to design their genotyping arrays-based studies. The tool is available at: https://genome.vinbigdata.org/tools/saa/ .


Landscape epidemiology of emerging infectious diseases in natural and human-altered ecosystems.
A central challenge to studying emerging infectious diseases (EIDs) is a landscape dilemma: Our best empirical understanding of disease dynamics occurs at local scales, whereas pathogen invasions and management occur over broad spatial extents. The burgeoning field of landscape epidemiology integrates concepts and approaches from disease ecology with the macroscale lens of landscape ecology, enabling examination of disease across spatiotemporal scales in complex environmental settings. We review the state of the field and describe analytical frontiers that show promise for advancement, focusing on natural and human-altered ecosystems. Concepts fundamental to practicing landscape epidemiology are discussed, including spatial scale, static versus dynamic modeling, spatially implicit versus explicit approaches, selection of ecologically meaningful variables, and inference versus prediction. We highlight studies that have advanced the field by incorporating multiscale analyses, landscape connectivity, and dynamic modeling. Future research directions include understanding disease as a component of interacting ecological disturbances, scaling up the ecological impacts of disease, and examining disease dynamics as a coupled human-natural system.


Most common oral alterations in the elderly--a review.
The population of Brazil is experiencing a fast and progressive aging process. Oral mucosa, which has a function as a barrier, is compromised by the aging process, allowing the action of predisposing agents. The older the population, the greater is the prevalence of lesions in oral mucosa. The causes may be neoplastic, infectious, bone pathologies, oral manifestations of systemic diseases, nutritional deficiencies, dental prostheses, medicaments, and bullous diseases, among others. Examination of the oral cavity should be carried out as an annual routine, and as a preventive measure for the entire elderly population, in order to reduce the morbidity and mortality from these diseases.


Self-assembled chitosan nanotemplates for biomineralization of controlled calcite nanoarchitectures.
Three-dimensional chitosan self-assembled nanostructures are reported whose morphology can be adjusted by tuning of the processing parameters, including the rate of solvent removal, the surface roughness of the substrate, and the polarity of the solvent used. Upon this, chitosan nanostructures of more interesting morphology and even higher complexity can be prepared, which can serve as nanotemplates for subsequent biomineralization of calcium carbonate, leading to controllable three-dimensional biominerals having the same complex morphology as that exhibited by the self-assembled chitosan nanotemplates.


Cell proliferation in the forebrain and midbrain of the adult bullfrog, Rana catesbeiana.
The distribution of proliferating cells in the midbrain, thalamus, and telencephalon of adult bullfrogs (Rana catesbeiana) was examined using immunohistochemistry for the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) and DNA dot-blotting. At all time points examined (2 to 28 days post-injection), BrdU-labeled cells were located in ventricular zones at all levels of the neuraxis, but with relatively more label around the telencephalic ventricles. Labeled cells, some showing profiles indicative of dividing and migrating cells, were present in brain parenchyma from 7 to 28 days post-injection. These labeled cells were particularly numerous in the dorsal and ventral hypothalamus, preoptic area, optic tectum, and laminar and principal nuclei of the torus semicircularis, with label also present, but at qualitatively reduced levels, in thalamic and telencephalic nuclei. Double-label immunohistochemistry using glial and early neural markers indicated that gliogenesis and neurogenesis both occurred, with new neurons observed particularly in the hypothalamus, optic tectum, and torus semicircularis. In all brain areas, many cells not labeled with BrdU were nonetheless labeled with the early neural marker TOAD-64, indicating that these cells were postmitotic. Incorporation of DNA measured by dot-blotting confirms the presence of DNA synthesis in the forebrain and brainstem at all time points measured. The pattern of BrdU label confirms previous experiments based on labeling with (3)H-thymidine and proliferating cell nuclear antigen showing cell proliferation in the adult ranid brain, particularly in hypothalamic nuclei. The consistent appearance of new cells in the hypothalamus of adult frogs suggests that proliferative activity may be important in mediating reproductive behaviors in these animals.


Capsaicin receptor VR1 and ATP purinoceptor P2X3 in painful and nonpainful human tooth pulp.
To investigate the levels of the capsaicin or vanilloid receptor-1 (VR1) and the ATP-gated purinoceptor P2X3 in painful and nonpainful human tooth pulps. Immunohistochemistry with specific antibodies and image analysis was used to quantify VR1- and P2X3-positive nerve fibers in painful (n = 13) and nonpainful (n = 33) human tooth pulps, and VR1 immunoreactivity was compared with immunoreactivity for the structural neuronal marker peripherin. Strong VR1-like immunoreactivity was documented for the first time in dental pulp neurons. Weaker P2X3-like immunoreactivity was also detected in fewer nerve fibers. The ratio of VR1 to peripherin immunoreactivity was not significantly different between nonpainful and painful tissues (mean +/- SE% area of VR1 to peripherin; nonpainful 53.4 +/- 4.7%, n = 33; pulpitis 35.1 +/- 7.1%, n = 13; P = .07). The presence of VR1 and P2X3 in fibers of human tooth pulp suggest that they may play a role in perception of dental pain, but further studies, including quantitation of their ligands, are necessary to elucidate any role they may play in pathophysiologic states.


Proteoglycan expression by human trabecular meshworks.
Proteoglycans may serve important roles in trabecular meshwork structure or function. Detailed molecular characterization and identification of specific trabecular proteoglycan core proteins has been limited. Radiolabeled proteoglycans were extracted from cultured human trabecular meshworks and subjected to ion exchange and molecular sieve chromatography. Peaks were subjected to glycosaminoglycan content analysis. Reverse transcription with polymerase chain reaction was used to identify trabecular mRNAs of several common proteoglycan core proteins. Western immunoblots of trabecular extracts were also utilized to identify these proteoglycan core proteins. The proteoglycans elute from ion exchange columns at high salt and molecular sieve column profiles, and they exhibit broad peaks typical of the proteoglycan microheterogeneity seen in other tissues. The four common glycosaminoglycan side-chains were identified on these proteoglycans. Trabecular cells in organ or cell culture contain mRNAs coding for decorin, biglycan, versican, perlecan and a basement membrane glycoprotein, SPARC. Syndecan-1 transcripts were present at very low levels, while aggrecan transcripts were not detectable. Decorin, biglycan, versican and perlecan core proteins were also identified by immunoblots of trabecular cell extracts. Several common proteoglycans are expressed by trabecular cells in organ explant or cell culture. Their general characteristics are not unlike those found in other tissues. These proteoglycans may serve important functions in the trabecular outflow pathway.


A numerical study of the electrostatic properties of two finite-width charged dielectric slabs in water.
A numerical algorithm based on the image charge method is introduced to calculate the electrostatic potential, energy, and forces present in systems involving multiple point charges embedded in an inhomogeneous dielectric environment composed of five parallel dielectric slabs. The methodology is implemented within Monte Carlo simulations to calculate the thermal properties of two charged dielectric plates of finite thickness immersed in water.


Maternal microbiota and antibodies as advocates of neonatal health.
Mammalian body surfaces are inhabited by vast numbers of microbes, the commensal microbiota, which help the host to digest food, provide nutrients, and mature its immune system. For a long time, postnatal colonization was believed to be the main stimulus for microbial-induced immune development. Using a model of reversible colonization of germ-free mice during gestation, we recently showed that the microbial shaping of the neonatal immune system begins even before birth through molecular signals derived from the microbiota of the mother. Maternal microbiota was important to mature intestinal innate immune cells and to alter intestinal gene expression profiles in the offspring. These changes prepare the newborn for postnatal colonization. The majority of the gestational colonization-dependent effects required maternal antibodies. Here, we discuss and provide further evidence how maternal antibodies are important players in transferring a signal originating from the maternal intestinal microbiota to the offspring.


Hypoxic fraction determinations with the BA1112 rat sarcoma: variation within and among assay techniques.
Measurement of the hypoxic fraction in the same tumor system by different assay techniques often gives incompatible results. The hypoxic fraction of the BA1112 sarcoma has been measured by three assay techniques: tumor control and growth delay assays in which the tumors remain in situ after irradiation, and paired survival curve assays in which the tumors are excised after irradiation. The assays were done with and without anesthesia on tumors growing in two different subcutaneous sites. Anesthesia of the hosts produced a statistically significant decrease in the calculated hypoxic fraction in a tumor control assay, but not in a paired survival assay. The excision assays gave consistently higher hypoxic fraction estimates than either the tumor control or growth delay assays. Some of the factors which could produce higher hypoxic fractions in excision assays than in in situ assays are discussed. Interpretation of the results was complicated by disagreements between the growth delay and tumor control assays, and by disparities between replicate determinations. The discrepancies among assays are caused almost entirely by variations in the response of the artificially hypoxic tumors, rather than variations in the response of aerobic tumors. These results indicate that assumptions commonly made when measuring hypoxic fractions may not be valid.


Genotypic and pathogenic characterization of genotype VII Newcastle disease viruses isolated from commercial farms in Egypt and evaluation of heterologous antibody responses.
Newcastle disease viruses (NDV) represent a major threat to poultry production worldwide. Recently in Egypt NDV circulated extensively, even in vaccinated farms. In the present study samples were collected from sixteen vaccinated broiler farms in animals exhibiting the typical gross lesions of NDV. Virus isolation and pathogenicity studies for positive samples were carried out in accordance to reference procedures and phylogenetic analysis was carried out based on partial sequences of the Fusion gene. Furthermore, in vivo investigation of the ability of heterologous antibody, induced by commercially available lentogenic strain-based vaccines, to efficiently reduce viral shedding was examined. Results revealed that all the sixteen farms were positive for the presence of NDV. Out of these fifteen were confirmed to due to velogenic viruses, based on a main death time (MDT) ≤ 48 hours and partial sequencing of the F gene that showed the presence of a polybasic amino acid motif. However, three patterns in the cleavage site of these velogenic viruses were identified in the present study. Phylogenetic analysis revealed that all fifteen isolates were clustered with class II genotype VIIb while the remaining isolate (B81) was class II genotype II. Results of the in vivo study revealed that adequate heterologous antibody levels, induced by the proposed vaccination program, sufficiently protected birds from morbidity and mortality. However, virus shedding was quantitatively affected in relation to the time of challenge after vaccination. Altogether, with an absence of vaccines able to induce homologous antibody to the presently circulating viruses, higher antibody levels, which depend on efficient and timely implementation of the vaccination program, are considered as highly important in relation to the reduction of virus shedding.


Visual Representations of Sexual Violence in Online News Outlets.
To study visual representations of sexual violence, photographs accompanying German Internet news articles that appeared between January 2013 and March 2015 (N = 42) were subjected to thematic analysis. Two main themes, consisting of several sub-themes, emerged from the data. The first theme was "rape myths," illustrating a stereotypical view of sexual violence. It consisted of three sub-themes: "beauty standards," referring to the fact that all women in our sample fit western beauty standards, "physical violence," as most images implied some form of physical violence, and finally "location," suggesting that rape only happens in secluded outdoor areas. These findings suggest that the images from our sample perpetuate certain rape myths. The second theme was "portrayal of victimhood," referring to the way victims of sexual violence were portrayed in photographs. The analysis of the sub-theme "passivity" showed that these portrayals fit a certain stereotype: the women were shown to be weak and helpless rather than individuals with agency and able to leave their status as a victim. Further sub-themes were "background," "organization of space," "camera perspective," and "lighting." We discuss these findings in relation to possibly reinforcing rape myths in society and as an issue in creating a biased perception of women who have experienced sexual violence.


Periodically Patterned Au-TiO2 Heterostructures for Photoelectrochemical Sensor.
Periodically patterned Au nanorods in TiO2 nanocavities (Au NRs@TiO2) were fabricated via magnetron sputtering followed by a thermal dewetting process. This innovative Au NRs@TiO2 heterostructure was used as a plasmonic sensing platform for photoelectrochemical detection of glucose and lactose. This Au NRs@TiO2 patterned heterostructure possesses superior sensing properties to other Au nanoparticle-based sensors because (i) localized surface plasmon resonance (LSPR) generated at Au/TiO2 interfaces enhanced sensitivity of glucose (lactose) amperometric detection; (ii) periodic Au nanocrystals in TiO2 nanocavities accelerated charge separation and transfer rate, especially under monochromatic blue light irradiation; (iii) discrete planar architectures comprising Au NRs immobilized on TiO2 substrates significantly improved stability and reusability of the sensors. A low detection limit of 1 μM (10 μM) and a high sensitivity of 812 μA mM-1 cm-2 (270 μA mM-1 cm-2) were achieved on the Au NRs@TiO2 heterostructures for glucose (lactose) detection without the addition of enzymes. Good selectivity and superb stability over more than 8 weeks was also demonstrated using these Au NRs@TiO2 heterostructures for glucose (lactose) detection. Additionally, this cost-efficient technique can be easily extended to other photoelectrochemical sensing systems when considering the combination of sensing and visible or infrared light source enhancement.


[Rational use of antibiotics in severe acute pancreatitis:controversy and progress].
Infection of pancreatic necrosis is the most frequent cause of late mortality in severe acute pancreatitis(SAP). Most clinical guidelines of acute pancreatitis recommended that prophylactic antibiotics should be avoided. Prophylactic antibiotics can not reduce the pancreatic infection rate or mortality in patients with SAP ornecrotizing pancreatitis. Definitive infection is the only indication for rational use of antibiotics in SAP patients. Broad-spectrum antibiotics for treatment should cover enteric bacteria, and the bacteriology and antibiotic pharmacokinetics of SAP should be considered when selecting antibiotics.


Taking a sexual history: the role of the nurse.
Patients' sexual health and well-being are important considerations for nursing practice in many clinical areas, but particularly for gynaecology nurses. This article discusses the problems many nurses encounter when taking a sexual history, and concentrates on the support and needs of gynaecology nurses. A survey to establish the practice of taking sexual histories by gynaecology nurses in different hospital departments is described. The results of the survey suggest that gynaecology nurses need clear guidelines and policies for sexual history-taking, supported by education and training.


Dentists' lived experience of providing dental care during the COVID-19 pandemic: A qualitative study in Mashhad, Iran.
This study aimed to explore the lived experiences of dentists practicing in Mashhad, Iran, during the COVID-19 pandemic and identify possible influencing factors for providing dental health in this era. Sixteen dentists took part in this qualitative phenomenological study. Semi-structured face-to-face interviews were performed and evaluated using a qualitative content analysis approach. The MAXQDA program (2020) was used to code and classify the data. Purposive sampling, audio recording, member checking, and peer review were employed to verify transferability, reliability, and validity. The interview transcripts were transcribed, and sentences and remarks relevant to the study's goal were retrieved and classified. Six hundred twenty-eight codes were extracted after several readings of the texts. Five core themes and fourteen sub-themes were determined after deleting repeated themes and axial coding. The main five themes included: "Coping with the COVID-19 pandemic", "Alternations in providing dental care," "Infection control," "COVID-19-related news and information sources", and "Positive and negative aspects of COVID-19 in dental care ". During the COVID-19 pandemic, dentists noted various challenges in delivering routine dental treatment, including a lack of resources, reliable and straightforward guidelines for dentists, and governmental policies for dental facility restrictions. Dentists concluded that financial, educational, and financial support from the government would significantly enhance the delivery of community dental care services. With the right strategies and lessons learned, dentists may be better prepared for future challenges in global health care.


The well-tempered auxiliary-field Monte Carlo.
The auxiliary-field Monte Carlo (AFMC) is a method for computing ground-state and excited-state energies and other properties of electrons in molecules. For a given basis set, AFMC is an approximation to full-configuration interaction and the accuracy is determined predominantly by an inverse temperature "beta" parameter. A considerable amount of the dynamical correlation energy is recovered even at small values of beta. Yet, nondynamical correlation energy is inefficiently treated by AFMC. This is because the statistical error grows with beta, warranting increasing amount of Monte Carlo sampling. A recently introduced multi-determinant variant of AFMC is studied, and the method can be tuned by balancing the sizes of the determinantal space and the beta-parameter with respect to a predefined target accuracy. The well-tempered AFMC is considerably more efficient than a naive AFMC. As a welcome "byproduct" low lying excitation energies of the molecule are supplied as well. We demonstrate the principles on dissociating hydrogen molecule and torsion of ethylene where we calculate the (unoptimized) torsional barrier and the vertical singlet-triplet splitting.


Recurrent Dystrophic Calcification of the Prostatic Resection Cavity After Transurethral Resection of the Prostate: Clinical Presentation and Endoscopic Management.
Background: Dystrophic calcification (DC) can occur as a reaction to tissue damage and necrosis. So far, this has never been described as a complication after conventional transurethral resection of the prostate (TURP). Case Presentation: We report on a 59-year-old man who underwent uncomplicated monopolar TURP for lower urinary tract symptoms caused by benign prostatic hyperplasia. The patient showed an excellent course up to 5 weeks after the initial operation. Afterward he suffered from a rapid onset of irritative and obstructive voiding symptoms and pain. Complete DC of the prostatic resection cavity was found by cystoscopy and recurred quickly twice after Re-TURP despite anti-inflammatory treatment and normal urinary and metabolic findings. Complete recovery was only achieved by gently scraping off the calcifications avoiding further trauma to the residual prostatic tissue. Conclusion: In rare cases, delayed occurrence of irritative and obstructive voiding symptoms after TURP can be caused by DC of the prostatic resection cavity and might be misinterpreted as post-TURP infection. The pathomechanism of DC and the presented case suggest minimizing tissue trauma by cautious removal of calcifications rather than performing extensive Re-TURP.


[Application of multiple tissue expanders for repair of facial and neck scar].
To repair facial and neck scar using tissue expanding technique. From January 1991 to January 1995, 16 cases with facial and neck scar were treated. Multiple tissue expanders were put under the normal skin of facial and neck area, after being fully expanded, the scars were excised and the expended skin flaps were transplanted to cover the defects. The size and number of tissue expanders were dependent on the location of the scars. Normally, 5 to 6 ml expanding volume was needed to repair 1 cm2 facial and neck defect. The incisions should be chosen along the cleavage lines or in the inconspicuous area, such as the nasolabial fold or submandibular region. The design of flap was different in the face and in the neck. In the face, direct advanced flap was most common used, whereas in the neck, transposition flap was often used. Appropriate tension was needed to achieve smooth and cosmetic effect. It was compared the advantages and disadvantages of several methods for repair of the defect after facial and neck scar excision. Fifteen cases had no secondary deformity after scar excision. Among them, 1 case showed blood circulation disturbance and cured through dressing change. Ten cases were followed up and showed better color and texture in the flap, and satisfactory appearances. Tissue expanding technique is the best method for the repair of facial and neck scar, whenever there is enough expandable normal skin.


Mesoporous Fluorinated Metal-Organic Frameworks with Exceptional Adsorption of Fluorocarbons and CFCs.
Two mesoporous fluorinated metal-organic frameworks (MOFs) were synthesized from extensively fluorinated tritopic carboxylate- and tetrazolate-based ligands. The tetrazolate-based framework MOFF-5 has an accessible surface area of 2445 m(2) g(-1), the highest among fluorinated MOFs. Crystals of MOFF-5 adsorb hydrocarbons, fluorocarbons, and chlorofluorocarbons (CFCs)-the latter two being ozone-depleting substances and potent greenhouse species-with weight capacities of up to 225%. The material exhibits an apparent preference for the adsorption of non-spherical molecules, binding unusually low amounts of both tetrafluoromethane and sulfur hexafluoride.


Expression of microRNA in male reproductive tissues and their role in male fertility.
MicroRNA (miRNA) are small non-coding RNA, approximately 22 nucleotides in length, that regulate gene expression through their ability to bind to mRNA. The role of miRNA in cellular and tissue development is well documented and their importance in male reproductive tissue development is actively being evaluated. They are present in spermatogonia, Sertoli and Leydig cells within the testis and are present in mature spermatozoa, indicating roles in normal testicular development, function and spermatogenesis. Their presence in spermatozoa has led to postulations about the roles of male miRNA during early embryonic development after fertilisation, including chromatin restructuring and possible epigenetic effects on embryo development. MiRNAs are also present in body fluids, such as blood serum, milk, ovarian follicular fluid and seminal fluid. Circulating miRNAs are stable, and aberrant expression of cellular or extracellular miRNA has been associated with multiple pathophysiological conditions, the most studied being numerous forms of cancer. Considering that miRNAs are present in spermatozoa and in seminal fluid, their stability and the relatively non-invasive procedures required to obtain these samples make miRNAs excellent candidates for use as biomarkers of male reproduction and fertility. Biomarkers, such as miRNAs, identifying fertile males would be of financial interest to the animal production industry.


Process of Hypertrophic Scar Formation: Expression of Eukaryotic Initiation Factor 6.
Hypertrophic scar is one of the most common complications and often causes the disfigurement or deformity in burn or trauma patients. Therapeutic methods on hypertrophic scar treatment have limitations due to the poor understanding of mechanisms of hypertrophic scar formation. To throw light on the molecular mechanism of hypertrophic scar formation will definitely improve the outcome of the treatment. This study aimed to illustrate the negative role of eukaryotic initiation factor 6 (eIF6) in the process of human hypertrophic scar formation, and provide a possible indicator of hypertrophic scar treatment and a potential target molecule for hypertrophic scar. In the present study, we investigated the protein expression of eIF6 in the human hypertrophic scar of different periods by immunohistochemistry and Western blot analysis. In the hypertrophic scar tissue, eIF6 expression was significantly decreased and absent in the basal layer of epidermis in the early period, and increased slowly and began to appear in the basal layer of epidermis by the scar formation time. This study confirmed that eIF6 expression was significantly related to the development of hypertrophic scar, and the eIF6 may be a target molecule for hypertrophic scar control or could be an indicator of the outcomes for other treatment modalities.


Role of leukotriene receptor antagonists in the management of mild-to-moderate asthma.
To date the position of Leukotriene Receptor Antagonists (LTRAs) in asthma is not yet fully established. Recent asthma guidelines consider LTRAs as 'alternative' to low doses of inhaled corticosteroids (ICS) for treatment of patients with mild persistent asthma, while in Europe LTRAs are licensed as additional therapy to ICS. Our aim in this paper is to review comparative studies between ICS and antileukotrienes in mild to moderate asthma, looking at their efficacy on asthma outcomes and on patient expectations (compliance, quality of life, and safety). Some studies report a superior efficacy of ICS, while others, in particular in patients aged < 12 years, found no differences. When considering patients' expectations LTRAs seem to be superior, with higher compliance and quality of life. Even if no differences in adverse effects have been found between ICS and LTRAs, whose safety profiles are not different from placebo, some concerns exist on long term treatment with ICS, even at low doses, in children and postmenopausal women. For this reason, even if ICS are superior to LTRAs in controlling asthma outcomes and in improving pulmonary function, in children and elderly patients LTRAs can be considered an alternative to low-dose ICS.


A new perfusion system to reduce the burden of central-venous-line-associated bloodstream infections in neonates.
Central-venous-line-associated bloodstream infection (CLABSI) is a significant cause of morbidity and mortality in preterm infants. As there is large variation in the reported effect of multi-modal preventive strategies, it could be relevant to propose new additional strategies. To assess the impact of a new perfusion system on CLABSI rate. A before-and-after study was performed in infants born at <32 weeks of gestation or with birth weight <1500 g who required a multi-perfusion system connected to a central venous line. In the first 12-month period ('before'), the pre-existing perfusion system (multiple stopcocks) was used. An intervention period then occurred with implementation of a new perfusion closed system, without change in 'bundles' related to various aspects of central line care. During the second 12-month period ('after'), the CLABSI rate was assessed and compared with the pre-intervention period. In total, 313 infants were included in this study (before: N=163; after: N=150), and 46% had birth weight <1000 g. The change in perfusion system resulted in a significant decrease in CLABSI rate from 11.3 to 2.2 per 1000 catheter-days (P<0.001). The period was independently associated with an 88% reduction in the risk of CLABSI after implementation of the new perfusion system [odds ratio (OR) 0.12, 95% confidence interval (CI) 0.03-0.39; P<0.001]. The duration of central line use was also associated with CLABSIs (for each additional day: OR 1.05, 95% CI 1.02-1.07; P<0.001). Implementation of the new perfusion system was feasible in a large neonatal unit, and reduced the CLABSI rate soon after implementation.


Vibrational coherence of I2 in solid Kr.
Time-resolved coherent anti-Stokes Raman scattering, with a resolution of 20 fs, is used to prepare a broadband vibrational superposition on the ground electronic state of I2 isolated in solid Kr. The coherent evolution of a packet consisting of nu=1-6 is monitored for as many as 1000 periods, allowing a precise analysis of the material response and radiation coherence. The molecular vibrations are characterized by omega(e)=211.330(2) cm(-1), omega(e)x(e)=0.6523(6) cm(-1), omega(e)y(e)=2.9(1) x 10(-3) cm(-1); the dephasing rates at 32 K range from 110 ps for nu=1 to 34 ps for nu=6, with nu dependence: gamma(nu)=8.5 x 10(-3)+4.9 x 10(-4)nu2+2.1 x 10(-6)nu4 ps(-1). The signal amplitude is also modulated at omega(q)=41.56(3) cm(-1); which can be interpreted as coupling between the molecule and a local mode. The surprising implication is that this resonant local mode is decoupled from the lattice phonons, a finding that cannot be rationalized based on a normal-mode analysis.


Identification of fibronectin 1 (FN1) and complement component 3 (C3) as immune infiltration-related biomarkers for diabetic nephropathy using integrated bioinformatic analysis.
Immune cell infiltration (ICI) plays a pivotal role in the development of diabetic nephropathy (DN). Evidence suggests that immune-related genes play an important role in the initiation of inflammation and the recruitment of immune cells. However, the underlying mechanisms and immune-related biomarkers in DN have not been elucidated. Therefore, this study aimed to explore immune-related biomarkers in DN and the underlying mechanisms using bioinformatic approaches. In this study, four DN glomerular datasets were downloaded, merged, and divided into training and test cohorts. First, we identified 55 differentially expressed immune-related genes; their biological functions were mainly enriched in leukocyte chemotaxis and neutrophil migration. The CIBERSORT algorithm was then used to evaluate the infiltrated immune cells; macrophages M1/M2, T cells CD8, and resting mast cells were strongly associated with DN. The ICI-related gene modules as well as 25 candidate hub genes were identified to construct a protein-protein interactive network and conduct molecular complex detection using the GOSemSim algorithm. Consequently, FN1, C3, and VEGFC were identified as immune-related biomarkers in DN, and a related transcription factor-miRNA-target network was constructed. Receiver operating characteristic curve analysis was estimated in the test cohort; FN1 and C3 had large area under the curve values (0.837 and 0.824, respectively). Clinical validation showed that FN1 and C3 were negatively related to the glomerular filtration rate in patients with DN. Six potential therapeutic small molecule compounds, such as calyculin, phenamil, and clofazimine, were discovered in the connectivity map. In conclusion, FN1 and C3 are immune-related biomarkers of DN.


Dynamics in Quaternary Ionic Liquids with Non-Flexible Anions: Insights from Mechanical Spectroscopy.
The present work investigates how mechanical properties and ion dynamics in ionic liquids (ILs) can be affected by ILs' design while considering possible relationships between different mechanical and transport properties. Specifically, we study mechanical properties of quaternary ionic liquids with rigid anions by means of Dynamical Mechanical Analysis (DMA). We are able to relate the DMA results to the rheological and transport properties provided by viscosity, conductivity, and diffusion coefficient measurements. A good agreement is found in the temperature dependence of different variables described by the Vogel-Fulcher-Tammann model. In particular, the mechanical spectra of all the measured liquids showed the occurrence of a relaxation, for which the analysis suggested its attribution to a diffusive process, which becomes evident when the ion dynamics are not affected by the fast structural reorganization of flexible anions on a local level.


Amplified fragment length polymorphism (AFLP) fingerprinting of symbiotic fungi cultured by the fungus-growing ant Cyphomyrmex minutus.
A PCR-based fingerprinting technique based on amplified fragment length polymorphisms (AFLP) is used to screen symbiotic fungi of the fungus-growing ant Cyphomyrmex minutus for genetic differences. AFLP fingerprints reveal several fungal 'types' that (a) represent distinct clones propagated vegetatively by the ant, or (b) correspond to free-living fungi that may be acquired by the ant. Fungal types identified by AFLP fingerprints correspond to vegetative-compatibility groups established previously, suggesting that vegetative compatibility can be used as a crude indicator of genetic differences between fungi of C. minutus.


Depressive Symptoms and Associated Factors in a Rural Elderly Population: The MoVIES Project.
In a random population sample of 1,040 elderly persons participating in a community survey, subjects were screened for depressive symptoms using a modified Center for Epidemiological Studies-Depression Scale. About 10% reported five or more possible symptoms of depression present during 3 or more days of the previous week. Approximately 1% of the sample had a sufficient number of symptoms for a diagnosis of major depression, although severity, disability, and 2-week duration were not assessed. More depressive symptoms were found to be independently associated with the following: age, widowhood, and less education; general health and appetite self-rated as fair-to-poor; and a greater number of sleep problems, social support problems, and stressful life events in the previous year. Further, subjects with more depressive symptoms were significantly more likely to have been recently hospitalized and to have used home health and social services. These findings have implications for the public health importance of depressive symptomatology, even when subsyndromal, in older groups.


RX 821002 as a tool for physiological investigation of alpha(2)-adrenoceptors.
RX 821002 is the 2-methoxy congener of idazoxan. In binding and tissue studies it behaves as a selective antagonist of alpha(2)-adrenoceptors, with at least 5 times greater affinity for these receptors than any other binding site. It does not select between the different types of alpha(2)-receptor. Although this drug probably has no future as a therapeutic agent, it remains a good probe for physiological activity at alpha(2)-adrenoceptors in animal experiments. A particularly useful feature of this compound is its lack of binding at I(1) and I(2) imidazoline receptors. However, it has relatively high affinity for 5-HT(1A) receptors (at which it acts as an antagonist) and a tendency to behave as an inverse agonist at alpha(2A)-adrenoceptors in some cell culture systems. These potential drawbacks may be overcome by careful design of experiments, and the greater selectivity of RX 821002 renders it much superior to yohimbine or idazoxan as a tool for probing physiological actions at alpha(2)-receptors. It can be compared favorably with other selective antagonists such as atipamezole. In physiological studies, RX 821002 augments norepinephrine release in the frontal cortex and increases drinking behavior in rat. In rabbit, intrathecal administration of this drug enhances somatic and autonomic motor outflows, showing that tonic adrenergic descending inhibition of withdrawal reflexes and sympathetic pre-ganglionic neurons is strong in this species. The potentiation of reflexes may be considered a pro-nociceptive action. In the same model, RX 821002 antagonizes the inhibitory effects of the mu opioid fentanyl, indicating that exogenous opioids synergize with endogenously released norepinephrine in the spinal cord. Thus, the careful use of RX 821002 has revealed several aspects of the physiological activity of alpha(2)-adrenoceptors in rabbit spinal cord and rat brain. We recommend that RX 821002 and/or compounds with similar selectivity for alpha(2)-adrenoceptors (atipamezole, MK-912, RS-79948) should be used in preference to yohimbine or idazoxan in all future studies of this type.


[Advances in the Role of Low-Dose Interleukin-2 in Immune-Mediated Dermatosis].
Immune-mediated dermatoses are the skin diseases caused by the breakdown of immune tolerance,including lupus erythematosus and dermatomyositis.The imbalance between regulatory T cells (Tregs) and effector T cells (Teffs) plays a key role in the pathogenesis of these diseases.Low-dose interleukin-2 can preferentially activate Tregs and reverse the imbalance between Tregs and Teffs to recover the immune tolerance,which has attracted attention in the treatment of immune-mediated dermatoses.This review summarizes the research progress in the immunomodulatory mechanism and clinical application of low-dose interleukin-2 in immune-mediated dermatoses,providing a new idea for the clinical treatment of these diseases.


Use of Arbuscular Mycorrhiza and Organic Amendments to Enhance Growth of Macaranga peltata (Roxb.) Müll. Arg. in Iron Ore Mine Wastelands.
Macaranga peltata (Roxb.) Mull. Arg. is a disturbance tolerant plant species with potential in mine wasteland reclamation. Our study aims at studying the phyto-extraction potential of M. peltata and determining plant-soil interaction factors effecting plant growth in iron ore mine spoils. Plants were grown in pure mine spoil and spoil amended with Farm Yard Manure (FYM) and Vermicompost (VC) along with arbuscular mycorrhizal (AM) species Rhizophagus irregularis. Pure and amended mine spoils were evaluated for nutrient status. Plant growth parameters and foliar nutrient contents were determined at the end of one year. FYM amendment in spoil significantly increased plant biomass compared to pure mine spoil and VC amended spoil. Foliar Fe accumulation was recorded highest (594.67 μg/g) in pure spoil with no mortality but considerably affecting plant growth, thus proving to exhibit phyto-extraction potential. FYM and VC amendments reduced AM colonization (30.4% and 37% resp.) and plants showed a negative mycorrhizal dependency (-30.35 and -39.83 resp.). Soil pH and P levels and, foliar Fe accumulation are major factors determining plant growth in spoil. FYM amendment was found to be superior to VC as a spoil amendment for hastening plant growth and establishment in iron ore mine spoil.


Identification and characterization of Arcobacter isolates from broilers by biochemical tests, antimicrobial resistance patterns and plasmid analysis.
A total of 89 Arcobacter butzleri isolates obtained from freshly slaughtered broilers was investigated for their biochemical capacities by using the API CAMPY system as well as additional growth and tolerance tests, for their antimicrobial resistance patterns and their plasmid content. Among these techniques, biochemical profiling and antimicrobial resistance testing proved to be the most discriminatory methods as confirmed by the calculation of discriminatory indices. These two methods might represent valuable tools for epidemiological analysis of A. butzleri isolates. Small plasmids of up to 5 kbp were detectable in only 21 of the 89 isolates while the remaining 68 A. butzleri isolates were plasmid-free.


Prediction of CYP-mediated drug interactions in vivo using in vitro data.
Over the past 15 years, a concerted effort has been undertaken by the pharmaceutical industry to reduce the attrition of clinical candidates resulting from undesirable ADME characteristics. Increasing regulatory and competitive pressures demand that pharmaceutical products brought to the market possess pristine safety and drug co-administration profiles for most therapeutic areas. The high-profile withdrawal of drugs such as mibefradil from the market because of unfavorable drug-drug interaction profiles has focused efforts on screening for cytochrome P450 (CYP)-mediated drug interactions early in the discovery paradigm and on predicting the impact of inhibition on the in vivo situation. This paper discusses current practices used to screen for CYP-mediated drug-drug interactions in vitro (inhibition and induction) and how these data are being used to predict whether a clinically relevant drug-drug interaction is likely to occur in vivo.


The potential of pro-insecticides for resistance management.
Pro-insecticides have been a significant part of the insecticide market for decades. Bioactivation of such compounds is generally an enzyme-controlled process, in which the target insect metabolizes the pro-form into an active compound. This approach has several potential advantages, including improved bio-kinetic properties and safety profiles of the pro-insecticide relative to the active form. A less common advantage of pro-insecticides is increased activity on metabolically resistant strains. Specific cases in which a pro-insecticide demonstrates negative cross-resistance (NCR) on a metabolically resistant strain due to increased bioactivation of the pro-insecticide have been noted sporadically over the past 50+ years but have not been reviewed before. The purpose of this mini-review is to catalog the cases in which a pro-insecticide demonstrated improved activity on an insect strain resistant to a second insecticide via a metabolic mechanism. Cases are relatively rare, but where it does occur the mechanism of NCR is generally recognized as being due to the increased metabolic activity of the resistant strain. These observations can provide learnings with potential application for resistance management if the correct pro-insecticide is selected for a resistant strain which is better able to bioactivate it. A better understanding of the bioactivation of pro-insecticides by resistant insects could also aid in insecticide discovery, potentially leading to improved pro-insecticide design. © 2021 Society of Chemical Industry.


Deep neural networks for single shot structured light profilometry.
In 3D optical metrology, single-shot structured light profilometry techniques have inherent advantages over their multi-shot counterparts in terms of measurement speed, optical setup simplicity, and robustness to motion artifacts. In this paper, we present a new approach to extract height information from single deformed fringe patterns, based entirely on deep learning. By training a fully convolutional neural network on a large set of simulated height maps with corresponding deformed fringe patterns, we demonstrate the ability of the network to obtain full-field height information from previously unseen fringe patterns with high accuracy. As an added benefit, intermediate data processing steps such as background masking, noise reduction and phase unwrapping that are otherwise required in classic demodulation strategies, can be learned directly by the network as part of its mapping function.


(Chitosan-g-glycidyl methacrylate)-xanthan hydrogel implant in Wistar rats for spinal cord regeneration.
This work reports the results of in vivo assays of an implant composed of the hydrogel Chitosan-g-Glycidyl Methacrylate-Xanthan [(CTS-g-GMA)-X] in Wistar rats. Degradation kinetics of hydrogels was assessed by lysozyme assays. Wistar rats were subjected to laminectomy by cutting the spinal cord with a scalpel. After the surgical procedure, hydrogels were implanted in the injured zone (level T8). Somatosensory evoked potentials (SEPs) obtained by electric stimulation onto periphery nerves were registered in the corresponding central nervous system (CNS) areas. Rats implanted with the biomaterials showed a successful recovery compared with the non-implanted rats after 30days. Lysozyme, derived from egg whites, was used for in vitro assays. This study serves as the basis for testing the biodegradability of the hydrogels (CTS-g-GMA)-X that is promoted by enzymatic hydrolysis. Hydrogels' hydrolysis was studied via lysozyme kinetics at two pH values, 5 and 7, under mechanical agitation at 37°C. Results show that our materials' hydrolysis is slower than pure CTS possibly due to the steric hindrance imposed by the GMA grafting of functionalization. This hydrolysis helps degrade the biomaterial and at the same time it provides support for spinal cord recovery. Combination of these results may prove useful in the use of these hydrogels as scaffolds for cells proliferation and their application as implants in living organisms.


Manufacturing Techniques and Surface Engineering of Polymer Based Nanoparticles for Targeted Drug Delivery to Cancer.
The evolution of polymer based nanoparticles as a drug delivery carrier via pharmaceutical nano/microencapsulation has greatly promoted the development of nano- and micro-medicine in the past few decades. Poly(lactide-co-glycolide) (PLGA) and chitosan, which are biodegradable and biocompatible polymers, have been approved by both the Food & Drug Administration (FDA) and European Medicine Agency (EMA), making them ideal biomaterials that can be advanced from laboratory development to clinical oral and parental administrations. PLGA and chitosan encapsulated nanoparticles (NPs) have successfully been developed as new oral drug delivery systems with demonstrated high efficacy. This review aims to provide a comprehensive overview of the fabrication of PLGA and chitosan particulate systems using nano/microencapsulation methods, the current progress and the future outlooks of the nanoparticulate drug delivery systems. Especially, we focus on the formulations and nano/micro-encapsulation techniques using top-down techniques. It also addresses how the different phases including the organic and aqueous ones in the emulsion system interact with each other and subsequently influence the properties of the drug delivery system. Besides, surface modification strategies which can effectively engineer intrinsic physicochemical properties are summarised. Finally, future perspectives and potential directions of PLGA and chitosan nano/microencapsulated drug systems are outlined.


Thinking styles of gifted and nongifted students in Iran.
This study was designed to compare thinking styles of gifted and nongifted Iranian students and to examine the appropriateness in a nonwestern context of the Thinking Styles Inventory. 200 students in junior high school, including 109 nongifted students (55 girls and 54 boys) and 91 gifted students (46 girls and 45 boys), whose mean age was 12.4 yr. (SD = .69), responded to the short version of the Thinking Styles Inventory. Analysis indicated that gifted students scored significantly higher than nongifted students on Type 1 and Type 3 thinking styles, while the nongifted students had statistically significant higher scores on the Type 2 thinking styles. These results are discussed in terms of the previous research and thinking styles model proposed by Sternberg in 1997.


Comparative studies on the electrical and mechanical behavior of catalytically grown multiwalled carbon nanotubes and scrolled graphene.
The electrical and mechanical properties of multiwalled carbon nanotubes and of scrolled graphene structures, synthesized from iron-phthalocyanine in a catalytic chemical vapor deposition process, were investigated in situ in a transmission electron microscope. These experiments enabled us to get a more detailed quantitative picture of the peculiarities of the two different types of carbon nanostructures. The nanoscrolls showed superior conductance >10G(o), against ≤1G(o) of the nested tubes, and a much enhanced electric sustainability (∼10(8) A/cm(2)). While the pronounced nonlinear increase in current in the nested tube structure with increasing applied voltage is directly related to an increasing number of tubes involved, the electric breakdown has correspondingly been characterized by fractional ablation of the successive layers. Scrolls, on the contrary, do not show any fractional electric response. Mechanical bending has been found easier with scrolled graphenes than with nested tubes. This observation confirms the prediction of higher flexibility of the scroll structure in interesting phenomena like intercalation and electroactuation.


Misdiagnosing the problem: mental health profiles of incarcerated juveniles.
Aggression, antisocial and delinquent behavior frequently result in the incarceration of a large number of young people, but these problems pale in comparison to the mental health challenges faced by many of these youth. Recent studies show a high prevalence of mental disorders among adolescents within the justice system. These findings have led researchers, clinicians and policy-makers to re-evaluate the assessment and treatment options that are available for youth within correctional facilities. This article provides a concise review of the most recent research related to mental health disorders among incarcerated juveniles within Canada and the United States. Rates of some of the most common mental health disorders among juveniles, including depression, anxiety, attention deficit hyperactivity and substance use are summarized. Throughout the review, issues related to co-morbidity and gender differences are highlighted. The implications of mental health disorders for juvenile justice policy and practice are discussed.


Age-dependent association of pulse wave velocity with coronary artery disease and myocardial aging in high-risk patients.
Progressive arterial stiffening, as a marker of arterial aging, may reach a plateau in elderly patients and may thus lose its clinical utility. This phenomenon may be more prominent in high-risk patients. We aimed to investigate if carotid-to-femoral pulse wave velocity (cf-PWV) is related to coronary artery disease (CAD) and diastolic dysfunction in elderly high-risk patients as compared to a control group of younger individuals. One-hundred and ninety-two high-risk stable patients who underwent coronary artery angiography and assessment of cf-PWV were consecutively recruited. Indices of diastolic dysfunction were also measured by echocardiography, including the volume of the left atrium and the ratio of early transmitral peak velocity (E) to the mitral annular early diastolic velocity (E'). Increased cf-PWV was associated with the presence of CAD [odds ratio (OR) 1.34, P = 0.02], number of diseased coronary vessels (OR 1.17, P = 0.029) and CAD severity (P = 0.023) as assessed by Gensini score, in patients less than 65 years old after adjustment for traditional risk factors. Moreover, cf-PWV correlated with E/E' (P = 0.019) and increased the odds by 16% (OR 1.16, P = 0.048) for more severe diastolic dysfunction in patients aged below 65 years old. None of these outcomes correlated with cf-PWV in the elderly. In high cardiovascular risk patients, an age-dependent association of cf-PWV with CAD and diastolic dysfunction was evinced. In contrast to younger patients, these results suggest that measuring arterial stiffness in elderly high-risk patients may lack clinical value.


Soft X-ray Chlorine Photolysis on Chlorobenzene Ice: An Experimental and Theoretical Study.
An experimental and theoretical study of the photoinduced homolysis of the carbon-chlorine bond in an ice matrix of chlorobenzene is presented. A condensed chlorobenzene film has been grown in situ and near edge X-ray fine structure (NEXAFS) spectra were collected after exposing the condensed film to a monochromatic photon beam centered at the 2822 eV resonant excitation of chlorine and at 2850 eV. The photoabsorption to the Cl 1s → σ* and Cl 1s → π* states has been measured and the hypothesis of free radical coupling reactions was investigated via time-dependent density functional theory (TD-DFT) and complete active space self-consistent field (CASSCF) calculations. Also, potential energy pathways to the C-Cl cleavage have been obtained at the CASSCF level to the Cl 1s → σ*, 1s → π*, and 1s → ∞ states. A strong dissociative character was only found for the Cl 1s → σ* resonance.


Investigation of residual core ellipticity induced nonreciprocity in air-core photonic bandgap fiber optical gyroscope.
Air-core photonic bandgap fiber (PBF) is an excellent choice for fiber optic gyroscope owing to its incomparable adaptability of environment. Strong and continuous polarization mode coupling is found in PBFs with an average intensity of ~-30 dB, but the coupling arrives at the limit when the maximum optical path difference between the primary waves and the polarization-mode-coupling-induced secondary waves reaches ~10mm, which is corresponding to the PBF length of ~110 m according to the birefringence in the PBF. Incident light with the low extinction ratio (ER) can suppress the birth of the polarization-mode-coupling-induced secondary waves, but the low-ER light obtained by the conventional Lyot depolarizers does not work here. Consequently, a large nonreciprocity and a bias error of ~13°/h are caused in the air-core photonic bandgap fiber optical gyroscope (PBFOG) with a PBF coil of ~268 m.


Omics Approaches for the Study of Adaptive Immunity to Staphylococcus aureus and the Selection of Vaccine Candidates.
Staphylococcus aureus is a dangerous pathogen both in hospitals and in the community. Due to the crisis of antibiotic resistance, there is an urgent need for new strategies to combat S. aureus infections, such as vaccination. Increasing our knowledge about the mechanisms of protection will be key for the successful prevention or treatment of S. aureus invasion. Omics technologies generate a comprehensive picture of the physiological and pathophysiological processes within cells, tissues, organs, organisms and even populations. This review provides an overview of the contribution of genomics, transcriptomics, proteomics, metabolomics and immunoproteomics to the current understanding of S. aureus‑host interaction, with a focus on the adaptive immune response to the microorganism. While antibody responses during colonization and infection have been analyzed in detail using immunoproteomics, the full potential of omics technologies has not been tapped yet in terms of T-cells. Omics technologies promise to speed up vaccine development by enabling reverse vaccinology approaches. In consequence, omics technologies are powerful tools for deepening our understanding of the "superbug" S. aureus and for improving its control.


Changes in the fecal concentrations of cortisol and androgen metabolites in captive male jaguars (Panthera onca) in response to stress.
In the present study we determined the efficacy of the measurement of fecal cortisol and androgen metabolite concentrations to monitor adrenal and testicular activity in the jaguar (Panthera onca). Three captive male jaguars were chemically restrained and electroejaculated once or twice within a period of two months. Fecal samples were collected daily for 5 days before and 5 days after the procedure and stored at -20 degrees C until extraction. Variations in the concentrations of cortisol and androgen metabolites before and after the procedure were determined by solid phase cortisol and testosterone radioimmunoassay and feces dry weight was determined by drying at 37 degrees C for 24 h under vacuum. On four occasions, fecal cortisol metabolite levels were elevated above baseline (307.8 +/- 17.5 ng/g dry feces) in the first fecal sample collected after the procedure (100 to 350% above baseline). On one occasion, we did not detect any variation. Mean (+/- SEM) fecal androgen concentration did not change after chemical restraint and electroejaculation (before: 131.1 +/- 26.7, after: 213.7 +/- 43.6 ng/g dry feces). These data show that determination of fecal cortisol and androgen metabolites can be very useful for a noninvasive assessment of animal well-being and as a complement to behavioral, physiological, and pathological studies. It can also be useful for the study of the relationship between adrenal activity and reproductive performance in the jaguar.


Suicidal behavior, impulsiveness and serotonin.
The authors review the accumulating evidence from preclinical, clinical and postmortem studies suggesting that abnormality in serotonin systems may be associated with both attempts at suicide and aggression towards others and inanimate objects. Although these behaviors are multidetermined they often involve poor impulse control, which may reflect low central serotonin turnover. The need for further studies of possible peripheral biological markers for suicidal and impulsive behavior is discussed.


Culture shock: microglial heterogeneity, activation, and disrupted single-cell microglial networks in vitro.
Microglia, the resident immune cells of the brain, play a critical role in numerous diseases, but are a minority cell type and difficult to genetically manipulate in vivo with viral vectors and other approaches. Primary cultures allow a more controlled setting to investigate these cells, but morphological and transcriptional changes upon removal from their normal brain environment raise many caveats from in vitro studies. To investigate whether cultured microglia recapitulate in vivo microglial signatures, we used single-cell RNA sequencing (scRNAseq) to compare microglia freshly isolated from the brain to primary microglial cultures. We performed cell population discovery, differential expression analysis, and gene co-expression module analysis to compare signatures between in vitro and in vivo microglia. We constructed causal predictive network models of transcriptional regulators from the scRNAseq data and identified a set of potential key drivers of the cultured phenotype. To validate this network analysis, we knocked down two of these key drivers, C1qc and Prdx1, in primary cultured microglia and quantified changes in microglial activation markers. We found that, although often assumed to be a relatively homogenous population of cells in culture, in vitro microglia are a highly heterogeneous population consisting of distinct subpopulations of cells with transcriptional profiles reminiscent of macrophages and monocytes, and are marked by transcriptional programs active in neurodegeneration and other disease states. We found that microglia in vitro presented transcriptional activation of a set of "culture shock genes" not found in freshly isolated microglia, characterized by strong upregulation of disease-associated genes including Apoe, Lyz2, and Spp1, and downregulation of homeostatic microglial markers, including Cx3cr1, P2ry12, and Tmem119. Finally, we found that cultured microglia prominently alter their transcriptional machinery modulated by key drivers from the homeostatic to activated phenotype. Knockdown of one of these drivers, C1qc, resulted in downregulation of microglial activation genes Lpl, Lyz2, and Ccl4. Overall, our data suggest that when removed from their in vivo home environment, microglia suffer a severe case of "culture shock", drastically modulating their transcriptional regulatory network state from homeostatic to activated through upregulation of modules of culture-specific genes. Consequently, cultured microglia behave as a disparate cell type that does not recapitulate the homeostatic signatures of microglia in vivo. Finally, our predictive network model discovered potential key drivers that may convert activated microglia back to their homeostatic state, allowing for more accurate representation of in vivo states in culture. Knockdown of key driver C1qc partially attenuated microglial activation in vitro, despite C1qc being only weakly upregulated in culture. This suggests that even genes that are not strongly differentially expressed across treatments or preparations may drive downstream transcriptional changes in culture.


Adaptation of the Gabby conversational agent system to improve the sexual and reproductive health of young women in Lesotho.
Young women from the low-middle-income country of Lesotho in southern Africa frequently report limited knowledge regarding sexual and reproductive health issues and engage in risky sexual behaviors. The purpose of this study is to describe the adaptation of an evidence-based conversational agent system for implementation in Lesotho and provide qualitative data pertaining to the success of the said adaptation. An embodied conversational agent system used to provide preconception health advice in the United States was clinically and culturally adapted for use in the rural country of Lesotho in southern Africa. Inputs from potential end users, health leaders, and district nurses guided the adaptations. Focus group discussions with young women aged 18-28 years who had used the newly adapted system renamed "Nthabi" for 3-4 weeks and key informant interviews with Ministry of Health leadership were conducted to explore their views of the acceptability of the said adaptation. Data were analyzed using NVivo software, and a thematic content analysis approach was employed in the study. A total of 33 women aged 18-28 years used Nthabi for 3-4 weeks; eight (24.2%) of them were able to download and use the app on their mobile phones and 25 (75.8%) of them used the app on a tablet provided to them. Focus group participants (n = 33) reported that adaptations were culturally appropriate and provided relevant clinical information. The participants emphasized that the physical characteristics, personal and non-verbal behaviors, utilization of Sesotho words and idioms, and sensitively delivered clinical content were culturally appropriate for Lesotho. The key informants from the Ministry leadership (n = 10) agreed that the adaptation was successful, and that the system holds great potential to improve the delivery of health education in Lesotho. Both groups suggested modifications, such as using the local language and adapting Nthabi for use by boys and young men. Clinically tailored, culturally sensitive, and trustworthy content provided by Nthabi has the potential to improve accessibility of sexual and reproductive health information to young women in the low-middle-income country of Lesotho.


Changing concept in treatment of asymptomatic severe aortic stenosis and normal ejection fraction: time for biomarkers reappraisal.
The uncertainty of whether/how to treat asymptomatic patients with isolated severe aortic stenosis and normal left ventricular ejection fraction is one of the most topical in cardiovascular medicine. Recently, the AVATAR trial: first ever randomized trial in the setting of aortic stenosis has been started in an attempt to adequately address this 'burning issue'. In light of this fact it is important to identify biomarkers which might help in risk stratification of these patients, not only in the referring physician's office during a routine exam, but also for preoperative patients scheduled for surgical replacement/transcatheter aortic valve implantation. This report is focusing on novel laboratory parameters which might be helpful in this risk stratification.


An on-chip instrument for white blood cells classification based on a lens-less shadow imaging technique.
Routine blood tests provide important basic information for disease diagnoses. The proportions of three subtypes of white blood cells (WBCs), which are neutrophils, monocytes, lymphocytes, is key information for disease diagnosis. However, current instruments for routine blood tests, such as blood cell analyzers, flow cytometers, and optical microscopes, are cumbersome, time consuming and expensive. To make a smaller, automatic low-cost blood cell analyzer, much research has focused on a technique called lens-less shadow imaging, which can obtain microscopic images of cells in a lens-less system. Nevertheless, the efficiency of this imaging system is not satisfactory because of two problems: low resolution and imaging diffraction phenomena. In this paper, a novel method of classifying cells with the shadow imaging technique was proposed. It could be used for the classification of the three subtypes of WBCs, and the correlation of the results of classification between the proposed system and the reference system (BC-5180, Mindray) was 0.93. However, the instrument was only 10 × 10 × 10 cm, and the cost was less than $100. Depending on the lens-free shadow imaging technology, the main hardware could be integrated on a chip scale and could be called an on-chip instrument.


Determinants of Probability Neglect and Risk Attitudes for Disaster Risk: An Online Experimental Study of Flood Insurance Demand among Homeowners.
Little is known about why individuals place either a high or a very low value on mitigating risks of disaster-type events, like floods. This study uses panel data methods to explore the psychological factors affecting probability neglect of flood risk relevant to the zero end-point of the probability weighting function in Prospect Theory, and willingness-to-pay for flood insurance. In particular, we focus on explanatory variables of anticipatory and anticipated emotions, as well as the threshold of concern. Moreover, results obtained under real and hypothetical incentives are compared in an experiment with high experimental outcomes. Based on our findings, we suggest several policy recommendations to overcome individual decision processes, which may hinder flood protection efforts.


Antioxidant Potential of Ethiopian Medicinal Plants and Their Phytochemicals: A Review of Pharmacological Evaluation.
Free radicals are very reactive molecules produced during oxidation events that in turn initiate a chain reaction resulting in cellular damage. Many degenerative diseases in humans, including cancer and central nervous system damage, are caused by free radicals. Scientific evidence indicates that active compounds from natural products can protect cells from free radical damage. As a result, the aim of this review is to provide evidence of the use of diverse Ethiopian medicinal plants with antioxidant properties that have been scientifically validated in order to draw attention and foster further investigations in this area. The keywords antioxidant, radical scavenging activities, reactive oxygen species, natural product, Ethiopian Medicinal plants, and 2, 2-Diphenyl-1-picrylhydrazyl radical scavenging assay (DPPH) were used to identify relevant data in the major electronic scientific databases, including Google Scholar, ScienceDirect, PubMed, Medline, and Science domain. All articles with descriptions that were accessed until November 2022 were included in the search strategy. A total of 54 plant species from 33 families were identified, along with 46 compounds isolated. More scientific studies have been conducted on plant species from the Brassicaceae (19%), Asphodelaceae (12%), and Asteraceae (12%) families. The most used solvent and extraction method for plant samples are methanol (68%) and maceration (88%). The most examined plant parts were the leaves (42%). Plant extracts (56%) as well as isolated compounds (61%) exhibited significant antioxidant potential. The most effective plant extracts from Ethiopian flora were Bersama abyssinica, Solanecio gigas, Echinops kebericho, Verbascum sinaiticum, Apium leptophyllum, and Crinum abyssinicum. The best oxidative phytochemicals were Rutin (7), Flavan-3-ol-7-O-glucoside (8), Myricitrin (13), Myricetin-3-O-arabinopyranoside (14), 7-O-Methylaloeresin A (15), 3-Hydroxyisoagatholactone (17), β-Sitosterol-3-O-β-D-glucoside (22), Microdontin A/B (24), and Caffeic acid (39). Many crude extracts and compounds exhibited significant antioxidant activity, making them excellent candidates for the development of novel drugs. However, there is a paucity of research into the mechanisms of action as well as clinical evidence supporting some of these isolated compounds. To fully authenticate and then commercialize, further investigation and systematic analysis of these antioxidant-rich species are required.


O2L-001, an innovative thrombolytic to evacuate intracerebral haematoma.
Intracerebral haemorrhage is an unmet medical need affecting more than 3 million people worldwide every year and leading to the formation of an intracerebral haematoma. Updated guidelines (2022) for the management of intracerebral haemorrhage patients recognize that minimally invasive approaches for the evacuation of supratentorial intracerebral haemorrhage have demonstrated reductions in mortality compared with medical management alone. However, improvement of functional outcome with a procedure involving thrombolytic therapy was neutral in the last large phase 3 clinical trial and requires a more effective and safer thrombolytic agent than those currently available. Here, we demonstrate that O2L-001 allows for the extended release of W253R/R275S recombinant tissue-type plasminogen activator (rtPA). A new rtPA variant, called optimized tPA (OptPA), offers improved efficacy for haematoma evacuation as well as improved safety. OptPA was produced in a Chinese hamster ovary cell line before purification, nanoprecipitation using the NANOp2Lysis® technological platform followed by suspension in a solution of 17% poloxamer 407 to obtain O2L-001. Plasmin generation assays were performed to demonstrate O2L-001 safety. Ex vivo haematoma models using human blood were used to demonstrate O2L-001 thrombolysis properties and efficacy. For the best translational significance, a clinical sized haematoma was used to ensure catheter placement and to allow administration of the thrombolytic agent into the core of the haematoma via a minimally invasive procedure. The capacity of OptPA to convert plasminogen into plasmin is strongly decreased compared to rtPA, thereby reducing potential bleeding events. However, a clot lysis assay showed that OptPA had the same fibrinolytic activity as rtPA. We demonstrated that long-term exposure to a thrombolytic agent was essential to achieve high thrombolysis efficacy. Indeed, 24 h continuous exposure to 0.1 µg/ml rtPA had similar efficacy than repeated short exposure to 30 µg/ml rtPA. This finding led to the development of O2L-001, allowing the extended release of OptPA in the first 6 h following injection. An ex vivo model using human blood was used to demonstrate O2L-001 efficacy. Interestingly, unlike rtPA, O2L-001 was able to induce the complete lysis of the 5 ml haematoma. In clinical sized haematomas (obtained from 30 ml of human blood), a single injection of O2L-001 at 1 mg/ml into the core of the haematoma led to a 44% increase in thrombolysis compared to rtPA. Taken together, these results demonstrate that O2L-001 provides new hope for haematoma evacuation and the treatment of patients with intracerebral haemorrhage.


Applications of population genetics to animal breeding, from wright, fisher and lush to genomic prediction.
Although animal breeding was practiced long before the science of genetics and the relevant disciplines of population and quantitative genetics were known, breeding programs have mainly relied on simply selecting and mating the best individuals on their own or relatives' performance. This is based on sound quantitative genetic principles, developed and expounded by Lush, who attributed much of his understanding to Wright, and formalized in Fisher's infinitesimal model. Analysis at the level of individual loci and gene frequency distributions has had relatively little impact. Now with access to genomic data, a revolution in which molecular information is being used to enhance response with "genomic selection" is occurring. The predictions of breeding value still utilize multiple loci throughout the genome and, indeed, are largely compatible with additive and specifically infinitesimal model assumptions. I discuss some of the history and genetic issues as applied to the science of livestock improvement, which has had and continues to have major spin-offs into ideas and applications in other areas.


Intrathecal dextrose to prevent seizures after metrizamide myelography in dogs.
Seizures are possible complications of metrizamide myelography. The protective effect (as measured by reduction in seizure incidence) of dextrose in solution with metrizamide was studied by conducting a double-blind trail. Fourteen dogs each had two myelograms at five- to 16-day intervals in a crossover study, while ten additional dogs each had a single myelogram. Metrizamide alone and metrizamide in dextrose were used for the myelograms. No significant protective effect of dextrose was found.


EnvCNN: A Convolutional Neural Network Model for Evaluating Isotopic Envelopes in Top-Down Mass-Spectral Deconvolution.
Top-down mass spectrometry has become the main method for intact proteoform identification, characterization, and quantitation. Because of the complexity of top-down mass spectrometry data, spectral deconvolution is an indispensable step in spectral data analysis, which groups spectral peaks into isotopic envelopes and extracts monoisotopic masses of precursor or fragment ions. The performance of spectral deconvolution methods relies heavily on their scoring functions, which distinguish correct envelopes from incorrect ones. A good scoring function increases the accuracy of deconvoluted masses reported from mass spectra. In this paper, we present EnvCNN, a convolutional neural network-based model for evaluating isotopic envelopes. We show that the model outperforms other scoring functions in distinguishing correct envelopes from incorrect ones and that it increases the number of identifications and improves the statistical significance of identifications in top-down spectral interpretation.


The role of monocytes in models of infection by protozoan parasites.
The confirmation of developmental differences between tissue macrophages and peripheral monocytes has changed our view of the functions and dynamics of these two important components of the innate immune system. It has been demonstrated conclusively that homeostasis of tissue resident macrophages is maintained by a low proliferative turn over. During an inflammatory response, bone marrow derived monocytes enter the tissue in large numbers and take part in the defense against the pathogens. After the destruction of invading pathogens, these cells disappear and tissue resident macrophages can be detected again. This new appreciation of the innate immune response has not only answered many outstanding questions regarding the role of the different myeloid cell types in inflammation, but also opened up new areas of research relating to the tissue- and pathogen-specific fate of the inflammatory macrophages or dendritic cells (DCs), and the transfer of this knowledge from mouse models to the human immune system. Nevertheless, there is still confusion in infection models, and especially in studies of human infections, as to what extent these recent observations and findings influence previous interpretations of data. This review will focus on insights from mouse models, summarize the literature on the ontogeny of macrophages and monocytes, explain the role of frequently used monocyte markers and effector molecules, and finally, discuss the role of inflammatory monocytes/macrophages/DCs in two experimental parasitic diseases.


Kinetic analysis of human T-cell leukemia virus type I Tax-mediated activation of NF-kappa B.
The human T-cell leukemia virus type I (HTLV-I) Tax protein induces the expression of cellular genes, at least in part, by activating the endogenous NF-kappa B transcription factors. Induced expression of cellular genes is thought to be important for transformation of T cells to continued growth, a prelude to the establishment of adult T-cell leukemia. However, neither underlying mechanisms nor kinetics of the Tax-mediated activation of NF-kappa B are understood. We have analyzed a permanently transfected Jurkat T-cell line in which the expression of Tax is entirely dependent on addition of heavy metals. The initial NF-kappa B binding activity seen after induction of Tax is due almost exclusively to p50/p65 heterodimers. At later times, NF-kappa B complexes containing c-Rel and/or p52 accumulate. The early activation of p50/p65 complexes is a posttranslational event, since neither mRNA nor protein levels of NF-kappa B subunits had increased at that time. We demonstrate for the first time a Tax-induced proteolytic degradation of the NF-kappa B inhibitor, I kappa B-alpha, which may trigger the initial nuclear translocation of NF-kappa B. As nuclear NF-kappa B rapidly and potently stimulates resynthesis of I kappa B-alpha, the steady-state level of I kappa B-alpha does not significantly change. Thus, the dramatic Tax-induced increase in the I kappa B-alpha turnover may continually weaken inhibition and activate NF-kappa B. Additional, distinct actions of Tax may contribute further to the high levels of NF-kappa B activity seen.


Paradoxical whole genome DNA methylation dynamics of 5'aza-deoxycytidine in chronic low-dose exposure in mice.
Decitabine (5-aza-2'deoxycytidine; DAC) is a DNA methyltransferase inhibitor used to hypomethylate the epigenome. Current dosing regimens of DAC for use in mice vary widely and their hypomethylating ability has not been robustly characterized, despite reliable results of hypomethylation of the epigenome with cell lines in vitro and tissue specificity in vivo. We investigated the effects on the DNA methylome and gene expression within mice exposed to chronic low doses of DAC ranging from 0 to 0.35 mg/kg over a period of 7 weeks without causing toxicity. Our dose paradigm resulted in no cytotoxic effects within target tissues, although testes weight and sperm concentration significantly reduced as dose increased (p-value <0.05). By whole genome bisulphite sequencing (WGBS), we identify tissue and dose-specific differentially methylated CpGs (DMCs) and regions (DMRs) in testes and liver. Testes methylation is more sensitive to DAC exposure when compared to liver, cortex, and hippocampus. Gene expression was dysregulated in testes and liver, targeting non-specific pathways as dose increases. Together our data suggest DNA methylation and gene expression are disrupted by in vivo DAC treatment in a non-uniform manner contrary to expectations, and that no dose level or regimen is sufficient to cause systemic hypomethylation in whole mice.


An investigation of factors affecting test equating in latent trait theory.
The study investigated five factors which can affect the equating of scores from two tests onto a common score scale. The five factors were: (a) item distribution type (i.e., normal versus uniform; (b) standard deviation of item difficulty (i.e.,.68,.95,.99); (c) number of items or test length (i.e., 50, 100, 200); (d) number of common items (i.e., 10, 20, 30); and (e) sample size (i.e., 100, 300, 500). SIMTEST and BIGSTEPS programs were used for the simulation and equating of 4,860 item data sets, respectively. Results from the five-way fixed effects factorial analysis of variance indicated three statistically significant two-way interaction effects. Simple effects for the interaction between common item length and test length only were interpreted given Type I error rate considerations. The eta-squared values for number of common items and test length were small indicating the effects had little practical importance. The Rasch approach to equating is robust with as few as 10 common items and a test length of 100 items.


Identification, characterization and subcellular localization of TcPDE1, a novel cAMP-specific phosphodiesterase from Trypanosoma cruzi.
Compartmentalization of cAMP phosphodiesterases plays a key role in the regulation of cAMP signalling in mammals. In the present paper, we report the characterization and subcellular localization of TcPDE1, the first cAMP-specific phosphodiesterase to be identified from Trypanosoma cruzi. TcPDE1 is part of a small gene family and encodes a 929-amino-acid protein that can complement a heat-shock-sensitive yeast mutant deficient in phospho-diesterase genes. Recombinant TcPDE1 strongly associates with membranes and cannot be released with NaCl or sodium cholate, suggesting that it is an integral membrane protein. This enzyme is specific for cAMP and its activity is not affected by cGMP, Ca2+, calmodulin or fenotiazinic inhibitors. TcPDE1 is sensitive to the phosphodiesterase inhibitor dipyridamole but is resistant to 3-isobutyl-1-methylxanthine, theophylline, rolipram and zaprinast. Papaverine, erythro-9-(2-hydroxy-3-nonyl)-adenine hydrochloride, and vinpocetine are poor inhibitors of this enzyme. Confocal laser scanning of T. cruzi epimastigotes showed that TcPDE1 is associated with the plasma membrane and concentrated in the flagellum of the parasite. The association of TcPDE1 with this organelle was confirmed by subcellular fractionation and cell-disruption treatments. The localization of this enzyme is a unique feature that distinguishes it from all the trypanosomatid phosphodiesterases described so far and indicates that compartmentalization of cAMP phosphodiesterases could also be important in these parasites.


Speech recognition in noise by children with minimal degrees of sensorineural hearing loss.
It is well recognized that the acoustical environment in a classroom is an important variable in the psychoeducational achievement of hearing-impaired children. To date, however, there remains a paucity of information concerning the importance of classroom acoustics for children with minimal degrees of sensorineural hearing loss (SNHL). The present investigation examined the effects of commonly reported classroom signal to noise ratios (+6, +3, 0, -3, and -6 dB) on the sentence recognition of 20 normal-hearing children and 20 children with minimal degrees of SNHL (i.e., pure-tone averages of 15-30 dB HL through the speech frequency range). Results indicated that children with minimal degrees of SNHL obtained poorer recognition scores than normal-hearing children across most listening conditions. Moreover, the performance decrement between the two groups increased as the listening environment became more adverse. Educational implications of these data, such as acoustical modification of the classroom and/or the utilization of frequency modulation sound field amplification systems, are discussed.


Preliminary Results of the Induced Membrane Technique for the Reconstruction of Large Bone Defects.
During past decades, gradual bone transplant using external fixators and vascularized fibular or rib transplants widely contributed to solve difficult problems related to the reconstruction of large bone defects in children. However, these surgeries are time consuming and require specialized surgical skills, not always available in a general hospital setting, mainly in rural areas. To report the preliminary results of the more recently described induced membrane technique in a consecutive series of 8 children and to identify some factors related to the procedure's success. Nine consecutive children with bone defects ranging from 5 to 14 cm were included in the study. The age at surgery ranged from 3 to 16 years. There were 3 congenital pseudarthrosis (CP) of the fibula, 1 CP of the tibia, 1 Ewing sarcoma of the tibia, 1 Ewing sarcoma of the ulna, 1 tibial osteosarcoma, 1 fibular osteosarcoma, and 1 chronic diffuse tibial osteomyelitis. The procedure was performed according to the original Masquelet's description in 2 stages. Follow-up ranged from 1 to 7 years. The child with tibial osteosarcoma died 3 months after the surgery from complications related to chemotherapy. Among the 8 remaining children, 6 healed uneventfully, and 2 required revision with additional grafting and/or better internal fixation, one with Ewing sarcoma of the tibia and a 13-cm bone defect and the second with CP of the fibula. Both of them had suboptimal internal stabilization. The induced membrane technique is a useful, efficient, and simple alternative to highly specialized surgical procedures used for the reconstruction of large bone defects in children. Risk factors for failure include chemotherapy, suboptimal bone fixation, and persistent axial malalignment. Level IV.


Use of fluorescent probes to assess membrane integrity in mammalian spermatozoa.
Carboxyfluorescein diacetate and propidium iodide were used as fluorescent stains to assess membrane integrity in sperm populations from ram and boar. The living spermatozoa were immobilized with low concentrations of formaldehyde so that individual stained cells could be observed in a suspension with the aid of a fluorescence microscope. Intracellular esterases liberated impermeant-free carboxyfluorescein from the permeant carboxyfluorescein diacetate and caused the product to accumulate and fluoresce green within the acrosome and the mitochondria as well as within the cytoplasm. Most of the spermatozoa (the intact ones) accumulated carboxyfluorescein in all compartments; however, a few cells (those with damaged plasma membranes) accumulated the stain only in the acrosome and/or the mitochondria, while others (all of whose membranes were damaged) remained entirely unstained. The impermeant propidium iodide did not stain any of the (intact) spermatozoa that accumulated carboxyfluorescein throughout their length, but stained all the others (the heads fluoresced red). The technique appeared to provide more reliable estimations of the percentage of functional cells than did motility estimations or assessments of acrosomal integrity (presence of normal apical ridge). The technique also demonstrated the sensitivity of the sperm plasma membrane to cold shock: virtually all cells rapidly became permeable to the stains after such stress. Assessments of boar sperm samples during preparative incubation for in-vitro fertilization indicated a considerable increase in the percentage of cells with damaged plasma membranes as incubation proceeded, in advance of the increase in the percentage of cells with discharged acrosomes.


RNA tertiary structure of the HIV RRE domain II containing non-Watson-Crick base pairs GG and GA: molecular modeling studies.
We have used molecular modeling techniques to model the RNA tertiary structure of the viral RNA element (referred to as domain II of Rev responsive element, RRE) bound by the Rev protein of HIV. In this study, the initial three-dimensional model was built from its established RNA secondary structure, including three non-Watson-Crick G:G, G:A and G:U base pairs. Molecular dynamics (MD) simulations were performed with hydrated or unhydrated sodium ions. Our results indicate that the non-Watson-Crick base pairs in the simulation with unhydrated sodium ions and water are more stable than those with hydrated sodium ions only. The RNA can maintain its compact double helical structure throughout the course of the MD simulations with water and unhydrated sodium ions, although the non-Watson-Crick base pairs and two bulge loops show much more flexibility and conformational distortion than the classical RNA helical region. The distinct distortion of the sugar-phosphate backbone significantly widens the RNA major groove so that the major groove is readily accessible for hydrogen bonding by specific Rev binding. This model emphasizes the importance of specific hydrogen bonding in the stabilization of the three-dimensional structure of the HIV Rev core binding element, not only between the nucleotide bases, but also among the ribose hydroxyls, phosphate anionic oxygens, base oxygens and nitrogens, and bridging water molecules. Moreover, our results suggest that sodium ions play an important role in the formation of base pairs G:G and G:A of the RRE by a manner similar to the arginine of the Rev-RRE complex.


Effects of papaverine and prostaglandin E1 on corpus cavernosum smooth muscle of arteriogenically and diabetically impotent men.
Relaxant effect of prostaglandin E1 (PGE1) and papaverine (PAP) were measured in strips of corpus cavernosum smooth muscle taken from a healthy control group of men (A; n = 5), from arteriogenically impotent men (B; n = 6) and from additionally diabetic impotent men (C; n = 5) with venous leakage. Maximal relaxant effect was achieved with PAP at a mean of 10(-4) mol/l and PGE1 at a mean of 5.8 x 10(-6) mol/l. PAP induced complete relaxation in all strips. There was no difference in relaxant effects between groups. Relaxant effect was less pronounced and depended significantly on etiology: phenylephrine-induced tension was reduced by 76 +/- 8% (A), 54 +/- 14% (B) and 23 +/- 18% (C), respectively. In conclusion, our data suggest degradation of PGE1 receptors depending on the cause of erectile dysfunction. Furthermore, relaxant capacity of cavernous smooth muscle per se seems not to be impaired in impotence. Therefore, pathophysiology of venous leakage cannot sufficiently be explained by a lack of relaxation.


Characterization of the expression and function of N-methyl-D-aspartate receptor in keratinocytes.
The N-methyl-D-aspartate (NMDA) receptor is expressed on neural tissue where it gates calcium ion entry upon stimulation. Using immunohistochemistry, it has been demonstrated in this study that the NMDAR1 receptor is also expressed on keratinocytes (KCs) in normal human skin and inflamed psoriatic skin in vivo. Furthermore, the NMDA receptor was functional as demonstrated by the ability of this receptor to trigger Ca++ influx in KCs. Incubation of cultured, human KCs with MK-801 decreases the cell growth and induces an increase in apoptosis. These findings demonstrate that the KC expression of NMDA receptor is a mechanism through which the influx of Ca++ into the cell can be regulated and suggest that the expression of this receptor may play a role in the regulation of KC growth and differentiation.