EEG hyper-connectivity in high-risk infants is associated with later autism.
It has been previously reported that structural and functional brain connectivity in individuals with autism spectrum disorders (ASD) is atypical and may vary with age. However, to date, no measures of functional connectivity measured within the first 2 years have specifically associated with a later ASD diagnosis. In the present study, we analyzed functional brain connectivity in 14-month-old infants at high and low familial risk for ASD using electroencephalography (EEG). EEG was recorded while infants attended to videos. Connectivity was assessed using debiased weighted phase lag index (dbWPLI). At 36 months, the high-risk infants were assessed for symptoms of ASD. As a group, high-risk infants who were later diagnosed with ASD demonstrated elevated phase-lagged alpha-range connectivity as compared to both low-risk infants and high-risk infants who did not go on to ASD. Hyper-connectivity was most prominent over frontal and central areas. The degree of hyper-connectivity at 14 months strongly correlated with the severity of restricted and repetitive behaviors in participants with ASD at 3 years. These effects were not attributable to differences in behavior during the EEG session or to differences in spectral power. The results suggest that early hyper-connectivity in the alpha frequency range is an important feature of the ASD neurophysiological phenotype.


Monitoring change requires a rethink of assessment practices in voice and speech.
Assessment for the purpose of monitoring change over time requires a different practical and statistical approach to that of assessment for diagnosing impairment. Sophisticated methods exist for identifying strengths and weaknesses in a patient's voice/speech profile, yet our understanding of the impact of repeated assessment is limited. Monitoring change necessitates that stimuli are stable in the absence of any true change in functioning, while remaining sensitive to influences that are considered to alter functioning (degeneration, therapy). The current paper discusses the issues relating to stimuli selection, identifying error within the sample and appropriate statistical models for identifying intra-individual change in the context of clinical and experimental speech or voice examinations.


Dicentric breakage at telomere fusions.
Nonhomologous end-joining (NHEJ) inhibition at telomeres ensures that native chromosome ends do not fuse together. But the occurrence and consequences of rare telomere fusions are not well understood. It is notably unclear whether a telomere fusion could be processed to restore telomere ends. Here we address the behavior of individual dicentrics formed by telomere fusion in the yeast Saccharomyces cerevisiae. Our approach was to first stabilize and amplify fusions between two chromosomes by temporarily inactivating one centromere. Next we analyzed dicentric breakage following centromere reactivation. Unexpectedly, dicentrics often break at the telomere fusions during progression through mitosis, a process that restores the parental chromosomes. This unforeseen result suggests a rescue pathway able to process telomere fusions and to back up NHEJ inhibition at telomeres.


[Drugs and health. 1. An experience with health education in a scholastic environment].
The paper describes the aim and the realization of a health education project on "Drugs and Health". The scheme was undertaken by the Hygiene Institute of the University of Padua, at the request of the ULSS (Local Health Unit) n. 31, of Adria (Rovigo), and it was directed to the teachers of the local "Grammar School" and indirectly also to the pupils and their families. At the end of the training programme, the teachers did not only learn the fundamental concepts on drugs and their correct use, but were also able in their turn to spread the acquired knowledge. During the six sessions, in which the project was divided, various aspects of the problems were studied. An active methodology was used: at the beginning a questionnaire was distributed, then the main subject was treated and finally the answers to the questionnaires were discussed. The meetings with the teachers and the pupils were organized in the same way. The subjects of the meetings were the following: 1st meeting: "What do I know about drugs?" 2nd meeting: "How do I use drugs?" 3rd meeting: "Do I use drugs correctly?" 4th meeting: "Why don't I use drugs properly?" 5th meeting: "Consequences of improper use of drugs" 6th meeting: "How can I improve my approach to the use of drugs?" Ten teachers of different disciplines, each responsible for a class of about 25 pupils, attended the meetings. All the teachers agreed to apply the proposed methodology to their classes. This methodology enabled both teachers and pupils to identify wrong concepts, or incorrect usage, autonomously. An important number of pupils have benefited from the educational project. Moreover, as part of health education scheme, a questionnaire on the domestic presence, use, conservation, and disposal of drugs was distributed to a number of pupils to involve their families. The results of this survey will be described in another paper.


A bibliometric analysis of Wnt signaling pathway: from the top-100 cited articles to emerging trends.
Wnt signaling pathway plays a vital role in the regulation of development. An increasing number of articles about Wnt pathway components have been published. By analyzing these studies' characteristics and qualities, we aim to reveal the current research focus and emerging trends in Wnt signaling. The databases of Web of Science Core Collection, BIOSIS Citation Index, MEDLINE, etc. were utilized to identify articles on May 23rd, 2020. Wnt signaling pathway-related articles were identified, the 100 most cited articles and articles in the last decade were selected and calculated for citations without self-citation. The subsequent analysis included citation density (citations/article age), time-related flux, authorship, institution, journal, geographic distribution, and theme. These articles were published mainly from 2000 to 2009 (62%). Citations per article ranged from 599 to 3,780 with a median number of 880 times. Most studies (66%) came from the United States. Nusse Roel and Clevers Hans (15 and 13 papers) have contributed significantly to the field. The most highlighted study themes were cancer (15%), embryo development (14%), and cytoplasm signal transduction (11%). From 2011 to 2020, interest in emerging subtopics, including osteogenesis, immune, apoptosis, autophagy, microRNA, and cancer stem cell, are rising. Cancer, embryo development, stem cell, and signal transduction process still play a major role in the field. With multiple emerging subtopics and investigation on an integrated view of the Wnt signal network, the association of Wnt with diseases was further revealed.


Subarachnoid hemorrhage in childhood and adolescence.
The authors have reviewed 167 cases of subarachnoid hemorrhage (SAH) occurring in patients aged 20 years and younger in a 23-year period. The modes of presentation and etiology of SAH are similar in childhood and adolescence and in the adult population, but there was a different incidence of the specific pathology producing the bleeding in this series. Twenty-six percent of cases were due to bleeding arteriovenous malformations, 52% were due to ruptured aneurysms, and in 19% no cause was found. Aneurysms in this young age group differed in several important respects from those in the adult population: there was a male predominance, a higher incidence of internal carotid bifurcation aneurysms was seen, and multiple aneurysms were encountered less commonly.


Advancing cross-sectoral data linkage to understand and address the health impacts of social exclusion: Challenges and potential solutions.
The use of administrative health data for research, monitoring, and quality improvement has proliferated in recent decades, leading to improvements in health across many disease areas and across the life course. However, not all populations are equally visible in administrative health data, and those that are less visible may be excluded from the benefits of associated research. Socially excluded populations - including the homeless, people with substance dependence, people involved in sex work, migrants or asylum seekers, and people with a history of incarceration - are typically characterised by health inequity. Yet people who experience social exclusion are often invisible within routinely collected administrative health data because information on their markers of social exclusion are not routinely recorded by healthcare providers. These circumstances make it difficult to understand the often complex health needs of socially excluded populations, evaluate and improve the quality of health services that they interact with, provide more accessible and appropriate health services, and develop effective and integrated responses to reduce health inequity. In this commentary we discuss how linking data from multiple sectors with administrative health data, often called cross-sectoral data linkage, is a key method for systematically identifying socially excluded populations in administrative health data and addressing other issues related to data quality and representativeness. We discuss how cross-sectoral data linkage can improve the representation of socially excluded populations in research, monitoring, and quality improvement initiatives, which can in turn inform coordinated responses across multiple sectors of service delivery. Finally, we articulate key challenges and potential solutions for advancing the use of cross-sectoral data linkage to improve the health of socially excluded populations, using international examples.


Bone sialoprotein expression in primary human breast cancer is associated with bone metastases development.
Breast cancer metastasizes to bone more frequently than to any other organ, and over 80% of advanced breast cancer patients develop bone metastases. Our recent demonstration that human breast cancer cells express bone sialoprotein (BSP), a bone matrix protein, provides a possible clue for the selective affinity of breast cancer cells for bone. We tested the hypothesis that detection of BSP in primary human breast cancer could be a potential indicator of the ability of breast cancer cells to metastasize to bone. BSP expression was evaluated in the primary breast cancers of 39 patients using immunoperoxidase and two specific anti-BSP antibodies. None of these patients presented clinically or scintigraphically detectable bone metastases at the time of surgery. In the course of their disease, 22 patients developed clinically diagnosed bone metastases. Expression of BSP in breast cancer cells from patients who developed bone metastases was significantly higher (p = 0.008, according to the Mann-Whitney test) than in patients with no bone involvement. No association was found between BSP expression in the primary breast lesions and axillary lymph node metastases. BSP expression was significantly increased in infiltrating ductal carcinoma compared with infiltrating lobular carcinoma (p = 0.0023). No correlation was found between immunoreactivity to BSP antibodies and estrogen receptor (ER) status, progesterone receptor (PR) status, or age. Our data suggest that BSP could help to identity which women will develop bone metastases and provide new bases for the understanding of the molecular mechanism(s) responsible for breast cancer cells osteotropism.


Differential wear of teeth and restorative materials: clinical implications.
This study reviewed the wear of commonly used dental restorative materials and their effects on the opposing dentition. Key words were used with PubMed to retrieve pertinent references to publications on tooth and restoration wear. The wear resistance of newer esthetic restorative materials has generally improved, and the damage caused by several materials to the opposing dentition has been reduced. However, the different structures and physical properties of tooth substance and restorative materials will eventually lead to varying degrees of differential wear. The extent and rate of wear are influenced by many intraoral factors. Selection of restorative materials must be based on knowledge of their wear behavior and the individual needs of each patient. The lowest wear rates for restorations and the opposing dentition occur with metal alloys, machined ceramics, and microfilled and microfine hybrid resin composites.


Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy.
Although many genes that predispose for epilepsy in humans have been determined, those that underlie the classical syndromes of idiopathic generalized epilepsy (IGE) have yet to be identified. We report that an Ala322Asp mutation in GABRA1, encoding the alpha1 subunit of the gamma-aminobutyric acid receptor subtype A (GABA(A)), is found in affected individuals of a large French Canadian family with juvenile myoclonic epilepsy. Compared with wildtype receptors, GABA(A) receptors that contain the mutant subunit show a lesser amplitude of GABA-activated currents in vitro, indicating that seizures may result from loss of function of this inhibitory ligand-gated channel. Our results confirm that mutation of GABRA1 predisposes towards a common idiopathic generalized epilepsy syndrome in humans.


Selective and signal-dependent recruitment of membrane proteins to secretory granules formed by heterologously expressed von Willebrand factor.
von Willebrand factor (vWF) is a large, multimeric protein secreted by endothelial cells and involved in hemostasis. When expressed in AtT-20 cells, vWF leads to the de novo formation of cigar-shaped organelles similar in appearance to the Weibel-Palade bodies of endothelial cells in which vWF is normally stored before regulated secretion. The membranes of this vWF-induced organelle, termed the pseudogranule, are uncharacterized. We have examined the ability of these pseudogranules, which we show are secretagogue responsive, to recruit membrane proteins. Coexpression experiments show that the Weibel-Palade body proteins P-selectin and CD63, as well as the secretory organelle membrane proteins vesicle-associated membrane protein-2 and synaptotagmin I are diverted away from the endogenous adrenocorticotropic hormone-containing secretory granules to the vWF-containing pseudogranules. However, transferrin receptor, lysosomal-associated membrane protein 1, and sialyl transferase are not recruited. The recruitment of P-selectin is dependent on a tyrosine-based motif within its cytoplasmic domain. Our data show that vWF pseudogranules specifically recruit a subset of membrane proteins, and that in a process explicitly driven by the pseudogranule content (i.e., vWF), the active recruitment of at least one component of the pseudogranule membrane (i.e., P-selectin) is dependent on residues of P-selectin that are cytosolic and therefore unable to directly interact with vWF.


Clinical efficacy of temporal artery biopsy in Nashville, Tennessee.
A retrospective study of temporal artery biopsies done over one decade in four Nashville hospitals yielded 412 procedures on 394 patients. Diagnosis was obtained in 17%, and the procedure was helpful in 21% of patients. Only two complications were recorded. There was no correlation between length of biopsy specimen and diagnostic yield. The Nashville experience with temporal artery biopsy is probably representative. Some refinement of procedure application appears necessary.


Description of a new laboratory evaluation method of interdental brush abrasion as a clinical hazard.
To simulate the abrasive potential of an interdental brush when applied with toothpastes and prophylactic gels/solutions in a novel laboratory brushing simulation set-up. A brushing device was customized to treat dentin samples mimicking a simplified interdental space with an interdental brush (ISO 2). The brushing, that is, 7200 strokes for 1 h, was performed with artificial saliva (control), a povidone-iodine solution, and slurries of chlorhexidine and fluoride gels as well as three toothpastes with different RDA values ranging from 29 to 100, respectively. The loss of dentin was profilometrically assessed and compared with ANOVA and Fishers LSD. While artificial saliva as control, the solution and the gel slurries showed no measurable dentin loss, toothpastes resulted in a measurable linear surface damage with respect to the actual intrinsic RDA values and ranged from 12.6 to 26.5 μm (p < 0.001). Any interdental cleaning product should be tailored and carefully instructed. Any over- and misuse should be avoided, which applies especially to the use of interdental brushes in combination with abrasive toothpastes.


Circulating form of beta-2-microglobulin in dialysis patients.
The circulating profile of beta-2-microglobulin (beta 2M) was determined in 8 end-stage renal disease patients on long-term dialysis (6 on hemodialysis, 2 on CAPD) by measuring beta 2M in different fraction after molecular sieve separation of their sera. Four patients had carpal tunnel syndrome with demonstrated amyloid in excised wrist tissues of which 2 were positive for beta 2M. In all patients despite very high blood levels (34.3-63.1 mg/l), beta 2M eluted exclusively as a single peak in the molecular weight region of about 12,000 daltons on a calibrated Sephacryl S-200 column. Recoveries from within the peak accounted for 96% of the applied beta 2M serum concentrations. These results were confirmed by molecular sieve separation of the enriched beta 2M-containing fractions by high-pressure liquid chromatography. We conclude that immunoreactive beta 2M in dialysis patients circulates as an intact monomer without evidence for the formation of aggregates or fragments. The pathogenesis of tissue deposition of this low-molecular-weight protein and its polymerisation to form a specific amyloid remains to be defined.


Prevalence and Correlates of Unmet Supportive Needs of Nigerian Patients With Cancer.
Diagnosis and treatment of cancer are associated with significant psychological distress, and patients face a broad range of challenges that create a vacuum of unmet needs felt by patients, such as a loss of personal control and frustration. The aim of the current study was to determine the magnitude, distribution, and correlates of unmet needs in Nigerian patients with cancer. Using a descriptive cross-sectional approach, we assessed 205 patients with cancer who attended oncology outpatient clinics at the Lagos University Teaching Hospital. Eligible patients were administered the Supportive Care Needs Survey (SCNS) -Short Form 34 with a focus on five domains of need: psychological, health system and information, physical and daily living, patient care and support, and sexuality. Mean age was 47.4 ± 12.3 years and patients were predominantly female (96.6%). The most common diagnosis was breast cancer (92.2%), and mean duration since diagnosis was 20.9 ± 21.9 months for all patients. Mean SCNS score was 83.9 ± 24.8 and at least 46% of participants indicated unmet needs in 15 items of the SCNS. The most frequent unattended needs were related to the health information (53.4%), physical and daily living (49.4%), psychological (48.5%), sexuality, and patient care and support domains. None of the factors considered-age, sex marital status, family type, educational attainment, employment status, economic status, the presence of financial support, social support, and cancer type-was significantly predictive of unmet needs in these patients (P > .05). Nigerian patients with cancer experience considerable levels of unmet needs. These needs require urgent and long-term interventions to help patients achieve increased care satisfaction and a better quality of life.


Silencing and re-expression of retinoic acid receptor beta2 in human melanoma.
Many melanoma cells are resistant to the anti-proliferative effect of all trans retinoic acid (ATRA). Retinoic Acid Receptor-beta2 (RAR-beta2) mediates the ATRA growth inhibition. We found a correlation between the anti-proliferative activity of ATRA and expression of RAR-beta2. There was not a strict correlation between DNA methylation of RAR-beta gene and its expression. There was no difference in global and RARbeta specific nucleosome repeat length (NRL) in melanoma and melanocytes or between control and ATRA treated cells. Pan-acetylation of H3 and H4 within the RAR-beta gene promoter was higher in cells expressing RAR-beta2. All trans retinoic acid treatment of responsive cells did not change pan-acetylation of H3/H4, but addition of ATRA to non-responsive cells increased H4 pan-acetylation. Phytochemicals or the histone deacetylase inhibitor Trichostatin A did not restore expression of RAR-beta2. Treatment of WM1366 melanoma cells with 5-aza 2'-deoxycytidine reactivated RAR-beta2 gene expression and restored the ability of ATRA to further induce the expression of this gene. Therefore, promoter methylation is responsible for silencing of RAR-beta2 in some melanoma cells and pan-acetylation of H3 likely plays a permissive role in expression of RAR-beta2.


[Artificial insemination in pigs: study of conception conditions with use of 2 inseminations in heat with about 24 hours interval].
140 sows and gilts of Danish Landrace were inseminated twice per heat with an interval of approximately 24 hours. Half of the females had their first insemination with semen of Danish Landrace and their second insemination with semen of Yorkshire, the other half vice versa. 114 females became pregnant. At farrowing the number of offspring of Danish Landrace and/or Danish Landrace X Yorkshire per sow/gilt was registrated. The results have been set out in tables I and II, from which it can be seen, that 59% conceived only after first insemination, 18% only after second insemination and 23% after both first and second insemination. In the last group 52% of the offspring were from the first insemination and 48% from the second insemination. In the sows no increase in av. litter size after two inseminations was found. The results are discussed and apparent discrepancy with earlier results is explained with a presumbably existing competition in the female genital tract between sperms from two inseminations at different times in the heat, resulting in ageing of the first inseminated sperms.


Validation of the Youth Acute Pain Functional Ability Questionnaire in Children and Adolescents Undergoing Inpatient Surgery.
Half of children admitted after surgery experience intense pain in hospital, and many experience continued pain and delayed functional recovery at home. However, there is a gap in tools available to measure acute functional ability in pediatric postsurgical settings. We aimed to validate the Youth Acute Pain Functional Ability Questionnaire (YAPFAQ) in a large inpatient pediatric surgical population, evaluate its responsiveness to expected functional recovery, and develop a short form for broad clinical implementation. The YAPFAQ is a self-report measure assessing acute functional ability, developed in children admitted for acute sickle cell pain. We evaluated psychometric properties of the measure in 564 children ages 8 to 18 years admitted after surgery. A sample of 54 participants completed the YAPFAQ daily for 3 days after major surgery to assess responsiveness. The measure showed good reliability (Cronbach α = .96) and construct validity, with expected relationships with physical health-related quality of life (r = -.53, P < .001) and pain intensity (r = .42, P < .001). YAPFAQ scores decreased over time showing good responsiveness to expected recovery. A 3-item short form of the YAPFAQ showed promising psychometric properties. Early assessment of functioning after surgery may identify children at risk for poor functional outcomes and allow targeting of therapies to improve postsurgical recovery. The YAPFAQ showed promising psychometric properties in a pediatric postsurgical population. This study addresses a gap in tools available to monitor functional recovery during hospitalization after pediatric surgery. Early detection of problems with recovery may enable targeted therapies to improve postsurgical outcomes.


Integrated perovskite/bulk-heterojunction toward efficient solar cells.
We successfully demonstrated an integrated perovskite/bulk-heterojunction (BHJ) photovoltaic device for efficient light harvesting and energy conversion. Our device efficiently integrated two photovoltaic layers, namely a perovskite film and organic BHJ film, into the device. The device structure is ITO/TiO2/perovskite/BHJ/MoO3/Ag. A wide bandgap small molecule DOR3T-TBDT was used as donor in the BHJ film, and a power conversion efficiency (PCE) of 14.3% was achieved in the integrated device with a high short circuit current density (JSC) of 21.2 mA cm(-2). The higher JSC as compared to that of the traditional perovskite/HTL (hole transporting layer) device (19.3 mA cm(-2)) indicates that the BHJ film absorbs light and contributes to the current density of the device. Our result further suggests that the HTL in traditional perovskite solar cell, even with good light absorption capability, cannot contribute to the overall device photocurrent, unless this HTL becomes a BHJ layer (by adding electron transporting material like PC71BM).


Activation parameters for the carbonic anhydrase II-catalyzed hydration of CO2.
We have determined the activation parameters of kcat and kcat/Km for the carbonic anhydrase II-catalyzed hydration of CO2. The enthalpy and entropy of activation for kcat is 7860 +/- 120 cal mol-1 and -3.99 +/- 0.42 cal mol-1 K-1, respectively, for the human enzyme. Results for the bovine enzyme were statistically indistinguishable from those of the human enzyme. The entropy of activation of kcat for the human enzyme was further decomposed into partially compensating electrostatic(es) (delta S*es = +15.1 cal mol-1 K-1) and nonelectrostatic(nes) (delta S*nes = -19.1 cal mol-1 K-1) terms. Computer simulations of a formal kinetic mechanism for carbonic anhydrase II-catalyzed CO2 hydration show that 82% of the temperature effect on kcat can be attributed to the temperature effect on the intramolecular proton transfer step. The reported activation parameters are consistent with a substantial enzyme or active site solvent conformational change in the transition state of the intramolecular proton transfer step, and is consistent with the mechanism of proton transfer proposed by Venkatasubban and Silverman (Venkatasubban, K. S., and Silverman, D. N. (1980) Biochemistry 19, 4984-4989).


Intrinsic Rattler-Induced Low Thermal Conductivity in Zintl Type TlInTe2.
Understanding the nature of chemical bonding and lattice dynamics together with their influence on phonon-transport is essential to explore and design crystalline solids with ultralow thermal conductivity for various applications including thermoelectrics. TlInTe2, with interlocked rigid and weakly bound substructures, exhibits lattice thermal conductivity as low as ca. 0.5 W/mK near room temperature, owing to rattling dynamics of weakly bound Tl cations. Large displacements of Tl cations along the c-axis, driven by electrostatic repulsion between localized electron clouds on Tl and Te ions, are akin to those of rattling guests in caged-systems. Heat capacity of TlInTe2 exhibits a broad peak at low-temperatures due to contribution from Tl-induced low-frequency Einstein modes as also evidenced from THz time domain spectroscopy. First-principles calculations reveal a strong coupling between large-amplitude coherent optic vibrations of Tl-rattlers along the c-axis, and acoustic phonons that likely causes the low lattice thermal conductivity in TlInTe2.


Mutations in the rpsL gene are involved in streptomycin resistance in Campylobacter coli.
To characterize the mechanisms of streptomycin (STR) resistance in Campylobacter coli, we chose 17 isolates that were resistant to STR, erythromycin (ERY), or both, and the putative STR resistance target genes rpsL, rrs, and gidB were analyzed for mutations. The presence of the aadE gene encoding aminoglycoside 6-adenylyltransferase was also evaluated. To reveal putative connection between ERY and STR resistance mechanisms, 13 C. coli isolates initially susceptible to STR and ERY were exposed to STR, and resistant variants were characterized. We also assessed the development of ERY resistance with a similar method. Finally, the effect of the putative CmeABC efflux pump inhibitor phenyl-arginine-beta-naphthylamine on STR resistance was tested. Our studies showed an association between mutations in the rpsL gene and STR resistance in C. coli. Further, mutations obtained in vitro were more diverse than those occurring in vivo. However, we observed no resistance associated mutations in the other genes studied, and selection with STR did not result in variants resistant to ERY and vice versa. None of the isolates harbored the aadE gene, and no differences in STR minimum inhibitory concentration levels were detected in the presence or absence of phenyl-arginine-beta-naphthylamine. In conclusion, we found that STR resistance was associated with mutations in the rpsL gene, but no obvious association between STR and ERY resistance mechanisms was found in C. coli.


Vertical distribution and environmental significance of sulfur and oxygen heterocyclic aromatic hydrocarbons in soil samples collected from Beijing, China.
Vertical distribution of the concentration and composition of some sulfur and oxygen heterocyclic aromatic hydrocarbons (SOHAHs), such as, fluorene, dibenzofuran, dibenzothiophene and their alkyl homologues in 10 soil profiles in Beijing have been investigated. The results showed that the concentrations and composition of SOHAHs in topsoil (0-30cm) from different profiles are different. The concentrations of SOHAHs in topsoils are much higher than that in bottom soils where the concentrations are relatively constant. The fingerprints of SOHAHs from same profile are similar in topsoil samples, which are obviously different at the deep part, which suggested that the sources of these compounds are consistent in topsoil and are discriminating between surface and bottom soils. The main sources of SOHAHs in surface soil were fossil fuel combustion, petroleum and wastewater irrigation, while those at deep part were likely derived from the degradation products of soil organic matters.


Nursing care time in the Intensive Care Unit: evaluation of the parameters proposed in COFEN Resolution Nº 293/04.
This study aimed to evaluate the parameters established in COFEN Resolution 293/04 concerning nursing staff dimensioning in adult intensive care units (AICU). The research was conducted in six hospitals in São Paulo City. The daily quantitative average of professionals needed for patient care was calculated according to the parameters established by COFEN. The obtained results were compared with the existing number of daily staff members in these units. It was observed that the proportions recommended by COFEN for the nurse category are superior to those used in the hospitals studied, which represents a challenge for Brazilian nursing. Mean care time values were found appropriate and represent important standards for dimensioning the minimum number of professionals in AICU. This study contributed to the validation of the parameters indicated in Resolution 293/04 for nursing staff dimensioning in the AICU.


Transcatheter Pulmonary Valve Replacement: Current State of Art.
The past couple of decades have brought tremendous advances to the field of pediatric and adult congenital heart disease (CHD). Percutaneous valve interventions are now a cornerstone of not just the congenital cardiologist treating patients with congenital heart disease, but also-and numerically more importantly-for adult interventional cardiologists treating patients with acquired heart valve disease. Transcatheter pulmonary valve replacement (tPVR) is one of the most exciting recent developments in the treatment of CHD and has evolved to become an attractive alternative to surgery in patients with right ventricular outflow tract (RVOT) dysfunction. This review aims to summarize (1) the current state of the art for tPVR, (2) the expanding indications, and (3) the technological obstacles to optimizing tPVR. Since its introduction in 2000, more than ten thousands tPVR procedures have been performed worldwide. Although the indications for tPVR have been adapted earlier from those accepted for surgical intervention, they remain incompletely defined. The new imaging modalities give better assessment of cardiac anatomy and function and determine candidacy for the procedure. The procedure has been shown to be feasible and safe when performed in patients who received pulmonary conduit and or bioprosthetic valves between the right ventricle and the pulmonary artery. Fewer selected patients post trans-annular patch repair for tetralogy of Fallot may also be candidates for this technology. Size restrictions of the currently available valves limit deployment in the majority of patients post trans-annular patch repair. Newer valves and techniques are being developed that may help such patients. Refinements and further developments of this procedure hold promise for the extension of this technology to other patient populations.


Enantioselective recognition of radezolid by cyclodextrin modified capillary electrokinetic chromatography and electronic circular dichroism.
A method for the enantioseparation of radezolid (RAD), an analogue of a truly new class of antibacterial agents, oxazolidinones, was developed based on capillary electrokinetic chromatography using a cyclodextrin as a chiral pseudophase (CD-cEKC). The mechanism of RAD separation, together with its precursor, were investigated to directly define the relationship between the oxazolidinone structure and the complexation process. During the development of the method, anionic single isomer cyclodextrins were tested. They were ranked in order from hydrophilic to hydrophobic as follows: heptakis-(2,3-dihydroxy-6-sulfo)-β-cyclodextrin (HS-β-CD), heptakis-(2,3-diacetyl-6-sulfo)-β-cyclodextrin (HDAS-β-CD) and heptakis-(2,3-dimethyl-6-sulfo)-β-cyclodextrin (HDMS-β-CD). Experiments were performed at pH values of 2.5, 6.6, 8.2 and 9.6. The cyclodextrins that had an acetyl or methyl group at the C2 and C3 positions, referred to as HDAS-β-CD and HDMS-β-CD, respectively, exhibited partial and baseline separation of enantiomers in a low pH buffer. However, higher temperatures were required for HDAS-β-CD and acetonitrile addition was required for HDMS-β-CD. During the experiments, different organic solvents, varying in their amphiprotic or aprotic nature, were tested. The best results for the separation of enantiomers using the CD-cEKC method were obtained with 40mM HDMS-β-CD dissolved in a 50mM phosphate buffer (pH 2.5) with the addition of acetonitrile (65:35, v/v) at 27°C, reversed polarity and a voltage equal to 28kV. The apparent binding constants for each enantiomer to HDAS-β-CD or HDMS-β-CD were calculated. Finally, the stereochemistry of (S) and (R)-RAD and the behaviour of selected complex formations were established using electronic circular dichroism.


First-principles study of the H(2) interaction with transition metal (Ti, V, Ni) doped Mg(0001) surface: Implications for H-storage materials.
Using first-principles calculations we have investigated the interaction of hydrogen molecules with clean and M (Ti, V, and Ni) doped Mg(0001) surfaces. The calculations have been carried out using plane-wave-based pseudopotential method under the formalism of density functional theory. First we have calculated the stability of the M atoms on the Mg surface. On the basis of the energetic criteria, we found that all these M atoms prefer to substitute one of the Mg atoms from the second layer than the top surface atom. In the second step we have studied the interaction of a hydrogen molecule with the clean and doped Mg surface. The results show that for M atoms at the surface, the hydrogen molecule undergoes spontaneous dissociative chemisorptions. However, for M atoms in the second layer, it requires to cross an activation barrier to undergo molecular dissociation. Furthermore, to understand the mobility of hydrogen atoms on the surface we have calculated the diffusion energy barriers for the M doped surface. Contrary to the molecular dissociation behavior, it is found that the mobility of hydrogen atoms on the surface is easier if the M atoms are placed in the second layer in comparison to that in the top surface layer. It is believed that the results of the present study provide useful information based on the first-principles calculations for synthesizing Mg based materials for hydrogen storage with optimal performance.


Ultrahigh volatile iodine uptake by hollow microspheres formed from a heteropore covalent organic framework.
We herein report the construction of a new heteropore COF which consists of two different kinds of micropores with unprecedented shapes. It exists as hollow microspheres and exhibits an extremely high volatile iodine uptake (up to 481 wt%) by encapsulating iodine in the inner cavities and porous shells of the microspheres.


Investigation of Newly Diagnosed Drug-Naive Patients with Systemic Autoimmune Diseases Revealed the Cleaved Peptide Tyrosine Tyrosine (PYY 3-36) as a Specific Plasma Biomarker of Rheumatoid Arthritis.
There is a current imperative to reveal more precisely the molecular pathways of early onset of systemic autoimmune diseases (SADs). The investigation of newly diagnosed drug-naive SAD patients might contribute to identify novel disease-specific and prognostic markers. The multiplex analysis of 30 plasma proteins in 60 newly diagnosed drug-naive SADs, such as RA (rheumatoid arthritis, n = 31), SLE (systemic lupus erythematosus, n = 19), and SSc (systemic scleroderma, n = 10) patients, versus healthy controls (HCs, n = 40) was addressed. Thirty plasma cytokines were quantified using the Procarta Plex™ panel. The higher expression of IL-12p40, IL-10, IL-13, IFN-γ, M-CSF, IL-4, NTproBNP, IL-17A, BMP-9, PYY (3-36), GITRL, MMP-12, and TNFRSF6 was associated with RA; IL-12p40, M-CSF, IL-4, GITRL, and NTproBNP were higher in SLE; or NTproBNP, PYY (3-36), and MMP-12 were increased in SSc over HCs, respectively. The cleaved peptide tyrosine tyrosine (PYY 3-36) was elevated in RA (361.6 ± 47.7 pg/ml) vs. HCs (163.96 ± 14.5 pg/ml, mean ± SEM, ∗∗∗ p = 4 × 10-5). The CI (95%) was 268.05-455.16 pg/ml for RA vs. 135.55-192.37 pg/ml for HCs. The elevated PYY (3-36) level correlated significantly with the increased IL-4 or GITRL concentration but not with the clinical scores (DAS28, CRP, ESR, RF, aMCV). We are the first to report cleaved PYY (3-36) as a specific plasma marker of therapy-naive RA. Additionally, the multiplex plasma protein analysis supported a disease-specific cytokine pattern in RA, SLE, and SSc, respectively.


Identification of ilaprazole metabolites in human urine by HPLC-ESI-MS/MS and HPLC-NMR experiments.
Ilaprazole is a new proton pump inhibitor designed for the treatment of gastric ulcers, and limited data is available on the metabolism of the drug. In this article, the structural elucidation of urinary metabolites of ilaprazole in human was described by HPLC-ESI-MS/MS and stopped-flow HPLC-NMR experiments. Urinary samples were precipitated by sodium carbonate solution, and then extracted by liquid-liquid extraction after adding ammonium acetate buffer solution. The enriched sample was separated using a C(18) reversed-phase column with the mobile phase composed of acetonitrile and 0.05 mol/L ammonium acetate buffer solution in a gradient solution, and then directly coupled to ESI-MS/MS detection in an on-line mode or (1)H-NMR (500 MHz) spectroscopic detection in a stopped-flow mode. As a result, four sulfide metabolites, ilaprazole sulfide (M1), 12-hydroxy-ilaprazole sulfide (M2), 11,12-dihydroxy-ilaprazole sulfide (M3) and ilaprazole sulfide A (M4), were identified by comparing their MS/MS and NMR data with those of the parent drug and available standard compounds. The main biotransformation reactions of ilaprazole were reduction and the aromatic hydroxylation of the parent drug and its relative metabolites. The result testified that HPLC-ESI-MS/MS and HPLC-NMR could be widely applied in detection and identification of novel metabolites.


Impression Cytology in a Series of Clinically Diagnosed Ocular Surface Melanocytic Lesions.
To report impression cytology (IC) results of clinically diagnosed ocular surface melanocytic lesions. Ten patients with a clinical diagnosis of an ocular surface melanocytic lesion underwent IC using cellulose acetate strips and Periodic acid Schiff-Papanicolaou staining. Excisional biopsy of lesions was performed in case of observing atypical cells on IC or at the patient's request, and excised specimens were subjected to histopathological analysis. Agreement between clinical diagnoses and IC results and between IC results and histopathology were evaluated. Clinical diagnoses were nevi in 6, primary acquired melanosis (PAM) with atypia/melanoma in 2, and atypical nevus versus pigmented conjunctival intraepithelial neoplasia (CIN) in 2 cases. IC results were suggestive of a benign nevus in 7, PAM with atypia/melanoma in 2 and CIN versus an atypical epithelioid type melanocytic lesion in 1 case. IC results were consistent with the clinical diagnoses in 9 cases (Cohen's kappa index of 0.83) and excluded CIN in 1. Histopathology in 6 cases disclosed benign melanonevus in 3, malignant melanoma in the context of PAM with atypia in 2, and CIN in 1 case. Histologic results were well correlated with the IC features (Cohen's kappa index of 0.74). By demonstrating typical cytomorphological features of ocular superficial layers IC diagnosed the true nature of melanocytic ocular surface lesions in the majority of cases. Although IC does not substitute histopathology, given the high correlation between IC results and histopathology, it can be of great assistance in diagnosis and management of ocular surface melanocytic lesions.


Antiplatelet effects of R,S-(meso)-alpha, alpha'-bis[3-(N,N-diethylcarbamoyl) piperidino]-p-xylene ex vivo in the dog and in vivo in the mouse.
1. The nipecotamide alpha,alpha'-bis[3-(N,N-diethylcarbamoyl)piperidino]-p-xylene (A-1) is a platelet aggregation inhibitor. The meso diastereomer A-1c is superior in potency and duration to the synthetic diastereomeric mixture consisting of the R,R-, S,S-, and R,S- (meso) isomers in inhibiting collagen-induced platelet aggregation ex vivo in the dog. 2. A-1c also is more potent and longer acting than A-1 in protecting mice from collagen+epinephrine-induced thromboembolic death. 3. The mechanism of antiplatelet action of this compound appears to be related to its ability to prevent agonist-induced inhibition of platelet cyclic adenosine monophosphate (cAMP) levels.


ABC transporters and immunity: mechanism of self-defense.
The transporter associated with antigen processing (TAP) is a prototype of an asymmetric ATP-binding cassette (ABC) transporter, which uses ATP binding and hydrolysis to translocate peptides from the cytosol to the lumen of the endoplasmic reticulum (ER). Here, we review molecular details of peptide binding and ATP binding and hydrolysis as well as the resulting allosteric cross-talk between the nucleotide-binding domains and the transmembrane domains that drive translocation of the solute across the ER membrane. We also discuss the general molecular architecture of ABC transporters and demonstrate the importance of structural and functional studies for a better understanding of the role of the noncanonical site of asymmetric ABC transporters. Several aspects of peptide binding and specificity illustrate details of peptide translocation by TAP. Furthermore, this ABC transporter forms the central part of the major histocompatibility complex class I (MHC I) peptide-loading machinery. Hence, TAP is confronted with a number of viral factors, which prevent antigen translocation and MHC I loading in virally infected cells. We review how these viral factors have been used as molecular tools to decipher mechanistic aspects of solute translocation and discuss how they can help in the structural analysis of TAP.


The impact of pulmonary cachexia on inpatient outcomes: A national study.
Cachexia has been associated with chronic lung disease (pulmonary cachexia syndrome), which is associated with increased mortality. However, studies that looked into this association was relatively small, and national level data are lacking. Herein, we aim to study the association between chronic obstructive lung disease (COPD) and cachexia. Do patients with COPD and cachexia has worse inpatient outcomes in comparison to those with no cachexia? We used the Nationwide Readmissions Database from 2016 to 2019, extracting adult patients with a primary diagnosis of COPD who were admitted between January and November of each year studied. We excluded patients with missing data on event time or length of stay. Furthermore, we excluded all cases with cormobidities associated with cachexia. We used SAS 9.4 for data exploration and analysis. We included 1,446,431 COPD-related weighted hospitalizations for which 115,276 cases (7.9%) had a concurrent diagnosis of cachexia (or cachexia-related diagnoses). Overall, patients with cachexia (COPD-C), compared to patients with COPD and no cachexia (COPD-NC), were older (mean age 69 vs. 66 years, respectively, P < 0.001) with similar gender distribution (58%). COPD-C patients had more inpatient complications including cardiac arrest, and use of mechanical ventilation (P < 0.001). Furthermore, they had longer mean lengths of stay (5.2 days vs. 3.8 days, P < 0.001). In-hospital mortality during index, admission was significantly higher in these patients at 2.2% compared to 0.5% for COPD-NC (P < 0.001). COPD-related cachexia is associated with increased inpatient mortality, resource utilization, and prolonged hospitalization.


Ganoderma boninense Disease of Oil Palm to Significantly Reduce Production After 2050 in Sumatra if Projected Climate Change Occurs.
Palm oil is a valuable crop. This relates to the high economic return from sales of the commodity, where Indonesia is the major producer in the world and the island of Sumatra is the most important region for palm oil production in the country. The island can be considered as a model for other oil palm growing regions in SE Asia. The area in Sumatra with a suitable climate for growing oil palm will decrease in size due to projected climate change as demonstrated specifically herein. The more unsuitable climate will lead to concomitant increases in basal stem rot (BSR) by Ganoderma boninense, as previously predicted, which is of major concern to sustainability in SE Asia. A novel approach is described herein, whereby (a) a determination of suitable climate for growing oil palm in Sumatra and (b) deductions to determine future BSR levels on the island were undertaken. The unsuitability of the climate for oil palm is predicted to increase dramatically after 2050 when BSR is predicted to increase to very high levels on most parts of the island. This is likely to make palm oil production unsustainable at some stage between 2050 and 2100. North Sumatra may be more sustainable than the other areas considered in Sumatra. These effects of projected climate change require amelioration before the high levels of BSR and the unsuitable climate for oil palm are realized.


PFKFB3 potentially contributes to paclitaxel resistance in breast cancer cells through TLR4 activation by stimulating lactate production.
Paclitaxel is a commonly used agent for breast cancer therapy, which comes across the obstacle "drug resistance", resulting in shortened overall survival of patients. Warburg effect has become one character of cancer cell and was reported to induce paclitaxel resistance, the mechanism of which is poorly understood. In this study, we sought to examine the role of 6-Phosphofructo-2-kinase (PFKFB3), a critical regulator of glycolysis, in paclitaxel resistance development. Two clones of paclitaxel resistant breast cancer cells, MCF-7RA and MCF-7RB, were established by a long term exposure of MCF-7 cells to paclitaxel. Consequently, PFKFB3 expression was found to be increased in MCF-7RA and MCF-7RB cells compared with MCF-7 cells. Silencing PFKFB3 expression markedly reduced the IC50 concentrations of MCF-7RA and MCF-7RB cells. Moreover, PFKFB3 modulated toll like receptor 4 (TLR4) and MyD88 expression as well as interleukin (IL)-6 and IL-8 release from breast cancer cells in response to paclitaxel exposure. In addition, PFKFB3 overexpression boosted up fructose-2,6-bisphosphate (F2,6BP) and lactate production. The enhanced lactate contributed to TLR4 signaling activation, IL-6 and IL-8 generation, and cell viability promotion in MCF-7 cells. In all, we characterized the novel role of PFKFB3 in induction of paclitaxel resistance by raising lactate production and activating TLR4 signaling.


Gene synthesis technology: recent developments and future prospects.
Gene synthesis is a potentially powerful tool in molecular biology that has not yet reached widespread use because of the relatively high cost and labor-intensive nature of the process. This paper reviews some recent technological developments and current research activities of this laboratory which promise to greatly reduce the cost of gene synthesis and to increase the speed and efficiency of the process. We recently developed an improved device for "segmented" synthesis of oligonucleotides, which utilizes porous Teflon wafers containing derivatized controlled pore glass supports to simultaneously synthesize up to 100 different DNA sequences. The stepwise coupling efficiency with the "wafer synthesis device" is as high as that attained with current automated "gene machines" producing 1-4 oligonucleotides at a time, whereas the reagent usage is only 20-50% that of the current DNA synthesizers. At present, we are optimizing the conditions for rapid, efficient assembly of genes on a solid-phase support, wherein ordered, stepwise annealing/washing is performed to segmentally elongate a "starting" oligonucleotide attached to a solid-phase support. We expect that the wafer synthesis device (operated at reduced scale of synthesis), together with solid-phase gene assembly, will permit the synthesis and assembly of an average size gene (1 kb) in one week at a cost of less than $1000. These developments should make gene synthesis a routine and powerful tool in molecular biology.


Application of FLOW 800 in extracranial-to-intracranial bypass surgery for moyamoya disease.
The surgical treatment of moyamoya disease is heavily reliant upon a real-time understanding of cerebral hemodynamics. The application of FLOW 800 allows the surgeon to semiquantify the degree of perfusion to the cerebral cortex following extracranial-to-intracranial (EC-IC) bypass surgery. The authors present three illustrative cases demonstrating common intraoperative findings prior to and following anastomosis using FLOW 800. All patients were diagnosed by catheter angiogram with moyamoya disease and noninvasive imaging demonstrating hemispheric hypoperfusion. Superficial temporal artery (STA)-to-middle cerebral artery (MCA or M4) bypasses were performed to augment intracranial perfusion. The patients tolerated the procedures well and were discharged without event in stable neurological condition. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21191.


Diagnostic Implications of Ultrasound Evaluation in Patients With Shoulder Impingement Syndrome.
To evaluate the diagnostic value of musculoskeletal ultrasound measurements of subacromial bursa (SAB) thickness, supraspinatus tendon (SUP) thickness, acromiohumeral distance (AHD), and SUP-to-AHD ratio (AHD%) in patients with shoulder impingement syndrome (SIS). This was a prospective cross-sectional observational study. Thirty patients with SIS (60 shoulders) admitted between January 2019 and January 2020 were enrolled. The SUP thickness, SAB thickness, AHD, and AHD% (calculated as AHD% = [(SUP / AHD) × 100%]) were measured in 60 shoulders using musculoskeletal ultrasound. The affected shoulder displayed thicker SUP and SAB (t = 7.838), narrower AHD (t = 2.324), and larger AHD% (t = 6.875) than the unaffected shoulder (P < .05). The SUP thickness showed a linear positive correlation with AHD (r = .503) and AHD% (r = .792) in the affected shoulder (P < .05). On receiver operating characteristic analysis, AHD*AHD% showed the best diagnostic performance in both measurements (area under the curve: 0.877). This study revealed that SIS symptoms may be related to a larger AHD% with SUP thickening. As diagnostic criteria, the cut-off values of AHD% (65.6%) and AHD*AHD% (0.504) have good sensitivity and specificity and can help improve the differential diagnosis of patients with SIS.


Rheumatoid Arthritis of Knee Joints: MRI-Pathological Correlation.
To evaluate the correlation between features of knee joint rheumatoid arthritis (RA) identified on MRI and histological examination as a means of elucidating the pathogenesis of joint destruction in RA. This is a prospective analysis of 26 knee joints of 22 patients who underwent total knee arthroplasty (TKA) for the treatment of RA. Based on the degree of destruction of articular cartilage and the menisci, the occurrence of bone marrow edema and bone erosion, and synovial thickening, the stage of the knee joints were classified using MRI by two radiologists. Differences in the severity of destruction of the articular cartilage of the medial and lateral femoral condyles and medial and lateral tibial plateaus, the medial and lateral menisci, and bone were compared using analysis of variance with a post-hoc test, and the Mann-Whitney U-test. Samples of cartilage, subchondral bone, menisci, and synovium were obtained from the resected knee specimens during TKA and analyzed semiquantitatively using microscopy and immunohistochemistry. Histological differences between areas of bone erosion and bone marrow edema were evaluated using a Mann-Whitney U-test. The extent of articular destruction was classified as grade 4 for the medial and lateral femoral condyles and the medial and lateral tibial plateaus for most patients, with an average destruction grade of 3.6 (F = 5.455, P = 0.002), with the least amount of destruction identified on the lateral femoral condyle. The majority of knee joints in the RA patients were at stage 3 (21/26, 80.8%), followed by stage 4 (4/26, 15.4%). Fibrosis, thinning and destruction, and hyperplasia were the most severe pathological changes in cartilage. In a total of 26 specimens, 36 areas of bone marrow edema and 68 areas of bone erosion were identified, with fibrosis, a mosaic structure of bone, and lymphocyte infiltration being the most severe changes in these areas. The degree of meniscus destruction was classified as grade 4 in the majority patients for both the medial and lateral meniscus, with an average degree of meniscal destruction over all specimens of 3.85, and greater destruction of the medial meniscus than of the lateral meniscus (Z = 2.062, P = 0.039). Fibrosis and engulfing calcified debris were the most severe pathological manifestations. Synovitis was also identified in all 26 specimens, with hyperplasia of intima cells and lymphocyte and plasma cell infiltration being the most severe pathological manifestations. Severe destruction of the articular cartilage and menisci is a characteristic feature of RA. Bone marrow edema and bone erosion can both also be found, but are less characteristic. Synovial infiltration may be the triggering mechanism of the destruction of the cartilage, menisci, and bone marrow. However, the origin of bone marrow edema requires further investigation.


Getting off on the wrong foot? How community groups in Zimbabwe position themselves for partnerships with external agencies in the HIV response.
Partnerships are core to global public health responses. The HIV field embraces partnership working, with growing attention given to the benefits of involving community groups in the HIV response. However, little has been done to unpack the social psychological foundation of partnership working between well-resourced organisations and community groups, and how community representations of partnerships and power asymmetries shape the formation of partnerships for global health. We draw on a psychosocial theory of partnerships to examine community group members' understanding of self and other as they position themselves for partnerships with non-governmental organisations. This mixed qualitative methods study was conducted in the Matobo district of Matabeleland South province in Zimbabwe. The study draws on the perspectives of 90 community group members (29 men and 61 women) who participated in a total of 19 individual in-depth interviews and 9 focus group discussions (n = 71). The participants represented an array of different community groups and different levels of experience of working with NGOs. Verbatim transcripts were imported into Atlas.Ti for thematic indexing and analysis. Group members felt they played a central role in the HIV response. Accepting there is a limit to what they can do in isolation, they actively sought to position themselves as potential partners for NGOs. Partnerships with NGOs were said to enable community groups to respond more effectively as well as boost their motivation and morale. However, group members were also acutely aware of how they should act and perform if they were to qualify for a partnership. They spoke about how they had to adopt various strategies to become attractive partners and 'supportable' - including being active and obedient. Many community groups in Zimbabwe recognise their role in the HIV response and actively navigate representational systems of self and other to showcase themselves as capable actors. While this commitment is admirable, the dynamics that govern this process reflect knowledge encounters and power asymmetries that are conditioned by the aid architecture, undermining aspiring efforts for more equitable partnerships from the get-go.


Complete Genome Sequences of 15 Chikungunya Virus Isolates from Puerto Rico.
Here, we report the complete genome sequences of 15 chikungunya virus strains isolated from human plasma from infected patients in Puerto Rico. The results show that currently circulating chikungunya strains in Puerto Rico are closely related.


Enterovirus uveitis.
Enterovirus uveitis (EU) is a new infant eye disease that was first observed in 1980. Three distinct subtypes of human echoviruses, EV19/K, EV11/A and EV11/B, caused five hospital outbreaks of EU in different Siberian cities in 1980-1989, affecting approximately 750 children, predominantly below 1 year of age. Sporadic EU cases were also retrospectively diagnosed in other regions of Russia and in different countries of the Former Soviet Union. The illness was characterised by rapid iris destruction and severe complications, including cataract and glaucoma. The disease has been a subject of intensive studies and was reproduced in lower primates after intraocular inoculation of isolated enterovirus strains. Importantly, prototype EV11 and EV19 strains did not induce notable disease in experimental monkeys. Some of the EU-causing strains were shown to be similar phylogenetically and in their pathogenetic properties to the enterovirus strains associated with multisystem hemorrhagic disease of newborns. In this review we present a summary of the vast epidemiological, virological, clinical and experimental data on this new form of ophthalmic infection.


Response of alternative splice isoforms of OsRad9 gene from Oryza sativa to environmental stress.
Rad9 protein plays an important role in cell-cycle checkpoint signal transduction in human and yeast cells, but knowledge about Rad9 in plants is limited. This study reports that the Rad9 gene of rice can generate the transcript products OsRad9.1 and OsRad9.2 through alternative splicing. OsRad9.1, with all nine exons, is the main cell-cycle checkpoint protein involved in the response of rice to genotoxic stresses (ultraviolet radiation and antibiotic stress), environmental stresses (drought, salt, and heavy metal stress), and auxin stimuli (2,4-D, IAA, and IBA). Meanwhile, transcript isoform OsRad9.2, which lost exon7 and exon8, showed different preferential stimulation effects on these stresses and pollen development duration. These results might indicat that besides the monitoring and repair of DNA damage, Rad9 might involve in the development of pollen.


[To attach great importance to the identification of refractory myasthenia gravis].
Refractory myasthenia gravis is an intractable state during treatment. The common causes of refractory treatment in most patients include: overwork, malnutrition, infections, insomnia, cognitive and emotional disorders, and so on. Only targeting the poor curative effect from the surface of the intractable state caused indecisive decisions and is difficult to win a success. Therefore, identifying "refractory state" can not only see the essence through the phenomenon, but also apply the right medicine, thereby killing two birds with one stone.


Cerebellar oxidative DNA damage and altered DNA methylation in the BTBR T+tf/J mouse model of autism and similarities with human post mortem cerebellum.
The molecular pathogenesis of autism is complex and involves numerous genomic, epigenomic, proteomic, metabolic, and physiological alterations. Elucidating and understanding the molecular processes underlying the pathogenesis of autism is critical for effective clinical management and prevention of this disorder. The goal of this study is to investigate key molecular alterations postulated to play a role in autism and their role in the pathophysiology of autism. In this study we demonstrate that DNA isolated from the cerebellum of BTBR T+tf/J mice, a relevant mouse model of autism, and from human post-mortem cerebellum of individuals with autism, are both characterized by an increased levels of 8-oxo-7-hydrodeoxyguanosine (8-oxodG), 5-methylcytosine (5mC), and 5-hydroxymethylcytosine (5hmC). The increase in 8-oxodG and 5mC content was associated with a markedly reduced expression of the 8-oxoguanine DNA-glycosylase 1 (Ogg1) and increased expression of de novo DNA methyltransferases 3a and 3b (Dnmt3a and Dnmt3b). Interestingly, a rise in the level of 5hmC occurred without changes in the expression of ten-eleven translocation expression 1 (Tet1) and Tet2 genes, but significantly correlated with the presence of 8-oxodG in DNA. This finding and similar elevation in 8-oxodG in cerebellum of individuals with autism and in the BTBR T+tf/J mouse model warrant future large-scale studies to specifically address the role of OGG1 alterations in pathogenesis of autism.


A simple method for controllable preparation of polymer nanotubes via a single capillary electrospinning.
Polymer nanotubes have been successfully electrospun via a single capillary spinneret instead of coaxial electrospinning. By altering the volume of ethanol under a fixed amount of poly(vinyl pyrrolidone) (PVP) and tetraethyl orthosilicate (TEOS) in the precursor, the nanotubes could be controllably produced for a proper concentration of PVP solution. Further investigation showed that the diameters of nanotubes, the thicknesses of nanotube walls, and the ratios of the thickness of the nanotube wall to the nanotube diameter (RTNWND) could be controlled by altering the amount of TEOS in the precursor. With increasing the ratios of TEOS to PVP solution, the nanotube diameters were increased and the nanotube walls were decreased. Thus, the RTNWND were decreased. The applied voltages also have an effect on the nanotube diameter and the thickness of the nanotube wall, but little on the RTNWND. The effects of ethanol and TEOS on evaporation and phase separation processes were discussed.


Response to cadmium and phytostabilization potential of Platycladus orientalis in contaminated soil.
The tolerance characteristics and phytostabilization potential of Platycladus orientalis grown in soil contaminated by cadmium (Cd) were studied using a greenhouse experiment. The results showed that the ornamental plant P. orientalis had high tolerance for Cd in contaminated soil at 24.6 mg·kg-1 and its physiological activities were slightly affected after 203 days (d) of cultivation. Moreover, Cd in soil at 9.6 mg·kg-1 was beneficial for P. orientalis growth, and the total biomass after 203 d cultivation was significantly (p < 0.05) increased by 35.03%, while the contents of chlorophyl a, chlorophyl b and carotenoid in leaves also increased by 20.84%, 44.06% and 28.25% compared to the control, respectively. Meanwhile, the Cd content in the tissues of P. orientalis was increased with both plant growth and the Cd content in the soil. The uptake of Cd in P. orientalis roots was greater than in shoots, with the Cd content in roots reaching 41.45 mg·kg-1. P. orientalis, an ornamental plant, that accumulates Cd predominantly in its roots, can be suggested as a promising plant for phytostabilization in Cd-contaminated soil.


Inhalation devices: from basic science to practical use, innovative vs generic products.
Inhalation therapy is a convenient method of treating respiratory diseases. The key factors required for inhalation are the preparation of drug carriers (aerosol particles) allowing reproducible dosing during administration. These technical challenges are accomplished with a variety of inhalation devices (inhalers) and medicinal formulations, which are optimized to be easily converted into inhalable aerosols. Areas covered: This review is focused on the most important, but often overlooked, effects, which are required for the reliable and reproducible inhalable drug administration. The effects of patient-related issues that influence inhalation therapy, such as proper selection of inhalers for specific cases is discussed. We also discuss factors that are the most essential if generic inhalation product should be considered equivalent to the drugs with the clinically confirmed efficacy. Expert opinion: Proper device selection is crucial in clinical results of inhalation therapy. The patients' ability to coordinate inhalation with actuation, generation of optimal flow through the device, use of optimal inspiratory volume, all produces crucial effects on disease control. Also the severity of the disease process effects proper use of inhalers. Interchanging of inhalers can produce potentially conflicting problem regarding efficacy and safety of inhalation therapy.


A case of papillary carcinoma in a thyroglossal cyst without a carcinoma in the thyroid gland.
The thyroglossal duct cyst is the most common developmental anomaly of the thyroid gland. We present a patient with a papillary thyroid carcinoma diagnosed after surgical resection of a thyroglossal cyst. The 39-year-old patient reported to our hospital due to a swelling of this throat. The results of the ultrasonography were reported as showing multiple nodules in both thyroid lobes, and an ~3-cm diameter image in the submental area, in keeping with lymphadenomegalia. In the fine-needle aspiration cytology (FNAC) evaluation from the nodules in the thyroid, it was observed that the thyrocites with uniform nuclei made up single-layer groups. FNAC from the thyroglossal cyst, a few histiocytes were observed on a ground with a large number of erythrocytes. The patient was subjected to a total thyroidectomy, pyramidal lobe excision, and total excision of the 3-cm diameter soft mass, starting at the tip of the pyramidal lobe. The case was diagnosed as papillary thyroid carcinoma in thyroglossal duct cyst with histopathological and immunohistochemical findings. If the thyroglossal channel cyst had been diagnosed preoperatively, total thyroidectomy and a Sistrunk operation would have been performed. For this reason, repeated FNAC, particularly, if performed under ultrasound guidance, may improve the diagnostic value of FNAC. Thus, in such patients, throat ultrasonography must be carried out in expert hands, thin-needle aspiration biopsy, computerized tomography, and thyroid scintigraphy must be done if necessary, and the necessary treatment protocols carried out after a definite diagnosis.


[Morphological studies of the effect of chromium-III-chloride on the islet cell organ in rats under the conditions of high and low fat diets].
It is well known, that the glucose tolerance factor amplifies the peripheral action of insulin. This factor contains trivalent chromium. This investigation deals with the influence of trivalent chromium on morphometric and histological parameters of pancreatic islets of wistar rats. Animals were given chromium-III-chloride for 8 weeks (perorally, daily 15 ppm or 3 ppm) under conditions of high (HFD) and low (LFD) fat diet. Staining of pancreatic slices was performed with Victoria blue and acid Fuchsin. The relative volume density of the endocrine cells was obtained as the ratio of the number of islet cells to the number of exocrine pancreatic cells. The statistical evaluation was performed by using Students t-test. In HFD animals (n = 12) chromium supplementation caused an increase by 41% of volume of islets compared to HFD controls. A lot of small islets were found, which may be newly formed. Moreover, polynesia and hyperplasia of islets were observed. LFD animals (n = 12) do not show any morphometric changes in comparison with LED controls; but macronesia, micronesia and polynesia of islets were observed. In conclusion we suggest, that under special conditions trivalent chromium has growth stimulatory effects on the endocrine pancreas.


Antibiotic sensitivity patterns of actinomycetes isolated from patients of actinomycetoma.
The effectiveness of eight antibiotics against 30 human isolates of actinomycetoma agents belonging to 7 different species were tested by agar dilution and disc diffusion methods to evaluate the susceptibility patterns and to study drug resistance among the organisms. It was found that many of the isolates had developed partial or complete resistance to conventionally used antibiotics like cotrimoxazole, streptomycin and ampicillin, but almost all were sensitive to amikacin and ciprofloxacin. The two methods were equally effective for detecting sensitivity patterns of the Nocardia isolates.


Massive cerebral calcifications associated with increased renal phosphate reabsorption.
Extensive bilateral cerebral cortical calcifications were demonstrated in a young patient with a history of convulsions since the age of 4 years. Initial metabolic workup showed normal serum calcium levels, hyperphosphatemia, normal renal function, low urinary calcium excretion, and normal serum immunoreactive parathyroid hormone levels. The intravenous infusion of edetate disodium (disodium EDTA) showed a normal phosphaturic and cyclic adenosine monophosphate response, ruling out the diagnosis of pseudohypoparathyroidism. The infusion of acetazolamide produced a blunted phosphaturia with almost no change in the renal phosphorus threshold, suggesting a tubular defect that allows enhanced proximal tubular reabsorption of phosphorus. Although the exact mechanisms responsible for the localized calcifications remain obscure, we suggest that an enhanced proximal tubular reabsorption of phosphorus could be involved in the pathophysiologic basis of this abnormality.


Prevention and treatment of diabetic nephropathy: role of angiotensin-converting enzyme inhibitors.
To discuss the role of angiotensin-converting enzyme inhibitors in the management of diabetes-related renal disease. We review the published data from animal studies and clinical trials and outline the adverse effects that may limit the use of these drugs. Diabetic nephropathy is the most common cause of end-stage renal disease and dialysis in the United States. With improving measures to optimize blood glucose control and blood pressure, the progression from mild proteinuria to overt renal insufficiency can now be retarded or even arrested. Studies of therapeutic interventions have shown that angiotensin-converting enzyme inhibitors have a superior beneficial effect on nephropathy. Few adverse effects are associated with use of these drugs: a nonproductive cough is the most frequent side effect, and angioedema and agranulocytosis are the most serious (albeit rarely reported) effects. Angiotensin-converting enzyme inhibitors should be considered as first-line therapy for patients with diabetes who have microalbuminuria or macroalbuminuria.


Current status of musculoskeletal application of shear wave elastography.
Ultrasonography (US) is a very powerful diagnostic modality for the musculoskeletal system due to the ability to perform real-time dynamic high-resolution examinations with the Doppler technique. In addition to acquiring morphologic data, we can now obtain biomechanical information by quantifying the elasticity of the musculoskeletal structures with US elastography. The earlier diagnosis of degeneration and the ability to perform follow-up evaluations of healing and the effects of treatment are possible. US elastography enables a transition from US-based inspection to US-based palpation in order to diagnose the characteristics of tissue. Shear wave elastography is considered the most suitable type of US elastography for the musculoskeletal system. It is widely used for tendons, ligaments, and muscles. It is important to understand practice guidelines in order to enhance reproducibility. Incorporating viscoelasticity and overcoming inconsistencies among manufacturers are future tasks for improving the capabilities of US elastography.


Breast Cancer and Transplantation.
Breast cancer is an important cancer among solid organ transplant recipients. While the incidence of breast cancer in solid organ transplant recipients is comparable to the age-matched general population, the outcomes are generally poor. Interventions such as cancer screening that preclude the development of late-stage disease through early detection are not well studied, and clinical practice guidelines for cancer screening rely solely on recommendations from the general population. Among patients with a prior breast cancer history, disease recurrence after transplantation is a rare but fearful event. Once disease recurs, the risk of death is high. The focus of this review is to present the epidemiology of breast cancer in solid organ transplant recipients, screening and preventive strategies for those who may be at risk, novel genomic profiling for determining tumor progression, and the newer targeted interventions for recipients who have developed breast cancers after solid organ transplantation.


[Evaluation of an analgesic activity in man: thermodolorimetery].
The authors propose an experimental technique which makes possible the evaluation in man of the activity of analgesic or anti-inflammatory medications. The principle of thermodolorimetre threshold of painful thermic sensitivity (S.S.T.D. in the french text) which is stable over a period of time in a given individual receiving a placebo but which varies in a significant fashion in groups treated with a medication belonging to one of the two classifications studied.


[Distal fracture of the humerus].
Independently of lacerated anatomic structures, the ensuing fracture type, concomitant injuries around the joint, the primary aim in treating distal humeral fractures is the restoration of a painfree, mechanically loadable elbow that has a free range of motion. To achieve these goals the fracture and its associated injuries have to be adequately diagnosed, adequately surgically treated, and after reconstruction must undergo an early physical therapy (PT) protocol. Adequate diagnostics, except for standard X-ray films, include in most cases an additional preoperative CT for evaluation and planning of the surgical approach. Adequate surgical treatment entails anatomic reconstruction and stable fixation via an approach that causes a minimum of additional iatrogenic injury to the adjacent soft tissues. Adequate PT is synonymous with early onset of movement, i.e. as early as the 1st postoperative day if the fixation is stable enough. However, a demanding problem is the increasing number of osteoporosis-associated distal humeral fractures in the elderly population with the development of complex fracture types, partly due to poor bone quality, that are not easily addressed and might lead to unsatisfactory results even after applying standardized protocols including anatomically contoured angular stable plates.


Role of cognitive assessment for high school graduates prior to choosing their college major.
[Purpose] Academic performance of college students can be impacted by the efficacy of students' ability and teaching methods. It is important to assess the progression of college students' cognitive abilities among different college majors and as they move from junior to senior levels. However, dearth of studies have been examined the role of cognitive ability tests as a tool to determine the aptitude of the perspective students. Therefore, this study assessed cognitive abilities of computer science and ART students. [Subjects and Methods] Participants were 130 college students (70 computer and 60 art students) in their first and final years of study at King Saud University. Cognitive ability was assessed using the Test of Nonverbal Intelligence, Third Edition. [Results] The cognitive ability of computer science students were statistically better than that of art students and were shown improvement from junior to senior levels, while the cognitive ability of art students did not. [Conclusion] The cognitive ability of computer science college students was superior compared to those in art, indicating the importance of cognitive ability assessment for high school graduates prior to choosing a college major. Cognitive scales should be included as an aptitude assessment tool for decision-makers and prospective students to determine an appropriate career, which might reduce the rate of university drop out.


Neuroprotective effect of pseudoginsenoside-f11 on a rat model of Parkinson's disease induced by 6-hydroxydopamine.
Pseudoginsenoside-F11 (PF11), a component of Panax quinquefolism (American ginseng), plays a lot of beneficial effects on disorders of central nervous system. In this paper, the neuroprotective effect of PF11 on Parkinson's disease (PD) and the possible mechanism were investigated in a rat PD model. PF11 was orally administered at 3, 6, and 12 mg/kg once daily for a period of 2 weeks before and 1 week after the unilateral lesion of left medial forebrain bundle (MFB) induced by 6-hydroxydopamine (6-OHDA). The results showed that PF11 markedly improved the locomotor, motor balance, coordination, and apomorphine-induced rotations in 6-OHDA-lesioned rats. The expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and the content of extracellular dopamine (DA) in striatum were also significantly increased after PF11 treatment. Moreover, significant reduction in the levels of striatal extracellular hydroxyl radical ( (∙) OH), detected as 2,3- and 2,5-dihydroxy benzoic acid (2,3- and 2,5-DHBA), and increase in the level of striatal extracellular ascorbic acid (AA) were observed in the PF11-treated groups compared with 6-OHDA-lesioned rats. Taken together, we propose that PF11 has potent anti-Parkinson property possibly through inhibiting free radical formation and stimulating endogenous antioxidant release.


A complete logical approach to resolve the evolution and dynamics of mitochondrial genome in bilaterians.
Investigating how recombination might modify gene order during the evolution has become a routine part of mitochondrial genome analysis. A new method of genomic maps analysis based on formal logic is described. The purpose of this method is to 1) use mitochondrial gene order of current taxa as datasets 2) calculate rearrangements between all mitochondrial gene orders and 3) reconstruct phylogenetic relationships according to these calculated rearrangements within a tree under the assumption of maximum parsimony. Unlike existing methods mainly based on the probabilistic approach, the main strength of this new approach is that it calculates all the exact tree solutions with completeness and provides logical consequences as highly robust results. Moreover, this method infers all possible hypothetical ancestors and reconstructs character states for all internal nodes of the trees. We started by testing our method using the deuterostomes as a study case. Then, with sponges as an outgroup, we investigated the evolutionary history of mitochondrial genomes of 47 bilaterian phyla and emphasised the peculiar case of chaetognaths. This pilot work showed that the use of formal logic in a hypothetico-deductive background such as phylogeny (where experimental testing of hypotheses is impossible) is very promising to explore mitochondrial gene order in deuterostomes and should be applied to many other bilaterian clades.


Activity of coagulation factor XI in patients with spontaneous miscarriage: the presence of risk alleles.
The aim of this study was to compare the activity of coagulation factor XI (FXI) between patients with spontaneous miscarriage versus control group with no history of miscarriage and thrombosis, and then we evaluated the occurrence of risk alleles in the relation to miscarriage. FXI activity was determined using a coagulometer (Sysmex, CA 1500, Japan). Single nucleotide polymorphisms (SNPs) of F11 and CYP4V2 genes were evaluated. We examined 55 patients versus 31 control subjects. We found significantly higher activity of FXI (p = 0.04) in patients versus control subjects. The occurrence of two SNPs (rs2289252 and rs2036914) of the F11 gene and SNP (rs13146272) of CYP4V2 gene was not significantly different between both groups. Increased activity of FXI may be a potential risk factor for miscarriage. High activity of FXI diagnosed in women with history of miscarriage is not probably caused by the presence of studied SNPs.


[Changes in the serum immunoglobulin levels in mice with methylcholanthrene-induced fibrosarcoma].
The serum immunoglobulin levels in mice with methylcholanthrene-induced sarcomas are studied. The results differ in the several groups of mice according to the localization of the tumor, and to the presence or absence of spleen.


Behavioural signatures of backward planning in animals.
Goal-directed planning in behavioural and neural sciences is theorized to involve a prospective mental simulation that, starting from the animal's current state in the environment, expands a decision tree in a forward fashion. Backward planning in the artificial intelligence literature, however, suggests that agents expand a mental tree in a backward fashion starting from a certain goal state they have in mind. Here, we show that several behavioural patterns observed in animals and humans, namely outcome-specific Pavlovian-to-instrumental transfer and differential outcome effect, can be parsimoniously explained by backward planning. Our basic assumption is that the presentation of a cue that has been associated with a certain outcome triggers backward planning from that outcome state. On the basis of evidence pointing to forward and backward planning models, we discuss the possibility of brain using a bidirectional planning mechanism where forward and backward trees are expanded in parallel to achieve higher efficiency.


Moral decision making in adolescents: The effects of peer attachment, interpersonal affect, and gender.
Sacrificial moral dilemmas are a useful tool for understanding how individuals reconcile concerns for aggregate welfare with the emotional aversion to deliberately, personally harming others. Yet little is known about how adolescents respond to such dilemmas, even though adolescence is a crucial period for moral development. The present study sought to investigate how adolescents respond to such dilemmas, with a focus on gender differences, age differences, and the role of two individual differences factors: peer attachment and dampened interpersonal affect. For this cross-sectional study, 103 adolescents (mean age = 14.5, SD = 0.81, range = 12-16; 54% girls; 41% Black, 24% White, 15% multiracial, 9% Hispanic/Latin, 3% Other, 2% Asian/Pacific Islander, 1% Native American, 5% no response) were recruited from the local community (Brooklyn, NY, USA). Adolescents responded to a series of sacrificial moral dilemmas. Then, participants and their caregivers completed questionnaires to assess adolescents' callous-unemotional traits (e.g., lack of empathy) and the quality of their peer relationships. On average, participants endorsed committing personal harm for the greater good in 53% of their responses. Girls endorsed personal utilitarian sacrifice more than boys. Peer attachment, but not dampened interpersonal affect, was associated with increased endorsement of personal utilitarian sacrifice. Age and responses to dilemmas were not associated. Our results suggest that peer relationships are an important part of adolescent moral decision-making, for girls in particular. Our results also indicate that adolescents' utilitarian responses to conventional sacrificial moral dilemmas do not reflect a decreased aversion to interpersonal harm.


β-Elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway.
Benign airway stenosis is a clinical challenge because of recurrent granulation tissues. Our previous study proved that a Chinese drug, β-elemene, could effectively inhibit the growth of fibroblasts cultured from hyperplastic human airway granulation tissues, which could slow down the progression of this disease. The purpose of the present study is to find out the mechanism for this effect. We cultured fibroblasts from normal human airway tissues and human airway granulation tissues. These cells were cultured with 160 μg/ml normal saline (NS), different doses of β-elemene, or 10 ng/ml canonical Wnt/β-catenin pathway inhibitor (Dickkopf-1, DKK-1). The proliferation rate of cells and the expression of six molecules involved in canonical Wnt/β-catenin pathway, Wnt3a, glycogen synthase kinase-3β (GSK-3β), β-catenin, α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and Collagen I (Col-I), were measured. At last, we used canonical Wnt/β-catenin pathway activator (LiCl) to further ascertain the mechanism of β-elemene. Canonical Wnt/β-catenin pathway is activated in human airway granulation fibroblasts. β-Elemene didn't affect normal human airway fibroblasts; however, it had a dose-responsive inhibitive effect on the proliferation and expression of Wnt3a, non-active GSK-3β, β-catenin, α-SMA, TGF-β, and Col-I of human airway granulation fibroblasts. More importantly, it had the same effect on the expression and nuclear translocation of active β-catenin. All these effects were similar to 10 ng/ml DKK-1 and could be attenuated by 10 mM LiCl. Thus, β-elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway. This pathway is possibly a promising target to treat benign tracheobronchial stenosis.


Quantifying the contribution of changes in healthcare expenditures and smoking to the reversal of the trend in life expectancy in the Netherlands.
Since 2001 the Netherlands has shown a sharp upturn in life expectancy (LE) after a longer period of slower improvement. This study assessed whether changes in healthcare expenditure (HCE) explain this reversal in trends in LE. As an alternative explanation, the impact of changes in smoking behavior was also evaluated. To quantify the contribution of changes in HCE to changes in LE, we estimated a health-production function using a dynamic panel regression approach with data on 19 OECD countries (1980-2009), accounting for temporal and spatial correlation. Smoking-attributable mortality was estimated using the indirect Peto-Lopez method. As compared to 1990-1999, during 2000-2009 LE in the Netherlands increased by 1.8 years in females and by 1.5 years in males. Whereas changes in the impact of smoking between the two periods made almost no contribution to the acceleration of the increase in LE, changes in the trend of HCE added 0.9 years to the LE increase between 2000 and 2009. The exceptional reversal in the trend of LE and HCE was not found among the other OECD countries. This study suggests that changes in Dutch HCE, and not in smoking, made an important contribution to the reversal of the trend in LE; these findings support the view that investments in healthcare are increasingly important for further progress in life expectancy.


[Prevention of hemolytic disease in newborn infants using anti-D immunoglobulin G].
The authors have analyzed the prevention of Rh-immunization from 1972 to 1983. Results are presented in two six-year periods, i.e. from 1972 to 1977 and from 1978 to 1983. Prevention was applied to all rh-negative women, who have been delivered from a rh-negative baby in their first childbirth (with negative sensibilization tests). Anti D IgG was also applied to all women after their second, third, fourth or subsequent delivery, if they were willing to have more children. Women with Du variant of the Rh factor and having a Rh-positive child were also protected. Preparations containing 250 to 300 micrograms of IgG anti-D were used. During the first period we found rh-negative mothers in 18.41 per cent, in 63.48 per cent of them the newborn was Rh-positive. During the second period 17.89 per cent of our women were rh-negative with 58.45 per cent Rh-positive babies. During the first period, protection was afforded to 60.26 per cent of the rh-negative women with incompatible babies, and in the second period to 79.11 per cent, respectively (P less than 0.05). During the second period, 99.70 per cent of women were protected after their first delivery (except of one case with immunization already during pregnancy), in contrast to the first period, where this percentage amounted only to 84.66 per cent (P less than 0.05). During both periods, a total of 69.51 per cent of the rh-negative women having Rh-positive babies received anti-D-immunization.(ABSTRACT TRUNCATED AT 250 WORDS)


Mapping DNA adducts of mitomycin C and decarbamoyl mitomycin C in cell lines using liquid chromatography/ electrospray tandem mass spectrometry.
The antitumor antibiotic and cancer chemotherapeutic agent mitomycin C (MC) alkylates and crosslinks DNA, forming six major MC-deoxyguanosine adducts of known structures in vitro and in vivo. Two of these adducts are derived from 2,7-diaminomitosene (2,7-DAM), a nontoxic reductive metabolite of MC formed in cells in situ. Several methods have been used for the analysis of MC-DNA adducts in the past; however, a need exists for a safer, more comprehensive and direct assay of the six-adduct complex. Development of an assay, based on mass spectrometry, is described. DNA from EMT6 mouse mammary tumor cells, Fanconi Anemia-A fibroblasts, normal human fibroblasts, and MCF-7 human breast cancer cells was isolated after MC or 10-decarbamoyl mitomycin C (DMC) treatment of the cells, digested to nucleosides, and submitted to liquid chromatography electrospray-tandem mass spectrometry. Two fragments of each parent ion were monitored ("multiple reaction monitoring"). Identification and quantitative analysis were based on a standard mixture of six adducts, the preparation of which is described here in detail. The lower limit of detection of adducts is estimated as 0.25 pmol. Three initial applications of this method are reported as follows: (i) differential kinetics of adduct repair in EMT6 cells, (ii) analysis of adducts in MC- or DMC-treated Fanconi Anemia cells, and (iii) comparison of the adducts generated by treatment of MCF-7 breast cancer cells with MC and DMC. Notable results are the following: Repair removal of the DNA interstrand cross-link and of the two adducts of 2,7-DAM is relatively slow; both MC and DMC generate DNA interstrand cross-links in human fibroblasts, Fanconi Anemia-A fibroblasts, and MCF-7 cells as well as EMT6 cells; and DMC shows a stereochemical preference of linkage to the guanine-2-amino group opposite from that of MC.


Comparison of clinical and surgical-pathological staging in IIIA non-small cell lung cancer patients.
The heterogeneous group of IIIA NSCLC patients requires careful preoperative clinical staging as tumor size and lymph node involvement guide treatment. The purpose of our study was to analyze the correctness of clinical staging in IIIA patients. Retrospective analysis of all patients resected due to lung cancer that had been staged IIIA either clinically using invasive and noninvasive techniques or surgical-pathologically after surgical resection. Correctness, sensitivity, specificity, and positive and negative predictive values of clinical staging were calculated. From our tumor database, 49 patients who met the inclusion criteria were identified. The histology of the primary tumor included adenocarcinoma (53%), squamous cell carcinoma (41%), and other (6%). Preoperative clinical staging consisted of computed tomography (CT), integrated positron emission tomography-CT (PET-CT), bronchoscopy, and mediastinoscopy. The predominant surgical procedures performed were lobectomies (57%) and pneumonectomies (29%). Clinical staging for UICC, T and N stage was correct in 36.7, 38.7, and 40.8%, respectively. In terms of T4 stage, sensitivity was 28.5%, specificity was 80.9%, positive predictive value was 20%, and negative predictive value was 87.1%. As for N2 involvement, we found a sensitivity of 66.6% and a specificity of 35.7%. Positive and negative predictive values for N2 involvement were 43.7 and 58.8% in that order. Despite multimodal preoperative invasive and noninvasive staging techniques, the correctness of clinical staging in IIIA NSCLC patients is low. Hence, in doubt more invasive staging or probatory thoracotomy should be performed not to deny potentially curative surgery in those patients.


From Identification to Characterization of the Multiple Sclerosis Susceptibility Gene CLEC16A.
Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system that develops in genetically susceptible individuals, probably triggered by common environmental factors. Human leukocyte antigen (HLA) loci were early shown to confer the strongest genetic associations in MS. Now, more than 50 non-HLA MS susceptibility loci are identified, of which the majority are located in immune-regulatory genes. Single nucleotide polymorphisms (SNPs) in the C-type lectin-like domain family 16A (CLEC16A) gene were among the first non-HLA genetic variants that were confirmed to be associated with MS. Fine-mapping has indicated a primary association in MS and also other autoimmune diseases to intronic CLEC16A SNPs. Here, we review the identification of MS susceptibility variants in the CLEC16A gene region, functional studies of the CLEC16A molecule and the recent progress in understanding the implications thereof for MS development. This may serve as an example of the importance for further molecular investigation of the loci identified in genetic studies, with the aim to translate this knowledge into the clinic.


Emergence of canine hookworm treatment resistance: Novel detection of Ancylostoma caninum anthelmintic resistance markers by fecal PCR in 11 dogs from Canada.
To describe dogs with detected Ancylostoma caninum anthelmintic treatment resistance markers in Canada. 11 client-owned dogs with fecal quantitative PCR (qPCR) assay detected A caninum with benzimidazole (BZ) resistance genotypic markers. Signalment, presenting concern, duration of clinical signs, fecal testing, treatment, and outcomes were obtained. Where available, follow-up data were collected via telephone or email with the primary veterinarian. Ancylostoma spp was detected from 184/32,205 dog fecal samples by reference laboratory qPCR surveillance, between May 15, 2022, and April 26, 2023. 11 of these 184 samples had A caninum with genetic BZ F167Y resistance marker detection. 4 dogs had not traveled outside Canada, 6 had been imported from the US, and the travel history was unclear in 1 dog. 7 of the dogs had gastro-intestinal signs (diarrhea or soft stool) on initial presentation. Clinical improvement was reported in 6 of these dogs (resolution of diarrhea and soft stool), with 1 dog lost to follow-up. All 11 dogs received anthelmintic treatment (varied drugs and duration). Identification of genetic markers of BZ resistance raises concerns about the potential animal and human impacts of resistant hookworms. 4 dogs lacked an origin from or travel history to the US, indicating true emergence and/or novel spread within Canada, not just importation from an area where resistance has been reported. Fecal surveillance was performed with a qPCR test incorporating treatment (BZ) resistance markers. There is a need to raise clinician awareness around treatment-resistant hookworm in dogs and the capability of fecal surveillance for genotypic and phenotypic resistance.


Cytotoxicity and genotoxicity effects of arsenic trioxide on SQ20B human laryngeal carcinoma cells.
This study investigates the cytotoxicity and the genotoxicity induced by arsenic trioxide As2O3in human laryngeal SQ20B carcinoma cell line. SQ20B cells were exposed to graded concentrations of arsenic trioxide (2 and 5μM) for 48h. Comet assay and γ-H2AX foci formation were used for measuring DNA damages, flow cytometry was used to identify cell cycle alterations and apoptosis, while cell morphology was visualized using transmission electron microscopy. The results show a dose-dependent induction of DNA damages and double strand breaks, alterations in cell cycle and morphologic alterations of cells. These results prove that As2O3 is highly cytotoxic and genotoxic at the micromolar range ina human laryngeal carcinoma cell line.